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Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Estudios Retrospectivos , Adulto , Análisis Multivariante , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
Both combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and cholangiolocarcinoma are rare primary liver cancers. cHCC-CCA is believed to originate from transformed hepatocellular carcinoma or liver stem/progenitor cells. Cholangiolocarcinoma is characterized by ductular reaction-like anastomosing cords and glands resembling cholangioles or canals containing hepatocellular carcinoma components and adenocarcinoma cells. According to the 2019 revision of the World Health Organization criteria, a subtype with stem cell features as a subclassification of cHCC-CCA was abolished for lack of conclusive evidence of the stem cell origin theory. That led to the classification of cholangiolocarcinoma with hepatocytic differentiation as cHCC-CCA. Consequently, cholangiolocarcinoma without hepatocytic differentiation is classified as a subtype of small-duct cholangiocarcinoma and is assumed to originate from the bile duct. Herein, we report the first case of double primary cHCC-CCA and cholangiolocarcinoma without hepatocytic differentiation in different hepatic segments of a cirrhotic liver. We believe this case supports the validity of the new World Health Organization criteria because the pathological finding of cHCC-CCA in this case shows the transformation of hepatocellular carcinoma to cholangiocarcinoma. Furthermore, this case may demonstrate that immature ductular cell stemness and mature hepatocyte cell stemness in hepatocarcinogenesis can coexist in the same environment. The results provide valuable insights into the mechanisms of growth, differentiation, and regulation of liver cancers.
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Anorexia nervosa (AN) can cause severe protein energy malnutrition and the consequent development of various organ disorders. AN is known to cause hepatic complications. We report two cases of starvation and refeeding-induced liver injury in patients with AN, and review the literature on the hepatic complications of AN. Acute liver injury can be induced by both starvation and refeeding, although the underlying pathomechanisms and management of liver injury differ between these two conditions. Clinicians should carefully identify the clinical features to ensure an accurate diagnosis and appropriate management of these conditions.
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Anorexia Nerviosa , Humanos , Anorexia Nerviosa/complicaciones , Anorexia Nerviosa/diagnóstico , Anorexia Nerviosa/metabolismo , HígadoRESUMEN
We examine the historical changes of 236U/238U and 235U/238U in a sediment core collected in Tokyo Bay and elucidate the anthropogenic sources of uranium in the 1960s-2000s. Uranium-236 was detected in samples deposited in the 1960s-2000s, and the 236U/238U ratio of the sediment core shows peak values in the 1970s. The 235U/238U isotopic ratios in samples deposited in the early 1960s are almost identical to that of natural uranium, implying that the 236U might have originated from global fallout. A decrease in 235U/238U was observed in the late 1960s-2000s, suggesting that depleted uranium from nuclear fuel reprocessing increased the 236U/238U ratios in the sediment. The 236U/238U values in sediments from the 1980s-2000s were lower than those in the 1970s but considerably higher than those in the 1960s, suggesting that the main source of depleted uranium still remains around Tokyo Bay. Our results demonstrated that the depleted uranium released in the 1970s should be considered as an important end-member when using uranium isotopic ratios as environmental tracers in closed aquatic environments around industrial cities.
