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1.
Dig Dis Sci ; 68(6): 2553-2560, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609732

RESUMO

BACKGROUND: Sessile serrated lesions (SSLs) are precursors of colon cancer, especially in cases of large, right colon. However, they are difficult to not only detect, but only clarify the margin of the lesion, which can lead to the poor endoscopic treatment outcomes. AIMS: This study evaluated the usefulness of acetic acid spray with narrow-band imaging (A-NBI) for the better visualization of the margin of SSLs. METHODS: From January 2013 to March 2022, patients with superficial elevated polyps suspected of being SSLs ≥ 10 mm with an endoscopic diagnosis that had been endoscopically resected at Hiroshima City Hiroshima Citizens Hospital were enrolled. Endoscopic images with white-light imaging (WLI), narrow-band imaging (NBI), indigo-carmine (IC), and A-NBI were recorded in each lesion and were randomly arranged and assessed by 10 endoscopists. We compared the visibility score (1 to 4) and color differences (ΔE) between inside and outside of the lesions among WLI, NBI, IC, and A-NBI. RESULTS: Forty-one lesions in 33 cases were included, and a total of 164 images were evaluated. As for the visibility score, most of the lesions were scored as 1 or 2 on WLI, whereas most were scored 4 on A-NBI. The median ΔE of A-NBI was also significantly higher than that of WLI, NBI, or IC (20.5 vs. 8.3 vs. 8.2 vs. 12.3, P < 0.01). A significant correlation was observed between the color difference and visibility score (r = 0.53, P < 0.01). CONCLUSIONS: A-NBI may be a useful modality for identifying the margin of SSLs.


Assuntos
Adenoma , Neoplasias do Colo , Humanos , Colonoscopia/métodos , Ácido Acético , Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/cirurgia , Imagem de Banda Estreita/métodos , Índigo Carmim
2.
Surg Today ; 52(9): 1329-1340, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35089444

RESUMO

PURPOSE: To establish whether gastrectomy for early gastric cancer (EGC) in elderly patients is related to poor survival. METHODS: The subjects of this retrospective study were patients aged ≥ 75 years with primary stage IA EGC, who underwent curative resection with endoscopic submucosal dissection (ESD) or surgery. RESULTS: We analyzed data on 365 patients who underwent ESD and 170 patients who underwent surgery. Overall survival (OS) was not significantly different for the ESD group vs. the surgery group (5-year cumulative rates, 81.5% vs. 79.7%; log-rank test, P = 0.506). Multivariate analysis revealed that treatments; namely, ESD or surgery, were not associated with OS (hazard ratio 1.09, 95% confidence interval 0.77-1.51). Similar results were observed even in the subgroups with worse conditions, such as age > 80 years, Eastern Cooperative Oncology Group performance status 2-3, Charlson comorbidity index ≥ 2, and prognostic nutritional index ≤ 46.7. Using propensity score matching, we selected 88 pairs of patients who underwent ESD or surgery with baseline characteristics matched and found that OS was not different between the two groups (log-rank test, P = 0.829). CONCLUSION: OS was comparable for elderly patients who underwent ESD and those who underwent surgery for EGC. Surgical invasiveness did not worsen the prognosis, even for elderly patients.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Idoso , Ressecção Endoscópica de Mucosa/métodos , Gastrectomia , Mucosa Gástrica/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
3.
Acta Med Okayama ; 75(4): 471-477, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34511614

RESUMO

The characteristics of gastric polyps in patients with Peutz-Jeghers (PJ) syndrome (PJS) have not been fully investigated. The objective of this study was to reveal the endoscopic and pathologic findings of gastric polyps in patients with PJS. We reviewed 11 patients with PJS treated at 6 institutions, and summarized the endo-scopic and pathologic features of their gastric polyps. The polyps were mainly classified into 2 types: (i) soli-tary or sporadic polyps > 5 mm, reddish in color with a sessile or semi-pedunculated morphology (n = 9); and (ii) multiple sessile polyps ≤ 5 mm with the same color tone as the peripheral mucosa (n = 9). Patients who underwent endoscopic mucosal resection for polyps > 5 mm were diagnosed with PJ polyps (n = 2), whereas those who underwent biopsy were diagnosed with hyperplastic polyps. Polyps ≤ 5 mm were pathologically diagnosed as fundic gland polyps or hyperplastic polyps. This study revealed that patients with PJS present with 2 types of polyps in the stomach. Endoscopic mucosal resection of polyps > 5 mm seems necessary for the pathologic diagnosis of PJ polyps.


