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An 87-year-old woman was hospitalized for liver abscesses and cholangitis due to common bile duct stones. She developed worsening anemia and abdominal pain. Contrast-enhanced computed tomography revealed an intrahepatic pseudoaneurysm and an arteriovenous fistula between the hepatic arteries and inferior vena cava. The initial endovascular treatment was transarterial embolization. The pseudoaneurysm was embolized with an N-butyl-2-cyanoacrylate mixture, and the inflow arteries of the arteriovenous fistula were embolized with microcoils. However, the residual perfusion of the arteriovenous fistula remained. A second endovascular treatment was performed using the transarterial and transvenous approaches. The inflow arteries were embolized using microcoils and gelatin sponges and the dominant outflow vein was embolized using microcoils, resulting in the disappearance of the perfusion in the arteriovenous fistula.
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Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate; therefore, the development of effective treatments is a priority. The stimulator of interferon genes (STING) pathway enhances tumor immunity by inducing the production of type 1 interferon (IFN) and proinflammatory cytokines and chemokines and promoting the infiltration of cytotoxic T cells. To assess the function of STING on pancreatic tumorigenesis, Ptf1aER-Cre/+ LSL-KrasG12D/+ p53loxP/loxP mice (KPC mice) and Ptf1aER-Cre/+ LSL-KrasG12D/+ p53loxP/loxP/STING-/- mice (KPCS mice) were generated. However, STING deletion did not affect pancreatic tumorigenesis in mice. Because STING is expressed not only in immune cells but also in cancer-associated fibroblasts (CAFs), we evaluated the STING function in PDAC CAFs. A mouse STING agonist 5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid (DMXAA) was administered to KPC mice and CAFs from KPC mice and the resulting immune response was evaluated. DMXAA activated STING in PDAC CAFs in KPC mice, promoting cytotoxic T cell infiltration by secreting proinflammatory cytokines and enhancing tumor immunity. We next generated STING-deficient PDAC cells and subcutaneous tumors in which STING was expressed only in CAFs by performing bone marrow transplantation and assessed the antitumor effect of STING-activated CAFs. The administration of DMXAA to subcutaneous tumors expressing STING only in CAFs sustained the antitumor effect of DMXAA. About half of human PDACs lacked STING expression in the cancer stroma, suggesting that STING activation in PDAC CAFs exerts an antitumor effect, and STING agonists can be more effective in tumors with high than in those with low STING expression in the stroma.
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Fibroblastos Asociados al Cáncer , Carcinoma Ductal Pancreático , Proteínas de la Membrana , Neoplasias Pancreáticas , Animales , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Ratones , Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Humanos , Xantonas/farmacología , Línea Celular Tumoral , Linfocitos T Citotóxicos/inmunologíaRESUMEN
The differential diagnosis of solid pancreatic lesions (SPLs) using B-mode endoscopic ultrasonography (EUS) is challenging. Detective flow imaging (DFI) offers the potential for detecting low-flow vessels in the pancreas, thus enhancing diagnostic accuracy. This retrospective study aimed to investigate DFI-EUS findings of SPLs and analyze their differential diagnostic accuracy for pancreatic cancer. We included 104 patients with pathologically confirmed SPLs who underwent EUS between April 2021 and June 2023. Expert endosonographers, blinded to the patients' clinical data, evaluated images obtained through B-mode, eFLOW, and DFI-EUS. The frame rate and vessel detection sensitivity were compared between eFLOW and DFI, and the diagnostic criteria for pancreatic cancer were established. The visualization rate for vessels in SPLs was significantly higher with DFI-EUS (96%) compared to eFLOW (27%). Additionally, DFI showed a superior frame rate, sensitivity (99%), and accuracy (88%) for detecting pancreatic cancer, although with a modest specificity (43%). On DFI-EUS, characteristics such as hypovascularity, peritumoral vessel distribution, or spotty vessel form were suggestive of pancreatic cancer. DFI-EUS significantly improved the visualization of vascular structures within the SPLs, highlighting its efficacy as a diagnostic modality for pancreatic cancer.
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Sistema Biliar , Cateterismo , Humanos , Gastrectomía , Anastomosis en-Y de Roux , Resultado del TratamientoAsunto(s)
Fístula Biliar , Laparoscopía , Seudoquiste Pancreático , Humanos , Fístula Biliar/diagnóstico por imagen , Fístula Biliar/etiología , Seudoquiste Pancreático/diagnóstico , Seudoquiste Pancreático/diagnóstico por imagen , Colangiopancreatografia Retrógrada Endoscópica , Vesícula Biliar , Fístula PancreáticaRESUMEN
Miwa and colleagues report on their experience with a newly developed peroral cholangioscope that is effective for the removal of difficult stones in the common bile duct and the cystic duct. The scope offers a large working channel and a high mobility bending section, increasing the efficacy of electrohydraulic lithotripsy.
