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Cowden syndrome (CS)/PTEN hamartoma tumor syndrome (PHTS) is a rare autosomal dominantly inherited condition caused by germline pathogenesis. It is associated with multiple hamartomatous lesions occurring in various organs and tissues, including the gastrointestinal tract, skin, mucous membranes, breast, thyroid, endometrium, and brain. Macrocephaly or multiple characteristic mucocutaneous lesions commonly develop in individuals in their 20s. This syndrome is occasionally diagnosed in childhood due to the occurrence of multiple gastrointestinal polyps, autism spectrum disorders, and intellectual disability. CS/PHTS can be diagnosed taking the opportunity of multigene panel testing in patients with cancer. Appropriate surveillance for early diagnosis of associated cancers is required because patients have a high risk of cancers including breast, thyroid, colorectal, endometrial, and renal cancers. Under these circumstances, there is growing concern regarding the management of CS/PHTS in Japan, but there are no available practice guidelines. To address this situation, the guideline committee, which included specialists from multiple academic societies, was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour, and Welfare, Japan. The present clinical guidelines explain the principles in the diagnosis and management of CS/PHTS, together with four clinical questions and the corresponding recommendations, incorporating the concept of the Grading of Recommendations Assessment, Development, and Evaluation system. Herein, we present an English version of the guideline, some of which have been updated, to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with CS/PHTS.
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Juvenile polyposis syndrome (JPS) is a rare disease characterized by multiple hamartomatous polyps within the gastrointestinal tract. SMAD4 or BMPR1A is known as a causative gene of JPS. Approximately 75% of newly diagnosed cases have an autosomal-dominantly inherited condition, whereas 25% are sporadic without previous history of polyposis in the family pedigree. Some patients with JPS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood. JPS is classified into three categories according to phenotypic features of polyp distributions, including generalized juvenile polyposis, juvenile polyposis coli, and juvenile polyposis of the stomach. Juvenile polyposis of the stomach is caused by germline pathogenic variants of SMAD4 with a high risk leading to gastric cancer. Pathogenic variants of SMAD4 are also associated with hereditary hemorrhagic telangiectasia-JPS complex, inducing regular cardiovascular survey. Despite growing concerns regarding the managing JPS in Japan, there are no practical guidelines. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labor and Welfare involving specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of JPS with three clinical questions and corresponding recommendations based on a careful review of the evidence and involve incorporating the concept of the Grading of Recommendations, Assessment, Development, and Evaluation system. Herein, we present the clinical practice guidelines of JPS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with JPS.
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BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. SUMMARY: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. KEY MESSAGES: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.
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Endoscopía Capsular , Síndrome de Peutz-Jeghers , Adolescente , Humanos , Adulto , Niño , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/terapia , Calidad de Vida , Pólipos Intestinales/patología , Intestino Delgado/patologíaRESUMEN
BACKGROUND: Local tumor recurrence of hepatocellular carcinoma (HCC) often occurs in blood drainage areas. Corona enhancement is determined by computed tomography during hepatic arteriography (CTHA) and is considered to represent the blood drainage area. This study aimed to investigate the relationship between embolization of corona enhancement area and local tumor recurrence of patients with HCC who underwent transcatheter arterial chemoembolization (TACE). PATIENTS AND METHODS: The study retrospectively selected 53 patients with 60 HCC nodules that showed corona enhancement area on late-phase CTHA and showed homogenous accumulation of iodized oil throughout the nodule on non-contrast-enhanced CT performed immediately after TACE. We divided the nodules into two groups, according to whether the accumulation of iodized oil covered the entire corona enhancement area (group A) or not (group B). Local tumor recurrence was compared between the two groups. RESULTS: The cumulative local tumor recurrence rates for group A (n = 36) were 2.8%, 2.8%, 8.3% at 3, 6, and 12 months, respectively, whereas the recurrence rates for group B (n = 24) were 20.8%, 45.8%, 75% at 3, 6, and 12 months, respectively. The cumulative local tumor recurrence rates for group A were significantly lower than those for group B (hazard ratio, 0.079; 95% confidence interval, 0.026-0.24; p < 0.001). CONCLUSIONS: The results of the study suggest that the corona enhancement area may be an accurate safety margin in TACE which should be performed until the embolic area covers the entire corona enhancement area.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Humanos , Aceite Yodado , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Estudios RetrospectivosRESUMEN
