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1.
Intern Med ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38599864

RESUMEN

Atopic dermatitis is common in children and often treated with topical corticosteroids (TCs). A boy in his late teens who had been using TCs for atopic dermatitis was diagnosed with liver damage during a health checkup. A medical examination revealed severe steatotic liver disease and elevated liver enzyme levels despite the absence of typical symptoms such as central obesity. After discontinuation of TCs, an improvement in liver enzyme levels was observed, leading to the diagnosis of drug-induced steatohepatitis. This case underscores the potential liver risks associated with prolonged TC use in children, highlighting the need for parental education.

3.
Br J Clin Pharmacol ; 90(1): 354-359, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37596710

RESUMEN

Clozapine (CLZ) is extensively used for treatment-resistant schizophrenia (TRS) with caution to avoid serious adverse events such as agranulocytosis and drug-drug interactions (DDIs). In the current report, we present a case of a 35-year-old male non-smoking TRS patient whose steady-state plasma trough concentrations (Ctrough ) of CLZ and its active metabolite, N-desmethylclozapine (NDMC), were significantly increased after initiating oral administration of lemborexant (LEM), a dual orexin receptor antagonist, for the treatment of insomnia. The patient experienced oversedation with sleepiness and fatigue while maintaining high levels of Ctrough of CLZ. The increased concentrations of CLZ returned to normal ranges after the discontinuation of LEM dosing, implying a pharmacokinetic DDI between CLZ and LEM. To gain insight into possible mechanisms, we performed in vitro assays of CYP1A2- and CYP3A4-mediated CLZ metabolism by measuring the formations of NDMC and clozapine N-oxide (CNO). In accordance with previous studies, the incubation of CLZ with each enzyme resulted in the production of both metabolites. LEM had only a weak inhibitory effect on CYP1A2- and CYP3A4-mediated CLZ metabolism. However, the preincubation of LEM with CYP3A4 in the presence of NADPH showed a significant enhancement of inhibitory effects on CLZ metabolism with IC50 values for the formations of CNO and NDMC of 2.8 µM and 4.1 µM, respectively, suggesting that LEM exerts as a potent time-dependent inhibitor for CYP3A4. Taken together, the results of the current study indicate that co-medication of CLZ with LEM may lead to increase in exposure to CLZ and risks of CLZ-related adverse events.


Asunto(s)
Antipsicóticos , Clozapina , Masculino , Humanos , Adulto , Clozapina/efectos adversos , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A/metabolismo , Antipsicóticos/efectos adversos , Interacciones Farmacológicas
4.
Drug Des Devel Ther ; 17: 3023-3031, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37789971

RESUMEN

This review aims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of schizophrenia. Lurasidone has antagonistic effects on the dopamine D2, 5-hydroxytryptamine (5-HT)2A, and 5-HT7 receptors and a partial agonistic effect on the 5-HT1A receptor with low affinities for muscarinic M1, histamine H1, and a1 adrenergic receptors. The receptor-binding profile of lurasidone is thought to be associated with fewer side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Behavioral pharmacological studies have demonstrated that lurasidone exerts anxiolytic and antidepressive effects and improves cognitive function, which are associated with the modulation of 5-HT7 and 5-HT1A receptors. Literature search using PubMed was performed to find published studies of randomized controlled trials and recent meta-analyses regarding efficacy and safety, particularly metabolic side effects of lurasidone in schizophrenia. In short-term studies, the results of randomized placebo-controlled trials and meta-analyses have suggested that lurasidone was superior to placebo in improving total psychopathology, positive symptoms, negative symptoms, and general psychopathology in patients with acute schizophrenia. Regarding safety, lurasidone had minimal metabolic side effects, and was identified as one of the drugs with the most benign profiles for metabolic side effects. Long-term trials revealed that lurasidone had the preventive effects on relapse, with minimal effects on weight gain and other metabolic side effects. Furthermore, lurasidone improves cognitive and functional performance of patients with schizophrenia, especially in long-term treatment. Patients with schizophrenia require long-term treatment with antipsychotics for relapse prevention; thus, minimizing weight gain and other side effects is crucial. Lurasidone is suitable as one of the first-line antipsychotic drugs in the acute phase, and a switching strategy should be considered during the maintenance phase, to balance efficacy and adverse effects and achieve favorable outcomes in the long-term course of schizophrenia.


