RESUMO
BACKGROUND: Type 1 diabetes is an autoimmune disease characterized by T-cell-mediated destruction of pancreatic beta-cells. Islet transplantation is an effective therapy, but its success is limited by islet quality and availability along with the need for immunosuppression. New approaches include the use of stem cell-derived insulin-producing cells and immunomodulatory therapies, but a limitation is the paucity of reproducible animal models in which interactions between human immune cells and insulin-producing cells can be studied without the complication of xenogeneic graft-versus-host disease (xGVHD). METHODS: We expressed an HLA-A2-specific chimeric antigen receptor (A2-CAR) in human CD4 + and CD8 + T cells and tested their ability to reject HLA-A2 + islets transplanted under the kidney capsule or anterior chamber of the eye of immunodeficient mice. T-cell engraftment, islet function, and xGVHD were assessed longitudinally. RESULTS: The speed and consistency of A2-CAR T-cell-mediated islet rejection varied depending on the number of A2-CAR T cells and the absence/presence of coinjected peripheral blood mononuclear cells (PBMCs). When <3 million A2-CAR T cells were injected, coinjection of PBMCs accelerated islet rejection but also induced xGVHD. In the absence of PBMCs, injection of 3 million A2-CAR T cells caused synchronous rejection of A2 + human islets within 1 wk and without xGVHD for 12 wk. CONCLUSIONS: Injection of A2-CAR T cells can be used to study rejection of human insulin-producing cells without the complication of xGVHD. The rapidity and synchrony of rejection will facilitate in vivo screening of new therapies designed to improve the success of islet-replacement therapies.
Assuntos
Doença Enxerto-Hospedeiro , Insulinas , Transplante das Ilhotas Pancreáticas , Receptores de Antígenos Quiméricos , Humanos , Camundongos , Animais , Antígeno HLA-A2 , Leucócitos Mononucleares , Rejeição de Enxerto/prevenção & controleRESUMO
ATP6AP2, also known as (pro)renin receptor, has been shown to be expressed in several tissues including pancreatic ß cells. Whereas ATP6AP2 plays an important role in regulating insulin secretion in mouse pancreatic ß cells, the expression profiles and roles of ATP6AP2 in human pancreatic endocrine cells and neuroendocrine tumor cells remain unclear. Here in this study, we investigated the expression profiles of ATP6AP2 in pancreatic endocrine cells, and found that ATP6AP2 is robustly expressed in pancreatic insulinoma cells as well as in normal ß cells. Although ATP6AP2 was also expressed in low-grade neuroendocrine tumors, it was not or faintly detected in intermediate- and high-grade neuroendocrine tumors. Knockdown experiments of the Atp6ap2 gene in rat insulinoma-derived INS-1 cells demonstrated decreased cell viability accompanied by a significant increase in apoptotic cells. Taken together, these findings suggest that ATP6AP2 plays a role in maintaining cellular homeostasis in insulinoma cells, which could lead to possible therapeutic approaches for endocrine tumors.
Assuntos
Células Secretoras de Insulina , Insulinoma , Tumores Neuroendócrinos , Neoplasias Pancreáticas , ATPases Vacuolares Próton-Translocadoras , Camundongos , Ratos , Animais , Humanos , Células Secretoras de Insulina/metabolismo , Insulinoma/genética , Insulinoma/metabolismo , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Sobrevivência Celular/genética , ATPases Vacuolares Próton-Translocadoras/metabolismo , Receptores de Superfície Celular/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Receptor de Pró-ReninaRESUMO
AIMS/HYPOTHESIS: While pancreatic beta cells have been shown to originate from endocrine progenitors in ductal regions, it remains unclear precisely where beta cells emerge from and which transcripts define newborn beta cells. We therefore investigated characteristics of newborn beta cells extracted by a time-resolved reporter system. METHODS: We established a mouse model, 'Ins1-GFP; Timer', which provides spatial information during beta cell neogenesis with high temporal resolution. Single-cell RNA-sequencing (scRNA-seq) was performed on mouse beta cells sorted by fluorescent reporter to uncover transcriptomic profiles of newborn beta cells. scRNA-seq of human embryonic stem cell (hESC)-derived beta-like cells was also performed to compare newborn beta cell features between mouse and human. RESULTS: Fluorescence imaging of Ins1-GFP; Timer mouse pancreas successfully dissected newly generated beta cells as green fluorescence-dominant cells. This reporter system revealed that, as expected, some newborn beta cells arise close to the ducts (ßduct); unexpectedly, the others arise away from the ducts and adjacent to blood vessels (ßvessel). Single-cell transcriptomic analyses demonstrated five distinct populations among newborn beta cells, confirming spatial heterogeneity of beta cell neogenesis such as high probability of glucagon-positive ßduct, musculoaponeurotic fibrosarcoma oncogene family B (MafB)-positive ßduct and musculoaponeurotic fibrosarcoma oncogene family A (MafA)-positive ßvessel cells. Comparative analysis with scRNA-seq data of mouse newborn beta cells and hESC-derived beta-like cells uncovered transcriptional similarity between mouse and human beta cell neogenesis including microsomal glutathione S-transferase 1 (MGST1)- and synaptotagmin 13 (SYT13)-highly-expressing state. CONCLUSIONS/INTERPRETATION: The combination of time-resolved histological imaging with single-cell transcriptional mapping demonstrated novel features of spatial and transcriptional heterogeneity in beta cell neogenesis, which will lead to a better understanding of beta cell differentiation for future cell therapy. DATA AVAILABILITY: Raw and processed single-cell RNA-sequencing data for this study has been deposited in the Gene Expression Omnibus under accession number GSE155742.