A 74-year-old man was diagnosed with hepatocellular carcinoma. The tumor in the liver showed a complete response after transcatheter arterial chemoembolization, but lung, bone, and lymph node metastases were observed, so treatment with atezolizumab plus bevacizumab was initiated. After administration, the scans showed tumor growth, but after continuous administration of atezolizumab plus bevacizumab, the tumors finally reduced in size and showed a partial response. The transient growth of the tumors was considered to be pseudoprogression. Herein, we report a case of pseudoprogression in hepatocellular carcinoma treated with atezolizumab plus bevacizumab.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Anciano , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , MasculinoRESUMEN
PURPOSE: Ascites can cause compression of the inferior vena cava (IVC), leading to increased renal venous pressure and renal congestion. Previously, the left renal vein diameter in liver cirrhosis patients with ascites was measured using computed tomography, showing that enlargement of the left renal vein diameter affects the prognosis. Herein, the diameter and flow velocity of the renal veins were measured using ultrasonography. METHODS: Abdominal ultrasonography was performed on 186 patients. The patients were divided into four groups: normal liver (n = 102), liver cirrhosis (LC) without ascites (n = 37), LC with ascites (n = 30), and congestive liver (n = 17). Ultrasonographic measurements for diameter and flow velocity of the IVC, left renal vein main trunk, and segmental renal vein were performed. RESULTS: The left renal vein diameter increased in the following order: normal liver, LC, LC with ascites, and congestive liver groups (P < 0.001). IVC flow velocity was lower and left renal vein diameter was larger in the congestive liver and LC with ascites groups. These results suggest that the two groups have different pathological conditions, but the mechanism of renal congestion is similar. In patients with LC, IVC compression due to ascites might cause blood stagnation and renal congestion. CONCLUSION: The left renal vein and IVC can be measured using ultrasonography. It might help in furthering our understanding of the pathophysiology of renal congestion in these patients.
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Insuficiencia Cardíaca/complicaciones , Cirrosis Hepática/complicaciones , Venas Renales/diagnóstico por imagen , Venas Renales/patología , Ultrasonografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/diagnóstico por imagen , Ascitis/patología , Estudios Transversales , Femenino , Insuficiencia Cardíaca/patología , Humanos , Cirrosis Hepática/patología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: We aimed to investigate whether contrast-enhanced ultrasound (CEUS) could be useful for early evaluation of the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). METHODS: This study retrospectively selected HCCs in which homogeneous retention of iodized oil was confirmed on non-contrast-enhanced computed tomography performed immediately after TACE. Therapeutic responses of HCCs were evaluated by CEUS 1 to 2 days after TACE and by contrast-enhanced computed tomography (CECT) approximately 4 weeks after TACE. We investigated the noninferiority of CEUS 1 to 2 days after TACE to CECT approximately 4 weeks after TACE in terms of the diagnostic accuracy of the therapeutic response to TACE on HCC. RESULTS: Eighty-nine HCCs were enrolled in this study between April 2014 and June 2016. A complete response was observed in 57 of 89 nodules (64.0%), and an incomplete response was observed in the remaining 32 nodules (36.0%). The accuracy rates for CEUS 1 to 2 days after TACE and CECT approximately 4 weeks after TACE in the therapeutic effect of TACE on HCCs were 83.1% (95% confidence interval, 73.7%-90.2%) and 83.1% (95% confidence interval, 73.7%-90.2%), respectively. The difference in diagnostic accuracy between methods was 0%, which was below the predetermined noninferiority limit of 15%, and CEUS 1 to 2 days after TACE was noninferior to CECT approximately 4 weeks after TACE. CONCLUSIONS: Our results suggest that CEUS is a useful modality for early therapeutic evaluation of TACE for HCC, and we can thus plan the next treatment strategies for HCC within a few days after TACE.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Medios de Contraste , Aumento de la Imagen/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Anciano , Femenino , Humanos , Hígado/diagnóstico por imagen , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía/métodosRESUMEN
The patient was a 72-year-old woman whose alkaline phosphatase levels had been elevated since she was 56 years old. Liver biopsies obtained when the patient was 64 and 66 years of age led to a suspicion of cholangitis caused by vasculitis. Furthermore, proteinase-3 anti-neutrophil cytoplasmic antibody positivity led to a suspicion of granulomatosis with polyangiitis, but subjective symptoms and disorders in other organs were absent, so this suspicion was not confirmed. Cholangitis caused by vasculitis rarely occurs without vasculitis in other organs. We herein report this case in which we obtained distinctive laparoscopic and imaging findings that raised suspicions of liver circulatory failure.