Asunto(s)
Antipsicóticos , Esquizofrenia , Humanos , Clorhidrato de Lurasidona/efectos adversos , Esquizofrenia/tratamiento farmacológico , Serotonina , Isoindoles/farmacología , Tiazoles/farmacología , Antipsicóticos/efectos adversos , Aumento de Peso
5.
Clin J Gastroenterol ; 16(6): 829-835, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37594614

RESUMEN

We report an autopsy case of a large duodenal adenocarcinoma that produced alpha-fetoprotein (AFP). The patient was a man in his 70s with diabetes mellitus. He presented with epigastralgia and was referred to our hospital. Upper gastrointestinal endoscopy and abdominal computed tomography revealed a large tumor of 11 cm in diameter in the descending limb of the duodenum. A tumor biopsy showed poorly differentiated adenocarcinoma. Although his carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range, his AFP levels were significantly elevated (42,078.4 ng/mL). Due to vascular invasion, curative resection was not feasible, and chemotherapy was chosen as the treatment option. After gastrojejunostomy was performed to enable oral intake, one cycle of modified leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) therapy was administered. However, it proved ineffective, and the patient's anorexia gradually worsened. Ultimately, he succumbed to the progression of cancer cachexia. Autopsy findings revealed a 14-cm-long duodenal carcinoma primarily located in the duodenal bulb, with direct invasion into the stomach, pancreas, and liver. A pathological examination confirmed a diagnosis of poorly differentiated adenocarcinoma with AFP production. Duodenal cancer is rare, and AFP-producing duodenal cancer is even rarer, with only 21 reported cases, including our own. We present this autopsy case of AFP-producing duodenal adenocarcinoma and review the cases reported in the relevant literature.


Asunto(s)
Adenocarcinoma , Neoplasias Duodenales , Masculino , Humanos , alfa-Fetoproteínas , Autopsia , Adenocarcinoma/cirugía , Antígeno CA-19-9
6.
J Clin Sleep Med ; 19(10): 1753-1758, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37243798

RESUMEN

STUDY OBJECTIVES: We conducted a retrospective study to investigate the efficacy and safety of switching from other hypnotics, including benzodiazepines and Z-drugs, suvorexant, ramelteon, mirtazapine, trazodone, and antipsychotics, to lemborexant, a dual orexin receptor antagonist, for 3 months. METHODS: Clinical data obtained from the medical records of 61 patients treated at the Horikoshi Psychosomatic Clinic between December 2020 and February 2022 were analyzed, including the Athens Insomnia Scale, Epworth Sleepiness Scale, and Perceived Deficits Questionnaire-5. The primary outcome was the mean change in Athens Insomnia Scale score after 3 months. Secondary outcomes were the mean changes in the Epworth Sleepiness Scale and Perceived Deficits Questionnaire-5 scores over 3 months. We also compared pre- and post-diazepam equivalents. RESULTS: The mean Athens Insomnia Scale score decreased over 3 months after switching to lemborexant (1 mo: -2.98 ± 5.19, P < .001; 2 mo: -3.20 ± 5.64, P < .001; 3 mo: -3.38 ± 5.61, P < .001). Mean Epworth Sleepiness Scale score did not change from baseline to 1 month (-0.49 ± 3.41, P = 0.27), 2 months (0.082 ± 4.62, P = .89), or 3 months (-0.64 ± 4.80, P = .30). Mean Perceived Deficits Questionnaire-5 score did improve from baseline to 1 month (-1.17 ± 2.47, P = .004), 2 months (-1.05 ± 2.97, P = .029), and 3 months (-1.24 ± 3.06, P = .013). There was also a reduction in the total diazepam equivalent (baseline vs 3 mo: 14.0 ± 20.2 vs 11.3 ± 20.6, P < .001). CONCLUSIONS: Our study showed that, by switching to lemborexant from other hypnotics, the risks associated with benzodiazepines and Z-drugs may be reduced. CITATION: Horikoshi S, Miura I, Suzuki Y, et al. Switching to lemborexant for the management of insomnia in mental disorders: the SLIM study. J Clin Sleep Med. 2023;19(10):1753-1758.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Estudios Retrospectivos , Somnolencia , Hipnóticos y Sedantes/uso terapéutico , Antagonistas de los Receptores de Orexina/uso terapéutico , Benzodiazepinas , Diazepam
7.
Intern Med ; 62(21): 3151-3156, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36927965

