RESUMO
Multiple sclerosis (MS), a putative autoimmune disease of the central nervous system (CNS), commonly presents as relapsing-remitting MS (RRMS), characterized by recurrent episodes of peripheral disabling symptoms resulting from inflammatory CNS damage. Many RRMS patients transition to a chronic disease course with progressive neurological dysfunctions (secondary progressive MS, SPMS), with the progression rate varying between patients and over time. SPMS pathogenesis is now linked to immune-cell-mediated processes, although the mechanisms driving SPMS transition and progression remain elusive, and SPMS lacks biomarkers and effective treatments. We report the crucial involvement of cytotoxic CD4+ T cells expressing Eomes (Eomes+ Th cells) in SPMS pathogenesis-a Th cell subset previously identified in a mouse model of late/chronic autoimmune CNS inflammation. Few Eomes+ Th cells circulate in RRMS patient peripheral blood (n = 44), primary progressive MS (PPMS) patients (n = 25), or healthy controls (n = 42), but Eomes+ Th cells were significantly increased in SPMS (n = 105, P < 0.0001). Strikingly, lymphocytes isolated from SPMS autopsy brain samples revealed CD4+ T cells infiltrating CNS that coexpressed Eomes and the cytotoxic molecule granzyme B. In particular, the Eomes+ Th cell levels were increased in SPMS patients in progressive disease phases versus SPMS patients without current disability increases (P < 0.0001). Moreover, Eomes level acted as a biomarker to predict SPMS patients at risk of disease worsening with over 80% accuracy (ROC-AUC = 0.8276). Overall, our results indicate that granzyme B-expressing Eomes+ T helper cells are involved in the pathogenesis of SPMS, with significant implications for SPMS biomarkers and therapeutic targets.
Assuntos
Esclerose Múltipla Crônica Progressiva/patologia , Proteínas com Domínio T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Encéfalo/patologia , Progressão da Doença , Feminino , Granzimas/metabolismo , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/sangue , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto JovemRESUMO
BACKGROUND: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. METHODS: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, ß-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. RESULTS: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. CONCLUSION: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.
Assuntos
Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Duodenais/patologia , Neoplasias do Jejuno/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Idoso , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Neoplasias Duodenais/tratamento farmacológico , Neoplasias Duodenais/metabolismo , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias do Jejuno/tratamento farmacológico , Neoplasias do Jejuno/metabolismo , Leucovorina/administração & dosagem , Masculino , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND AIM: Peyer's patches (PPs) play a major role in intestinal mucosal immunity; however, their role in ulcerative colitis (UC) is not well investigated. We evaluated endoscopic features of PPs on narrow-band imaging with magnifying endoscopy (NBI-ME) and investigated their association with clinical factors. METHODS: We prospectively recruited 105 patients with UC, 18 with Crohn's disease, 16 with disease control, and 33 healthy control subjects at three institutions from 2014 to 2017. NBI-ME images of the villi of PPs were evaluated according to the Villi Index, and patients were divided into the Villi Index low (L) and high (H) types. The 1-year sustained clinical remission rate was evaluated between L-type and H-type PPs in patients with UC. RESULTS: The proportions of patients with H-type PPs were significantly higher among UC, Crohn's disease, and disease control patients than among healthy control patients (P = 0.0125, 0.018, 0.0007). In UC, age, gender, endoscopic score, and extent of disease involvement were not significantly different between L-type and H-type PPs, whereas the sustained clinical remission rate was significantly higher in L-type PPs than in H-type PPs (88% [57/65] vs 65% [17/26], P = 0.019). Multivariate analysis revealed that the L type of PPs was a significant factor for sustained clinical remission (odds ratio 3.8, 95% confidence interval 1.1-12.9, P = 0.033). CONCLUSIONS: Patients with UC showed endoscopic alterations in PPs on NBI-ME, and highly altered appearance of PPs can be associated with a high risk of clinical relapse in patients with UC.
