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2.
Intern Med ; 63(4): 541-545, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37316269

RESUMO

Cryoglobulins are immunoglobulins that precipitate in cold conditions. Type I cryoglobulinemic vasculitis is associated with hematological malignancies. We herein report a case of steroid-resistant type 1 cryoglobulinemic vasculitis associated with monoclonal gammopathy of undetermined significance (MGUS) in a 47-year-old woman. By immunofixation of cryoglobulin, we found that the main component of cryoglobulin was the M protein due to MGUS, so treatment of MGUS was needed. Bortezomib+dexamethasone therapy resulted in a rapid decrease in cryoglobulin and improvement in the symptoms of cryoglobulinemic vasculitis. In refractory type I cryoglobulinemic vasculitis, treatment of the underlying gammaglobulinopathy should be considered.


Assuntos
Crioglobulinemia , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Vasculite , Feminino , Humanos , Pessoa de Meia-Idade , Bortezomib/uso terapêutico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Crioglobulinas , Paraproteinemias/complicações , Crioglobulinemia/complicações , Crioglobulinemia/tratamento farmacológico , Dexametasona/uso terapêutico , Vasculite/complicações , Vasculite/tratamento farmacológico
3.
Cancer Sci ; 114(11): 4172-4183, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37675556

RESUMO

Adoptive immunotherapy using genetically engineered patient-derived lymphocytes to express tumor-reactive receptors is a promising treatment for malignancy. However, utilization of autologous T cells in this therapy limits the quality of gene-engineered T cells, thereby inhibiting the timely infusion of the cells into patients. In this study, we evaluated the anti-tumor efficacy and the potential to induce graft-versus-host disease (GVHD) in T cell receptor (TCR) gene-engineered allogeneic T cells that downregulate the endogenous TCR and HLA class I molecules with the aim of developing an "off-the-shelf" cell product with expanded application of genetically engineered T cells. We transduced human lymphocytes with a high-affinity TCR specific to the cancer/testis antigen NY-ESO-1 using a novel retrovirus vector with siRNAs specific to the endogenous TCR (siTCR vector). These T cells showed reduced expression of endogenous TCR and minimized reactivity to allogeneic cells in vitro. In non-obese diabetic/SCID/γcnull mice, TCR gene-transduced T cells induced tumor regression without development of GVHD. A lentivirus-based CRISPR/Cas9 system targeting ß-2 microglobulin in TCR gene-modified T cells silenced the HLA class I expression and prevented allogeneic CD8+ T cell stimulation without disrupting their anti-tumor capacity. This report is the first demonstration that siTCR technology is effective in preventing GVHD. Adoptive cell therapy with allogeneic T cells engineered with siTCR vector may be useful in developing an "off-the-shelf" therapy for patients with malignancy.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Camundongos , Animais , Humanos , RNA Interferente Pequeno/genética , Células Alógenas/metabolismo , Camundongos SCID , Receptores de Antígenos de Linfócitos T , Genes Codificadores dos Receptores de Linfócitos T , Imunoterapia Adotiva , Neoplasias/genética , Doença Enxerto-Hospedeiro/prevenção & controle
4.
BMJ Case Rep ; 16(9)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37751977

RESUMO

A man in his early 70s was transferred to our hospital due to rapid decline in renal function and inflammation throughout the colon, indicating severe ischaemic enteritis. On the day following the start of intensive care, a stool specimen tested positive for verotoxin, and haemolytic uraemic syndrome (HUS) was diagnosed. On the same day, his vital signs deteriorated suddenly, and emergency surgery was performed due to the possibility of intestinal necrosis and perforation. Severe inflammation extending to the serosal surface of the whole colon was observed, but there was no obvious intestinal necrosis or perforation. Advanced mucosal necrosis of the entire colon suggested sepsis due to bacterial translocation, and subtotal colectomy was performed to remove the infection source. Postoperative management was successful. This case demonstrates the importance of considering HUS in patients with severe renal dysfunction and bloody stools, as well as the significance of colectomy in such patients.


