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1.
Artigo em Inglês | MEDLINE | ID: mdl-39228860

RESUMO

Objectives: Radial incision and cutting (RIC) is being investigated as an alternative endoscopic dilation method for lower intestinal tract stenosis, providing a high technical success rate and improving subjective symptoms. However, several patients develop re-stenosis following RIC. In this pilot study, we aimed to evaluate the safety and efficacy of triamcinolone acetonide (TA) addition after RIC. Methods: RIC with TA was performed in 20 patients with lower gastrointestinal tract stenosis. We evaluated the rate of adverse events 2 months after RIC with TA. We investigated the short- and long-term prognoses, as well as the improvement in subjective symptoms, using a visual analog scale. Results: The delayed bleeding rate after RIC was 23.8%. Endoscopic hemostasis was achieved in all patients with delayed bleeding. No perforations were observed. The cumulative re-stenosis-free, re-intervention-free, and surgery-free rates 1 year after RIC were 52.9%, 63.7%, and 85.2%, respectively. Subjective symptoms, including abdominal pain, abdominal bloating, nausea, and dyschezia, significantly improved after RIC with TA. Conclusion: Although additional TA administration after RIC could be safe, additional TA may not be effective on luminal patency after dilation. Further investigation is warranted.

2.
Cancer Sci ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377143

RESUMO

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

3.
Metabolites ; 14(9)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39330520

RESUMO

Imaging tests, tumor marker (TM) screening, and biochemical tests provide a definitive diagnosis of hepatocellular carcinoma (HCC). However, some patients with HCC may present TM-negative results, warranting a need for developing more sensitive and accurate screening biomarkers. Various diseases exhibit increased blood levels of bile acids, biosynthesized from cholesterol in the liver, and they have been associated with HCC. Herein, we analyzed plasma bile acids using liquid chromatography/tandem mass spectrometry and integrated them with conventional biomarkers to develop a diagnostic screening model for HCC. Plasma samples were obtained from patients diagnosed with chronic hepatitis, hepatic cirrhosis (HC), and HCC. A QTRAP 6500 mass spectrometer and a Nexera liquid chromatograph with a YMC-Triart C18 analytical column were used. The mobile phase A was a 20 mmol/L ammonium formate solution, and mobile phase B was a methanol/acetonitrile mixture (1:1, v/v) with 20 mmol/L ammonium formate. After determining the concentrations of 32 bile acids, statistical analysis and diagnostic screening model development were performed. Plasma concentrations of bile acids differed between sample groups, with significant differences observed between patients with HC and HCC. By integrating bile acid results with conventional biochemical tests, a potential diagnostic screening model for HCC was successfully developed. Future studies should increase the sample size and analyze the data in detail to verify the diagnostic efficacy of the model.

5.
Pancreas ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39259846

RESUMO

OBJECTIVES: Endoscopic pancreatic stenting (EPS) is an effective treatment modality for painful chronic pancreatitis. However, little is known about the factors that cause pain recurrence after stent removal, and there are no clear criteria for stent removal. We aimed to develop a prediction model for pain recurrence by identifying its risk factors. METHODS: We retrospectively reviewed 95 patients who underwent EPS due to pain for the first time using a single plastic stent between January 2007 and July 2022 at our institute. Univariate and multivariate stepwise Cox proportional hazards models were used to identify the risk factors for pain recurrence, and a prediction model was developed based on the identified factors. RESULTS: Of the 95 enrolled patients, 89 (93.7%) achieved pain relief and 73 (76.8%) did stent removal. Of the 69 patients with a follow-up period ≥6 months after stent removal, 29 (42.0%) had pain recurrence during the median follow-up period of 59 months. Serum lipase level (p = 0.034) and pancreatic parenchymal thickness (p = 0.022) on computed tomography or magnetic resonance imaging were identified as independent risk factors for pain recurrence. The prediction model based on the identified factors had good discrimination ability, with a concordance index of 0.74, and could stratify pain recurrence rates. CONCLUSIONS: We identified the risk factors and developed a new prediction model for pain recurrence following stent removal. This model might be useful for decision-making in pancreatic stent management, such as deciding whether to remove a pancreatic stent, continue EPS, or convert to surgery.