Assuntos
Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/patologia , Endoscopia Gastrointestinal/métodos , Nódulos Linfáticos Agregados/diagnóstico por imagem , Nódulos Linfáticos Agregados/patologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Imagem de Banda Estreita/métodos , Estudos Prospectivos , Recidiva , Indução de Remissão , Risco , Adulto JovemRESUMO
BACKGROUND AND AIM: Transabdominal ultrasonography (US) examination for the intestine is often difficult, and its precedence for intestinal examination depends on accessibility to experienced ultrasonographers. Real-time virtual sonography (RVS) assists examination of US as a fusion method by synchronizing US images with pre-captured computed tomography or magnetic resonance images. We aimed to evaluate the feasibility to use RVS for the examination of the intestine. METHODS: The time to scan three parts of the intestine was compared between conventional US and RVS in seven participants without intestinal diseases. Whether RVS accurately synchronized US images with reference images of intestinal target lesions was judged in 20 patients with inflammatory bowel disease. RESULTS: Examination time to scan the ascending colon and the ileocecum using intestinal RVS was significantly shorter than that using conventional US alone (36.7 vs 50.0 s [P = 0.0313] and 35.4 vs 66.4 s [P = 0.0156], respectively) in participants without intestinal diseases. Well-synchronized US images of the intestinal lesions, such as stenosis, with reference computed tomography/magnetic resonance images were obtained by RVS in all the lesions in the fixed parts of the colon (ascending and descending colon), and images of nine lesions in 12 lesions (75%) were well synchronized in the unfixed part of the intestine in Crohn's disease patients. CONCLUSION: Real-time virtual sonography significantly reduced the examination time of intestinal US. Intestinal RVS can help the ultrasonographer to guide the US probe to detect and monitor intestinal lesions by synchronizing reference images, especially in inflammatory bowel disease patients (UMIN Clinical Trials Registry number: UMIN000011571).
Assuntos
Doenças Inflamatórias Intestinais/diagnóstico por imagem , Intestinos/diagnóstico por imagem , Ultrassonografia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Valor Preditivo dos Testes , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Fatores de Tempo , Tomografia Computadorizada por Raios X , Fluxo de Trabalho , Adulto JovemRESUMO
BACKGROUND: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells. OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in patients with MS. METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts. RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38(int-high)), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138(+)) among whole plasmablasts, in the patients treated with fingolimod. CONCLUSIONS: The marked reduction of Ki-67(+) memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138(+) plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.
Assuntos
Subpopulações de Linfócitos B/efeitos dos fármacos , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Propilenoglicóis/uso terapêutico , Esfingosina/análogos & derivados , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Resistência a Medicamentos , Feminino , Cloridrato de Fingolimode , Citometria de Fluxo , Humanos , Memória Imunológica , Antígeno Ki-67/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Fenótipo , RNA Mensageiro/metabolismo , Receptores de Lisoesfingolipídeo/genética , Receptores de Lisoesfingolipídeo/metabolismo , Esfingosina/uso terapêutico , Receptores de Esfingosina-1-Fosfato , Sindecana-1/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
Neuromyelitis optica is an autoimmune-mediated inflammatory disease affected predominantly optic nerve and spinal cord. The pathogenic mechanism was found to be distinct from multiple sclerosis since the discovery of the disease specific autoantibody against water channel aquaporin-4. The pathogenicity of anti-aquporin-4 antibody causes complement-dependent and cell-mediated astrocyte damage in the central nervous system, resulting in the severe inflammatory lesions including loss of aquaporin-4. The recent elucidation of pathological mechanism contributed to the development of treatment with monoclonal antibodies, e.g., rituximab, tocilizumab and eculizumab. It also raises the possibility that neutralization of the pathogenic autoantibodies, attenuation of polymorphonuclear leukocyte accumulation, and regulation of the proinflammatory cytokine and chemokine production can be efficacious for acute exacerbation and prevention of the relapses.
