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In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.
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Pancreatitis Autoinmune , Consenso , Técnica Delphi , Diagnóstico Diferencial , Humanos , JapónRESUMEN
OBJECTIVES: Autoimmune pancreatitis (AIP) responds well to steroid therapy but frequently relapses after discontinuing the steroid. It is difficult to know which cases are most likely to relapse. The aim of this study was to investigate the relation between the rate of decrease in serum IgG4 level after initial steroid therapy and a relapse. METHODS: The subjects were 47 AIP patients who received steroid therapy. We calculated the difference between their serum IgG4 levels before and 2 months after the start of therapy, and their rate of decrease in serum IgG4 level after treatment (Δ') by dividing the difference between the 2 values by the number of days between them. RESULTS: The rates of decrease were significantly higher in the nonrelapse groups than in the relapse groups. A receiver operating characteristic curve showed that the area under the curve for the Δ' value was 0.781, and that at the Δ' cutoff value of 10.7, the sensitivity and the specificity of the Δ' value for discriminating between the 2 groups were 0.846 and 0.632, respectively. CONCLUSIONS: Our data suggest that the rate of decrease in serum IgG4 level may be a useful predictor of a relapse of AIP after steroid therapy.
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Pancreatitis , Enfermedades Autoinmunes , Humanos , Inmunoglobulina G , Curva ROC , RecurrenciaRESUMEN
OBJECTIVE: Differentiated gastric cancer generally develops in the atrophic gastric mucosa, although undifferentiated cancer is sometimes encountered in patients with severe atrophic gastritis. We characterized the endoscopic features of undifferentiated gastric cancer in patients with severe atrophic gastritis. METHODS: Stage IA early gastric cancer was diagnosed in 501 patients who were admitted to our hospital between April 2003 and March 2012. The endoscopic and pathological findings were compared among 29 patients with undifferentiated cancer and severe atrophic gastritis, 104 patients with undifferentiated cancer and mild/moderate atrophic gastritis and 223 patients with well-differentiated cancer and severe atrophic gastritis. Endoscopic atrophic gastritis was classified according to the Kimura-Takemoto classification as no gastritis, C-1 and C-2 (mild), C-3 and O-1 (moderate) or O-2 and O-3 (severe). RESULTS: The tumors were larger and showed deeper mural invasion in the patients with undifferentiated cancer and severe atrophic gastritis than in those with well-differentiated cancer and severe gastritis or undifferentiated cancer and mild/moderate gastritis. On endoscopy, undifferentiated cancer associated with severe gastritis was often red in color. CONCLUSION: It is often difficult to diagnose early undifferentiated gastric cancer, especially in patients with severe atrophic gastritis. The present study characterized the important endoscopic features of such tumors.
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Gastritis Atrófica/fisiopatología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/fisiopatología , Anciano , Diagnóstico Diferencial , Detección Precoz del Cáncer , Femenino , Mucosa Gástrica/fisiopatología , Gastritis Atrófica/complicaciones , Gastritis Atrófica/diagnóstico , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Neoplasias Gástricas/etiologíaRESUMEN
Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.
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Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/terapia , Guías de Práctica Clínica como Asunto , Medicina Basada en la Evidencia/métodos , Humanos , Japón , Manejo del Dolor/métodos , Pancreatitis Crónica/patología , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
AIM: Recently, the short-term efficacy of the vasopressin V2 receptor antagonist tolvaptan for the treatment of ascites in cirrhosis was reported. However, the long-term effects remain unknown. Here, we report the clinical features of decompensated cirrhosis treated using long-term tolvaptan therapy, and evaluate its safety and efficacy. METHODS: Fifty-five cirrhotic patients hospitalized due to ascites, despite receiving appropriate diuretic treatment, were treated with tolvaptan. We excluded 35 patients due to liver transplant (20.0%), death (28.6%), poor general status (14.3%), improved ascites (5.7%) or other reasons (31.4%). In 20 cases treated with tolvaptan for 6 months, total body water (TBW) and extracellular fluids (ECW) were measured using bioelectric impedance analysis (BIA) with an InBody720. RESULTS: The median age of the 20 patients was 64 years (range, 48-90), and 60% were male. The etiology of cirrhosis included hepatitis C (45%), alcohol-induced (20%) and other (35%). The percentage of patients with Child-Pugh class A, B and C was 0%, 40% and 60%, respectively. Biochemical findings revealed that serum creatinine levels and estimated glomerular filtration rate were not affected during 6 months of treatment with tolvaptan, and there was no renal disturbance. The median serum sodium levels were increased from 138 to 139 mEq/L, but serious adverse events related to renal and liver function were not observed. Data also revealed that long-term treatment reduced the BIA-estimated ECW/TBW ratio. CONCLUSION: Long-term tolvaptan treatment was a safe and effective treatment for decompensated cirrhosis.