RESUMEN

A woman in her 70s presented with gallbladder carcinoma with liver metastases and peritoneal dissemination. After standard chemotherapy failed, a liver biopsy was performed. A FoundationOne CDx analysis showed that the tumor mutational burden (TMB) was high (34 mutations/megabase). Treatment with pembrolizumab, which is an immune checkpoint inhibitor (ICI), resulted in a partial response, and there were no significant immune-related adverse events. According to recently published reports, the frequency of TMB-high biliary tract cancer (BTC) is 3.4-4%, which makes it extremely rare. In conclusion, ICIs may be effective in patients with TMB-high BTC.


Asunto(s)
Carcinoma , Neoplasias de la Vesícula Biliar , Neoplasias Pulmonares , Femenino , Humanos , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/genética , Mutación/genética , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Biomarcadores de Tumor
8.
Clin J Gastroenterol ; 16(3): 422-431, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36821067

RESUMEN

We herein report three cases of immune-related hypopituitarism after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1 was a man in his 60s with hepatitis C-related liver cirrhosis. He had been diagnosed with HCC and undergone surgical resection. However, HCC recurred 17 months after surgery. After 13 cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. The plasma levels of adrenocorticotropic hormone (ACTH) and cortisol were decreased. He was diagnosed with central adrenal insufficiency associated with hypopituitarism. Glucocorticoid therapy rapidly improved his symptoms. Case 2 was a man in his 70s with HCC associated with non-alcoholic steatohepatitis (NASH). After eight cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. Hyponatremia and eosinophilia were observed. He was also diagnosed with hypopituitarism, and glucocorticoid therapy rapidly improved his symptoms. Case 3 was a man in his 60s with HCC associated with alcoholic liver cirrhosis. After 10 cycles of atezolizumab-bevacizumab therapy, hypopituitarism developed. In these cases, the presence of hyponatremia and/or eosinophilia was useful for making a diagnosis. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody is reported to be likely to induce hypophysitis two to three months after its administration. In contrast, anti-programmed cell death 1 (PD-1) antibody is likely to induce hypopituitarism six to seven months after its administration. These three patients treated with anti-programmed death ligand 1 (PD-L1) antibody developed hypopituitarism six to nine months later, close to the condition with anti-PD-1 antibody administration. Although immune-related hypopituitarism after atezolizumab-bevacizumab treatment is rare, we should be alert for hypopituitarism developing during atezolizumab-bevacizumab treatment.


Asunto(s)
Carcinoma Hepatocelular , Hiponatremia , Neoplasias Hepáticas , Masculino , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab/efectos adversos , Glucocorticoides , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia , Paresia , Anticuerpos Monoclonales Humanizados/efectos adversos
9.
Oncology ; 101(3): 193-202, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36649691

RESUMEN

INTRODUCTION: We previously reported 2 cases of esophageal varices rupture during atezolizumab and bevacizumab (Atez/Bev) treatment, in which the spleen volume gradually increased. The aim of this retrospective study is to compare the chronological change in spleen volume of patients treated with Atez/Bev and lenvatinib (LEN). METHODS: Seventy-two patients (Atez/Bev group, n = 26; LEN group, n = 46) were included in this retrospective study. The splenic parenchyma area was measured based on CT imaging. We used mixed-effect regression models with random intercepts to test the difference in the rate of change in spleen volume between the Atez/Bev and LEN groups. RESULTS: The median age of the Atez/Bev and LEN groups was 74.0 (71.0-82.0) and 72.0 (67.5-76.0), respectively. About 80% patients were male. The mALBI grade was classified as 1, 2a, 2b, and 3 in 10 (38.5%), 6 (23.1%), 10 (38.5%), and zero (0.0%) patients, respectively, in the Atez/Bev group and 21 (45.7%), 9 (19.6%), 15 (32.6%), and 1 (2.2%) patient in the LEN group (p = 0.9). The median baseline neutrophil-to-lymphocyte ratio (NLR) was 2.61 (1.80-3.41) in the Atez/Bev group and 2.71 (1.76-3.67) in the LEN group (p = 1.0). The median baseline spleen volume was 185 (132-246) cm3 in the Atez/Bev group and 231 (150-355) cm3 in the LEN group. The spleen volume gradually increased during Atez/Bev treatment (2.41 cm3 per week), while it was mostly consistent during LEN treatment (0.32 cm3 per week). Among patients with mALBI grade 2b or 3, the spleen volume increased in the Atez/Bev group (2.99 cm3 per week) and slightly decreased in the LEN group (0.82 cm3 per week), without statistical significance (p = 0.07). Among patients with a baseline NLR of >2.68, the spleen volume increased at a rate of 2.57 cm3 per week in the Atez/Bev group and decreased at a rate of 1.18 cm3 per week in the LEN group. The difference in the slope of the two groups was statistically significant (p = 0.04). DISCUSSION/CONCLUSION: Atez/Bev treatment could result in an increased spleen volume. Caution is required when managing patients treated with Atez/Bev, especially those with a high NLR.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Masculino , Femenino , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Bevacizumab/efectos adversos , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Bazo/diagnóstico por imagen , Bazo/patología
10.
Oncology ; 100(8): 449-459, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35816996

