RESUMO
OBJECTIVES: This cross-sectional study investigated the factors associated with weight gain ≥ 10 kg after 20 years of age in the general Japanese population, with a focus on the number of teeth. MATERIALS AND METHODS: We included individuals aged ≥ 40 years from Yamagata prefecture, Japan from 2017-2021. A postal survey was conducted using a self-administered questionnaire; 5,940 participants were included in the final analysis. The questionnaire included items on lifestyle factors, medical history, physical and mental conditions, oral health, and dietary intake. A multivariate logistic regression analysis was used to identify independent associations between weight gain ≥ 10 kg after 20 years of age and various parameters; adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: Less than 20 teeth, male sex, drinking habit frequency, eating very fast or fast, and a higher frequency of eating-away-from-home were significant factors associated with weight gain ≥ 10 kg after 20 years of age; individuals with < 20 versus > 20 teeth exhibited a 1.35-fold higher OR (95% CI 1.15-1.59; p < 0.01). CONCLUSIONS: Our results suggest that having < 20 teeth may affect weight gain ≥ 10 kg after 20 years of age. However, owing to the cross-sectional study design, causality could not be determined. Therefore, maintaining healthy lifestyle behaviors to avoid tooth loss may also affect weight gain ≥ 10 kg after 20 years of age. CLINICAL RELEVANCE: Having < 20 teeth has the potential to affect long-term weight gain after 20 years of age.
Assuntos
Vida Independente , Saúde Bucal , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Estudos Transversais , Japão/epidemiologia , Comportamentos Relacionados com a Saúde , Aumento de Peso , Comportamento AlimentarRESUMO
Although liver regeneration has been extensively studied, the effects of bile-derived extracellular vesicles (bile EVs) on hepatocytes has not been elucidated. We examined the influence of bile EVs, collected from a rat model of 70% partial hepatectomy (PH), on hepatocytes. We produced bile-duct-cannulated rats. Bile was collected over time through an extracorporeal bile duct cannulation tube. Bile EVs were extracted via size exclusion chromatography. The number of EVs released into the bile per liver weight 12 h after PH significantly increased. Bile EVs collected 12 and 24 h post-PH, and after sham surgery (PH12-EVs, PH24-EVs, sham-EVs) were added to the rat hepatocyte cell line, and 24 h later, RNA was extracted and transcriptome analysis performed. The analysis revealed that more upregulated/downregulated genes were observed in the group with PH24-EVs. Moreover, the gene ontology (GO) analysis focusing on the cell cycle revealed an upregulation of 28 types of genes in the PH-24 group, including genes that promote cell cycle progression, compared to the sham group. PH24-EVs induced hepatocyte proliferation in a dose-dependent manner in vitro, whereas sham-Evs showed no significant difference compared to the controls. This study revealed that post-PH bile Evs promote the proliferation of the hepatocytes, and genes promoting cell cycles are upregulated in hepatocytes.
Assuntos
Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Ratos , Animais , Hepatectomia , Bile , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Hepatócitos/metabolismo , Regeneração Hepática , Proliferação de Células , Vesículas Extracelulares/metabolismoRESUMO
OBJECTIVES: The aim of this study is to propose and evaluate a new method of volumetric perfusion computed tomography (PCT) incorporated into pancreatic multiphasic contrast enhanced (CE)-CT in the clinical setting. METHODS: In this ethically approved study, PCT was incorporated into our existing scanning protocol in 17 patients and effective doses related to PCT were evaluated. CT values and signal-to-noise ratio (SNR) of anatomical structure were compared in diagnostic images that were acquired using 320-detector volumetric scan mode and 64-detector helical scan mode. In addition, focal lesion depiction was qualitatively assessed in the two groups. Perfusion parameters in normal pancreas were measured by two radiologists and the interobserver-reliability was assessed. RESULTS: The effective dose of PCT was 5.1 ± 0.3 mSv. The actual effective dose (AED) including the dose used in volumetric scans for diagnostic imaging was 22.8 ± 5.3 mSv and the putative effective dose (PED) was 21.9 ± 9.1 mSv on average. There was no significant difference between AED and PED (p = 0.404). Compared with conventional helical scans, volumetric scans did not decrease CT values or SNR, but rather significantly increased those of the aorta in the arterial phase. Both groups had acceptable qualitatively assessed image quality with no significant difference in the depiction of each structure. There was almost perfect interobserver agreement in the measurement of perfusion parameters (mean ICCs > 0.9). CONCLUSIONS: Our scanning protocol for pancreatic perfusion CT provides high-quality images while requiring lower radiation doses than conventional methods.