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OBJECTIVES: In addition to surgery, procedures for patients with pancreatolithiasis are developing; therefore, establishing practical guidelines for the management of pancreatolithiasis is required. METHODS: Three committees (the professional committee for asking clinical questions (CQs) and statements by Japanese endoscopists, the expert panel committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Eight endoscopists and a surgeon for pancreatolithiasis made the CQs and statements from a total of 694 reports of published literature by PubMed search (from 1983 to 2012). The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. RESULTS: The professional committee made 3, 7, and 10 CQs and statements for the concept and pathogenesis, diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. CONCLUSIONS: After evaluation by the moderators, the Japanese clinical guidelines for pancreatolithiasis were established. Further discussions and studies for international guidelines are needed.
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Endoscopía/métodos , Litiasis/terapia , Enfermedades Pancreáticas/terapia , Guías de Práctica Clínica como Asunto , Técnica Delphi , Humanos , Japón , Litiasis/diagnóstico , Enfermedades Pancreáticas/diagnósticoRESUMEN
Aim: Pegylated-interferon/ribavirin/simeprevir (PEG-IFN/RBV/SMV) combination therapy is widely used for hepatitis C virus (HCV) treatment after liver transplantation (LT). Here, we observed two cases of extended severe anemia during PEG-IFN/RBV/SMV therapy for HCV serological type 1 re-infected after LT. Immunosuppressants consisted of tacrolimus and mycophenolate mofetil (MMF). Case 1 was a 65-year-old-woman treated with PEG-IFN/RBV/SMV therapy and 500 mg MMF/day 9 months after LT. Her serum hemoglobin (Hb) level decreased from 10 to 8.4 mg/dL on day 25. Despite discontinuing the PEG-IFN/RBV/SMV treatment on day 32, her Hb level decreased to 5.1 mg/dL on day 40. Case 2 was a 61-year-old-woman started on PEG-IFN/RBV/SMV therapy 20 months after LT. Her serum Hb level decreased from 12.2 to 7.1 mg/dL on day 39. The MMF dose was reduced from 1,500 to 1,000 mg/day, and her Hb level was maintained. Red blood cell transfusions were required in both cases, and anemia persisted for 2 months. These patients had the C/C major type inosine triphosphatase (ITPA) polymorphism. In conclusion, MMF induced severe persistent anemia by co-treatment with IFN/RBV in patients who underwent LT. Thus, the immunosuppressant dose should be chosen carefully for patients with the high-risk ITPA allele.
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Anemia/inducido químicamente , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Inmunosupresores/efectos adversos , Trasplante de Hígado , Ácido Micofenólico/análogos & derivados , Anciano , Anemia/terapia , Transfusión de Eritrocitos , Femenino , Hepatitis C Crónica/inmunología , Humanos , Huésped Inmunocomprometido , Interferón-alfa/uso terapéutico , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Recurrencia , Ribavirina/uso terapéutico , Simeprevir/uso terapéutico , Tacrolimus/efectos adversosRESUMEN
BACKGROUND/AIMS: A patency capsule (PC) is used to assess intestinal patency in patients with known or suspected stricture, but PC localization by plain abdominal X-ray (AXR) is difficult in those patients in whom the PC is not detected in the feces. Tomosynthesis is a promising, cost-effective, and low-radiation digital tomographic technique. This prospective study evaluated its use for PC localization in the intestinal tract. METHODS: The study subjects were 49 patients in whom the PC was not detected in the feces and was identified intra-abdominally on AXR films. PC localization in the small or large intestines by AXR alone or by tomosynthesis with AXR was compared with abdominal computed tomography (CT), which is the gold standard. RESULTS: The PC was judged in the large and small intestines in 22 and 27 patients by AXR alone versus 34 and 15 patients, respectively, by tomosynthesis combined with AXR. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for PC detection by AXR alone were 52.9, 53.3, 56.2, 50.0, and 53.1%, respectively. The same parameters were 100, 100, 100, 100, and 100%, respectively, for tomosynthesis with AXR, which were identical to those of CT. CONCLUSIONS: Tomosynthesis with AXR is superior to AXR alone, though similar to CT, with respect to localization of the PC.