6.
Intern Med ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261065

RESUMO

Objective The impact of Helicobacter pylori infection on gastric endoscopic findings in non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) remains unclear. This study investigated the influence of H. pylori infection on the prevalence and distribution of gastric lesions. Methods The details of 75 patients diagnosed with non-EoE EGIDs were retrospectively reviewed. Of the 56 patients with a definitive diagnosis according to the Japanese criteria (any GI tract; ≥20 eosinophils/high-power field), 25 patients with pathologic gastric eosinophil infiltration (gastric EI; ≥30 eosinophils/high-power field) were investigated in detail. The prevalence and distribution of gastric endoscopy findings were assessed according to the gastric mucosal atrophy status, an indicator of H. pylori infection. Results Erythema (76%) was the most common finding in the gastric EI-positive group, followed by erosions (36%), ulcers (28%), ulcer scars (28%), and edema (24%). None of these lesions differed significantly in frequency between the patients with and without gastric atrophy. When erosions, ulcers, and ulcer scars were unified, they were slightly more common in the gastric bodies of patients with gastric atrophy than those without gastric atrophy; however, no preferential site was found in those without gastric atrophy. We identified six patients with active gastric ulcers, and half had large, deep ulcers with marginal swelling/irregularity. Conclusion Gastric endoscopy findings in non-EoE EGIDs with gastric EI were evenly observed in the stomach, with no specific trend in frequency or distribution depending on atrophic gastritis, an indicator of H. pylori infection. Gastric ulcers in patients with non-EoE EGIDs should be considered in the differential diagnosis of idiopathic peptic ulcers.

7.
J Infect Chemother ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270848

RESUMO

Hepatitis B virus (HBV) can be transmitted within a family, but an interspousal transmission in elderly cases is rare and the change of viral quasispecies during the event is unclear. We experienced two acute hepatitis B males (AH1 and AH2, 67 and 71 years old, respectively) whose HBV was transmitted from their wives with chronic HBV infection (CH1 and CH2, 67 and 66 years old, respectively). To clarify the characteristics of HBV quasispecies in such cases, we performed long-read deep sequencing of HBV preS1/preS2/S domain using samples from the 2 couples. HBV full-genome sequences determined with direct sequencing showed that the HBV sequences belonged to subgenotype B1. AH1 was 98.0-99.2 % identical to CH1, and AH2 was 98.5-99.5 % identical to CH2, whereas the identity between AH1 and AH2 was 96.9 %. The long-read deep sequencing of amplicons including preS1/preS2/S domains with PacBio Sequel IIe showed the numbers of nucleotides with >5 % substitution frequencies in AH1, AH2, CH1 and CH2 were 0 (0 %), 4 (0.31 %), 39 (3.06 %) and 28 (2.20 %), respectively, indicating that CH1 and CH2 were more heterogeneous than AH1 and AH2. From a phylogenetic analysis based on the deep sequencing, minor CH1/CH2 clones that were close to AH1/AH2 clones were considered to be substantially distinct from the major populations in CH1/CH2. The major population formed during chronic infection under the immune pressure might not be suitable to establish new infection and this might be one of the reasons why the transmission had not occurred for a long time after marriage.

8.
J Hepatobiliary Pancreat Sci ; 31(9): 647-657, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39123289

RESUMO

BACKGROUND: Patients with isolated IgG4-related sclerosing cholangitis (IgG4-SC) often undergo unnecessary resection. The aim of this study was to validate the revised Japanese diagnostic criteria for isolated IgG-4-SC and to improve awareness about this condition in the population. METHODS: This was a Japanese retrospective multicenter study. We focused on the data and diagnostic yield obtained using the Japanese diagnostic criteria published initially in 2012 and revised later in 2020 for the diagnosis of isolated IgG4-SC. RESULTS: Patients with isolated IgG4-SC could be classified into two groups based on the primary location of the lesion: the hilar type (n = 40) and the extrahepatic type (n = 13). In total, 10 patients with the hilar type had undergone unnecessary resection. The revised 2020 criteria are useful for the diagnosis of extrahepatic lesions, which are not included in the 2012 criteria. The need for a steroid trial was reduced from 37.7% when the diagnosis was based on the 2012 criteria to 7.6% when the diagnosis was based on the revised 2020 criteria. The diagnostic specificity also improved from 58.5% for the 2012 criteria to 88.7% for the revised 2020 criteria. CONCLUSION: Our validation of the 2020 criteria for the diagnosis of IgG4-SC could contribute to avoiding unnecessary resection in patients with isolated IgG4-SC, which can be classified into the hilar and extrahepatic types. The 2020 criteria can enhance the diagnosis rate of isolated IgG4-SC and uncover this tough-to-diagnose entity based on inclusion of the imaging findings and decrease the dependence on a steroid trial.