Assuntos
Fibrossarcoma , Células Secretoras de Insulina , Transcriptoma , Animais , Diferenciação Celular/genética , Fibrossarcoma/metabolismo , Glucagon/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Camundongos , Ductos Pancreáticos , RNARESUMO
Cytomegalovirus meningitis/meningoencephalitis is a potentially fatal complication following hematopoietic stem cell transplantation that causes significant morbidity and mortality. In the pre-transplant setting, a few cases involving lymphoid malignancies have been reported. However, there have been no reports of patients with myeloid malignancies. A 36-year-old man with relapsed acute myeloid leukemia received high-dose cytarabine-containing salvage chemotherapies and then developed grade 4 lymphopenia for more than one month. Subsequently, the patient developed pyrexia, accompanying headache, nausea, and vomiting with no abnormal brain imaging. Despite receiving antimicrobial treatment, his febrile status and headache persisted. Given that the patient had symptoms consistent with viral meningitis with no evidence of etiology other than positive cytomegalovirus-DNA in his cerebrospinal fluid and cytomegalovirus pp65 antigenemia, cytomegalovirus meningitis was diagnosed. After commencing ganciclovir treatment, the patient's headache and febrile status rapidly improved. Cytomegalovirus meningitis/meningoencephalitis is rare before hematopoietic stem cell transplantation, but may be useful in differential diagnoses in heavily treated acute myeloid leukemia patients with central nervous system symptoms.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Leucemia Mieloide Aguda/complicações , Meningite Viral/diagnóstico , Adulto , Antivirais/uso terapêutico , Citarabina/uso terapêutico , Diagnóstico Diferencial , Ganciclovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Stenotrophomonas maltophilia (S. maltophilia) bacteremia causes significant morbidity and mortality in immunocompromised hosts. However, incidence and risk factors for mortality in S. maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain controversial. The primary aim of this study is to clarify factors associated with poor prognosis of allo-HSCT recipients with S. maltophilia bacteremia. METHODS: From January 2005 to December 2014, patients with hematological diseases and S. maltophilia bacteremia at a single transplantation center in Japan were examined for incidence and 90-day mortality. Prognostic factors associated with 90-day mortality among allo-HSCT recipients were analyzed by log-rank test, and significant variables in the univariate analysis were included in the multivariate Cox proportional-hazards regression model. RESULTS: A total of 65 patients, including 47 patients undergoing allo-HSCT, developed S. maltophilia bacteremia. The incidence of S. maltophilia bacteremia was significantly higher in allo-HSCT recipients compared to patients not receiving allo-HSCT (6.53 vs. 0.36 per 100 admissions, respectively; p < 0.01). The overall 90-day mortality in allo-HSCT recipients was 43%. Independent risk factors for 90-day mortality were low serum albumin (<3.0 g/dl) (HR = 10.86; 95% CI, 3.27-36.12) and high serum C-reactive protein (CRP) (≥10.0 mg/dl) (HR = 3.28; 95% CI, 1.00-10.72). Among 9 patients with both high CRP and low albumin, 5 had pneumonia at the onset of bacteremia and the remaining 4 patients developed pneumonia in a median of 3 days (range, 1 to 8 days) even under effective treatment. All 9 patients eventually died in a median of 2 days (range, 2 to 32 days). The probabilities of developing pneumonia in patients with or without high CRP and low albumin levels were 100% (9/9) and 10.5% (4/38), respectively (p < 0.01). CONCLUSIONS: Allo-HSCT recipients had higher rates of S. maltophilia bacteremia than did patients not receiving allo-HSCT. High serum CRP and low serum albumin at the onset of bacteremia are predictive of disease progression to pneumonia and poor prognosis.