Assuntos
Meios de Contraste , Pâncreas/diagnóstico por imagem , Imagem de Perfusão/métodos , Lesões por Radiação/prevenção & controle , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Neoplasias Pancreáticas/diagnóstico por imagem , Doses de Radiação , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
We herein report the case of a 64-year-old male patient with hypopituitarism associated with autoimmune pancreatitis (AIP). The patient was previously diagnosed with AIP based on the presence of a swollen pancreas, elevated serum immunoglobulin G4, and narrowing of the pancreatic duct by imaging. Magnetic resonance imaging revealed a pituitary stem tumor, and loading test showed a decrease in the function of the anterior lobe suggesting severe failure of growth hormone secretion. Treatment with steroids was effective in reducing the pituitary lesion and improving the function of the anterior lobe. The present case illustrates the importance of pituitary function evaluation before steroid treatment in patients with AIP.
Assuntos
Doenças Autoimunes/diagnóstico , Hipopituitarismo/diagnóstico , Pancreatite/diagnóstico , Idoso , Doenças Autoimunes/complicações , Humanos , Hipopituitarismo/complicações , Imunoglobulina G , Masculino , Pâncreas , Pancreatite/complicaçõesRESUMO
BACKGROUND: The incidence of pancreatic cancer is increasing year-by-year in Japan. Among the diseases that complicate pancreatic cancer, diabetes is the most common. Recently, it has become evident that patients suffering from diabetes and obesity show increased expression of osteopontin (OPN). The purpose of this study was to investigate the effect of high glucose and high insulin culture conditions on a human pancreatic duct epithelial cell line (HPDE-6), focusing particularly on OPN expression. METHODS: HPDE-6 were cultured under various conditions, employing several combinations of glucose (normal, 6 mM high, 30 mM, and 60 mM) and insulin (0.1 nM, 1 nM) concentration. RESULTS: HPDE-6 cell proliferation was significantly accelerated under high glucose culture conditions in comparison to samples in 6 mM glucose, and was more prominent under high insulin conditions. At the same time, the expression of OPN mRNA was also increased significantly. In comparison with 6 mM glucose, the expression of 8-OHdG DNA was increased in high glucose culture. CONCLUSION: HPDE-6 cells show accelerated proliferation and increased OPN expression when cultured under high glucose and high insulin conditions. Furthermore, the cells show increased oxidative stress in the presence of high glucose.
Assuntos
Glicemia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Osteopontina/genética , Osteopontina/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Insulina/metabolismo , Neoplasias Pancreáticas/patologia , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genéticaRESUMO
We report a case of pancreatic intraepithelial neoplasia-3 (PanIN-3) with autoimmune pancreatitis (AIP). The patient, a 75-year-old man, had been diagnosed to have AIP with stenosis of the main pancreatic duct. After six years, computed tomography demonstrated dilatation of the main pancreatic duct in the mid-pancreas. Although we could not confirm the presence of any pancreatic tumor on the basis of imaging modalities alone, cytological examination of the pancreatic juice obtained by endoscopic retrograde pancreatography revealed atypical cells. Therefore, we performed pancreatoduodenectomy and obtained a pathologic diagnosis of PanIN-3 with AIP. The present case is informative in the context of pancreatic carcinogenesis in AIP.