Assuntos
Síndrome Hemolítico-Urêmica , Enteropatias , Doenças Vasculares , Humanos , Masculino , Colectomia , Colo , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/cirurgia , Inflamação , Necrose , Idoso
6.
Blood ; 142(5): 477-492, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37216687

RESUMO

Calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis is standard in allogeneic hematopoietic stem cell transplantation (HCT) but fails to induce long-term tolerance without chronic GVHD (cGVHD) in a considerable number of patients. In this study, we addressed this long-standing question in mouse models of HCT. After HCT, alloreactive donor T cells rapidly differentiated into PD-1+ TIGIT+ terminally exhausted T cells (terminal Tex). GVHD prophylaxis with cyclosporine (CSP) suppressed donor T-cell expression of TOX, a master regulator to promote differentiation of transitory exhausted T cells (transitory Tex), expressing both inhibitory receptors and effector molecules, into terminal Tex, and inhibited tolerance induction. Adoptive transfer of transitory Tex, but not terminal Tex, into secondary recipients developed cGVHD. Transitory Tex maintained alloreactivity and thus PD-1 blockade restored graft-versus-leukemia (GVL) activity of transitory Tex and not terminal Tex. In conclusion, CSP inhibits tolerance induction by suppressing the terminal exhaustion of donor T cells, while maintaining GVL effects to suppress leukemia relapse.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Camundongos , Animais , Inibidores de Calcineurina/farmacologia , Linfócitos T , Doença Enxerto-Hospedeiro/prevenção & controle , Receptor de Morte Celular Programada 1 , Ciclosporina/farmacologia , Tolerância Imunológica
7.
Intern Med ; 62(21): 3231-3235, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36927968

RESUMO

We herein report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) resembling adult-onset Still's disease (AOSD). A 40-year-old woman presented with a fever, erythema, and painful subcutaneous nodules on the trunk. Laboratory data and a bone marrow analysis showed hemophagocytic syndrome. Although AOSD was suspected, based on a histopathological evaluation of the erythema, she was diagnosed with SPTCL. She was refractory to combination chemotherapy but achieved durable remission with cyclosporine monotherapy. Genetic testing revealed a homozygous HAVCR2 c.245A>G variant (rs184868814) that had caused NLRP3 inflammasome activation. SPTCL and AOSD share a pathogenesis in terms of NLRP3 inflammasome activation, so the clinical phenotype of SPTCL reasonably mimics AOSD.


Assuntos
Linfoma de Células T , Paniculite , Doença de Still de Início Tardio , Adulto , Feminino , Humanos , Doença de Still de Início Tardio/diagnóstico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Inflamassomos , Paniculite/diagnóstico , Paniculite/genética , Paniculite/patologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Eritema
8.
PLoS One ; 18(3): e0283626, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36996098

RESUMO

BACKGROUND: Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model. METHODS: Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15. RESULTS: The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-ß1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption. CONCLUSION: DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.


Assuntos
Enterite , Mucosite , Panax , Ratos , Animais , Metotrexato/toxicidade , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/patologia , Mucosa Intestinal/metabolismo , Enterite/patologia
9.
J Glaucoma ; 32(6): 520-525, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36847662

RESUMO

PRCIS: A novel visual field screening program with a head-mounted perimeter 'imo' could detect glaucoma at all stages in a short time with high accuracy. PURPOSE: The present study aimed to examine the accuracy and availability of a novel glaucoma visual field screening program using a head-mounted visual perimeter 'imo.' PARTICIPANTS AND METHODS: Eyes of 76 non-glaucoma participants and 92 glaucoma patients were examined. All patients underwent visual field tests using the Humphrey Visual Field Analyzer (30-2 or 24-2 Swedish Interactive Thresholding Algorithm standard program) and imo (the visual field screening program). We evaluated five visual field screening program indicators: sensitivity, specificity, positive predictive value, negative predictive value, and testing time. We also evaluated the ability of this visual field screening program to differentiate between glaucoma patients and normal controls using the receiver operating characteristic curves and areas under the receiver operating characteristic curves. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the visual field screening program were 76%-100%, 91%-100%, 86%-89%, and 79%-100%, respectively. The visual field screening program test time was 46±13 seconds for normal controls and 61±18, 82±21, and 105±16 econds, respectively for mild, moderate, and advanced-stage patients. The areas under the receiver operating characteristic curves were 0.77, 0.97, and 1.0 in the mild, moderate, and advanced stages, respectively. CONCLUSIONS: Visual field screening using a head-mounted perimeter 'imo' detected glaucoma at all stages in a short time with high accuracy.