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Colangitis/diagnóstico , Colangitis/etiología , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Anciano , Anticuerpos Anticitoplasma de Neutrófilos , Biopsia , Femenino , Humanos , MieloblastinaRESUMEN
Background: The involvement of serum ornithine carbamoyltransferase (OCT) in the progression of chronic hepatitis and liver cirrhosis is unclear. Methods: A total 256 patients with chronic hepatitis C and 5 healthy controls were examined. Serum OCT concentrations were measured by enzyme-linked immunosorbent assay. Serum OCT concentrations were compared with serum cytokine and chemokine levels, and with disease severity and development of hepatocellular carcinoma (HCC). Results: The median OCT concentrations were 21.8 ng/ml for healthy controls, 36.7 ng/ml for F0 stage disease, 48.7 ng/ml for F1 stage, 77.9 ng/ml for F2 stage, 104.8 ng/ml for F3 stage, and 121.4 ng/ml for F4 stage. OCT concentrations were correlated with aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, platelet counts, indocyanine green retention rate at 15 min, prothrombin times, the molar ratio of branched chain amino acids to tyrosine, and tyrosine. Furthermore, there were significant correlations among OCT concentrations and IP10 and IL18 levels. There were weak correlations between serum OCT concentrations and liver histology. The cumulative incidence of HCC in the high-OCT concentration group (≥75.3 ng/ml) was higher than that in the low-OCT concentration group. Conclusion: The measurement of serum OCT concentration may provide a useful marker of disease severity, and thus could be a useful marker for a high risk of HCC occurrence.
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Biomarcadores de Tumor/sangre , Hepatitis C Crónica/sangre , Cirrosis Hepática/sangre , Ornitina Carbamoiltransferasa/sangre , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Femenino , Hepatitis C Crónica/enzimología , Hepatitis C Crónica/patología , Humanos , Hígado/enzimología , Hígado/patología , Cirrosis Hepática/enzimología , Cirrosis Hepática/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND/AIM: To compare the complete resection rate of hot and cold snare polypectomy for small colorectal polyps. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 233 consecutive patients with 461 colorectal polyps up to 10 mm in diameter that were treated by hot or cold snare polypectomy between April 2014 and August 2016. Lesions treated by hot snare polypectomy (n = 137) and cold snare polypectomy (n = 324) were compared. The histological complete resection rates were evaluated between the two groups. We analyzed the relationship between factors for complete resection and clinical factors using multivariate analysis. RESULTS: There was a significantly higher complete resection rate in hot snare polypectomy than in cold snare polypectomy (70.5% vs. 47.3%; P < 0.001). In the analysis of subgroups categorized according to polyp size, the complete resection rate for hot snare polypectomy was significantly higher than that for cold snare polypectomy among polyps ≥6 mm (69.0% vs. 43.5%; P < 0.001). Among polyps ≤5 mm, no significant difference regarding the complete resection rate was observed between the methods (81.3% vs. 53.4%; P = 0.057). There was no significant difference in the incidence of adverse events between the two groups. Multivariate analysis revealed that using hot snare polypectomy (odds ratio 3.03; P < 0.001), small lesion size (odds ratio 1.57; P = 0.049), and lesion location in the left colon (odds ratio 1.73; P = 0.007) were independent factors for complete resection. CONCLUSION: Hot snare polypectomy provides a higher complete resection rate than does cold snare polypectomy for larger (6-10 mm) subcentimeter colorectal polyps.
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Colon/patología , Pólipos del Colon/cirugía , Neoplasias Colorrectales/cirugía , Pólipos Intestinales/cirugía , Anciano , Pólipos del Colon/patología , Colonoscopía/métodos , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A 70-year-old man was referred to our hospital to undergo treatment for hepatocellular carcinoma. In hospital, he complained of hematochezia and a laboratory analysis revealed a decreased level of hemoglobin. Abdominal computed tomography revealed a tumor in the small intestine, with slow enhancement of the dorsal region. Double-balloon enteroscopy revealed a submucosal tumor with a depression in the jejunum. Partial enterectomy was performed and a pathological examination demonstrated the presence of a solitary varix. Solitary varix in the small intestine has not been reported previously. We herein report an extremely rare case of solitary varix in the jejunum.