Assuntos
Doenças Autoimunes/complicações , Células Epiteliais , Neoplasias Pancreáticas/diagnóstico por imagem , Pancreatite/complicações , Idoso , Dilatação Patológica , Células Epiteliais/patologia , Humanos , Masculino , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , PancreaticoduodenectomiaRESUMO
PURPOSE: We experienced an outbreak of enterohemorrhagic Escherichia coli (EHEC) colitis. The purpose of this study was to reveal the computed tomographic (CT) findings on EHEC colitis. METHODS: The subjects were 7 patients with EHEC colitis, which was caused by eating a contaminated Japanese rice cake. Contrast CT was performed on all patients. Two radiologists evaluated the CT findings (the thickness of colon wall, the range of thickened colon, and the existence of dirty fat signs around the colon, ascites, and swelling of lymph nodes), in accordance with our PACS system. RESULTS: Wall swelling of the proximal colon from cecum to ascending colon was noted in all patients. Small intestine lesions were not noted in any cases. CONCLUSIONS: We should consider EHEC infection as part of a differential diagnosis when the findings of severe right colitis are seen without enteritis.
Assuntos
Colite/diagnóstico por imagem , Colite/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Infecções por Escherichia coli/diagnóstico por imagem , Infecções por Escherichia coli/epidemiologia , Escherichia coli O157 , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite/microbiologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Objectives: Localized autoimmune pancreatitis is difficult to differentiate from pancreatic ductal adenocarcinoma on endoscopic ultrasound images. In recent years, deep learning methods have improved the diagnosis of diseases. Hence, we developed a special cross-validation framework to search for effective methodologies of deep learning in distinguishing autoimmune pancreatitis from pancreatic ductal adenocarcinoma on endoscopic ultrasound images. Methods: Data from 24 patients diagnosed with localized autoimmune pancreatitis (8751 images) and 61 patients diagnosed with pancreatic ductal adenocarcinoma (20,584 images) were collected from 2016 to 2022. We applied transfer learning to a convolutional neural network called ResNet152, together with our innovative imaging method contributing to data augmentation and temporal data process. We divided patients into five groups according to different factors for 5-fold cross-validation, where the ordered and balanced datasets were created for the performance evaluations. Results: ResNet152 surpassed the endoscopists in all evaluation metrics with almost all datasets. Interestingly, when the dataset is balanced according to the factor of the endoscopists' diagnostic accuracy, the area under the receiver operating characteristic curve and accuracy were highest at 0.85 and 0.80, respectively. Conclusions: It is deduced that image features useful for ResNet152 correlate with those used by endoscopists for their diagnoses. This finding may contribute to sample-efficient dataset preparation to train convolutional neural networks for endoscopic ultrasonography-imaging diagnosis.
RESUMO
Prolactin is not only a pituitary hormone but an immunoregulatory hormone secreted from lymphocytes. Prolactin induction in relation to hepatitis C virus (HCV) infection has not been elucidated. The serum levels of prolactin were examined in 232 HCV-infected subjects positive for anti-HCV antibody and 65 healthy controls negative for it, who were recruited in the cohort study. The prolactin mRNAs were measured in peripheral blood mononuclear cells (PBMCs) of eleven healthy volunteers including five men and six women before and after stimulation by HCV in vitro. The serum level of prolactin and prolactin mRNA in PBMCs were measured by chemiluminescence immunoassay and real-time PCR, respectively. The serum levels of prolactin were significantly higher in the HCV-infected subjects (median: 7.5, IQR: 5.7-10.9 ng/ml) than in the controls (median: 5.6, IQR: 4.4-8.3 ng/ml) (P < 0.01). They were significantly higher in HCV-infected males (median: 8.0, IQR: 5.9-11.8 ng/ml) than in the controls (median: 4.8, IQR: 4.2-5.9 ng/ml) (P < 0.001), however, the difference was not significant between HCV-infected females (median: 7.3, IQR: 5.6-10.5 ng/ml) and the controls (median: 6.4, IQR: 5.3-9.8 ng/ml). The mRNA expression of prolactin was induced in PBMCs of all males, but it was induced in PBMCs of the two of six females examined in vitro. These results suggest that the serum level of prolactin is higher in HCV-infected males than in healthy males, and that HCV infection induces the mRNA expression of prolactin in PBMCs that is more apparent in male than in females.