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Monitoreo de Radiación , Uranio , Contaminantes Radiactivos del Agua , Monitoreo de Radiación/métodos , Uranio/análisis , Tokio , Bahías , Contaminantes Radiactivos del Agua/análisisRESUMEN
OBJECTIVE: The human epidermis is formed by the proliferation and differentiation of keratinocytes adjacent to the basement membrane. The outermost layer, the stratum corneum, is equipped with a barrier function that prevents water evaporation, and intercellular lipids play an important role in this barrier function. When the barrier is functioning normally, evaporation is prevented; however, when barrier function is impaired, moisture evaporates, resulting in dry and rough skin. Therefore, maintenance of normal barrier function is critical for maintaining normal skin function. Peroxisome proliferator-activated receptor α (PPARα) is mainly not only involved in lipid metabolism in the liver but is also expressed in the epidermis and is involved in inducing keratinocyte differentiation, promoting lipid production, maintaining barrier function and suppressing skin inflammation. Hence, compounds that activate PPARα are expected to control skin function. Therefore, we identified PPARα activators from among extracts of natural resources that have been approved for use in humans and analysed the effects of these extracts on skin function. METHODS: First, extracts of 474 natural resources were screened using a PPARα activator screening cell line independently constructed in our laboratory. Next, reporter assays were performed using the Gal4-chimera system to evaluate whether these extracts act as ligands for PPARα. We then analysed their effect on primary normal human epidermal keratinocyte cells by using real-time RT-PCR. Finally, we evaluated PPARα activation effect by the combination of these extracts. RESULTS: We identified 36 extracts having the effect of activating PPARα. In particular, #419, a Typha angustifolia spike extract, showed concentration-dependent transcriptional activation through PPARα-LBD and was considered to be likely to contain a compound that is a ligand of PPARα. #419 increased the expression of PPARα target genes and genes related to skin function in primary cultured human epidermal keratinocytes. Finally, the use of #419 in combination with nine extracts increased PPAR activity more than twice as much as #419 alone treatment. CONCLUSIONS: These results showed that the reporter cell line could be useful for discovering extracts of natural resources and that the identified Typha angustifolia spike extract could be used in cosmetics that activate PPARα, which expected to improve skin function.
OBJECTIF: L'épiderme humain se forme grâce à la prolifération et à la différenciation des kératinocytes adjacents à la membrane basale. La couche externe, dite « couche cornée ¼, possède une fonction barrière qui empêche l'évaporation de l'eau, dans laquelle les lipides intercellulaires jouent un rôle important. Lorsque la barrière fonctionne normalement, l'évaporation est évitée ; mais lorsqu'elle est altérée, l'évaporation a lieu et la peau, privée d'hydratation, devient sèche et rêche. Par conséquent, il est capital de maintenir cette fonction barrière normale pour que la peau conserve son fonctionnement normal. Le récepteur alpha activé par proliférateurs de peroxysomes (PPARα) intervient surtout non seulement dans le métabolisme lipidique du foie, mais également dans l'épiderme ; il joue en effet un rôle dans l'induction de la différenciation des kératinocytes, la promotion de la production lipidique, le maintien de la fonction barrière et la suppression de l'inflammation de l'épiderme. Par conséquent, les activateurs du PPAR-α devraient être déterminants pour une bonne fonction cutanée. Nous avons donc identifié des activateurs du PPAR-α parmi des extraits de ressources naturelles dont l'utilisation chez l'homme est approuvée, et nous avons analysé les effets de ces extraits sur la fonction cutanée. MÉTHODES: Tout d'abord, des extraits de 474 ressources naturelles ont été sélectionnés à l'aide d'une lignée cellulaire de détection des activateurs du PPAR-α, construite indépendamment dans notre laboratoire. Ensuite, des tests de gènes rapporteurs ont été effectués à l'aide du système Gal4-chimera pour voir si ces extraits jouaient le rôle de ligands pour le PPAR-α. Nous avons ensuite analysé leur effet sur les cellules kératinocytaires épidermiques humaines normales primaires par RT-PCR en temps réel. Enfin, nous avons évalué l'effet d'activation du PPAR-α par l'association de ces extraits. RÉSULTATS: Nous avons identifié 36 extraits ayant pour effet d'activer le PPAR-α. En particulier, le n° 419, un extrait d'épi de Typha angustifolia, a montré une activation transcriptionnelle dépendante de la concentration par le PPAR-α-LBD et a été considéré comme susceptible de contenir un composé qui est un ligand du PPAR-α. Le n° 419 a augmenté l'expression des gènes cibles du PPAR-α et des gènes liés au fonctionnement de la peau dans les kératinocytes épidermiques humains primaires mis en culture. Enfin, l'utilisation du n° 419 en association avec neuf extraits a augmenté de plus du double l'activité du PPAR par rapport au traitement par le n° 419 seul. CONCLUSIONS: Ces résultats ont montré que la lignée cellulaire rapporteuse pourrait être utile pour découvrir des extraits de ressources naturelles et que l'extrait d'épi de Typha angustifolia identifié pourrait être utilisé dans des cosmétiques qui activent le PPAR-α, ce qui devrait améliorer la fonction cutanée.