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Cálculos Biliares , Laparoscopía , Litotricia , Humanos , Cálculos Biliares/terapia , Cálculos Biliares/cirugía , Resultado del Tratamiento , Conducto Colédoco , Colangiopancreatografia Retrógrada EndoscópicaRESUMEN
Background: Enhanced imaging techniques have the overwhelming advantages of being noninvasive and sensitive enough to evaluate the microcirculation of lesions, thus making them accurate in the diagnosis of hepatic lesions. Unfortunately, there is very little research on and knowledge of the imaging features of a rare cancerous condition: hepatic angiosarcoma (HA). Case summary: In this study, we retrospectively collected the data of six patients who underwent both contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT), and subsequently obtained a definitive histopathologic diagnosis of HA. We described the imaging appearances of HA by comparing CEUS and CECT images. Furthermore, we analyzed these imaging characteristics from the perspective of histopathology and tumorigenesis. The study included the largest number (six) of histopathologically confirmed HA patients who had received CEUS examinations to date. Conclusion: By offering readers comprehensive knowledge of contrast imaging, especially CEUS, in the diagnosis of HA, our study may reduce misdiagnosis and further improve treatment options.
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Cardiac resynchronization therapy (CRT) is a standard treatment for patients with severe congestive heart failure. However, one-third of patients receiving CRT are non-responders. Conduction system pacing (CSP), including His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP), has become an alternative to CRT therapy. Furthermore, CRT therapy with CSP has shown to be more effective than CRT alone. When an implantable cardiac defibrillator or CRT-defibrillator is implanted with CSP, the problem of which port the HBP lead and LBBAP lead should be connected to arises. We report 2 cases of upgrading to CRT with CSP by utilizing the atrial ports for HBP and LBBAP leads. The procedure is a simple, reasonable, and effective therapy for end-stage heart failure.
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Objectives: Recently, a novel clip device, SureClip® (Micro-Tech Co. Ltd., Nanjing, China), has been developed, which improved rotation and reopening performance. We aimed to assess the efficacy of the SureClip® in prophylactic closure of the mucosal break after endoscopic papillectomy (EP) for ampullary neoplasm. Methods: We retrospectively reviewed the medical records of 40 patients who underwent EP for ampullary neoplasms between October 2009 and March 2020. Prophylactic closure after resection was performed using the conventional clip between 2014 and 2018, and with the SureClip® after 2019. The baseline characteristics, techniques, outcomes, and complications of EP were analyzed. Results: The median age of the patients (25 males and 15 females) was 70 years. The en block resection rate was 82.5% and the curative resection rate was 80.0%. Histologically, 11 (27.5%) patients had malignancy. Prophylactic closure was performed in 29 (72.5%) patients (17 conventional clips, 12 SureClip®). Complications occurred in 18 (45.0%) patients, including postprocedure bleeding in 9 (22.5%) patients. However, no postprocedure bleeding was observed in the patients who received prophylactic closure using the SureClip® (p = 0.038). All other factors were not significantly correlated with postprocedure bleeding. The duration of hospital stay after EP was significantly shorter in patients treated with the SureClip® compared to those treated with a conventional clip or without clips (p < 0.05). Conclusions: In the present study, prophylactic clipping of the mucosal break using the SureClip® was effective in preventing bleeding after EP.