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Endoscopios en Cápsulas/efectos adversos , Migración de Cuerpo Extraño/diagnóstico por imagen , Tracto Gastrointestinal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Endoscopía Capsular , Constricción Patológica/diagnóstico , Heces , Femenino , Humanos , Intestino Delgado/irrigación sanguínea , Intestino Delgado/patología , Intestino Delgado/cirugía , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Grado de Desobstrucción VascularRESUMEN
Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we identified recurrent mutations of BRCA2 and FAT genes. BRCA2 showed somatic or germline premature termination mutations, with loss of the wild-type allele in 3 of 7 tumors. FAT1, FAT3, and FAT4 showed somatic or germline missense mutations in 4 of 7 tumors. The germline FAT mutations were with loss of the wild-type allele. Loss of BRCA2 expression was observed in 5 of 11 tumors. One patient with a BRCA2-mutated tumor experienced complete remission of liver metastasis following cisplatinum chemotherapy. In conclusion, acinar cell carcinomas show a distinct mutation pattern and often harbor somatic or germline mutations of BRCA2 and FAT genes. This result may warrant assessment of BRCA2 abrogation in patients with the carcinoma to determine their sensitivity to chemotherapy.
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Cadherinas/genética , Carcinoma de Células Acinares/genética , Exoma , Genes BRCA2 , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Pancreáticas/genética , Anciano , Alelos , Cadherinas/metabolismo , Carcinoma de Células Acinares/tratamiento farmacológico , Carcinoma de Células Acinares/mortalidad , Carcinoma de Células Acinares/patología , Biología Computacional/métodos , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Neoplasias PancreáticasRESUMEN
Primary hyperoxaluria (PH) is a rare, autosomal recessive disorder characterized by overproduction of oxalate caused by a deficiency in a hepatic enzyme. The excess oxalate combines with calcium in the kidneys to form deposits of calcium oxalate, which can lead to nephrocalcinosis and renal failure. PH type 1 (PH1), the most common form of this disease, is caused by a deficiency of the liver-specific enzyme alanine/glyoxylate aminotransferase (AGT). Liver transplantation is performed as a definitive therapy for PH to correct the enzyme defect. Usually, liver depositions are limited and liver function is normal without fibrosis. Here, we report an adult case of liver cirrhosis caused by PH1. A 28-year-old woman was admitted to our hospital under suspicion of PH1 and the presence of nephrocalcinosis. The patient had suffered from kidney stone recurrences from 17 years of age, and was initiated on hemodialysis due to renal failure at the age of 27 years. The serum level of oxalic acid was high, whereas the AGT level in the liver tissue was decreased. Thus, the patient was definitively diagnosed with PH1. Although she had normal liver function, surface nodularity and splenomegaly were detected by computed tomography, suggesting liver cirrhosis. The native liver showed micronodular cirrhosis and portal fibrosis. Several arterioles were filled with rhomboid and polyhedral refractile oxalate crystals and various portal tracts showed these crystals. Our case suggests that long-term oxalosis can lead to liver cirrhosis; thus, PH should be considered one of the causes of liver cirrhosis.
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OBJECTIVES: We aimed to identify molecular biomarkers for assessing the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN). METHODS: We retrospectively investigated molecular aberrations and their associations with clinicopathological features in 172 IPMNs. RESULTS: GNAS and KRAS mutations were detected in 48% and 56% of IPMNs, respectively. No mutations of EGFR, PIK3CA GNAO1, GNAQ, or GNAI2 were observed. Significant associations were observed between IPMN morphological types and GNAS mutations, KRAS mutations, the expression of phosphorylated MAPK (pMAPK), AKT, and phosphorylated AKT (pAKT), nuclear accumulation of ß-catenin, SMAD4 loss, and TP53 overexpression; histological grades and the expression of EGFR, pMAPK, AKT, and pAKT, the nuclear ß-catenin, SMAD4 loss, and TP53 overexpression; invasive phenotypes and KRAS mutations, the nuclear ß-catenin, and SMAD4 loss; and prognosis and SMAD4 loss and TP53 overexpression. Multivariate analysis to compare prognostic impacts of multiple molecular features revealed that TP53 overexpression was an independent prognostic factor (P = 0.030; hazard ratio, 5.533). CONCLUSIONS: These results indicate that mutations in GNAS and KRAS, the expression of EGFR and pMAPK, the nuclear ß-catenin, SMAD4 loss, and TP53 overexpression may be relevant for assessing the clinical course of IPMN, including its progression into different morphological types, invasion, and prognosis.