Assuntos
Pólipos Intestinais/patologia , Síndrome de Peutz-Jeghers/fisiopatologia , Adolescente , Adulto , Criança , Endoscopia do Sistema Digestório/métodos , Feminino , Humanos , Pólipos Intestinais/diagnóstico por imagem , Pólipos Intestinais/etiologia , Masculino , Pessoa de Meia-Idade , Síndrome de Peutz-Jeghers/complicações , Estudos Retrospectivos
4.
Target Oncol ; 16(2): 237-248, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33475927

RESUMO

BACKGROUND: Little is known about the association between immune-related adverse events (irAEs) and the efficacy and survival outcomes of nivolumab in patients with advanced gastric cancer (AGC). OBJECTIVE: The present study examined the association between irAEs and the prognosis of patients with AGC treated with nivolumab. PATIENTS AND METHODS: From July 2017 to November 2020, patients who had been diagnosed with advanced unresected gastric cancer and treated with nivolumab at our institution were included in this analysis. We compared the clinical and survival outcomes between the irAE and non-irAE groups. We also evaluated the factors associated with better survival in patients treated with nivolumab. RESULTS: A total of 52 patients were included in the present study, and irAEs were observed in 13 (25%). Among the patients with measurable lesions (n = 29), the disease control rates were significantly higher in the irAE group than in the non-irAE group (88 vs. 24%; P = 0.0033). At the 8- and 12-week landmark analyses, the median overall survival (OS) in the irAE group was significantly longer than that in the non-irAE group, whereas the median progression-free survival was comparable between the groups. A multivariate analysis by Cox proportional hazard regression at the 8-week landmark revealed that the development of irAEs (hazard ratio 0.18; 95% confidence interval 0.0099-0.86) alone was positively associated with a longer OS. CONCLUSIONS: The development of irAEs might be associated with survival outcomes with nivolumab treatment in patients with AGC.


Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Idoso , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Nivolumabe/farmacologia , Prognóstico , Estudos Retrospectivos
5.
J Gastroenterol Hepatol ; 36(1): 137-143, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32525567

RESUMO

BACKGROUND AND AIM: Although oral mesalamine is the first-choice drug for treating mild-to-moderate ulcerative colitis (UC), some patients show symptoms of intolerance, including exacerbation of diarrhea and abdominal pain. The present study clarified the current state and clinical courses of patients with mesalamine intolerance. METHODS: Patients who were diagnosed with UC and administered oral mesalamine at eight hospitals in Japan with a follow-up period exceeding 1 year were analyzed. RESULTS: Sixty-seven (11%) of 633 patients showed intolerance to at least one formulation of oral mesalamine. The frequency of mesalamine intolerance has increased in recent years, rising from 5.3% in 2007-2010 to 9.1% in 2011-2013 and 16.2% in 2014-2016. The most common complications were the exacerbation of diarrhea (n = 29), a fever (n = 25), and abdominal pain (n = 22). Readministration of mesalamine/sulfasalazine was attempted in 43 patients, mostly with other types of formulation of mesalamine, and more than half of these patients proved to be tolerant. The risk factors for mesalamine intolerance were female gender (odds ratio [OR] = 1.83; 95% confidence interval [CI], 1.08-3.12), age < 60 years old (OR = 2.82; CI, 1.19-8.33), and pancolitis (OR = 2.09; 95% CI, 1.23-3.60). There were no significant differences in the use of anti-tumor necrosis factor-α agents, colectomy, or steroid-free remission at the last visit between patients with and without mesalamine intolerance. CONCLUSIONS: Mesalamine intolerance is not rare, and its frequency has been increasing recently. The prognosis of patients with mesalamine intolerance did not differ significantly from that of those without intolerance.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Mesalamina/administração & dosagem , Mesalamina/efeitos adversos , Dor Abdominal/etiologia , Administração Oral , Adulto , Diarreia/etiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Sulfassalazina/administração & dosagem , Sulfassalazina/efeitos adversos , Fatores de Tempo
6.
Clin J Gastroenterol ; 13(5): 650-659, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32643119