Assuntos
Neuromielite Óptica/tratamento farmacológico , Ensaios Clínicos como Assunto , Desenho de Fármacos , Humanos , Neuromielite Óptica/prevenção & controle , RecidivaRESUMO
BACKGROUND: The previous Japanese clinical practice guidelines for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) were published in 2017. Recently, for the first time in 6 years, the MS and NMOSD guideline development committee revised the Japanese guidelines for MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). METHODS: The committee utilized the Grading of Recommendations Assessment, Development, and Evaluation system based on the "Minds Handbook for Clinical Practice Guideline Development 2020 Ver. 3.0â³ with a focus on clinical questions (CQs). The committee also discussed clinical issues other than CQs, categorizing them as a question-and-answer (Q&A) section, including "issues on which experts' opinions agree to a certain extent" and "issues that are important but not included in the CQ". RESULTS: The committee identified 3, 1, and 1 key CQs related to MS, NMOSD, and MOGAD, respectively, and presented recommendations. A Q&A session regarding disease-modifying therapies and relapse prevention therapies for MS, NMOSD, and MOGAD was conducted. The revised guidelines were published in September 2023. CONCLUSIONS: The Japanese guidelines for clinical practice on MS, NMOSD, and MOGAD were updated. Treatment strategies for MS, NMOSD, and MOGAD are changing, and these updated guidelines may assist with treatment decisions for these diseases in clinical practice.
Assuntos
Esclerose Múltipla , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Humanos , Autoanticorpos/sangue , Japão , Esclerose Múltipla/terapia , Esclerose Múltipla/imunologia , Esclerose Múltipla/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Neuromielite Óptica/terapia , Guias de Prática Clínica como AssuntoRESUMO
Neuromyelitis optica (NMO) is a disabling autoimmune disease associated with an elevation of anti-aquaporin 4 (AQP4) autoantibodies. Here, we present a case with NMO who responded to monthly administration of the anti-IL-6 receptor antibody tocilizumab. The treatment rapidly reduced the elevated numbers of plasmablasts and anti-AQP4 autoantibodies in the patient. Furthermore, neuropathic pain and disability scores gradually improved. Tocilizumab may be considered as a therapeutic option for NMO.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Interleucina-6/antagonistas & inibidores , Neuromielite Óptica/tratamento farmacológico , Adulto , Feminino , Humanos , Resultado do TratamentoRESUMO
Background: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that causes the damage to the myelin sheath as well as axonal degeneration. Individuals with MS appear to have changes in the numbers and functions of T-cell subsets, leading to an immunological imbalance accompanied by enhanced autoreactivity. In previous preclinical studies, (2 S,3 S,4R)-1-O-(α-D-Galactopyranosyl)-N-tetracosanoyl-2-amino-1,3,4-nonanetriol (OCH), a synthetic analog of α-galactosylceramide stimulatory for invariant NKT (iNKT) cells, has shown therapeutic or disease-preventive immunoregulatory effects in autoimmune disease models such as experimental autoimmune encephalomyelitis (EAE). Objectives: This study is the first-in-human study of oral OCH to evaluate the pharmacokinetics and to examine the effects on immune cells as well as related gene expression profiles. Methods: Fifteen healthy volunteers and 13 MS patients who met the study criteria were enrolled. They were divided into five cohorts and received oral administration of various doses of granulated powder of OCH (0.3-30 mg), once per week for 4 or 13 weeks. Plasma OCH concentrations were measured by high-performance liquid chromatography. Frequencies of lymphocyte subsets in peripheral blood were evaluated by flow cytometry, and microarray analysis was performed to determine OCH-induced changes in gene expression. Results: Oral OCH was well tolerated, and its bioavailability was found to be sufficient. Six hours after a single dose of OCH, increased frequencies of Foxp3+ regulatory T-cells were observed in some cohorts of healthy subjects and MS patients. Furthermore, gene expression analysis demonstrated an upregulation of several immunoregulatory genes and downregulation of pro-inflammatory genes following OCH administration. Conclusion: This study has demonstrated immunomodulatory effects of the iNKT cell-stimulatory drug OCH in human. Safety profiles together with the presumed anti-inflammatory effects of oral OCH encouraged us to conduct a phase II trial.