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Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Yeyuno/irrigación sanguínea , Várices/complicaciones , Anciano , Carcinoma Hepatocelular/complicaciones , Enteroscopía de Doble Balón , Hemorragia Gastrointestinal/terapia , Humanos , Neoplasias Hepáticas/complicaciones , Masculino , Tomografía Computarizada por Rayos XRESUMEN
AIM: The goal of the study was to evaluate the efficacy and safety of balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma (HCC) using miriplatin (a lipophilic anticancer drug) and gelatin particles. METHODS: B-TACE was performed for 62 HCC nodules in 33 patients who could not be treated by surgical resection or radiofrequency ablation. All 33 patients had a history of transarterial chemoembolization (TACE) treatment prior to B-TACE. As a historical comparison, we investigated 40 nodules in 28 patients treated by TACE using a conventional microcatheter (C-TACE), miriplatin and gelatin particles. The therapeutic effect per tumor was compared between the groups based on the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL) and side-effects were compared based on the Common Terminology Criteria for Adverse Events (ver. 4.0). RESULTS: The therapeutic efficacy after 4-12 weeks was evaluated in 59 nodules in the B-TACE group and in 37 nodules in the C-TACE group. Of these nodules, TE4 occurred in 29 (49.2%) in the B-TACE group and in 10 (27%) in the C-TACE group. Local efficacy was significantly higher in nodules treated by B-TACE than by C-TACE. The side-effects on hepatic function were similar in the two groups. CONCLUSION: Our results suggest that B-TACE with miriplatin is a useful treatment for hepatocellular carcinoma.
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The patient was a 79-year-old woman. We became introduction consultation than a nearby doctor in alpha-fetoprotein(AFP)high level. Abdominal ultrasonography showed 30mm great tumor in liver lateral segment area and gastric fiber showed type2 tumor which is AFP producing gastric cancer. On admission AFP level is high(403ng/ml). Multiple liver metastases were noted it by abdominal angiography. We started FLAP(5-fluorouracil, leucovorin, etoposide, cisplatin)combination chemotherapy by a diagnosis of AFP producing gastric cancer StageIV. It is reduction of a liver tumor after one course, and the stomach lesion almost disappeared after three courses end points.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/secundario , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , alfa-Fetoproteínas/biosíntesis , Adenocarcinoma/patología , Anciano , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Neoplasias Gástricas/patologíaRESUMEN
A 38-year-old woman was referred to our institution due to epigastralgia. She presented with obstructive jaundice and eosinophilia. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing from the distal common bile duct to the bifurcation of the hepatic ducts. An endoscopic plastic biliary stent was inserted; the specimen obtained from the common bile duct wall revealed dense infiltration by eosinophils. Treatment was started with prednisolone 60 mg daily. The patient's biliary stenosis and eosinophilia gradually improved. Eosinophilic infiltration in the lungs or stomach is relatively common, but it is rare in the common bile duct. Most of the reported cases of eosinophilic cholangitis presented with eosinophilia; our patient's eosinophil count was over 1000/mm(3). Since our patient had allergies to pollen and house dust, a relationship between the allergies and the eosinophilic cholangitis was suspected, but no cause was identified.
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Colangitis/diagnóstico por imagen , Eosinofilia/diagnóstico por imagen , Ultrasonografía/métodos , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Colangitis/patología , Conducto Colédoco/diagnóstico por imagen , Conducto Colédoco/patología , Medios de Contraste/administración & dosificación , Eosinofilia/patología , Eosinófilos/patología , Femenino , Humanos , Ictericia Obstructiva/diagnósticoRESUMEN
We report a case of hepatic pseudolymphoma in a 67-year-old woman that was detected during an abdominal sonography screening. The lesion was further evaluated using CT, MRI, angiography, and contrast-enhanced sonography. The imaging features of this tumor are discussed herein. The diagnosis of pseudolymphoma was achieved via sonographically guided biopsy. The lesion regressed completely within 1 year.
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Hepatopatías/diagnóstico por imagen , Seudolinfoma/diagnóstico por imagen , Seudolinfoma/diagnóstico , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Regresión Neoplásica Espontánea , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
PURPOSE: To determine the influence of capsule formation or presence of capsular invasion on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The patient group consisted of 70 patients with 74 HCC lesions who had been examined by US and undergone surgical tumor resection at our institution. For these patients, we conducted the following comparative studies: (a) comparison between halo findings on US and microscopic capsular results; (b) comparison between halo findings on US and tumor diameter, tumor histological differentiation, and serum value of each tumor marker; and (c) comparison between halo findings on US and tumor recurrence. RESULTS: (a) The corresponding value between sonographic halo and histological capsule was 90.1%, and that between presence of extracapsular invasion on US and that seen by histology was 88.0%. (b) There was no relation between US images and histological differentiation of tumors. (c) Presence of extracapsular invasion on US was a predisposing factor for the development of tumor recurrence. CONCLUSION: (1) Globally speaking, sonographic halo corresponded to the histological tumor capsule. (2) In patients with extracapsular invasion, tumor recurrence after treatment increased. Thus, a better understanding of sonographic halo findings helps determine diagnostic and therapeutic strategies in HCC patients.