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Cosméticos , PPAR alfa , Cosméticos/metabolismo , Cosméticos/farmacología , Humanos , Queratinocitos , Ligandos , Extractos Vegetales , Piel/metabolismoRESUMEN
Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare indolent B-cell neoplasm, and a gain-of-function mutation in the myeloid differentiation primary response 88 (MYD88), L265P, is a commonly recurring mutation in patients with WM/LPL. Histological transformation of WM/LPL to an aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL) is rare, and transformed DLBCL has a worse prognosis than de novo DLBCL, partly because transformed DLBCL is mostly classified as non-germinal center B-cell-like (non-GCB) subtype. We herein describe a 75-year-old man with DLBCL with a history of WM/LPL. DLBCL in this patient showed the GCB subtype, and the light chain restriction of DLBCL was different from that of the antecedent WM/LPL, indicating that the two types of lymphoma cells had distinctive origins. However, DLBCL in this patient harbored the MYD88 L265P mutation, and polymerase chain reaction and Sanger sequencing of the DLBCL and WM/LPL for immunoglobulin heavy chain gene rearrangement suggested a clonal relationship between the two lymphomas. Since the outcome of transformed DLBCL is worse than for de novo DLBCL, it is important to evaluate the clonal relationship between primary WM/LPL and the corresponding transformed DLBCL, even if the DLBCL expresses a GCB subtype or discordant light chain restriction.
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Linfocitos B/metabolismo , Linfocitos B/patología , Transformación Celular Neoplásica , Centro Germinal/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/etiología , Macroglobulinemia de Waldenström/patología , Anciano , Biomarcadores , Biopsia , Médula Ósea/patología , Análisis Mutacional de ADN , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hígado/patología , Masculino , Mutación , Factor 88 de Diferenciación Mieloide/genética , Tomografía Computarizada por Rayos XRESUMEN
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract with an annual incidence of 1-2 per 10 000 people. Although most GISTs are solid, they may present with predominantly cystic components. A 69-year-old Japanese woman presented with a recently elevated gamma-glutamyl transpeptidase level. Computed tomography revealed multiple space-occupying lesions (SOLs) in the liver. These SOLs appear cystic on magnetic resonance imaging and abdominal ultrasound and are associated with thick walls at the margins. In addition, these thick walls showed high intensity on diffusion-weighted images. She was diagnosed with liver metastasis of GIST by diagnostic biopsies from the thick parts of the cystic liver lesion (thick walls at the margins). The primary lesion was thought to be located along the medial side of the descending part of the duodenum, but a duodenal biopsy was initially undiagnosed. Liver metastases due to GISTs are known to cause cystic changes after treatment, such as imatinib mesylate. However, to the best of our knowledge, only six cases where hepatic GIST with predominantly cystic changes (prior to any treatment) have been reported. It should be noted that GISTs appear cystic in all organs.
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AIM: Nonalcoholic steatohepatitis (NASH) is a risk factor for nonvirus-related hepatocellular carcinoma, which is increasing in prevalence. The aim of this study was to clarify the clinical application of fucosylated alpha-fetoprotein (AFP-L3) in the process of nonalcoholic fatty liver (NAFL) disease development. METHODS: Serum samples from 115 diabetes mellitus (DM), 36 NAFL, and 119 NASH patients were analyzed for AFP-L3 expression using raw data of a micro total analysis system. These data were then compared with the clinical characteristics of the patients. A validation study was also undertaken with 55 samples (17 NAFL and 38 NASH). RESULTS: Trace amounts of AFP-L3 were detected in 3.5%, 16.7%, and 58.0% of patients with DM, NAFL, and NASH, respectively. The odds ratio of AFP-L3 positivity for the diagnosis of NASH in multivariate analysis was 9.81 (95% confidence interval, 3.77-25.5). The rates in patients without fibrosis or with stage 1, stage 2, stage 3, and stage 4 fibrosis were 14.7%, 31.3%, 63.0%, 86.2%, and 100%, respectively. The rates were significantly increased according to the advancement of liver fibrosis (p < 0.001); however, no difference in the positive rate of AFP-L3 was observed between patients with and without fatty livers and between patients with normal and abnormal transaminase. The same relationship was also observed in the validation cohort. CONCLUSION: Abnormal fucosylation of AFP occurred in patients with NASH, so it could be useful for the screening of NASH in patients with DM, as well as for the differential diagnosis of NASH and the evaluation of fibrosis.