RESUMO
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, chronic, autoimmune disease, characterized by astrocytopathic lesions in the central nervous system (Beekman et al., 2019; Fujihara et al., 2020). The main aim of NMOSD maintenance therapy is to reduce the frequency and severity of relapses and minimize future disability (Fujihara et al., 2020). Oral corticosteroids are used long-term to prevent relapses, but are associated with serious complications (Kessler et al., 2016; Kimbrough et al., 2012). In the SAkuraSky study, satralizumab reduced the risk of relapse in patients with NMOSD compared with placebo, with comparable rates of serious adverse events and infections between treatment arms (Yamamura et al., 2019). Here, we report on 16 patients who tapered their steroid dose during the openlabel extension (OLE) period of SAkuraSky. METHODS: SAkuraSky was a phase 3, multicenter, randomized, double-blind (DB), placebo-controlled study of satralizumab in combination with immunosuppressive therapies (ISTs) in patients with NMOSD. Patients were randomized 1:1 to receive 120 mg subcutaneous satralizumab or placebo in addition to a stable dose of their baseline IST. After completing the DB period or experiencing relapse, patients could enter the OLE period. In the OLE, all patients received satralizumab, and IST doses could be tapered at the investigator's discretion. We assessed the different steroid tapering patterns and their impact on relapse and safety. Patients were considered to have tapered their steroids if their steroid dose at the clinical cut-off date (CCOD: February 18, 2020) was lower than on the first day of the OLE. Annualized relapse rate (ARR) was calculated as the number of relapses divided by the total number of patientyears at risk. RESULTS: Overall, 36 patients receiving oral corticosteroids entered the OLE, of whom 16 tapered their steroid dose. The mean age (range) at baseline was 44.9 (16-73) years, all 16 were female, 14 (88%) were Japanese, and 15 (94%) were AQP4-IgG seropositive. None were receiving any additional ISTs. Patients tapered their steroids from a median of 10 (range: 5-25) mg/day at OLE baseline to 2.75 (0-15) mg/day at the CCOD. Three patients discontinued steroids entirely, and all three remained relapse free. One patient who remained relapse free had temporary increases in steroid dose. Three relapses were observed in two patients who tapered steroids during the OLE; all three relapses required treatment. One of the relapses occurred shortly after a drop in steroid dose from 25 to 10 mg/day. The ARR for steroid-tapered patients was numerically lower in the OLE period than the satralizumab group in the DB period. The safety profile of satralizumab was in line with the overall SAkuraSky population. Two serious infections were observed in steroid-tapered patients in the OLE, both in the same patient: one event (hepatitis E) occurred before the patient began tapering their steroid dose; and one event (influenza) occurred while the patient was tapering. CONCLUSION: During the OLE of SAkuraSky, 16 patients tapered steroids and the ARR did not increase from the DB period. Patient numbers limit interpretation.
Assuntos
Neuromielite Óptica , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Aquaporina 4 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Esteroides/uso terapêuticoRESUMO
The outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25-0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26-0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Idade de Início , Idoso , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pessoa de Meia-Idade , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/uso terapêuticoRESUMO
Idd5.1 regulates T1D susceptibility in nonobese diabetic (NOD) mice and has two notable candidate genes, Ctla4 and Icos. Reduced expression of one of the four CTLA-4 isoforms, ligand-independent CTLA-4 (liCTLA-4), which inhibits in vitro T cell activation and cytokine production similarly to full-length CTLA-4 (flCTLA-4), has been hypothesized to increase type 1 diabetes (T1D) susceptibility. However, further support of this hypothesis is required since the Idd5.1 haplotypes of the diabetes-susceptible NOD and the resistant B10 strains differ throughout Ctla4 and Icos. Using haplotype analysis and the generation of novel Idd5.1-congenic strains that differ at the disease-associated Ctla4 exon 2 single-nucleotide polymorphism, we demonstrate that increased expression of liCTLA-4 correlates with reduced T1D susceptibility. To directly assess the ability of liCTLA-4 to modulate T1D, we generated liCTLA-4-transgenic NOD mice and compared their diabetes susceptibility to nontransgenic littermates. NOD liCTLA-4-transgenic mice were protected from T1D to the same extent as NOD.B10 Idd5.1-congenic mice, demonstrating that increased liCTLA-4 expression alone can account for disease protection. To further investigate the in vivo function of liCTLA-4, specifically whether liCTLA-4 can functionally replace flCTLA-4 in vivo, we expressed the liCTLA-4 transgene in CTLA-4(-/-) B6 mice. CTLA-4(-/-) mice expressing liCTLA-4 accumulated fewer activated effector/memory CD4(+) T cells than CTLA-4(-/-) mice and the transgenic mice were partially rescued from the multiorgan inflammation and early lethality caused by the disruption of Ctla4. These results suggest that liCTLA-4 can partially replace some functions of flCTLA-4 in vivo and that this isoform evolved to reinforce the function of flCTLA-4.
Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Diabetes Mellitus Tipo 1/genética , Linfócitos T/imunologia , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Autoimunidade/imunologia , Antígeno CTLA-4 , Diabetes Mellitus Tipo 1/imunologia , Predisposição Genética para Doença , Haplótipos/genética , Haplótipos/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-17/biossíntese , Interleucina-17/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos Transgênicos , Polimorfismo de Nucleotídeo Único/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Linfócitos T/metabolismoRESUMO
A 64-year-old man was diagnosed as gastric cancer (cT4N1M0, Stage IIIB). Left upper abdominal evisceration was performed in July 2008. CT scan revealed liver metastases in the segments 6 and 8 about 4-month after the surgery. Liver metastases increased during postoperative adjuvant chemotherapy. We treated the metastases with local therapy. He received radiotherapy (total of 60 Gy) for a liver metastasis in the segment 8 in November 2009. He received radiotherapy (total of 50 Gy) for a liver metastasis in the segment 6 in November 2010 after a total of 3-radiofrequency ablation (RFA) was performed. Partial response was obtained. We have experienced a successful case of liver metastases from gastric cancer treated with RFA and radiotherapy.
Assuntos
Neoplasias Hepáticas/terapia , Neoplasias Gástricas/terapia , Ablação por Cateter , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
A 66-year-old man was referred to our hospital with obstructive jaundice. Computed tomography(CT)scan showed thickening of the gallbladder wall, invasion into the liver bed, and thickening of the rectal wall. Colonoscopy revealed a type 2 rectal cancer, in which adenocarcinoma was identified by endoscopic biopsy. He was diagnosed with double-cancer of the gallbladder and rectum. Because his gallbladder cancer was more life threatening than his rectal cancer, gemcitabine was administered at 1, 000 mg/m2 on days 1, 8, and 15 of a 28-day course. After 3 courses of gemcitabine, the CT scan showed that the lymph nodes in the hepatoduodenal ligament had been enlarged, and duodenal stenosis had occurred as a result of gallbladder cancer invasion. S-1 was administered orally at doses of 120 mg/day twice daily on days 1-28 of a 42-day course. Partial response was confirmed by CT scan. After 8 courses of S-1, the gallbladder cancer had progressed and liver metastases had appeared. He subsequently died of disease progression. He survived for 17 months after the first course of chemotherapy, and the progression-free survival with S-1 was 10 months. Therefore, S-1 could be an effective agent for synchronous double cancer of the gallbladder and rectum.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Terapia de Salvação , Tegafur/uso terapêutico , Idoso , Terapia Combinada , Combinação de Medicamentos , Evolução Fatal , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Tomografia Computadorizada por Raios XAssuntos
Amiloidose/diagnóstico , Mucosa Gástrica/patologia , Gastropatias/diagnóstico , Diagnóstico Diferencial , Endoscopia do Sistema Digestório , Endossonografia , Mucosa Gástrica/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Banda Estreita , Neoplasias Gástricas/diagnósticoRESUMO
The patient was a 55-year-old man with a large hepatic tumor measuring 12 × 12 cm in the left lobe. To obtain the histological diagnosis, the target liver biopsy was performed. Histologically, the tumor revealed as a neuroendocrine carcinoma. After the diagnosis, he received the chemotherapy (CTX) with etoposide and cisplatin. Serum levels of NSE and the tumor size were decreased after the first course of CTX. We here report a case of primary hepatic neuroendocrine carcinoma treated with CTX following the diagnosis by the needle biopsy.