Assuntos
Colangite Esclerosante , Imunoglobulina G , Humanos , Colangite Esclerosante/imunologia , Colangite Esclerosante/diagnóstico , Estudos Retrospectivos , Feminino , Masculino , Japão , Pessoa de Meia-Idade , Idoso , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico , Adulto , População do Leste Asiático
9.
Pancreatology ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39191596

RESUMO

BACKGROUND: The natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC). METHODS: The Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints. RESULTS: Among the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant. CONCLUSION: Careful attention should be given to "dual carcinogenesis" during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349).

10.
J Crohns Colitis ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052880

RESUMO

BACKGROUND AND AIM: Although sleep disorders are associated with the pathogenesis of inflammatory bowel disease, the causal relationship is unclear. Therefore, in this study we aimed to clarify the causal relationship between them. METHODS: We administered the Pittsburgh Sleep Questionnaire to participants during regular visits to evaluate their sleep condition and prospectively observed the participants. Participants were divided into poor sleep and non-poor sleep groups according to their first and second questionnaire scores. We compared inflammatory bowel disease relapse rates between the two groups. RESULTS: The study population included 139 patients with inflammatory bowel disease, including 60 with chronic poor sleep. Disease relapse rate was significantly higher in the poor sleep group than in the non-poor sleep group (28.3% vs. 8.9%; P=0.0033). Ulcerative colitis relapse rate was significantly higher in the poor sleep group than in the non-poor sleep group (34.5% vs. 10.3%, P=0.031). Multivariate analysis identified chronic poor sleep as a clinical factor that affected inflammatory bowel disease relapse (OR=6.69, 95% CI: 2.23-20.0, P=0.0007) and ulcerative colitis relapse (OR=8.89, 95% CI: 1.57-50.2, P=0.014). The Kaplan-Meier curve showed significantly lower cumulative treatment retention rates in the poor sleep group than in the non-poor sleep group (all patients, P=0.0061; ulcerative colitis, P=0.025). CONCLUSIONS: Concomitant chronic poor sleep may have a negative influence on the disease activity in patients with inflammatory bowel disease, especially in those with ulcerative colitis.

11.
Int J Mol Sci ; 25(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39063094

RESUMO

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas , Neoplasias Gástricas , Fumar Tabaco , Humanos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/genética , Consumo de Bebidas Alcoólicas/efeitos adversos , Fumar Tabaco/efeitos adversos , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Animais
13.
J Clin Transl Hepatol ; 12(7): 613-624, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-38993515

RESUMO

Background and Aims: Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). Given their diverse physiological activities, we hypothesized that plasma fatty acids might influence the progression of sarcopenia. This study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with HCC. Methods: In this single-center retrospective study, we registered 516 cases and analyzed 414 cases of liver cirrhosis and HCC. The skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar vertebra. The cutoff value for sarcopenia followed the criteria set by the Japan Society of Hepatology. Fatty acid concentrations were measured by gas chromatography. Results: Fatty acid levels, particularly omega-3 (n-3) polyunsaturated fatty acid (PUFA), were lower in patients with poor liver function (Child-Pugh grade B/C) and were negatively correlated with the albumin-bilirubin score (p<0.0001). The prognosis of HCC patients with low PUFA levels was significantly worse. Among the different fatty acid fractions, only n-3 PUFAs significantly correlated with skeletal muscle mass index (p=0.0026). In the multivariate analysis, the n-3 PUFA level was an independent variable associated with sarcopenia (p=0.0006). Conclusions: A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

14.
Ann Surg ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016004

RESUMO

OBJECTIVE: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection. SUMMARY BACKGROUND DATA: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown. METHODS: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated. RESULTS: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=-0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways. CONCLUSION: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.