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BACKGROUND ANDAIM: Human telomerase reverse transcriptase (TERT) promoter mutations were the most prevalent mutations in patients with hepatocellular carcinoma (HCC). We tried to detect the mutations with plasma circulating tumor DNA (ctDNA) in patients with advanced HCC and elucidated their clinical utility. METHODS: Circulating tumor DNA in plasma was extracted from 130 patients with advanced HCC who were treated with systemic chemotherapy (n = 86) or transcatheter arterial chemoembolization (n = 44), and TERT promoter mutations were examined with digital droplet polymerase chain reaction. The correlations between these mutations and the clinical outcome of patients were analyzed. RESULTS: Of the 130 patients examined, 71 patients (54.6%) were positive for TERT promoter mutations in ctDNA, of which 64 patients were -124bp G > A and 10 were -146bp G > A. The presence of TERT promoter mutations was correlated with large intrahepatic tumor size (P = 0.05) and high des-gamma carboxyprothrombin (P = 0.005). Overall survival of the patients with the mutations was significantly shorter than those without them (P < 0.001), and the patients with high (≥ 1%) fractional abundance of the mutant alleles showed shorter survival than those with low (< 1%) fractional abundance. Multivariate analysis revealed that TERT promoter mutation (hazard ratio [HR]: 1.94; 95% confidence interval [CI], 1.18-3.24; P < 0.01), systemic chemotherapy (HR: 2.38; 95% CI, 1.29-4.57; P < 0.01), and vascular invasion (HR: 2.16; 95% CI, 1.22-3.76; P < 0.01) were significant factors for poor overall survival. CONCLUSIONS: TERT promoter mutations in ctDNA were associated with short survival and could be a valuable biomarker for predicting the prognosis of patients with advanced HCC.
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Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Mutación , Regiones Promotoras Genéticas/genética , Telomerasa/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
CONTEXT: Pharmacologic treatment of dizziness is still not well-established. Consequently, traditional Japanese (Kampo) herbal medicine is commonly used. Ryokeijutsukanto is used to treat dizziness caused by orthostatic dysregulation (OD). OBJECTIVE: We aimed to evaluate the effectiveness of ryokeijutsukanto, a traditional Japanese (Kampo) herbal medicine, in treating dizziness, including light-headedness and/or palpitations. We focused on dizziness caused by OD, a condition commonly treated with ryokeijutsukanto. DESIGN: We used a case series design. SETTING: The study was centered in the department of internal medicine and department of otolaryngology at a general hospital. PATIENTS: We tested ryokeijutsukanto in four female patients who were experiencing dizziness and who were diagnosed with OD. INTERVENTION(S): The patients received ryokeijutsukanto (1.5 g to 4.2 g of dried extract daily). MAIN OUTCOME MEASURE(S): Ryokeijutsukanto was prescribed to the four patients; clinical efficacy and improvement in dizziness were assessed using the Clinical Global Impression-Improvement scale and Vertigo Symptom Scale-Short Form. RESULTS: All patients intended to continue Kampo treatment since high curative effects and no adverse effects were observed. CONCLUSIONS: To the best of our knowledge, this is the first report elucidating the effectiveness of ryokeijutsukanto in treating dizziness as a result of OD. Ryokeijutsukanto may be an appropriate complementary therapy for OD.