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PURPOSE: To evaluate the role of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC). METHODS: CEUS and angiography were performed in ten cases of ruptured HCC. We evaluated whether this technique allowed us to determine the bleeding point by observing an extravasation of contrast media into the ascites. RESULTS: In four of the ten cases, CEUS demonstrated an extravasation of Levovist into ascites. Angiography showed an extravasation of contrast medium in three of these four cases. In three of the remaining six cases, in which CEUS did not show the presence of contrast medium in ascites, angiography demonstrated an extravasation. In eight cases, it yielded cessation of bleeding. In two cases, embolization was not successful. The bleeding point was not determined by CEUS or angiography in one case. CONCLUSION: CEUS allows us to differentiate active bleeding (presence of contrast medium in the ascites) from nonactive bleeding.
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Although 4-META/MMA-TBB resin has adhesive properties to dentin, and has been clinically used for the bonding treatment of vertically fractured roots and apicoectomy, there has not been any investigation on the adhesion of 4-META/MMA-TBB resin to cementum. The purpose of this in vitro study was to evaluate the bonding and the sealing ability of 4-META/MMA-TBB resin to cementum. Bovine root cementum and dentin surfaces were treated with a citric acid and ferric chloride solution, and the 4-META/MMA-TBB resin was applied on the treated surfaces before testing. The microtensile bond strength and the leakage levels obtained for the cementum were almost equal to those for the dentin. In SEM and TEM observations, a hybrid layer approximately 2-3 microm in thickness was observed at the interface between the resin and the cementum. It is concluded that 4-META/MMA-TBB resin adhered to cementum via a hybrid layer on cementum, as previously reported for dentin.
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Compuestos de Boro/química , Cemento Dental/química , Recubrimientos Dentinarios/química , Metacrilatos/química , Metilmetacrilatos/química , Cementos de Resina/química , Grabado Ácido Dental , Adhesividad , Animales , Bovinos , Restauración Dental Permanente , Análisis del Estrés Dental , Incisivo/química , Incisivo/lesiones , Ensayo de Materiales , Propiedades de Superficie , Resistencia a la Tracción , Fracturas de los Dientes/terapia , Raíz del Diente/lesionesRESUMEN
The livers of woodchucks chronically infected with woodchuck hepatitis virus (WHV) contain foci of morphologically altered hepatocytes (FAH) with "basophilic", "amphophilic" and "clear cell" phenotypes, which are possibly pre-neoplastic in nature. Interestingly, most fail to express detectable levels of WHV proteins and nucleic acids. We studied sections of WHV-infected liver tissue to determine if all foci of hepatocytes that failed to express detectable levels of WHV, as assessed by immunoperoxidase staining for WHV core antigen, could be classified morphologically as FAH. We found that at least half of the foci of WHV core antigen-negative hepatocytes did not show clear morphological differences in either H&E or PAS (periodic acid Schiff) stained sections from surrounding hepatocytes, and were therefore not designated as FAH. In the second approach, we assayed core antigen-negative foci for the presence of fetuin B, a serum protein produced by normal hepatocytes, but not by neoplastic hepatocytes in hepatocellular carcinomas. Basophilic and amphophilic FAH had reduced levels of fetuin B compared to hepatocytes present in the surrounding liver; fetuin B staining was detected in clear cell FAH but the level could not be accurately assessed because of the displacement of fetuin B to the cell periphery by accumulated glycogen. The foci of morphologically normal WHV core antigen-negative hepatocytes had similar levels of fetuin B to that of the surrounding hepatocytes. The co-existence of at least four types of WHV core antigen-negative foci, including those with no obvious morphologic changes, raises the possibility that the different foci arise from distinct primary events. We hypothesize that a common event is loss of the ability to express WHV, allowing these hepatocytes to escape immune mediated cell death and to undergo clonal expansion to form distinct foci.