Assuntos
Biópsia por Agulha , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Fígado/patologia , Neoplasias Primárias Múltiplas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma de Células de Transição , Cisplatino/administração & dosagem , Diagnóstico Diferencial , Diagnóstico por Imagem , Etoposídeo/administração & dosagem , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga UrináriaRESUMO
BACKGROUND AND AIMS: Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition. METHODS: This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms. RESULTS: A total of 1078 IBD patients were enrolled, including 303 patients with Crohn's disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4-9.5) vs. 5 (3-7), p < .0001), but not in the non-PSTE group (5 (2-8) vs. 4 (3-7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group. CONCLUSIONS: A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress.
Assuntos
Doenças Inflamatórias Intestinais/psicologia , Transtornos do Sono-Vigília/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores Sexuais , Transtornos do Sono-Vigília/etiologia , Estresse Psicológico/etiologiaRESUMO
A 38-year-old man presented with distal-dominant limb weakness two weeks after an upper respiratory infection. He had no sensory and autonomic signs and no cranial nerve involvement during the course of the disease. Tendon reflexes were preserved except for an absent Achilles' tendon reflex. His disability at nadir was grade 2 on the Hughes functional scale. Cerebrospinal fluid analysis showed albuminocytologic dissociation and he was diagnosed with pure motor Guillain-Barré syndrome (GBS). Thin-layer chromatography immunostaining and an enzyme-linked immunosorbent assay revealed an immunoglobulin G antibody to the ganglioside complex GM1/GalNAc-GD1a in his acute phase serum. A serial nerve conduction study revealed conduction block in the median and ulnar nerve trunks and temporal dispersion in the tibial nerve, without an evident remyelination pattern during the course of the disease. A sensory nerve conduction study was normal. According to Hadden's criteria, the electrodiagnostic findings were judged as a primary demyelinating pattern. Weakness and abnormal motor nerve conduction recovered rapidly after intravenous immunoglobulin therapy. In view of the localization of GM1 and GalNAc-GD1a on the axolemma of the motor nerves, the clinical course and electrophysiological features may have resulted from functional conduction failure at the nodes of Ranvier of the motor nerves, rather than primary demyelination or axonal degeneration. The illness resembled acute motor conduction block neuropathy characterized by preserved sensory function, an early conduction block at intermediate nerve segments, and good recovery. GM1 and GalNAc-GD1a may form a complex in the axolemma at the nodes of Ranvier or paranodes of the motor nerves, and may be a target antigen in pure motor GBS; especially in the form with acute motor conduction block neuropathy. The present case is the first description of a GBS patient with an IgG anti-GM1/GalNAc-GD1a antibody.
Assuntos
Autoanticorpos/sangue , Gangliosídeo G(M1)/imunologia , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Imunoglobulina G/sangue , Doença dos Neurônios Motores/etiologia , Condução Nervosa , Humanos , Masculino , Doença dos Neurônios Motores/fisiopatologiaRESUMO
Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune diseases associated with a disease-specific autoantibody directed against the water channel protein aquaporin-4. Standard immunotherapy, immunosuppressive agents, and corticosteroids can prevent acute attacks and maintain remission in most patients with NMOSD. However, there is a strong need for additional options for patients who are refractory to standard treatments. Emerging therapies targeting specific molecules related to the pathogenicity of NMOSD are currently being developed. The review focuses on improving preventive treatments for NMOSD, including ongoing randomized clinical trials using biological drugs targeting CD19 and CD20 on B cells, interleukin-6, and complement protein C5. The anti-IL-6 receptor monoclonal antibody tocilizumab (TCZ), which can block IL-6 signaling, was shown to be highly effective for refractory patients with NMOSD. Notably, TCZ has marked effects on chronic neuropathic pain and general fatigue in patients refractory to standard medications. TCZ is a promising drug for preventing acute attacks in patients with NMOSD.