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A 74-year-old woman with a cyst in her pancreatic tail was referred to our hospital. Computed tomography confirmed a large cystic lesion with irregular wall thickening, abdominal lymph node swelling, and ascites. We diagnosed her with an unresectable mucinous cystic neoplasm, since ascites cytology revealed adenocarcinoma. The patient received chemotherapy up to the fifth line for 55.2 months. Gemcitabine plus nab-paclitaxel and modified FOLFIRINOX achieved a partial response with a progression-free survival time of 12.1 and 20.4 months, respectively. The overall survival time from the beginning of first-line chemotherapy was 69.4 months.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Anciano , Albúminas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Metástasis de la Neoplasia , Paclitaxel/uso terapéutico , Páncreas , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Supervivencia sin ProgresiónRESUMEN
According to cancer genome sequences, more than 90% of cases of pancreatic ductal adenocarcinoma (PDAC) harbor active KRAS mutations. Digital PCR (dPCR) enables accurate detection and quantification of rare mutations. We assessed the dynamics of circulating tumor DNA (ct-DNA) in patients with advanced PDAC undergoing chemotherapy using dPCR. KRAS G12/13 mutation was assayed by dPCR in 47 paired tissue- and ct-DNA samples. The 21 patients were subjected to quantitative ct-DNA monitoring at 4 to 8-week intervals during chemotherapy. KRAS mutation was detected in 45 of those 47 patients using tissue DNA. In the KRAS mutation-negative cases, next-generation sequencing revealed KRAS Q61K and NRAS Q61R mutations. KRAS mutation was detected in 23/45 cases using ct-DNA (liver or lung metastasis, 18/19; mutation allele frequency [MAF], 0.1%-31.7%; peritoneal metastasis, 3/9 [0.1%], locally advanced, 2/17 [0.1%-0.2%]). In the ct-DNA monitoring, the MAF value changed in concordance with the disease state. In the 6 locally advanced cases, KRAS mutation appeared concurrently with liver metastasis. Among the 6 cases with liver metastasis, KRAS mutation disappeared during the duration of stable disease or a partial response, and reappeared at the time of progressive disease. The median progression-free survival was longer in cases in which KRAS mutation disappeared after an initial course of chemotherapy than in those in which it was continuously detected (248.5 vs 50 days, P < .001). Therefore, ct-DNA monitoring enables continuous assessment of disease state and could have prognostic utility during chemotherapy.
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ADN Tumoral Circulante/genética , ADN/sangre , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/genética , Adulto , Anciano , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Estudios de Evaluación como Asunto , Femenino , Frecuencia de los Genes/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación/genética , Páncreas/patología , Neoplasias Pancreáticas/patología , Pronóstico , Supervivencia sin Progresión , Neoplasias PancreáticasRESUMEN
Pulmonary arterial hypertension (PAH) is known to develop as a consequence of multiple genetic and/or non-genetic factors. A 27-year-old woman with chronic hepatitis C virus (HCV) infection developed severe PAH after interferon (IFN) therapy. Although most of the reported clinical courses of IFN-induced PAH are poor despite the discontinuation of IFN, the present patient was successfully treated with a triple combination therapy. In this report, we discuss the crosstalk among chronic HCV infection, IFN therapy, autoimmune disorders, and portal hypertension in the pathogenesis and development of PAH.
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Antivirales/efectos adversos , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Interferones/efectos adversos , Interferones/uso terapéutico , Adulto , Femenino , Humanos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Osteopontin (OPN) is thought to play multiple roles in the progression of atherosclerotic plaque including diabetic vascular complications. However, it still remains unclear whether the level of OPN in vivo is indeed clinically associated with the progression of diabetic complications. This study evaluated whether the levels of OPN in plasma and urine are correlated with the progression of diabetic complications, such as retinopathy, neuropathy, and nephropathy in patients with type 2 diabetes. In 229 patients with type 2 diabetes, OPN level in plasma and urine was evaluated by both the severity of diabetic complications, such as retinopathy, neuropathy, and nephropathy, and the clinical characteristics and the substantial laboratory findings. Plasma OPN level increased significantly with aging and the progression of diabetic nephropathy, especially at the stage of renal failure (p<0.05). However, the level was not related to the progression of retinopathy or neuropathy, or to laboratory findings, such as HbA1c or serum lipids. In contrast, urinary OPN level was not associated with diabetic complications in any of the subjects. There was no correlation between the plasma and urinary values of OPN. The results established that the plasma OPN was elevated in proportion to the progression of diabetic nephropathy, indicating that the plasma concentration may be a potential diagnostic predictor of diabetic end-stage renal disease.
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Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Sialoglicoproteínas/sangre , Anciano , Envejecimiento , Biomarcadores , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/orina , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteopontina , Valor Predictivo de las Pruebas , Sialoglicoproteínas/orinaRESUMEN
OBJECTIVE: We investigated the regulation of p38 mitogen-activated protein kinase (MAPK) by platelet-derived growth factor (PDGF)-BB and its biological effects in cultured normal and diabetic rat vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: VSMC growth from diabetic rats was faster than that from normal rats. The expression of the PDGF beta-receptor in diabetic VSMCs was significantly elevated compared with that in normal cells, and PDGF-BB-induced p38 phosphorylation in diabetic cells was more enhanced via MAPK kinase (MKK) 3/6. The level of PKC activity in diabetic cells increased more than that in normal cells with or without PDGF-BB. Although protein kinase C (PKC)-betaII and PKC-delta were activated by diabetes, PDGF-BB could further enhance the level of PKC-delta alone. PDGF-BB-induced cell migration was more elevated in diabetic VSMCs, and the increase was significantly inhibited by SB-203580, rottlerin, and antisense oligodeoxynucleotides for PKC-delta. PDGF-BB-induced p38 phosphorylation also regulated cell growth, cyclooxygenase-2 levels, and arachidonic acid release, but not apoptosis. These levels were more elevated in diabetic cells, which were inhibited by SB-203580. CONCLUSIONS: Our study established that PDGF-BB phosphorylated p38 via PKC-delta and the subsequent MKK 3/6, leading to cell growth regulation and the progression of a chronic inflammatory process in diabetic VSMCs.