RESUMEN

INTRODUCTION: This retrospective study investigated the efficacy and safety of nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/L-leucovorin (5-FU/l-LV) treatment in the second-line or later setting for advanced pancreatic cancer under real-world conditions. METHODS: Between June 2020 and September 2021, a total of 44 patients with unresectable advanced pancreatic cancer treated with nal-IRI + 5-FU/l-LV in our affiliated hospitals were included. The prognosis, predictive factors (including systemic inflammation-based prognostic indicators), and adverse events were investigated. RESULTS: The median age was 68 (interquartile range 62-73) years old, and 22 patients (50.0%) were male. Concerning tumor factors, 9 patients (20.5%) had local advanced disease and 35 patients (79.5%) had metastases. Twenty-five of the 44 patients were receiving second-line treatment, and 19 were receiving third-line or later treatment. The median overall survival (OS) and progression-free survival were 9.0 (range, 0.7-15.4) months and 4.4 (range, 0.6-15.4) months, respectively. The overall response rate was 5.3%. The disease control rate was 44.7%. Patients with a neutrophil-to-lymphocyte ratio of ≥2.7 had a significant risk of a poor OS (HR = 0.275, p = 0.017). Adverse events were manageable, although gastrointestinal symptoms and neutropenia were observed. The most common grade ≥3 adverse event was neutropenia, which was reported in 20% of patients. CONCLUSIONS: Nal-IRI + 5-FU/l-LV therapy was considered to be a useful regimen as second-line or later treatment for unresectable advanced pancreatic cancer, even in clinical practice.


Asunto(s)
Neutropenia , Neoplasias Pancreáticas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina , Femenino , Fluorouracilo , Humanos , Irinotecán , Leucovorina , Liposomas/uso terapéutico , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Neoplasias Pancreáticas
11.
Clin J Gastroenterol ; 15(4): 776-783, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35585285

RESUMEN

We herein report a case of huge hepatocellular carcinoma (HCC) with adrenal metastasis and vascular invasion successfully treated by conversion hepatectomy after atezolizumab-bevacizumab treatment. A 77-year-old male patient with chest pain was admitted. He had a history of HCC treatment; however, the patient stopped receiving follow-up treatment based on his own decision. This time, he visited the emergency department of our hospital for the first time in 5 years. The tumor at the right lobe had grown into a lump with adrenal metastases and was 15 cm in diameter. It had invaded the inferior vena cava. Atezolizumab-bevacizumab treatment was selected for HCC treatment. Before starting treatment, his liver function was preserved (Child-Pugh A5). His alpha fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels were 759.0 ng/mL and 5,681 mAU/mL, respectively. Atezolizumab-bevacizumab treatment resulted in a marked decrease in tumor marker levels and tumor staining. After nine courses of atezolizumab-bevacizumab treatment, it became difficult to continue the administration of bevacizumab because of proteinuria. Because the tumor had decreased in size and the tumor markers were in the normal range, we decided to perform conversion hepatectomy. The tumor was completely removed by combined resection of the diaphragm, and pathological analyses showed a complete response to atezolizumab-bevacizumab treatment. No viable tumor cells remained on histological analyses. The patient is doing well without any signs of recurrence at 3 months after conversion surgery.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anciano , Anticuerpos Monoclonales Humanizados , Bevacizumab/uso terapéutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Recurrencia Local de Neoplasia/cirugía
12.
Artículo en Inglés | MEDLINE | ID: mdl-35130157