RESUMO

Endoscopic submucosal dissection (ESD) for gastric neoplasms is a useful treatment globally. However, postoperative bleeding after gastric ESD is a serious, and sometimes life-threatening complication in patients receiving antithrombotic drugs, because antithrombotic drugs are considered to increase the risk of postoperative bleeding after gastric ESD. In contrast, withdrawal of antithrombotic drugs during the perioperative period increases the risk of thrombotic complications. Guidelines for the management of antithrombotic drugs during the periendoscopic period have been published by different countries, and recent guidelines place greater emphasis on the risk of thromboembolism with the discontinuation of antithrombotic drugs than on the risk of bleeding with the continuation of antithrombotic drugs. Several studies have reported on the validity of these guidelines, and clinical evidence is being established. Most studies reported that gastric ESD under continuation of aspirin or cilostazol did not increase the risk of bleeding, whereas heparin replacement was strongly associated with a higher risk of bleeding. However, the data regarding some clinical issues about the management of antithrombotic drugs, such as the safety of gastric ESD under continuation of thienopyridine, administration of multiple antithrombotic drugs including dual antiplatelet and anticoagulants (warfarin and direct oral anticoagulant), and effective prophylactic methods for postoperative bleeding after gastric ESD are lacking. Larger clinical data are needed to resolve the remaining issues in the future.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Ressecção Endoscópica de Mucosa/efeitos adversos , Fibrinolíticos/efeitos adversos , Mucosa Gástrica/cirurgia , Humanos , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgia
7.
Nihon Shokakibyo Gakkai Zasshi ; 116(12): 1015-1021, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31827041

RESUMO

We retrospectively investigated 14 Japanese patients with Peutz-Jeghers (PJ) syndrome who were treated in six hospitals to determine the prevalence of cancer in Japanese patients with PJ syndrome. The study included seven males and seven females. The mean age at the time of diagnosis of PJ syndrome was 28.1 years (range 2-60 years). Hamartomatous polyps were observed in 13 (92.9%) patients, mucocutaneous pigmentation in 11 (78.6%), and positive family history in six patients (42.9%). The mean observation period after the diagnosis of PJ syndrome was 10.1 years (range 0-34 years). Although one patient died of cancer of unknown primary origin, the remaining 13 patients included in the study completed their last follow-up at each hospital. Cancers were detected in six patients (42.9%), including cancer of the uterine cervix (N=3), breast cancer (N=1), duodenal cancer (N=1), transverse colon cancer (N=1), and cancer of unknown primary origin (N=1). One patient presented with both cervical cancer and breast cancer. No patient presented with pancreatic cancer. This study highlights that patients with PJ syndrome are at high risk for intestinal and extra-intestinal cancers, such as uterine and breast cancer. Routine surveillance for intestinal and extra-intestinal malignancies is warranted in patients with PJ syndrome.


Assuntos
Neoplasias Intestinais/diagnóstico , Síndrome de Peutz-Jeghers/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Intestinos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
Gastroenterol Res Pract ; 2019: 8159072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582972