Assuntos
Proteína C-Reativa/análise , Infecções por Bactérias Gram-Negativas/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pneumonia/epidemiologia , Albumina Sérica Humana/análise , Stenotrophomonas maltophilia/imunologia , Adulto , Feminino , Infecções por Bactérias Gram-Negativas/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Hospedeiro Imunocomprometido , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Resultado do Tratamento , Adulto JovemAssuntos
Encéfalo/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/líquido cefalorraquidiano , Toxoplasmose Cerebral/patologia , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Ciclofosfamida/uso terapêutico , Febre/etiologia , Cefaleia/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Agonistas Mieloablativos/uso terapêutico , Reação em Cadeia da Polimerase , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/microbiologia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Vômito/etiologiaRESUMO
We herein report the case of a 25-year-old man who was referred to our hospital due to acute cytomegalovirus (CMV) colitis. The initial blood tests showed that the patient had concurrent primary human immunodeficiency virus (HIV) infection and severe thrombocytopenia. Raltegravir-based antiretroviral therapy (ART) was initiated without the use of ganciclovir or corticosteroids and resulted in a rapid clinical improvement. Platelet transfusions were only necessary for a short period, and subsequent colonoscopy revealed a completely healed ulcer. This case implies that ART alone could be effective for treating severe thrombocytopenia during primary HIV and CMV coinfection.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Colite/complicações , Colite/virologia , Infecções por Citomegalovirus/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Adulto , Coinfecção/tratamento farmacológico , Colite/tratamento farmacológico , Colonoscopia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir , Humanos , Masculino , Transfusão de Plaquetas , Raltegravir Potássico/uso terapêutico , Trombocitopenia/terapia , Resultado do TratamentoRESUMO
We herein report a 52-year-old man infected with human immunodeficiency virus (HIV) who was referred to our hospital due to the development of severe neurocognitive disorders and bilateral leukoencephalopathy. He has been treated with antiretroviral agents for 17 years, but low-level viremia has been detected consistently prior to admission. Drug resistant testing of the serum and the cerebrospinal fluid (CSF) both demonstrated a M184V mutation. A brain biopsy revealed perivascular CD8(+) T-lymphocyte infiltration, leading to the diagnosis of CD8 encephalitis. The clinical symptoms improved drastically after changing to a nucleoside reverse transcriptase inhibitor sparing regimen, which subsequently decreased the HIV viral load to an undetectable level in both the serum and CSF.
Assuntos
Linfócitos T CD8-Positivos/patologia , Encefalite/etiologia , Encefalite/patologia , Infecções por HIV/complicações , Adulto , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral Múltipla/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Humanos , Masculino , Carga Viral/efeitos dos fármacosRESUMO
We herein report a case of laryngeal Kaposi's sarcoma (KS) complicated by immune reconstitution inflammatory syndrome in a human immunodeficiency virus (HIV)-infected patient. The patient initially presented with KS involving the larynx, which was successfully treated with pegylated liposomal doxorubicin (PLD) and antiretroviral therapy (ART). PLD was discontinued after 2 courses because of a marked clinical improvement; however, the patient experienced progressive odynophagia and dyspnea 2 months after the initiation of ART. Laryngoscopy revealed a severely swollen, inflamed epiglottis. The readministration of PLD was successful, and the patient was thereafter discharged without any subsequent complications.
Assuntos
Infecções por HIV/complicações , Síndrome Inflamatória da Reconstituição Imune/etiologia , Neoplasias Laríngeas/etiologia , Sarcoma de Kaposi/etiologia , Adulto , Antirretrovirais/uso terapêutico , Antineoplásicos/uso terapêutico , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Neoplasias Laríngeas/tratamento farmacológico , Masculino , Polietilenoglicóis/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológicoRESUMO
We report a case of a 63-year-old HIV-positive Japanese male with a CD4 cell count of 127/µL who was admitted to our hospital because of suspected malignant lymphoma. Initial blood tests revealed anemia, thrombocytopenia, hypoalbuminemia, and hypergammaglobulinemia. Imaging tests revealed a lung nodule, bilateral pleural effusion, hepatosplenomegaly and generalized lymphadenopathy. No evidence of malignant lymphoma or multicentric Castleman's disease was noted on biopsy specimens; however, Kaposi sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen-1-positive cells were observed as well as an elevated interleukin (IL)-6, IL-10 and KSHV viral load. He fulfilled the novel diagnostic criteria for KSHV-associated inflammatory cytokine syndrome (KICS). After initiating antiretroviral therapy, his symptoms and radiological abnormalities drastically improved. After 1-year follow-up, his HIV was well controlled without any relapsing symptoms.