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Medicamentos Herbarios Chinos , Medicina Kampo , Mareo/diagnóstico , Mareo/tratamiento farmacológico , Mareo/etiología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Medicina de Hierbas , Humanos , Japón , Medicina Kampo/efectos adversos , Vértigo/complicaciones , Vértigo/diagnóstico , Vértigo/tratamiento farmacológicoRESUMEN
Squamous papilloma is a benign mass lesion of the oral mucosa. For papillomas of the tongue, surgery is recommended owing to their malignant potential; however, certain complications may be associated with surgery. A traditional Japanese (Kampo) herbal medicine, Keishibukuryogan-ka-yokuinin (KBGY), has been used to treat viral warts and various skin diseases in Japan. Therefore, the effect of KBGY on papillomas is promising. A 49-year-old Japanese man presented with a wart on his tongue that was about 3 months old. He smoked 5 cigarettes per day. He did not drink alcohol. He had no history of malignant illnesses. He was taking alprazolam for panic disorder. The patient was diagnosed with a suspected papilloma of the tongue at the Department of Otolaryngology and was advised to undergo an excision biopsy to exclude malignancy. However, he refused owing to the fear of an invasive procedure. After informed consent was obtained from the patient, KBGY was prescribed. Three months later, the wart on his tongue spontaneously prolapsed. The histopathological diagnosis was squamous papilloma. There was no indication of malignancy, and the patient discontinued Kampo treatment. He has had no recurrence in the past 3 years. KBGY is a combination of Keishibukuryogan and yokuinin (adlay seeds). Keishibukuryogan may be beneficial for skin or oral mucosal remodeling, and yokuinin may have antiviral properties. The present case report suggests the use of KBGY as an appropriate complementary therapy for squamous papilloma.
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Medicamentos Herbarios Chinos/uso terapéutico , Medicina Kampo , Papiloma , Extractos Vegetales/uso terapéutico , Medicina de Hierbas , Humanos , Japón , Masculino , Persona de Mediana Edad , Papiloma/tratamiento farmacológico , Lengua/patologíaRESUMEN
AIM: Tolvaptan is a newly available diuretic that has a specific function in water reabsorption inhibition. Given that spironolactone or furosemide induces the aggravation of cirrhotic hyponatremia and dehydration, tolvaptan affects the management strategy of liver cirrhosis. Representative predictive markers of its response include renal function-related markers such as urea nitrogen or creatinine. However, vascular function-related markers have not been well investigated. We investigated the effect of the vascular function-related marker asymmetric dimethylarginine (ADMA) and the effective arterial blood volume (EABV) marker, fractional excretion of sodium (FENa), on the early tolvaptan response and survival in liver cirrhosis. METHODS: We prospectively recruited 49 patients who required add-on tolvaptan for refractory ascites or edema. Laboratory data were obtained immediately before and 1 day after tolvaptan administration. Patients exhibiting >1.5 kg weight loss after 1 week were categorized as early responders to tolvaptan. Patients were followed for a median of 200 days and were assessed for survival. RESULTS: Early responders showed lower creatinine levels (<1.0 mg/dL), and higher ADMA levels (≥0.61 nmol/mL) than others in a multivariate analysis. Patients with a shorter survival were positive for hepatocellular carcinoma and had a low FENa (<0.35%). CONCLUSION: Early responders showed higher ADMA levels reflecting vascular stricture, suggesting that higher vascular tonus is required for a tolvaptan early response. Patients with a shorter survival showed a lower FENa, reflecting a lower EABV and suggesting that adequate EABV is required for the prolonged survival after tolvaptan administration.