RESUMO

BACKGROUND: Clinical characteristics and prognosis of patients with a solitary Peutz-Jeghers polyp (PJP) have not been fully investigated. METHODS: Solitary PJP was diagnosed when a single hamartomatous lesion was identified in the gastrointestinal tract of patients without mucocutaneous pigmentation or a family history of Peutz-Jeghers syndrome. We retrospectively reviewed 51 patients (32 men and 19 women) with a solitary PJP and analyzed the sex, age at diagnosis, endoscopic features, and outcomes in this patient group. The STK11/LKB1 germline mutation was not investigated in any of the patients. RESULTS: The mean age of the 51 patients was 66.1 years. The polyp was found in the duodenum (N = 10), jejunum (N = 2), cecum (N = 2), transverse colon (N = 5), sigmoid colon (N = 21), or rectum (N = 11). Most of the polyps presented as a pedunculated lesion (N = 40), followed by semipedunculated (N = 9) and sessile (N = 2) morphologies. The mean size of a solitary PJP was 15.6 mm (range: 5 to 33 mm). During a mean endoscopic follow-up period of 4.5 years (range: 0.1 to 16.1 years), no recurrence was identified. Eighteen of the enrolled patients had a history of cancer or concomitant cancer. Five patients died due to non-gastrointestinal-related causes. No additional cancer or death directly related to solitary PJP was observed. CONCLUSIONS: Solitary PJPs did not recur in this study. Although examination of the entire gastrointestinal tract using esophagogastroduodenoscopy, enteroscopy, and colonoscopy is desirable to exclude Peutz-Jeghers syndrome, follow-up endoscopy after endoscopic polyp resection may be unnecessary, once the diagnosis of a solitary PJP is made.

10.
Intern Med ; 58(2): 207-212, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30146577

RESUMO

A 50-year-old woman with epigastric discomfort was referred to our hospital. Esophagogastroduodenoscopy showed flat, elevated, submucosal tumor-like lesions in the esophagus. Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) of the esophagus was diagnosed based on the examination of an endoscopic biopsy specimen. Computed tomography showed the enlargement of a lymph node in the gastric cardia. The present case showed disease progression despite Helicobacter pylori eradication therapy and achieved partial remission after rituximab monotherapy. The patient remained in partial remission for 20 months. This case suggests that esophageal MALT lymphoma with lymph node involvement does not respond to H. pylori eradication therapy and that it requires systemic treatment.


Assuntos
Neoplasias Esofágicas/patologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B/patologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Progressão da Doença , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/microbiologia , Feminino , Infecções por Helicobacter/complicações , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/microbiologia , Masculino , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Tomografia Computadorizada por Raios X
11.
Clin Transl Gastroenterol ; 9(7): 167, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29970896

RESUMO

OBJECTIVE: Conscious sedation for colorectal endoscopic submucosal dissection (ESD) has not been standardized, and there are no studies of sedation for colorectal ESD. METHODS: We conducted a prospective double-blind randomized controlled trial to clarify the usefulness of DEX during colorectal ESD. In total 80 patients with colorectal ESD from April 2016 to May 2017 were assigned to the placebo group or the DEX group (40 cases each). The primary outcome was patient satisfaction (visual analogue scale: VAS). Secondary outcomes were evaluated for 13 factors, including patient pain level (VAS), endoscopist satisfaction (VAS), objective patient pain level viewed from the endoscopist's perspective (VAS), rate of patient response, rate of side effects, etc., from the patient's and endoscopist's perspectives. RESULTS: Patient satisfaction was 8.4 and 9.1 (P = 0.018) in the placebo group and the DEX group, respectively. Secondary outcomes of patient pain level, endoscopist satisfaction, objective patient pain level from the endoscopist's perspective for the placebo and DEX groups were 1.2 and 0.4 (P = 0.045), 8.2 and 9.3 (P < 0.001), and 1.2 and 0.5 (P = 0.002), respectively. All of these were significantly positive results (more comfortable and less pain) in the DEX group. The rate of a patient response was 100% in all cases. The side effects (hypoxia/bradycardia/hypotension) were 0%/0%/0% and 7.5%/7.5%/5% (P = 0.030). However, these rates were less than the reported side effect occurrence rate, and no additional medication was needed. CONCLUSION: DEX enables conscious sedation, and is useful not only for patient and endoscopist satisfaction but also for pain relief. DEX is an effective sedation method for colorectal ESD.