RESUMEN

Residual stress is one factor involved in the degradation and damage of industrial products. It is important to understand the magnitude and distribution of residual stress to maintain the integrity of a product. Magnetic measurements are a potential nondestructive method for evaluating residual stress in steel because the hysteresis properties are sensitive to stress. In recent years, spatial mapping of local magnetic hysteresis loop has been performed by using the acoustically stimulated electromagnetic (ASEM) method, which obtains the conversion coefficients from local hysteresis parameters to tensile stress. In this study, we demonstrate the evaluation and spatial imaging of tensile residual stress through local hysteresis parameters using welded steel specimens. We confirm that local coercivity can be used for evaluating residual tensile stress in the high-stress region. In addition, the spatial distribution of residual stress is well visualized by imaging the ASEM response signals due to remanent magnetization.


Asunto(s)
Fenómenos Electromagnéticos , Acero , Resistencia a la Tracción
13.
Clin J Gastroenterol ; 15(2): 451-459, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35179703

RESUMEN

We report two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral. He was diagnosed with HCC 8 years previously. He had undergone surgical resection 4 times, radio-frequency ablation (RFA) several times, and transcatheter arterial chemoembolization (TACE). However, HCC progressed and could not be controlled by locoregional treatment. Systemic chemotherapy was, therefore, selected. Atezolizumab-bevacizumab was administered after lenvatinib and sorafenib failure. Before starting treatment, his liver function was preserved (Child-Pugh score 5 and class A). His alpha fetoprotein and des-gamma-carboxyprothrombin levels were 3.6 ng/mL and 443 mAU/mL, respectively. Esophagogastroduodenoscopy showed no remarkable esophageal varices before atezolizumab-bevacizumab treatment. Nine months after the initiation of atezolizumab-bevacizumab, the patient was admitted for hematemesis from esophageal varices. The disease control of HCC was classified as stable disease (SD) for the liver and lung metastases, and partial response for the lymph node metastases. Neither AST nor ALT was markedly elevated in the clinical course. Endoscopic variceal ligation (EVL) for the spurting point of large esophageal varices with red wale signs was able to successfully achieve hemostasis. Atezolizumab-bevacizumab was stopped and additional EVL eradicated the esophageal varices. However, the post-banding ulcer was prolonged in comparison to usual cases. Case 2: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral therapy. He was diagnosed with HCC 6 years previously. He had received RFA 2 times and TACE 7 times. Atezolizumab-bevacizumab was administered after lenvatinib failure. The disease control of HCC was classified as SD; however, the esophageal varices ruptured after 15 courses of atezolizumab-bevacizumab. Neither AST nor ALT were markedly elevated in the clinical course. The esophageal varices of these patients did not require treatment before atezolizumab-bevacizumab; however, they rapidly worsened and ruptured during atezolizumab-bevacizumab treatment. Although rare, similar cases with rapid progression of portal hypertension after atezolizumab-bevacizumab have been reported. We should pay attention to the worsening of esophageal varices during atezolizumab-bevacizumab treatment and poor wound healing after EVL.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Várices Esofágicas y Gástricas , Hepatitis C Crónica , Neoplasias Hepáticas , Anticuerpos Monoclonales Humanizados , Antivirales/uso terapéutico , Bevacizumab/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Várices Esofágicas y Gástricas/etiología , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino
14.
Biol Trace Elem Res ; 200(2): 497-504, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33913092