15.
Intern Med ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39085073

RESUMO

A 68-year-old woman was diagnosed with leiomyosarcoma (LMS) based on preoperative biopsy of the gastric body. As tumor invasion confined to the submucosa with no breaking of the submucosal layer was confirmed on endoscopic ultrasonography (EUS), the patient underwent endoscopic submucosal dissection (ESD) for gastric LMS, resulting in complete tumor resection. No apparent recurrence was observed in the 2.5 years after treatment. This is an extremely rare case of gastric LMS that underwent ESD after a precise preoperative diagnosis, with no signs of recurrence after treatment. ESD may be an acceptable option for gastric LMS when EUS findings allow this treatment method.

16.
Microorganisms ; 12(7)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39065094

RESUMO

The gastrointestinal (GI) tract harbors trillions of microorganisms known to influence human health and disease, and next-generation sequencing (NGS) now enables the in-depth analysis of their diversity and functions. Although a significant amount of research has been conducted on the GI microbiome, comprehensive metagenomic datasets covering the entire tract are scarce due to cost and technical challenges. Despite the widespread use of fecal samples, integrated datasets encompassing the entire digestive process, beginning at the mouth and ending with feces, are lacking. With this study, we aimed to fill this gap by analyzing the complete metagenome of the GI tract, providing insights into the dynamics of the microbiota and potential therapeutic avenues. In this study, we delved into the complex world of the GI microbiota, which we examined in five healthy Japanese subjects. While samples from the whole GI flora and fecal samples provided sufficient bacteria, samples obtained from the stomach and duodenum posed a challenge. Using a principal coordinate analysis (PCoA), clear clustering patterns were identified; these revealed significant diversity in the duodenum. Although this study was limited by its small sample size, the flora in the overall GI tract showed unwavering consistency, while the duodenum exhibited unprecedented phylogenetic diversity. A visual heat map illustrates the discrepancy in abundance, with Fusobacteria and Bacilli dominating the upper GI tract and Clostridia and Bacteroidia dominating the fecal samples. Negativicutes and Actinobacteria were found throughout the digestive tract. This study demonstrates that it is possible to continuously collect microbiome samples throughout the human digestive tract. These findings not only shed light on the complexity of GI microbiota but also provide a basis for future research.

17.
Clin J Gastroenterol ; 17(5): 948-954, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39060756

RESUMO

Acetaminophen (APAP) is an over-the-counter (OTC) drug known worldwide for its safety and efficacy. However, in Japan, OTC drug overdose has become a prominent social problem in recent years due to stricter regulations for other drugs, especially among young people, and APAP is an increasing cause of acute liver injury due to overdose. This report describes three consecutive cases of acute liver failure in young women (22, 22 and 19 years old) due to APAP overdose in December 2023. Despite severe liver injury, indicated by high ALT levels and coagulopathy, these cases recovered without requiring liver transplantation. This report discusses three cases of acute liver failure in young Japanese women following APAP overdose, reflecting a national increase in such cases due to increased misuse of OTC drugs and societal factors. Key findings include the need for early treatment with N-acetylcysteine (NAC) and the importance of mental health assessment in the management of overdose patients. The cases underscore the need for prompt team-based care to prevent serious outcomes and highlight the complexity of liver transplantation decisions in Japan, highlighting the need for comprehensive strategies to address the escalating problem of APAP overdose.


Assuntos
Acetaminofen , Overdose de Drogas , Falência Hepática Aguda , Transplante de Fígado , Medicamentos sem Prescrição , Humanos , Feminino , Acetaminofen/intoxicação , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/cirurgia , Japão , Adulto Jovem , Medicamentos sem Prescrição/intoxicação , Analgésicos não Narcóticos/intoxicação , Acetilcisteína/uso terapêutico , Acetilcisteína/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , População do Leste Asiático
18.
Clin J Gastroenterol ; 17(5): 871-875, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39039400