Assuntos
Antirretrovirais/uso terapêutico , Citocinas/imunologia , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 8 , Infecções por HIV/complicações , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS/HYPOTHESIS: Lineage conversion of non-beta cells into insulin-producing cells has been proposed as a therapy for the cure of diabetes. Glucagon-like peptide-1 (GLP-1) and its derivatives can induce beta cell neogenesis in vitro and beta cell mass expansion in vivo, but GLP-1 signalling has not been shown to regulate cell fate decisions in vivo. We therefore tested the impact of GLP-1 receptor (GLP1R) expression on beta cell differentiation in vivo. METHODS: Mice overexpressing GLP1R in pancreatic exocrine cells were generated by Cre-mediated recombination in sex-determining region Y-box 9 (SOX9)-expressing cells and then treated with exendin-4 and/or gastrin. Histological analysis was performed to detect cellular reprogramming from the exocrine lineage into insulin-producing cells. RESULTS: Whereas no newly generated beta cells were detected in the mice treated with exendin-4 alone, treatment with gastrin only induced the conversion of exocrine cells into insulin-producing cells. Furthermore, the overexpression of GLP1R, together with gastrin and exendin-4, synergistically promoted beta cell neogenesis accompanied by the formation of islet-like clusters. These newly generated beta cells expressed beta cell specific transcription factors, such as pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). These mice showed no histological evidence of pancreatitis or pancreatic dysplasia in their acini and had normal plasma amylase levels. CONCLUSIONS/INTERPRETATION: Activation of GLP-1 and gastrin signalling induces beta cell neogenesis in the exocrine lineage without any deleterious pancreatic changes, which may lead to a potential therapy to cure diabetes by generating surrogate beta cells.
Assuntos
Reprogramação Celular/fisiologia , Gastrinas/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Células Secretoras de Insulina/metabolismo , Pâncreas Exócrino/metabolismo , Transdução de Sinais/fisiologia , Animais , Reprogramação Celular/efeitos dos fármacos , Exenatida , Insulina/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Camundongos , Pâncreas Exócrino/citologia , Pâncreas Exócrino/efeitos dos fármacos , Peptídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Peçonhas/farmacologiaRESUMO
BACKGROUND: Cystatin C is an overall biomarker of pathophysiologic abnormalities that accompany chronic kidney disease (CKD). The utility of cystatin C is not fully understood in an HIV-infected population. METHODS: This prospective study investigated 661 HIV-infected individuals for 4 years to determine the incidence of adverse outcomes, including all-cause mortality, cardiovascular disease, and renal dysfunction. The risk of developing the outcomes was discriminated with a 4 color-coded classification in a 3 × 6 contingency table, that combined 3 grades of dipstick proteinuria with 6 grades of estimated glomerular filtration rate (eGFR) calculated using either serum creatinine (eGFRcr) or cystatin C (eGFRcy): green, low risk; yellow, moderately increased risk; orange, high risk; and red, very high risk. The cumulative incidence of the outcomes was assessed by the Kaplan-Meier method, and the association between color-coded risk and the time to outcome was evaluated using multivariate proportional hazards analysis. RESULTS: Compared with eGFRcr, the use of eGFRcy reduced the prevalence of risk ≥ orange by 0.8%. The adverse outcomes were significantly more likely to occur to the patients with baseline risk category ≥orange than those with ≤ yellow, independent of risk categories based on eGFRcr or eGFRcy. However, in multivariate analysis, risk category ≥orange with eGFRcy-based classification was significantly associated with adverse outcomes, but not the one with eGFRcr. CONCLUSIONS: Replacing creatinine by cystatin C in the CKD color-coded risk classification may be appropriate to discriminate HIV-infected patients at increased risk of a poor prognosis.