RESUMEN

The aim of this study was to evaluate the efficacy of zinc acetate treatment for patients with decompensated liver cirrhosis complicated by hypozincemia. We retrospectively analyzed 49 patients with decompensated liver cirrhosis complicated by hypozincemia who received zinc acetate treatment from August 2017 to March 2020. The relationships between serum zinc levels and several parameters including the prognosis, sarcopenia, and immunity were evaluated. Serum zinc levels measured at 3 months post-treatment and the incidence of adverse events were also determined. The median age was 69.0 years (IQR:59.5-78.8) and the male to female ratio was 29:20. Twenty-seven patients had a Child-Pugh classification of B and 22 had a Child-Pugh classification of C; the median Child-Pugh score was 9.0 (IQR, 8.0-11.0). The median serum zinc levels measured at 3 months post-treatment (74.7 (IQR, 50.0-101.0) µg/dL) were significantly elevated in comparison to the pre-treatment levels (43.0 (IQR, 34.0-51.0) µg/dL, P < 0.0001). The overall survival of patients with pre-treatment serum zinc levels of ≥60 µg/dL was significantly better than that of those with pre-treatment serum zinc levels of <60 µg/dL (P = 0.013). The survival of patients with zinc levels of ≥70 µg/dL at 3 months post-treatment was significantly better than those with levels of <70 µg/dL (P = 0.013). The serum albumin level, Child-Pugh score, albumin-bilirubin (ALBI) score and model for end-stage liver disease (MELD) score were identified as factors predicting a good response at 3 months post-treatment. There were no significant relations between the pretreatment serum zinc levels and skeletal muscle mass, lymphocyte count, and neutrophil lymphocyte ratio. There were no obvious problematic adverse events in patients who received zinc acetate treatment. The patients with higher basal zinc levels and good responders to zinc acetate treatment had a better prognosis. Zinc acetate was useful and safe for patients with decompensated liver cirrhosis complicated by hypozincemia.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Acetato de Zinc , Anciano , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
15.
Clin J Gastroenterol ; 15(1): 177-184, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34811701

RESUMEN

We herein report a successfully treated case of huge ruptured hepatocellular carcinoma (HCC) by conversion hepatectomy after transarterial embolization (TAE) and lenvatinib therapy. A 33-year-old male patient with right hypochondralgia and liver tumor was referred to our hospital. He had a history of surgery for heart malformation. The tumor at the right lobe was 15 cm in diameter with bloody ascites. Right atrial thrombus 4.5 cm in diameter and marked cardiac dilatation were observed. TAE with ethanol suspended in lipiodol and gelatin sponge achieved hemostasis of the ruptured HCC. Although viable HCC remained after TAE, surgical treatment was abandoned because of abdominal wall invasion and his heart function. Lenvatinib and rivaroxaban were then initiated for HCC and atrial thrombus, respectively. Lenvatinib treatment resulted in a reduction in tumor marker levels and the tumor size. First, we planned conversion hepatectomy after 5 months of lenvatinib. However, recurrence of atrial thrombus prompted us to put off the surgery, and lenvatinib was re-administered. After improvement of atrial thrombus, we finally performed conversion hepatectomy 10 months after starting lenvatinib administration. The tumor was completely removed by combined resection of the diaphragm, and the patient has been doing well without any signs of recurrence.


Asunto(s)
Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Adulto , Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Compuestos de Fenilurea/uso terapéutico , Quinolinas
16.
Gan To Kagaku Ryoho ; 48(4): 531-535, 2021 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-33976040

RESUMEN

A 72‒year‒old man with hepatocellular carcinoma(HCC)was treated with transarterial chemoembolization(TACE)and radiofrequency ablation(RFA). Six months after RFA, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd‒ EOB‒DTPA)‒enhanced magnetic resonance imaging(MRI)revealed multiple metastatic recurrences in the liver. TACE was performed for the recurrent HCC. However, the treatment response on the Gd‒EOB‒DTPA‒enhanced MRI showed that the lesions had advanced and that the liver metastatic nodules had ring‒shaped contrast effects. We suspected metastatic liver cancer based on the MRI findings and performed colonoscopy. Finally, we diagnosed the patient with multiple hepatic metastases of sigmoid colon cancer based on the results of the endoscopic colon biopsy and percutaneous liver tumor biopsy. In conclusion, we had a teachable case of the treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Ablación por Catéter , Quimioembolización Terapéutica , Neoplasias del Colon , Neoplasias Hepáticas , Anciano , Carcinoma Hepatocelular/cirugía , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
17.
Clin J Gastroenterol ; 14(2): 570-576, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33507488

RESUMEN

It is very difficult to treat patients with liver metastasis presenting with jaundice or cachexia. We herein report a successfully treated case of huge liver metastasis of gastrointestinal stromal tumor (GIST) that initially showed jaundice and cachexia. The patient was a woman in her early 40 s. She had a history of duodenal GIST 4 years before this admission. She was admitted to our hospital for abdominal fullness and anorexia. Abdominal computed tomography revealed huge liver metastasis of GIST. She showed jaundice and cancer cachexia with a modified Glasgow Prognostic Score of 2. After applying nutritional support, 400 mg of imatinib was administered. Although leg edema transiently worsened, the withdrawal of imatinib and administration of diuretics improved it. Imatinib was re-administered, and nutritional support was continued. The total bilirubin level decreased, and the serum albumin level increased. The tumor gradually decreased in size. Finally, she received surgical resection after 16 months of treatment with imatinib. Although adjuvant imatinib administration was continued after surgery, and no recurrence was observed as of 18 months after surgery.