RESUMO

A 62-year-old male with a history of stent graft replacement for an infectious aortic aneurysm, followed by multiple interventions for postoperative complications, was admitted with melena and anemia. Enhanced computed tomography (eCT) demonstrated fluffing and hyperdensities surrounding the graft, despite no evidence of an aortoenteric fistula (AEF). Emergency esophagogastroduodenoscopy (EGD) showed a massive bleeding in the reconstructed tract and the protruding lesion of postoperative granulation tissue with clots at the end of the blind pouch. Thereafter, hemorrhage temporarily reoccurred several times; however, the source could not be identified using eCT or EGD. Finally, on the third attempt, we performed gel immersion endoscopy (GIE) with manual injection of VISCOCLEARⓇ, and it showed purulent blood flowing from one side of the protruding lesion in the pouch. Based on the eCT findings showing exudation of the contrast agent from the graft into the pouch, we made a diagnosis of an AEF. However, radical surgery was not performed because of the patient's poor general condition. During conservative management, he died of uncontrolled bleeding from the AEF on the 5th day of hospitalization. This is the first case in which the GIE might provide tips to identify herald bleeding from a lethal AEF.


Assuntos
Hemorragia Gastrointestinal , Fístula Intestinal , Fístula Vascular , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Intestinal/cirurgia , Fístula Intestinal/diagnóstico por imagem , Fístula Intestinal/etiologia , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/cirurgia , Fístula Vascular/etiologia , Hemorragia Gastrointestinal/etiologia , Doenças da Aorta/cirurgia , Doenças da Aorta/diagnóstico por imagem , Evolução Fatal , Endoscopia do Sistema Digestório/métodos , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/cirurgia , Complicações Pós-Operatórias , Géis , Tomografia Computadorizada por Raios X
19.
Oncology ; : 1-12, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39047713

RESUMO

INTRODUCTION: Cell-free DNA (cfDNA) is expected to contribute to the decision for treatment and prediction of effects with minimally invasion. We investigated the correlation between gene mutations before and after lenvatinib (LEN) treatment and its effectiveness, in order to find advanced hepatocellular carcinoma (HCC) patients who would benefit greatly from the therapy. METHODS: We analyzed cfDNA before and 6-8 weeks after the start of treatment in 20 advanced HCC patients who started LEN. A next-generation sequencer was used for CTNNB1 and TP53. Concerning TERT promoter, -124C>T and -146C>T mutations are researched using digital PCR. In addition, we examined liver tumor biopsy tissues by the same method. Computerized tomography evaluation was performed at 6-8 weeks and 3-4 months to assess the efficacy. RESULTS: Frequencies of TERT promoter, CTNNB1, and TP53 mutations in pretreatment cfDNA were 45%, 65%, and 65%, but 53%, 41%, and 47% in HCC tissues, respectively. There were no clear correlations between these gene mutations and the disease-suppressing effect or progression-free survival. Overall, there were many cases showing a decrease in mutations after LEN treatment. Integrating the reduction of CTNNB1 and TP53 genetic mutations increased the potential for disease suppression. CONCLUSION: This study suggests that analysis of cfDNA in advanced HCC patients may be useful for identifying LEN responders and determining therapeutic efficacy. Furthermore, it has potential for selecting responders for other molecular-targeted drugs.

20.
Intern Med ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39048367

RESUMO

Objective This study assessed the impact of dietary therapy and reduced body weight on the loss of skeletal muscle in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods This was a single-center retrospective observational study. We enrolled 129 patients with MASLD who had undergone dietary therapy at our facility. We assessed skeletal muscle mass using a bioelectrical impedance analysis (BIA) at the start of dietary treatment and 12 months after the first assessment. Variables related to muscle reduction were analyzed using a logistic regression model. Results One hundred and eighteen cases were analyzed, excluding those with missing data. In the muscle reduction group, there were more subjects with body weight reduction than in the control group (68% and 40%, respectively, p =0.002), and their body mass index (BMI) was decreased (-0.7 kg/m2 and +0.3 kg/m2, respectively, p =0.0003). There was a significant correlation between the changes in the BMI and muscle mass (R =0.48, p <0.0001). We standardized muscle mass change by dividing it by weight change to analyze the severe decrease in muscle mass compared to weight change. A logistic regression analysis revealed that type 2 diabetes mellitus (T2DM) was an independent variable related to severe skeletal muscle loss (odds ratio, 2.69; 95% CI: 1.13-6.42, p =0.03). Conclusion Weight loss is associated with skeletal muscle loss during dietary treatment for MASLD. T2DM is a risk factor for severe skeletal muscle loss.

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