Assuntos
Hepatite C/imunologia , Hepatite C/patologia , Leucócitos Mononucleares/imunologia , Prolactina/sangue , RNA Mensageiro/sangue , Soro/química , Idoso , Estudos de Coortes , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Fatores SexuaisRESUMO
AIM: To evaluate the effect of wire-guided biliary cannulation (WGC) on the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: We investigated the impact of the WGC technique on the incidence of PEP by comparing the conventional cannulation (CC) technique in selective bile duct cannulation during ERCP with a cross-over design in a prospective multicenter randomized controlled trial and the potential risk factors for PEP. This involved six tertiary referral centers and three university hospitals. A total of 322 patients with indications for ERCP requiring selective biliary cannulation were enrolled from April 2008 to March 2009. RESULTS: One hundred and sixty-three patients were assigned to the WGC group and 159 to the CC group. The incidence of PEP was the same between the groups (6.1% vs 6.3%, P = 0.95). Primary successful biliary cannulation was achieved in 136 patients (83%) in the WGC group and in 138 (87%) in the CC group (P = 0.40). The mean time required for primary successful biliary cannulation was 7.4 ± 8.3 min and 7.2 ± 7.9 min, respectively (P = 0.83). Multivariate analysis demonstrated that accidental guidewire insertions and unintended injections of contrast into the main pancreatic duct were the only independent risk factors for PEP (P = 0.001, relative risk [RR]: 8.70, 95% confidence interval [CI]: 2.46-30.81). CONCLUSION: The WGC technique does not reduce the risk of PEP and also does not improve the success rate of selective bile duct cannulation.
Assuntos
Ductos Biliares , Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/etiologia , Pancreatite/prevenção & controle , Idoso , Meios de Contraste/efeitos adversos , Estudos Cross-Over , Feminino , Humanos , Incidência , Masculino , Pancreatite/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
This cross-sectional study aimed to investigate the risk factors for low levels of subjective well-being (SWB) in the general population of Japan, specifically, the impact of the number of teeth and self-rated mastication. The surveyed population consisted of individuals aged between 40 and 79 years from Yamagata prefecture, Japan. A postal self-administered questionnaire survey of respondents lifestyles, medical history, oral health, and dietary intake, was conducted from 2017 to 2021. We included 6846 participants to confirm the independent associations between SWB and several parameters using multivariate ordinal logistic regression analysis to estimate adjusted odds ratios and 95% confidence intervals. Individuals withâ <â 20 teeth and poor mastication ability had a 1.3-fold risk for low levels of SWB compared with individuals withâ ≥â 20 teeth with good mastication ability (adjusted odds ratiosâ =â 1.300, 95% confidence intervalsâ =â 1.043-1.621, Pâ =â .020). There were no differences between individuals with good mastication ability, regardless of the number of remaining teeth. Our study emphasizes not only the importance of havingâ ≥â 20 teeth and good mastication ability for high levels of SWB but also the importance of restoring mastication ability using some form of prosthesis, to facilitate a high level of SWB when the number of remaining teeth isâ <â 20.
Assuntos
Mastigação , Dente , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Transversais , População do Leste Asiático , Ingestão de Alimentos , Japão/epidemiologiaRESUMO
Self-rated health (SRH) is a predictive factor for health-related prognoses such as mortality. This study aimed to comprehensively investigate the risk factors for poor SRH in the general population of Japan, focusing on the combination of the number of teeth and self-rated mastication. Individuals aged at least 40 years in Yamagata Prefecture, Japan, were surveyed from 2017 to 2021. The participants answered a self-administered postal survey on lifestyle factors, medical history, physical and mental conditions, oral health, and dietary intake, and 6739 participants were included. Multivariate logistic regression analysis showed that individuals with less than 20 teeth and who bite tightly on one side or neither side were at a 1.422- and 1.952-fold significantly higher risk, respectively, of poor SRH than individuals with at least 20 teeth and who bite tightly on both sides. Moreover, individuals who had less than 20 teeth but could bite tightly on both sides did not have a significant risk compared to those who had at least 20 teeth and could bite tightly on both sides. Regarding individuals with more than 20 teeth, there was no difference between those who could and could not bite tightly on both sides, although the odds ratios for poor SRH tended to increase for those who could bite on one side or neither side. Our results emphasize the importance of having at least 20 teeth without periodontal disease and oral rehabilitation using a type of prosthesis for SRH, even with less than 20 teeth.