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Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Quísticas, Mucinosas y Serosas/química , Neoplasias Quísticas, Mucinosas y Serosas/genética , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/genética , Distribución de Chi-Cuadrado , Cromograninas , Análisis Mutacional de ADN , Progresión de la Enfermedad , Receptores ErbB/análisis , Receptores ErbB/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Proteínas Quinasas Activadas por Mitógenos/análisis , Análisis Multivariante , Mutación , Recurrencia Local de Neoplasia , Neoplasias Quísticas, Mucinosas y Serosas/mortalidad , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Quísticas, Mucinosas y Serosas/terapia , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Fosforilación , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Estudios Retrospectivos , Factores de Riesgo , Proteína Smad4/análisis , Factores de Tiempo , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/análisis , Proteínas ras/genéticaRESUMEN
Mutations in RNF43, which encodes the ubiquitin E3 ligase ring finger protein 43, were recently found in intraductal papillary mucinous neoplasms of the pancreas. We evaluated somatic mutations of RNF43 and the expression of ring finger protein 43 as well as their associations with the molecular and clinicopathological features in 176 surgically resected intraductal papillary mucinous neoplasms. Frozen tissues were available for 57 cases and were used for next-generation sequencing analysis of the entire coding exons of RNF43. Formalin-fixed and paraffin-embedded tissues from all 176 cases were used for the immunohistochemical analysis of the expression of ring finger protein 43. Mutations detected with the next-generation sequencing analysis were validated by using Sanger sequencing. Statistical analysis was used to evaluate the associations between RNF43 aberrations and molecular and clinicopathological features including GNAS mutations, KRAS mutations, loss of SMA and MAD4 homologue expression, tumor protein 53 overexpression, tumor grade, histological type, mural nodule detection, macroscopic type, stage, recurrence, and survival. Somatic RNF43 mutations were found in 8 (14%) of the 57 examined cases, and included 5 frameshift mutations (p.F69fs, p.S264fs, p.L311fs, p.R363fs, and p.V490fs), 1 non-sense mutation (p.Q153X), and 2 missense mutations (p.I164N and p.P310A). The expression of ring finger protein 43 was downregulated in 52 (29.5%) of the 176 examined cases. RNF43 mutations were significantly associated with the downregulated expression of ring finger protein 43 (P=0.011), GNAS mutation (P=0.020), and mural nodule detection (P=0.038). The expression of ring finger protein 43 was not associated with any clinicopathological features except RNF43 mutation. These results indicate that RNF43 mutation might cause downregulation of the expression of ring finger protein 43 and play a crucial role and associate synergistically with GNAS mutation during development of intraductal papillary mucinous neoplasm of the pancreas.
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Adenocarcinoma Mucinoso/genética , Adenocarcinoma Papilar/genética , Carcinoma Ductal Pancreático/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Mutación , Proteínas Oncogénicas/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patología , Anciano , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Cromograninas , Análisis Mutacional de ADN , Proteínas de Unión al ADN/biosíntesis , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Masculino , Proteínas Oncogénicas/biosíntesis , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Transcriptoma , Ubiquitina-Proteína LigasasRESUMEN
Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant food consumption were significantly different in male NASH patients compared to normal male subjects. In women, differences were seen in the amount of rice at dinner, frequency of eating out, and proclivity for sweets. In male NASH patients, the frequency of physical exercise was significantly lower. The lifestyle tendencies of NASH were almost similar to those of NAFL. In the comparison between obese NASH and non-obese NASH, no clear lifestyle differences were found. In conclusion, the most striking result of this survey was that the lifestyle of males contributed significantly to the development of NASH. These results point to treatment of NASH in males. In female NASH patients, lifestyle differences were minimal, and the effects of other factors such as genetic background will need to be investigated.
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OBJECTIVE: Ornithine carbamoyltransferase (OCT) is a liver-specific mitochondrial matrix enzyme and potential biomarker of liver fibrosis. This study investigated the OCT levels in patients with chronic liver disease with or without cirrhosis in order to assess the usefulness of OCT as a biomarker of cirrhosis. METHODS: The subjects included 440 Japanese patients with chronic liver disease and 80 control subjects. The patients were divided into two groups, those with and without cirrhosis, both of which were further stratified into high-OCT and low-OCT subgroups. RESULTS: In the non-cirrhosis group, the patients with non-alcoholic steatohepatitis (NASH), alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis (PSC) comprised the high-OCT subgroup, while the patients with hepatitis B, hepatitis C and autoimmune hepatitis formed the low-OCT subgroup. There were significant differences in the OCT levels, OCT/aspartate aminotransferase ratios and OCT/alanine transaminase (ALT) ratios between these two subgroups (p<0.001). The same findings were observed in the cirrhosis group. The OCT levels were markedly higher in the cirrhosis group than in the non-cirrhosis group, particularly among the patients with PSC (p<0.001). The most useful biomarker for predicting cirrhosis was the OCT/ALT ratio in the patients with hepatitis C and NASH and the OCT level in patients with PSC. CONCLUSION: The OCT level differs among patients with different chronic liver diseases. The role of OCT should be further evaluated in order to improve our understanding of the pathogenesis of these diseases. The OCT level is a useful surrogate marker of cirrhosis, particularly in PSC patients.