Assuntos
Glaucoma , Campos Visuais , Humanos , Pressão Intraocular , Glaucoma/complicações , Glaucoma/diagnóstico , Testes de Campo Visual , Olho , Sensibilidade e Especificidade
10.
Rinsho Ketsueki ; 63(8): 870-875, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36058857

RESUMO

Bing-Neel syndrome (BNS) is a rare disease manifestation of Waldenström's macroglobulinemia characterized by abnormal lymphoplasmacytoid cells infiltration of the central nervous system. In September 2019, a 46-year-old man presented to a previous hospital with hand tremors, nausea, and dysuria. Demyelination of cerebral white matter and the spinal cord was discovered using MRI. Steroid pulse therapy was used to treat inflammatory demyelinating disease, and it provided temporary relief, but the symptoms returned when the steroids were stopped. He was referred to our hospital in June 2020, for further evaluation with the possibility of hematological malignancy. BNS was diagnosed based on the presence of abnormal lymphoplasmacytoid cells in the bone marrow and cerebrospinal fluid (CSF), as well as the presence of the MYD88L265P mutation in the CSF specimen. In July 2020, BR (bendamustine, rituximab) therapy was administered, but it was ineffective. Oral administration of tirabrutinib, which was recently approved for WM, began in August 2020. He has achieved long-term remission and steroid withdrawal, with no notable side effects. This is the second report of successful treatment of BNS with tirabrutinib. More research is needed to confirm tirabrutinib's efficacy in the treatment of BNS.


Assuntos
Encefalopatias , Macroglobulinemia de Waldenstrom , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirimidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/diagnóstico
11.
Transplant Proc ; 53(8): 2570-2575, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34511248

RESUMO

We report on the case of a 50-year-old female patient with symptomatic polycystic liver disease who underwent living donor liver transplantation (LDLT) using right liver graft from her ABO-identical husband. To achieve operational tolerance, regulatory T-cell (T-reg)-based cell therapy was applied, following the protocol introduced by Todo et al. Briefly, donor lymphocytes were collected by leukapheresis 20 days before LDLT without any adverse events, and the cells were irradiated with a dose of 30 Gy and kept frozen. Lymphopheresis of the recipient was conducted in a similar manner 1 day before LDLT, and donor cells and recipient cells were cultured with anti-CD80/86 antibodies to induce the donor-specific T-reg. At 14 days of culture, the CD4+CD25+Foxp3+ cells had increased from 1.51% to 5.21%, and mixed lymphocyte reaction assay using an intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester-labeling technique revealed donor-specific hyporesponsiveness of CD4-positive lymphocytes. On postoperative day (POD) 13 (14 days of culture), these cells were infused to the recipient intravenously without any adverse events. Initial immunosuppression consisted of tacrolimus, steroid and mycophenolate mofetil (MMF), and cyclophosphamide (40 mg/kg) administered on POD 5. Both the steroid and MMF were continued until 4 weeks after LDLT, and the patient was discharged on POD 30 with normal liver function. On POD 52, the patient developed acute cellular rejection and received appropriate reinforcement of immunosuppressive therapy and is currently doing well with normal liver function 30 months after LDLT with reduced anti-donor allo-activity. In summary, T-reg therapy was safely performed in adult LDLT, and we are following the patient carefully to determine whether she can achieve operational tolerance in the future.


Assuntos
Transplante de Fígado , Feminino , Rejeição de Enxerto , Humanos , Imunossupressores , Doadores Vivos , Pessoa de Meia-Idade , Linfócitos T Reguladores , Tacrolimo
12.
Int J Hematol ; 113(2): 207-213, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32949373