Assuntos
Vida Independente , Mastigação , Humanos , Adulto , Pessoa de Meia-Idade , Japão/epidemiologia , Estudos de Coortes , Nível de SaúdeRESUMO
This study examined the association between dental health conditions and scores on the University Personality Inventory (UPI) among university students in Japan. Participants were freshmen at Yamagata University between 2010 and 2019. Dental check-ups, including dental caries, periodontal disease, malocclusion, and temporomandibular disorders (TMD), and mental health screening using the UPI were performed; 12,433 students were included in the final analysis. A logistic regression analysis was performed to confirm the association between dental health conditions and >30 UPI scores, which indicate the need to consult mental health professionals. Overall, students who required treatment for TMD had a 3.165-fold higher risk of >30 UPI scores (OR = 3.165, 95% CI = 1.710−5.857). Periodontal disease and TMD in male participants (periodontal disease: OR = 1.329, 95% CI = 1.108−1.595; TMD: OR = 3.014, 95% CI = 1.107−8.204) and TMD in female participants (OR = 2.938, 95% CI = 1.340−6.445) were significant risk factors for >30 UPI scores. Students requiring treatment for TMD were at risk of obtaining >30 UPI scores. Although our study has several limitations, students with subjective symptoms (e.g., disturbance in opening the mouth) should take the UPI test or in some cases consult mental health professionals.
Assuntos
Cárie Dentária , Doenças Periodontais , Transtornos da Articulação Temporomandibular , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Inventário de Personalidade , Estudantes , Inquéritos e Questionários , UniversidadesRESUMO
Fish bone migration into the bile duct in patients with surgically altered anatomy is a very rare cause of bile duct stones. Recently, balloon-assisted endoscopic retrograde cholangiopancreatography (BAERCP) is performed for biliary lesions in patients with surgically altered anatomy. We report on a 73-year-old Japanese man with a history of pancreaticoduodenectomy for intraductal papillary mucinous adenoma. A 20 mm long linear hyperattenuating structure in the left intrahepatic bile duct was noted on routine follow-up computed tomography 14 years postoperatively. The linear structure persisted until follow-up computed tomography performed 15 years postoperatively, and the left intrahepatic bile duct was shown to be dilated. We performed BAERCP for the diagnosis and treatment of the linear structure but could not visualize the linear structure in the left intrahepatic bile duct via enteroscopy and fluoroscopy. We removed the enteroscope, leaving the overtube, and inserted the cholangioscope through the overtube over the guide wire. We observed a brown rod-shaped linear structure in the left intrahepatic bile duct and removed it under direct visualization via overtube-assisted cholangioscopy. We conclude that overtube-assisted cholangioscopy was useful for assessing undiagnosed biliary lesions using conventional BAERCP and removing fish bones in the bile duct of the patient with altered gastrointestinal anatomy.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Pancreaticoduodenectomia , Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/cirurgia , Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , HumanosRESUMO
Covered self-expandable metal stents (CSEMS) are often used for palliative endoscopic biliary drainage; however, the unobstructed period is limited because of sludge occlusion. The present study aimed to evaluate the biosafety of a novel poly(2-methoxyethyl acrylate)-coated CSEMS (PMEA-CSEMS) for sludge resistance and examine its biosafety in vivo. Using endoscopic retrograde cholangiopancreatography, we placed the PMEA-CSEMS into six normal porcine bile ducts and conventional CSEMS into three normal porcine bile ducts. We performed serological examination and undecalcified histological analysis at 1, 3, and 6 months during follow-up. In the bile ducts with PMEA-CSEMS or conventional CSEMS, we observed no increase in liver enzyme or inflammatory marker levels in the serological investigations and mild fibrosis but no inflammatory response in the histopathological analyses. Thus, we demonstrated the biosafety of PMEA-CSEMS in vivo.