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Cirrosis Hepática/diagnóstico , Ornitina Carbamoiltransferasa/sangre , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Humanos , Cirrosis Hepática/enzimología , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROCRESUMEN
AIMS: The aim of this study was to determine the clinicopathological features and surgical management of solid pseudopapillary neoplasms (SPNs) of the pancreas at a single institution. METHODS: We investigated 34 patients (5 males and 29 females) who underwent surgery for pathologically confirmed SPNs between 1994 and 2012. RESULTS: Clinical symptoms were absent in 58.8% of the patients. The median tumor diameter was 42.7 mm. All tumors were successfully removed by R0 resection. Pathologically, 5.9% had duodenum invasion and 2.9% had pancreatic serosal invasion, but there was no lymph node metastasis. Radiological findings showed calcification in 39.4% of the patients, capsule formation in 51.5%, cystic components in 69.7%, solid components in 93.9% and internal bleeding in 36.4%. Immunohistochemically, neuron-specific enolase was positive in 100% of the patients, nuclear accumulation of ß-catenin in 100% and CD10 in 78.8%. There were no recurrences reported at the median follow-up (67 months). Regarding gender differences, the cystic component in radiological imaging was the only significant finding among the features studied (p = 0.01). CONCLUSIONS: R0 resection with appropriate procedures appears to be sufficient for patients with SPNs, even for locally invasive tumors. There were no significant differences between genders except for the cystic component on radiological imaging.
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Calcinosis/diagnóstico por imagen , Hemorragia/diagnóstico por imagen , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neprilisina/análisis , Neoplasias Pancreáticas/cirugía , Fosfopiruvato Hidratasa/análisis , Radiografía , Estudios Retrospectivos , Factores Sexuales , Carga Tumoral , Adulto Joven , beta Catenina/análisisRESUMEN
Transforming growth factor-ß1 (TGF-ß1) potently inhibits human hepatocellular carcinoma (HCC) cell growth. Here we demonstrated that TGF-ß1-induced apoptosis is mediated by decreased phosphorylation of cdc2 at Tyr15 accompanied by down-regulation of Wee1 kinase expression. As expected from these results, a Wee1 kinase inhibitor efficiently induced apoptosis in HCC cells in the absence of TGF-ß1 treatment. In surgically resected samples, Wee1 kinase was expressed in moderately to poorly differentiated HCC, whereas no Wee1 kinase expression was observed in non-cancerous tissue, including cirrhotic tissue. Our results suggest that Wee1 kinase inhibitors may be a practical novel therapeutic option against advanced HCC.
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Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteína Quinasa CDC2 , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Quinasas Ciclina-Dependientes/metabolismo , Activación Enzimática/efectos de los fármacos , Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Interferencia de ARN , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
OBJECTIVES: Autoimmune pancreatitis (AIP) is a chronic fibro-inflammatory disease of the pancreas constituting, in part, a recently defined nosological entity of IgG4-related systemic sclerosing diseases. The pathogenetic factors of AIP have not been fully elucidated. We previously established a mouse model of AIP using chronic exposure to a commensal bacteria, Escherichia coli. METHODS: To determine the pathogenetically relevant antigen of E. coli, the outer membrane fractions of E. coli were subjected to two-dimensional gel electrophoresis followed by immunoblotting against sera from the AIP model. Immunoreactive spots were determined using MALDI TOF/MS and Mascot search. The recombinant protein of the identified antigen was examined for their ability to induce AIP-like disorder in C57BL/6 mice. Furthermore, the antibody titer against that antigen was determined in AIP patients. RESULTS: One representative spot reacting with sera from E. coli-inoculated mice was identified as FliC from E. coli, based on the results of TOF/MS. The repeated inoculation of recombinant FliC in C57BL/6 mice induced AIP-like pancreatitis and higher titers of anti-lactoferrin and anti-carbonic anhydrase II. Sera from patients with AIP had the highest antibody titer, while those from patients with pancreatic diseases other than AIP had a higher antibody titer against E. coli and FliC, compared with pancreatic disease-free controls. CONCLUSIONS: FliC from E. coli may pathogenetically generate an AIP-like inflammation status. A reconsideration of the importance of commensal bacteria as an environmental factor(s) capable of inducing autoimmunity could provide insight to overcoming AIP.