RESUMO

Translocation t(4;14) is an independent prognostic factor for adverse outcome in multiple myeloma (MM). However, reports concerning the therapeutic effects of novel drugs on t(4;14) MM are few. We retrospectively investigated the clinical and prognostic significance of symptomatic MM cases with t(4;14) treated with novel therapies. Ninety-three patients (IgG, 56; IgA, 23; BjP, 14) newly diagnosed with MM were included (median age, 71 years; median observation period, 27.8 months). t(4;14) MM was diagnosed in 17 (IgG, 7; IgA, 9; BjP, 1) patients (18%). An association between t(4;14) and the IgA isotype was confirmed (p = 0.02). Overall survival (OS) at 3 years was lower in the t(4;14) patients than without t(4;14) group (81.2% vs 66.7%, p = 0.04). Multivariate analysis showed that t(4;14) was an independent predictor of OS (hazard ratio [HR], 7.58; 95.0% confidence interval [CI], 1.43-39.9; p = 0.0017). The ORR after autologous blood stem cell transplantation (ASCT) did not differ with or without t(4;14); progression-free survival tended to be prolonged in the group without t(4;14) (p = 0.088). Thus, even in the era of novel drugs, t(4;14) MM still has a poor prognosis, and triplet consolidation therapy should be continued.


Assuntos
Cromossomos Humanos Par 14 , Cromossomos Humanos Par 4 , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Translocação Genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Feminino , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Prognóstico , Modelos de Riscos Proporcionais , Resultado do Tratamento
13.
J Gastrointest Cancer ; 52(2): 582-592, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32524305

RESUMO

PURPOSE: In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. METHODS: We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. RESULTS: The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade < 1b effect (p = 0.0282). The multivariate analysis showed that downstaging was the only factor significantly associated with RFS in DCF-treated patients. CONCLUSIONS: DCF therapy for stage ≥ III esophageal carcinoma is both feasible and effective. These findings suggest that downstaging and the histological effect might predict the effects of DCF therapy for EC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Idoso , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Esquema de Medicação , Mucosa Esofágica/diagnóstico por imagem , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/patologia , Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia , Esofagoscopia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Pirimidinas , Estudos Retrospectivos
14.
J Blood Med ; 11: 363-369, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117022

RESUMO

PURPOSE: Acute promyelocytic leukemia (APL) constitutes 5-10% of all cases of newly diagnosed acute myeloid leukemia. However, data on the epidemiology and risk factors for acute kidney injury (AKI) in patients with newly diagnosed APL are lacking. This study determined the incidence rate of AKI during induction chemotherapy for patients with newly diagnosed APL and the risk factors for AKI. PATIENTS AND METHODS: We conducted a retrospective observational study of patients with newly diagnosed APL in the Shonan Kamakura General Hospital between April 2004 and April 2020. Data of 27 patients with newly diagnosed APL were analyzed. The patients were classified as no AKI and AKI stages 1, 2 or 3. RESULTS: The incidence rate of AKI during induction chemotherapy was 40% (11/27). Among patients who developed AKI, four patients experienced AKI stage 3, and two patients required renal replacement therapy. No significant differences were found in the white blood cell count and baseline renal function between the groups; however, D-dimer and C-reactive protein levels upon admission were significantly higher in patients with AKI than in patients without AKI. Among patients who developed AKI, in hospital mortality at 90 days was 36% (4/11), which was significantly higher than among patients without AKI (p = 0.02). Patients who developed AKI were administered vancomycin more frequently, while almost all blood culture results were negative. CONCLUSION: Incidence of AKI development in patients with newly diagnosed APL during induction chemotherapy was approximately 40%. Moreover, patients who developed AKI tended to be administered vancomycin more frequently. Unnecessary use of vancomycin should be avoided in patients with newly diagnosed APL, and using alternative non-nephrotoxic drugs should be considered for patients at risk of AKI.

15.
Kurume Med J ; 66(1): 43-47, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32378536

RESUMO

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias Colorretais , Oxaliplatina , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Humanos , Irinotecano/uso terapêutico , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Qualidade de Vida , Tiazóis
16.
Intern Med ; 59(10): 1239-1245, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32074573