Assuntos
Acrilatos/química , Ductos Biliares/cirurgia , Polímeros/química , Stents Metálicos Autoexpansíveis/efeitos adversos , Acrilatos/efeitos adversos , Animais , Análise Química do Sangue , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Fígado/enzimologia , Modelos Animais , Polímeros/efeitos adversos , Sus scrofaRESUMO
The adhesion and deformation behavior of proteins at the inner surface of fully covered, self-expandable metallic stents coated with biocompatible polymers, poly(2-methoxyethyl acrylate) (PMEA) and poly(3-methoxypropyl acrylate) (PMC3A), were analyzed. Model bile solution, proteins, and bacteria were used to unravel the inhibitory ability of the polymer coatings. Adsorbance of proteins and adherence of bacteria were both strongly inhibited by the polymer coatings. Circulation tests were performed under clinical conditions using human bile from patients. Adsorption/deformation of proteins and early-stage sludge formation were inhibited on stent surfaces coated with PMEA derivatives. The present study revealed that early-stage biliary sludge formation on PMEA- and PMC3A-coated stents was suppressed due to the strong resistance of the polymers to protein adsorption/deformation, brought about by intermediate water in hydrated polymer coatings, which is not present in conventional coating materials, such as silicone and polyurethane.
Assuntos
Bile , Materiais Biocompatíveis , Acrilatos , Humanos , Polímeros , StentsRESUMO
BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each type is associated with specific clinicopathological features. We aimed to uncover the molecular mechanisms underlying the development of these types of IPMN. METHODS: We obtained 103 lesions of various types, including 49 gastric, 26 intestinal, 22 pancreatobiliary, and 6 oncocytic lesions, from 43 IPMNs, including 36 with multiple types. Comparative analysis was performed by targeted sequencing of 37 genes in different lesion types within each pancreas. RESULTS: Gastric-type low-grade lesions were observed in all 36 tumors with multiple types, with 245 mutations identified across all samples. The average number of mutations was significantly different between different lesion grades and types: 1.88 for low-grade lesions, 2.77 for high-grade lesions, and 2.38 for invasive lesions (p = 0.0067); and 1.96 for gastric-type lesion, 2.92 for intestinal-type lesion, 2.73 for pancreatobiliary-type lesion, and 2.17 for oncocytic-type lesion (p = 0.0163). Tracing of mutations between lesions containing multiple types in the same pancreas suggested three developmental pathways, denoted as "progressive", "divergent", and "independent". The progressive and divergent pathways indicate an ancestral lesion that was mostly gastric-type and low-grade may progress or diversify into lesions of other types and/or higher grades. The independent pathway suggests that some high-grade lesions of any type may develop independently. CONCLUSION: These findings suggest that gastric-type low-grade lesions have a risk of progression into high-grade lesions of other types. Therefore, low-grade gastric-type IPMNs should be under constant surveillance.
Assuntos
Epitélio/fisiopatologia , Neoplasias Intraductais Pancreáticas/fisiopatologia , Humanos , Imuno-Histoquímica/métodos , Japão/epidemiologia , Neoplasias Intraductais Pancreáticas/epidemiologiaRESUMO
Treatments for hepatolithiasis include peroral endoscopy, percutaneous cholangioscopy, and surgery. Balloon-assisted endoscopic retrograde cholangiopancreatography (BAERCP) has been widely performed in recent years for patients with hepatolithiasis after biliary reconstruction. However, accidental bowel perforation caused by BAERCP may need emergency surgery. Here, we describe a 77-year-old Japanese woman diagnosed with acute cholangitis due to hepatolithiasis after biliary reconstruction (a biliary diversion operation for pancreaticobiliary maljunction). She underwent BAERCP for treatment of hepatolithiasis, however, a small-bowel perforation occurred. She underwent an emergency operation to suture the perforation and add a catheter jejunostomy. She had no postoperative complications after surgery and was discharged 11 days after surgery. One month later, she was readmitted and underwent percutaneous transjejunal cholangioscopy-guided lithotripsy with complete removal of the calculi. Although endoscopists should be careful to avoid small-bowel perforation during BAERCP, if perforation occurs, addition of a catheter jejunostomy during emergency surgery can be easily transitioned to subsequent treatment of the hepatolithiasis.