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INTRODUCTION: Molecular targeting drugs are recommended as second-line treatment for intrahepatic advanced hepatocellular carcinoma (HCC). However, in Asia, hepatic arterial infusion chemotherapy (HAIC) is also considered as a second-line treatment because it improves the survival of responders. The aim of this study was to predict responders and non-responders to HAIC with low-dose cisplatin plus 5-fluorouracil (LFP) using tumor markers. OBJECTIVE AND METHODS: The data of 47 patients who received LFP for the first time in our hospital were analyzed retrospectively. We evaluated the association between treatment response by Response Evaluation Criteria in Solid Tumors and the changing ratio of the serum concentration of α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxy prothrombin (DCP) 2 weeks after LFP initiation. RESULTS: The number of patients showing a complete response (CR), a partial response (PR), stable disease (SD), and progressive disease (PD) was 0 (0%), 20 (43%), 18 (38%), and 9 (19%), respectively. The AFP ratio showed significant positive correlations for PR vs. SD (p = 0.004) and PR vs. PD (p = 0.003). The DCP ratio correlated significantly for PR vs. SD (p = 0.02). The optimal cutoff values for responders were 0.79 for the AFP ratio and 0.53 for the DCP ratio. Prediction using both or either cutoff value showed 93% sensitivity, 53% specificity, a 94% negative predictive value, and a 57% positive predictive value. CONCLUSION: Optimal cutoff values for AFP and DCP ratios enable prediction of nonresponders to HAIC with LFP. This simple and early assessment method allows the use of HAIC and molecular targeting drugs for HCC treatment.
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This study will assess the safety and efficacy of the administration of adenoviral vector expressing the human-reduced expression in immortalized cells (Ad-REIC) to a liver tumor in patients with hepatocellular carcinoma (HCC) or liver metastasis of pancreatic cancer. A Phase I clinical study of Ad-REIC administration to a liver tumor in a patient with HCC or liver metastasis of pancreatic cancer will be conducted. The study is a single-arm, prospective, nonrandomized, noncomparative, open-label, single-center trial performed in Okayama University Hospital, Okayama, Japan. Ad-REIC will be injected into the liver tumor under ultrasound guidance. Ad-REIC administration will be repeated a total of three-times every 2 weeks. The primary end point is the dose-limiting toxicity and incidence of adverse events. The secondary end points are the objective response rate and disease control rate. This study aims to expand the indication of Ad-REIC by assessing its safety and efficacy in patients with HCC or liver metastasis of pancreatic cancer.
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Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Protocolos Clínicos , Terapia Genética , Vectores Genéticos/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Biomarcadores de Tumor , Esquema de Medicación , Femenino , Terapia Genética/efectos adversos , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Humanos , Masculino , Proyectos de Investigación , Transgenes , Resultado del TratamientoRESUMEN
A 1-year-old female toddler who was under a great amount of psychological stress presented with acute hematemesis. She had no significant medical history; she displayed lethargy and was anemic. Although blood transfusion and famotidine were administered for upper gastrointestinal bleeding (UGIB), the anemia did not improve. Thus, early endoscopy was performed under general anesthesia, revealing a gastric ulcer with exposed vessels in the supra-angular region. Cauterization via bipolar hemostatic forceps was performed on the exposed vessels, and the bleeding was controlled successfully. We diagnosed the patient with hemorrhagic stress-induced gastric ulcer due to psychological stress. Three months later, endoscopy revealed that the gastric ulcer had healed.
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Hemorragia Gastrointestinal/etiología , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica Hemorrágica/etiología , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/etiología , Estrés Psicológico/complicaciones , Enfermedad Aguda , Endoscopía , Famotidina/uso terapéutico , Femenino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Lactante , Úlcera Péptica Hemorrágica/terapia , Úlcera Gástrica/terapiaRESUMEN
This case report refers to a 31-year-old patient with an 11-year history of Crohn's disease. The patient presented with an edematous elevated lesion in the splenic flexure. Two histological analyses revealed no signs of obvious dysplasia, and the patient subsequently began infliximab treatment. Nine months later, a worsening of the stricture of the edematous elevated lesion was observed in the splenic flexure, and transverse colonic resection was performed. A histological investigation of the lesion in the splenic flexure revealed advanced adenocarcinoma. Six months after the surgery, computed tomography revealed recurrent carcinoma and peritoneal metastases. The patient was administered palliative chemotherapy.