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Diabetes Mellitus/enzimología , Miocitos del Músculo Liso/enzimología , Factor de Crecimiento Derivado de Plaquetas/fisiología , Proteína Quinasa C/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Apoptosis/fisiología , Ácido Araquidónico/metabolismo , Becaplermina , Movimiento Celular/fisiología , Proliferación Celular , Ciclooxigenasa 2 , Diabetes Mellitus/patología , Activación Enzimática/fisiología , Isoenzimas/metabolismo , Masculino , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Fosforilación , Prostaglandina-Endoperóxido Sintasas/metabolismo , Proteína Quinasa C-delta , Proteínas Proto-Oncogénicas c-sis , Ratas , Ratas Sprague-DawleyRESUMEN
The objective of this study was to estimate postprandial hypertriglycemia by a newly designed oral fat-loading test. Twenty-three healthy normolipidemic volunteers were orally administered a test meal consisting of a mixture of Telmeal 2.0 and 20 g of salt-free butter after fasting for 12 h. To measure the levels of total cholesterol (T-Cho), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), remnant-like particle-cholesterol (RLP-C), lipoprotein (a) [Lp (a)], free fatty acid, apolipoproteins (Apos), plasma glucose (PG), immunoreactive insulin (IRI), and high-sensitivity C-reactive protein (hs-CRP), venous blood samples were collected before the meal and at each hour until 9 h after fat-loading. The levels of both TG and RLP-C were drastically elevated at 2 h after fat-loading and these levels remained high until 4 h (p < 0.01). A significant correlation between TG and RLP-C was also observed at 2, 3 and 4 h, and the values of the correlation coefficients (r) were 0.837, 0.838, and 0.908, respectively. In contrast, the levels of T-Cho, HDL-C, Lp (a), Apos, PG, and hs-CRP did not change. Furthermore, there were no gastrointestinal symptoms during or after the study. These results strongly suggested that this newly designed fat-loading test was very useful for evaluating postprandial hypertriglycemia, including remnant concentrations.
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Grasas de la Dieta , Hipertrigliceridemia/diagnóstico , Adulto , Apolipoproteínas A/sangre , Glucemia , Proteína C-Reactiva/metabolismo , Colesterol/sangre , HDL-Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Insulina/sangre , Lipoproteína(a)/sangre , Lipoproteínas/sangre , Masculino , Periodo Posprandial , Valores de Referencia , Triglicéridos/sangreRESUMEN
The aim of this study was to clarify the mechanism(s) of an inhibitory effect of cerivastatin on cultured rat vascular smooth muscle cell (VSMC) growth. After being starved, cultured VSMCs were stimulated by 5% fetal bovine serum with either various concentrations of cerivastatin or 10-4 M of mevalonate. Cerivastatin dose-dependently decreased the values of [3H]-thymidine incorporation and cell numbers and the level of phosphorylated extracellular signal-regulated protein kinase 1/2. It also suppressed the level of proliferative cell nuclear antigen in a dose-dependent manner. These reductions were abolished by the addition of mevalonate. Similarly, the level of phosphorylated p38 was also decreased by cerivastatin. In contrast, cerivastatin dose-dependently activated the phosphorylation of both c-jun NH2-terminal protein kinase and activating transcription factor-2, and these activations were abolished by the addition of mevalonate. The levels of phosphorylated Akt and p70 S6 kinase as well as those of Bcl-2 were dose-dependently reduced by cerivastatin, and these reductions were abolished by the addition of mevalonate. Cerivastatin could dose-dependently elevate the levels of CPP32/caspase-3 activity and cytoplasmic histone-associated DNA fragments in VSMCs without causing cytotoxicity. These results indicate that cerivastatin suppresses cell survival and activates the apoptotic cellular signaling in VSMCs, suggesting that it could be effective for preventing the progression of restenosis after angioplasty.