Assuntos
Neoplasias Colorretais/cirurgia , Sedação Consciente/métodos , Dexmedetomidina/administração & dosagem , Ressecção Endoscópica de Mucosa , Hipnóticos e Sedativos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Sedação Consciente/efeitos adversos , Dexmedetomidina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Satisfação Pessoal , Médicos/psicologia , Estudos Prospectivos
12.
World J Gastroenterol ; 23(33): 6155-6163, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28970731

RESUMO

AIM: To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1. METHODS: This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11;18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated. RESULTS: Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (P = 0.10). CONCLUSION: Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11;18) translocation or extra copies of MALT1.


Assuntos
Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Linfoma de Zona Marginal Tipo Células B/terapia , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/genética , Neoplasias Gástricas/terapia , Idoso , Aneuploidia , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 18/genética , Intervalo Livre de Doença , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Mucosa Gástrica/efeitos da radiação , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Hibridização in Situ Fluorescente , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Radioterapia/métodos , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidade , Translocação Genética , Resultado do Tratamento
13.
Acta Med Okayama ; 71(3): 241-247, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28655944

RESUMO

 Most gastric bezoars can be treated with endoscopic fragmentation combined with or without cola dissolution, whereas laparotomy or laparoscopic surgery is generally inevitable for small intestinal bezoars because they cause small bowel obstruction. Therefore, early diagnosis and management of gastric bezoars are necessary to prevent bezoar-induced ileus. To investigate the incidence of overlooked gastric bezoars during the initial esophagogastroduodenoscopy, we retrospectively reviewed the cases of 27 patients diagnosed with gastrointestinal bezoars. The bezoars were diagnosed using esophagogastroduodenoscopy (n=25), abdominal ultrasonography (n=1), and barium follow-through examination (n=1). Bezoars were overlooked in 9/25 patients (36.0%) during the initial endoscopy examination because the bezoars were covered with debris in the stomach. Of the 9 patients, 8 had concomitant gastric ulcers, and the other patient had gastric lymphoma. Although a computed tomography (CT) scan was performed before the second-look endoscopy in 8 of the 9 patients, the bezoars were mistaken as food debris on CT findings and were overlooked in these patients. In conclusion, gastric bezoars may not be discovered during the initial esophagogastroduodenoscopy and CT scan. In cases with debris in the stomach, second-look endoscopy is essential to detect bezoars.


Assuntos
Bezoares/diagnóstico por imagem , Gastroscopia/métodos , Estômago/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bezoares/complicações , Bezoares/patologia , Criança , Diagnóstico Tardio , Feminino , Esvaziamento Gástrico , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Úlcera Gástrica/complicações , Tomografia por Raios X , Adulto Jovem
14.
J Clin Pathol ; 69(3): 226-33, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26290259

RESUMO

BACKGROUND: Oxidative stress may play pathogenic roles in the mechanisms underlying chronic hepatitis C (CHC). The impact of excessive oxidative stress and iron dysregulation on the development of hepatocellular carcinoma (HCC) after interferon therapy has not been established. METHODS: We investigated the impact of oxidative stress and iron deposition on HCC development after therapy with pegylated interferon (PegIFN)+ribavirin in CHC patients. Systemic and intracellular iron homeostasis was evaluated in liver tissues, peripheral blood mononuclear cells and sera. RESULTS: Of 203 patients enrolled, 13 developed HCC during the 5.6-year follow-up. High hepatic 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were significantly associated with HCC development in multivariate analysis (p=0.0012) which was also significantly correlated with severity of hepatic iron deposition before therapy (p<0.0001). Systemic and intracellular iron regulators of hepcidin and F-box and leucine-rich repeat protein 5 (FBXL5) expression levels were significantly suppressed in CHC patients (p=0.0032 and p=0.016, respectively) despite their significantly higher levels of serum iron and ferritin compared with controls. However, intracellular iron regulators of FBXL5 and iron regulatory proteins were regulated in balance with hepatic iron deposition. Significant correlations were observed among IL-6, bone morphogenetic protein 6, hepcidin and ferroportin, as regards systemic iron regulation. CONCLUSIONS: Measurement of hepatic oxidative stress before antiviral therapy is useful for the prediction of HCC development after interferon therapy. Low baseline levels of the intracellular iron regulators of FBXL5 in addition to a suppressed hepcidin level might be associated with severe hepatic iron deposition in CHC patients. TRIAL REGISTRATION NUMBER: UMIN 000001031.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Distúrbios do Metabolismo do Ferro/metabolismo , Neoplasias Hepáticas/virologia , Fígado/efeitos dos fármacos , Estresse Oxidativo , Polietilenoglicóis/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Biomarcadores/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/metabolismo , Humanos , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/diagnóstico , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Fígado/metabolismo , Fígado/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
15.
World J Hepatol ; 7(19): 2220-8, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26380048