RESUMO

Objective In the treatment of advanced and recurrent colorectal cancer (ARCC), FOLFOXIRI regimens have been proven to be significantly superior to FOLFIRI in terms of the progression-free survival (PFS), response rate (RR), and overall survival (OS). Furthermore, the Tribe trial showed that the RR and PFS rates in patients who received bevacizumab (Bmab) +FOLFOXIRI were superior to those in patients treated with Bmab+FOLFIRI. A phase III trial of panitumumab (Pmab) +FOLFOXIRI is currently ongoing. A modified FOLFOXIRI regimen is also widely used to reduce adverse events. In our department, we introduced modified FOLFOXIRI+α (mFOLFOXIRI+α) in 2015. The present study reviewed the efficacy and safety of mFOLFOXIRI+α. Methods Eligible patients were retrospectively reviewed, and their results were compared to those of patients treated with other regimens (OTHERS) (n=134) to demonstrate the efficacy of this treatment. Patients: Between February 2015 and November 2018, 12 patients with ARCC (male/female=6/6; average age, 60.7 years old) received mFOLFOXIRI+α (Bmab: 10, Pmab: 1, alone: 1). Results The median PFS in the mFOLFOXIRI+α and OTHERS groups was 565 and 322 days, respectively (p=0.0544). The RR in the mFOLFOXIRI+α and OTHERS groups was 66.7% and 31.3%, respectively (p=0.0135). The conversion rate (Conv R) in the mFOLFOXIRI+α and OTHERS groups was 50.0% and 12.7%, respectively (p=0.0007). While 58% of patients treated with FOLFOXIRI+α developed grade ≥3 leukopenia, the incidence of febrile neutropenia (FN) was only 17%. In all patients with symptoms due to the tumor burden, the symptoms subsided with mFOLFOXIRI+α treatment. Conclusion Based on the RR, Conv R, and symptom palliation ability, mFOLFOXIRI+α was suggested to be a viable candidate for first-line treatment for patients with ARCC, especially those with a high tumor burden.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Panitumumabe , Intervalo Livre de Progressão , Estudos Retrospectivos
17.
Regen Ther ; 14: 79-86, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31988997

RESUMO

INTRODUCTION: Cell sheets consisting of adipose-derived stem cells (ADSCs) have been reported to be effective for wound healing. We conducted this study to clarify the efficacy of ADSC sheets in wound healing at the duct-to-duct biliary anastomotic site in pigs. METHODS: Eleven female pigs (20-25 kg) were divided into two groups: biliary anastomosis with an ADSC sheet (n = 6) or without an ADSC sheet (n = 5). To follow the transplanted ADSCs, PKH26GL-labeled sheets were used in one of the ADSC pigs. Two weeks prior to laparotomy, ADSCs were isolated from the lower abdominal subcutaneous adipose tissue. After three passages, ADSCs were seeded on temperature-responsive culture dishes and collected as cell sheets. ADSC sheets were gently transplanted on the anastomotic site. We evaluated specimens by PKH26GL labeling, macroscopic changes, infiltration of inflammatory cells, and collagen content. RESULTS: Labeled ADSCs remained around the bile duct wall. In the no-ADSC group, more adhesion developed at the hepatic hilum as observed during relaparotomy. Histopathological examination showed that the diameter and cross-sectional area of the bile duct wall were decreased in the ADSC group. In the no-ADSC group, a large number of inflammatory cells and more collagen fibers were identified in the bile duct wall. CONCLUSIONS: The present study demonstrated that autologous ADSC sheet transplantation reduced hypertrophic changes in the bile duct wall at the anastomotic site. A long-term follow-up is required to evaluate the efficacy of this mechanism in prevention of biliary anastomotic strictures.

18.
J Invest Surg ; 33(2): 118-122, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29856668

RESUMO

Purpose: Despite refinements in surgical techniques for liver resection, evaluation of hepatic reserve disparity remains one of the most common problems in liver surgery, especially for hepatic malignancies such as hepatocellular carcinoma (HCC). Portal venous pressure (PVP) is regarded one of the important factors in selecting treatment strategy, although its measurement can be invasive and complex. Methods: To establish a formula for calculating PVP preoperatively, intraoperative directly measured PVP was used in 177 patients with preoperative factors and liver function tests such as age, sex, virus status, platelet count, prothrombin time, albumin, total bilirubin, alanine aminotransferase (ALT), Child-Pugh grade, liver damage defined by the Liver Cancer Study Group of Japan, indocyanine green retention rate at 15 min (ICG-R15), and the aspartate transaminase (AST)-platelet ratio index (APRI). Results: Although 90% of the patients were classified as Child-Pugh A, median direct PVP was 16.5 cm H2O (5.5-37.0) and the percentage of PVP greater than 20 cm H2O was 27.1%, reflecting portal hypertension due to liver damage. After multiple regression analysis, the formula PVP (cmH2O) = EXP[2.606 + 0.01 × (ICG-R15) + 0.015 × APRI] was established from the measured data. Conclusion: Considering its simplicity of use, we have adopted this formula for predicting PVP in determining treatment strategy for HCC and other hepatic malignancies.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Hipertensão Portal/diagnóstico , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/complicações , Tomada de Decisão Clínica/métodos , Feminino , Humanos , Hipertensão Portal/sangue , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Testes de Função Hepática , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Pressão na Veia Porta/fisiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Medição de Risco/métodos , Adulto Jovem
19.
Medicine (Baltimore) ; 98(44): e17766, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689837