Asunto(s)
Antineoplásicos , Tumores del Estroma Gastrointestinal , Ictericia , Neoplasias Hepáticas , Adulto , Antineoplásicos/uso terapéutico , Caquexia/etiología , Femenino , Tumores del Estroma Gastrointestinal/complicaciones , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Mesilato de Imatinib/uso terapéutico , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia , Apoyo Nutricional
18.
Intern Med ; 59(18): 2261-2267, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32536644

RESUMEN

A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Inestabilidad de Microsatélites/efectos de los fármacos , Trombosis de la Vena/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Vena Porta/patología , Trombosis de la Vena/patología
19.
Artículo en Inglés | MEDLINE | ID: mdl-31794391

RESUMEN

Magnetic hysteresis properties are sensitive to stress in ferromagnetic materials. This suggests that magnetic measurements are a potential method to evaluate residual stress in steel products. Nevertheless, nondestructive inspection of residual stress by using magnetic properties has been limited, because bulk properties over the entire sample are usually obtained in conventional hysteresis curve measurements through electromagnetic induction, thus, local hysteresis properties are not measured. However, the spatial mapping of local hysteresis properties has been demonstrated recently by ultrasound focusing and scanning. This technique is based on the generation and detection of the acoustically stimulated electromagnetic (ASEM) response. In this study, we investigate the stress dependence of local hysteresis loops through the ASEM response using a tensile testing machine and provide conversion coefficients to estimate tensile stress from the values of local hysteresis properties. The results indicate that the hysteresis properties associated with coercivity, remanent magnetization, and hysteresis loss are promising parameters as an index for evaluating residual stress.

20.
Stem Cells ; 37(1): 89-101, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30270488

RESUMEN

Granulocyte colony stimulating factor (G-CSF) has been reported to ameliorate impaired liver function in patients with advanced liver diseases through mobilization and proliferation of hepatic progenitor cells (HPCs). However, the underlying mechanisms remain unknown. We previously showed that G-CSF treatment increased the number of bone marrow (BM)-derived cells migrating to the fibrotic liver following repeated carbon tetrachloride (CCl4 ) injections into mice. In this study, we identified opioid growth factor receptor-like 1 (OGFRL1) as a novel BM cell-derived accelerator of fibrotic liver regeneration in response to G-CSF treatment. Endogenous Ogfrl1 was highly expressed in the hematopoietic organs such as the BM and spleen, whereas the liver contained a relatively small amount of Ogfrl1 mRNA. Among the peripheral blood cells, monocytes were the major sources of OGFRL1. Endogenous Ogfrl1 expression in both the peripheral blood monocytes and the liver was decreased following repeated CCl4 injections. An intrasplenic injection of cells overexpressing OGFRL1 into CCl4 -treated fibrotic mice increased the number of HPC and stimulated proliferation of hepatic parenchymal cells after partial resection of the fibrotic liver. Furthermore, overexpression of OGFRL1 in cultured HPC accelerated their differentiation as estimated by increased expression of liver-specific genes such as hepatocyte nuclear factor 4α, cytochrome P450, and fatty acid binding protein 1, although it did not affect the colony forming ability of HPC. These results indicate a critical role of OGFRL1 in the mobilization and differentiation of HPC in the fibrotic liver, and administration of OGFRL1-expressing cells may serve as a potential regenerative therapy for advanced liver fibrosis. Stem Cells 2019;37:89-101.


Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Cirrosis Hepática/genética , Cirrosis Hepática/terapia , Regeneración Hepática/genética , Medicina Regenerativa/métodos , Células Madre/metabolismo , Animales , Diferenciación Celular , Humanos , Masculino , Ratones , Transfección
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