RESUMO

AIM: To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/mL before therapy and in non-SVR patients showing AFP ≥ 5 ng/mL before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/mL before therapy and no decrease in AFP to < 5 ng/mL 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/mL before therapy and decreased AFP (P = 0.043). AFP ≥ 5 ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/mL before therapy than in those showing AFP ≥ 5 ng/mL. CONCLUSION: The criteria of AFP < 5 ng/mL before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

16.
Acta Med Okayama ; 69(3): 137-44, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26101189

RESUMO

A predictive marker of the rapid progression to hepatic failure is desired for patients with asymptomatic primary biliary cirrhosis (aPBC). We performed a systematic cohort analysis of 101 patients diagnosed as having aPBC and the rapid progression to liver failure in some, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin7 (K-7) expressions in the patients' hepatocytes. Intralobular expressions of K-7 were found in 9 of the 101 patients. The grades of K-7 expression were significantly associated with the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin at the time of diagnosis, but not with bile duct loss or cholestasis. Stepwise logistic regression analysis revealed that high grades of K-7 expression correlated positively with high levels of total bilirubin. During the follow-up period, 8 patients developed jaundice, and the mean period until the development of jaundice was 5.2 years. The proportional hazards models for the risk of developing jaundice identified a high grade of aberrant K-7 expression in hepatocytes as the only significant risk factor. Aberrant K-7 expression in hepatocytes can be used as an additional marker to predict rapid progression to liver failure in patients with aPBC at the time of diagnosis.


Assuntos
Hepatócitos/química , Queratina-7/análise , Cirrose Hepática Biliar/metabolismo , Falência Hepática/metabolismo , Adulto , Idoso , Biomarcadores/análise , Progressão da Doença , Feminino , Humanos , Cirrose Hepática Biliar/complicações , Falência Hepática/diagnóstico , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade
17.
BMC Gastroenterol ; 15: 53, 2015 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-25925267

RESUMO

BACKGROUND: Oral tacrolimus therapy is effective for refractory ulcerative colitis (UC), but dose adjustment according to the trough concentrations which varies largely among individuals, is required. This study aimed to identify factors to predict the tacrolimus dose required for achieving the target trough level for remission induction of UC. METHODS: Forty-seven consecutive UC patients who were treated with tacrolimus were retrospectively analyzed. Tacrolimus doses were adjusted every 2 or 3 days to achieve trough concentrations of 10-15 ng/mL. The dose required for reaching the target trough level was analyzed based on disease characteristics, course of trough concentrations, and gene polymorphism related to tacrolimus metabolism. RESULTS: Median daily dose of tacrolimus required for achieving the target trough level was 0.19 (0.07-0.42) mg/kg, and patients were divided into high or low dose group (< 0.2 mg/kg or > 0.2 mg/kg). The value of initial trough concentration/starting dose was higher in the low dose group than in the high dose group (1.35 ng/mL/mg vs. 0.78 ng/mL/mg, p < 0.0001). Although presence of CYP3A5 *1 was more frequently observed in the high dose group, initial trough concentration was the only significant factor for determining requirement of high dose of tacrolimus (OR = 28.0, 95% confidence interval 3.20 - 631). CONCLUSIONS: The most practical predictor of the dose required for achieving the target trough concentration was the trough concentration measured 2 or 3 days after starting tacrolimus therapy. Our findings would make tarcolimus administration for UC safer, easier and more effective.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Imunossupressores/administração & dosagem , Quimioterapia de Indução/métodos , Tacrolimo/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Criança , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Resultado do Tratamento , Adulto Jovem
18.
Acta Med Okayama ; 68(1): 17-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24553484

RESUMO

The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p=0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p=0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p=0.049, and <0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy.