RESUMO

RATIONALE: Although essential thrombocythemia (ET) and immune thrombocytopenia (ITP) have different etiologies, 3 previous reports have described ET development in ITP patients, all of whom were positive for the JAK2 V617F mutation. Here, we report the first published case of ITP following ET in the absence of other platelet disorders. PATIENT CONCERNS: A 70-year-old woman with a five-year history of ET with JAK2 V617F mutation treated with hydroxycarbamide for five months presented with petechiae on her limbs. DIAGNOSIS: Her platelet count was 3 × 10/L, with the immature platelet fraction being 29%. White blood cell count and hemoglobin level were normal. Bone marrow examination showed increased number of megakaryocytes, but no morphologic dysplasia in any lineage. G-band analysis revealed no abnormalities. Platelet transfusion and cessation of hydroxycarbamide did not affect the platelet count. Thrombocytopenia was unlikely to have been induced by drugs, heparin, systemic lupus erythematosus, or human immunodeficiency virus. Hence, a diagnosis of ITP was made. INTERVENTIONS: The patient received oral prednisolone combined with intravenous immunoglobulin. OUTCOMES: Her platelet count rose to 310 × 10/L and remained stable, while her steroid dose was reduced. Further blood tests revealed the presence of antibodies against Helicobacter pylori, and appropriate treatment was administered. Resumption of hydroxycarbamide did not induce thrombocytopenia. LESSONS: Although ET and ITP have different etiologies, chronic inflammation and immune deregulation underlie both and may play an important role in the progression from one to the other. Further research is warranted to understand the relationship between ET and ITP.


Assuntos
Janus Quinase 2/sangue , Púrpura Trombocitopênica Idiopática/genética , Trombocitemia Essencial/genética , Idoso , Plaquetas , Feminino , Humanos , Contagem de Leucócitos , Mutação , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/etiologia , Trombocitemia Essencial/sangue , Trombocitemia Essencial/complicações
20.
Artif Organs ; 43(3): 270-277, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30332505

RESUMO

Intraoperative hyperglycemia during liver transplantation can induce infectious bacterial complications after surgery. The aim of this study was to evaluate the efficacy of the artificial endocrine pancreas in achieving perioperative blood glucose control and preventing infection in patients undergoing living donor liver transplantation (LDLT). We compared 14 patients with an artificial endocrine pancreas device to 14 patients who underwent glycemic control using the sliding scale method with respect to perioperative blood glucose level and postoperative infection. In this study, we aimed to control the perioperative glucose levels consecutively for 24 hours from the induction of anesthesia. The average blood glucose level in the artificial pancreas group was significantly lower than that in the sliding scale group (118 vs. 141 mg/dL, P < 0.05). The postoperative bacterial infection rate of the artificial pancreas group was significantly lower than that of the sliding scale group within one month after LDLT (35.7% vs. 78.6%, P < 0.05). Multiple regression analysis showed non-application of artificial endocrine pancreas as a significant risk factor of posttransplant infection. The artificial endocrine pancreas enabled the perioperative glucose level to be stably controlled without hypoglycemia. Artificial pancreas may reduce the incidence of postoperative infection after LDLT.


Assuntos
Infecções Bacterianas/prevenção & controle , Hiperglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Transplante de Fígado/efeitos adversos , Assistência Perioperatória/instrumentação , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Infecções Bacterianas/sangue , Infecções Bacterianas/etiologia , Glicemia/análise , Glicemia/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Humanos , Hiperglicemia/etiologia , Insulina/administração & dosagem , Cirrose Hepática/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Resultado do Tratamento
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