Assuntos
Cálculos , Litíase , Hepatopatias , Idoso , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Feminino , Humanos , Jejunostomia/efeitos adversosRESUMO
Extracellular vesicles (EVs) are released from all cells. Bile directly contacts bile duct tumor; bile-derived EVs may contain high concentrations of cancer biomarkers. We performed a proteomic analysis of human bile-derived EVs and identified a novel biomarker of cholangiocarcinoma (CCA). EVs were isolated using ultracentrifugation, and chelating agents, ethylenediaminetetraacetic acid and ethylene glycol tetraacetic acid (EDEG) and phosphate buffered saline (PBS) were used as dissolution solutions. Bile was collected from 10 CCA and 10 choledocholithiasis (stones) cases. Proteomic analysis was performed; subsequently, ELISA was performed using the candidate biomarkers in a verification cohort. The vesicles isolated from bile had a typical size and morphology. The expression of exosome markers was observed. RNA was more abundant in the EDEG group. The proportion of microRNA was higher in the EDEG group. EDEG use resulted in the removal of more contaminants. Proteomic analysis identified 166 proteins as CCA-specific. ELISA for Claudin-3 revealed statistically significant difference. The diagnostic accuracy was AUC 0.945 and sensitivity and specificity were 87.5%. We report the first use of EDEG in the isolation of EVs from human bile and the proteomic analysis of human bile-derived EV-proteins in CCA. Claudin-3 in bile-derived EVs is a useful biomarker for CCA.
Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Bile/metabolismo , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/metabolismo , Claudina-3/metabolismo , Vesículas Extracelulares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Humanos , MicroRNAs/metabolismo , Proteômica/métodosRESUMO
Intestinal-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas is clinicopathologically distinctive. Our research aimed to elucidate the molecular mechanism of the development and progression of the intestinal-type IPMN. In 60 intestinal-type IPMN specimens, histological transitions from gastric-type epithelia to intestinal-type epithelia were observed in 48 cases (80%). CDX2/MUC2/alcian blue triple staining indicated that CDX2 appeared to precede MUC2 expression and subsequent alcian blue-positive mucin production. Expression of p21 and Ki-67 seemed to be accelerated by CDX2 expression (p = 6.02e-13 and p = 3.1e-09, respectively). p21/Ki-67 double staining revealed that p21 was mostly expressed in differentiated cells in the apex of papillae, while Ki-67 was expressed in proliferative cells in the base of papillae. This clear cellular arrangement seemed to break down with the progression of atypical grade and development of invasion (p = 0.00197). Intestinal-type IPMNs harbored frequent GNAS mutations (100%, 25/25) and RNF43 mutations (57%, 8/14) and shared identical GNAS and KRAS mutations with concurrent gastric-type IPMNs or incipient gastric-type neoplasia (100%, 25/25). RNF43 mutations showed emerging or being selected in intestinal-type neoplasms along with ß-catenin aberration. Activation of protein kinase A and extracellular-regulated kinase was observed in CDX2-positive intestinal-type neoplasm. These results suggest that gastric-type epithelia that acquire GNAS mutations together with induction of intrinsic CDX2 expression may evolve with clonal selection and additional molecular aberrations including RNF43 and ß-catenin into intestinal-type IPMNs, which may further progress with complex villous growth due to disoriented cell cycle regulation, acceleration of atypical grade, and advance to show an invasive phenotype.