Assuntos
Fígado Gorduroso/genética , Hepatite C Crônica/tratamento farmacológico , Interleucinas/genética , Lipase/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Receptores de LDL/genética , Idoso , Feminino , Hepatite C Crônica/genética , Humanos , Interferons/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
J Clin Microbiol ; 52(2): 544-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24478486

RESUMO

We encountered a patient positive for anti-hepatitis C virus (HCV) whose serum HCV RNA was undetectable with the Roche AmpliPrep/Cobas TaqMan HCV assay (CAP/CTM) version 1 but showed a high viral load with the Abbott RealTime HCV assay (ART). Discrepancies in the detectability of serum HCV RNA were investigated among 891 consecutive patients who were positive for anti-HCV. Specific nucleotide variations causing the undetectability of HCV RNA were determined and confirmed by synthesizing RNA coding those variations. Serum samples with the discrepancies were also reassessed by CAP/CTM version 2. Among the 891 anti-HCV-positive patients, 4 patients had serum HCV RNA levels that were undetectable by CAP/CTM version 1 despite having levels of >5 log IU/ml that were detected by ART. All four patients had HCV genotype 2a and high titers of anti-HCV. Sequencing of the HCV 5' noncoding regions revealed 2 common variations, A at nucleotide (nt) 145 and T at nt 151. Synthesized RNAs of the HCV 5' noncoding region with standard (NCR145G151C) and variant nucleotides at nt 145 and nt 151 were quantified with CAP/CTM. RNAs of NCR145G151C and NCR145G151T were quantifiable with CAP/CTM version 1, while those of NCR145A151T and NCR145A151C went undetected. The substitution from G to A at nt 145 specifically conferred this undetectability, while this undetectability was reverted in synthesized HCV RNA with correction of this variation. Reassessment of these samples by CAP/CTM version 2 resulted in similar levels of HCV RNA being detected by ART. We conclude that HCV patients with undetectable HCV RNA by CAP/CTM version 1 should be reassessed for viral quantification.


Assuntos
Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , RNA Viral/sangue , Soro/virologia , Carga Viral , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , RNA Viral/genética
20.
J Gastroenterol Hepatol ; 29(2): 337-43, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23869873

RESUMO

BACKGROUND AND AIM: Chronic infection with hepatitis C virus (HCV) decreases health-related quality of life (HRQOL). The present study was planned to investigate the impact of HRQOL of patients with chronic hepatitis C (CHC) on the outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to IL28B polymorphisms. METHODS: The present study enrolled 228 CHC patients and assessed their HRQOLs prospectively with the 36-item short-form health survey. RESULTS: The patients with CHC have lower physical HRQOL status than the general population (P = 0.037, the Z-test). The patients with advanced liver diseases exhibited further decreases in HRQOL (P = 0.036, Spearman's rank correlation coefficient). The score of total HRQOL was significantly lower in the group with sustained virological response (SVR) to the therapy with pegylated interferon and RBV than the non-SVR group (P = 0.031, the Mann-Whitney U-test), with significantly lower scores of mental component and its comprising subscales in the SVR group. Stepwise multivariate logistic regression analysis showed that low HRQOL score ≤ 400 points was significantly associated with SVR (odds ratio = 2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients with low HRQOL score will have significantly less decrease in HRQOL score by 4 weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045). CONCLUSION: HRQOL is one of the significant predictor of the outcomes of therapy with pegylated interferon and RBV independently from IL28B polymorphism.


Assuntos
Antivirais/administração & dosagem , Inquéritos Epidemiológicos/métodos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Qualidade de Vida , Ribavirina/administração & dosagem , Idoso , Quimioterapia Combinada , Feminino , Previsões , Hepacivirus/classificação , Hepatite C Crônica/psicologia , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferons , Interleucinas/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Sorotipagem , Resultado do Tratamento
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