Assuntos
Creatinina/sangue , Cistatina C/sangue , Infecções por HIV/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/virologia , Adulto , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteinúria/virologia , Insuficiência Renal Crônica/fisiopatologiaRESUMO
While the exogenous expression of a combination of transcription factors have been shown to induce the conversion of non-ß cells into insulin-producing cells, the reprogramming efficiency remains still low. In order to develop an in vitro screening system for an optimized reprogramming protocol, we generated the reporter cell line mPac-MIP-RFP in which the reprogramming efficiency can be quantified with red fluorescent protein expressed under the control of the insulin promoter. Analysis with mPac-MIP-RFP cells sequentially infected with adenoviruses expressing Pdx1, Neurog3, and Mafa revealed that expression of Pdx1 prior to Neurog3 or Mafa augments the reprogramming efficiency. Next, infection with a polycistronic adenoviral vector expressing Pdx1, Neurog3 and Mafa significantly increased the expression level of insulin compared with the simultaneous infection of three adenoviruses carrying each transcription factor, although excessive expression of Mafa together with the polycistronic vector dramatically inhibited the reprogramming into insulin-producing cells. Thus, in vitro screening with the mPac-MIP-RFP reporter cell line demonstrated that the timing and dosage of gene delivery with defined transcription factors influence the reprogramming efficiency. Further investigation should optimize the reprogramming conditions for the future cell therapy of diabetes.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Reprogramação Celular , Proteínas de Homeodomínio/genética , Células Secretoras de Insulina/metabolismo , Fatores de Transcrição Maf Maior/genética , Proteínas do Tecido Nervoso/genética , Ductos Pancreáticos/citologia , Transativadores/genética , Adenoviridae/genética , Animais , Linhagem Celular , Regulação da Expressão Gênica , Vetores Genéticos/genética , Insulina/genética , Células Secretoras de Insulina/citologia , CamundongosRESUMO
We herein report the case of a 37-year-old type 1 diabetic pregnant woman treated with an insulin pump. Although the patient's glycemic control deteriorated following progesterone treatment for the prevention of preterm delivery and miscarriage, it was improved by adjusting the basal insulin rate on the days of progesterone treatment. Excess progesterone is known to impair both insulin sensitivity and secretion. The present case is the first report to evaluate deterioration of glycemic control induced by progesterone treatment and to determine the dose of insulin required in a type 1 diabetic pregnant woman whose insulin secretion was completely depleted.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Gravidez em Diabéticas/tratamento farmacológico , Progesterona/uso terapêutico , Adulto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Relação Dose-Resposta a Droga , Feminino , Humanos , Projetos Piloto , Gravidez , Gravidez em Diabéticas/sangue , Resultado do TratamentoRESUMO
We herein describe a 59-year-old woman who had undergone a total gastrectomy for gastric carcinoma and suffered from postprandial hypoglycemia characterized by a loss of consciousness and spasms. She was diagnosed with reactive hypoglycemia and treated with nutrition therapy, but the frequency and severity of the hypoglycemic episodes did not decrease. She was subsequently treated successfully with miglitol, an alpha-glucosidase inhibitor (α-GI) taken twice a day; other α-GIs (acarbose and voglibose) were not effective. In conclusion, the administration of miglitol was effective for preventing reactive hypoglycemia secondary to late dumping syndrome.
Assuntos
1-Desoxinojirimicina/análogos & derivados , Síndrome de Esvaziamento Rápido/complicações , Hipoglicemia/tratamento farmacológico , Hipoglicemia/etiologia , 1-Desoxinojirimicina/uso terapêutico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/uso terapêutico , Feminino , Inibidores de Glicosídeo Hidrolases , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
We herein report the case of a 41-year-old male patient with an incidentally identified large adrenal ganglioneuroma (GN). His endocrine examinations were normal except for one episode of elevated urinary dopamine and noradrenaline levels. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a large solid tumor with calcifications and a slightly lobular edge in the right adrenal gland. We performed open tumor excision and diagnosed it as adrenal ganglioneuroma. Adrenal GN is a rare benign tumor, and its hormonal activity and imaging characteristics are occasionally very similar to those of other adrenal tumors. Therefore, it needs careful evaluation by endocrine examinations and multiple imaging procedures to rule out other types of tumors.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Ganglioneuroma/diagnóstico , Ganglioneuroma/patologia , Achados Incidentais , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Biomarcadores Tumorais/urina , Dopamina/urina , Ganglioneuroma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Norepinefrina/urina , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We report a case of a 45-year-old Japanese man with AIDS-associated Kaposi's sarcoma (KS) involving skin, liver, and lungs. Antiretroviral therapy was started in conjunction with pegylated liposomal doxorubicin (PLD). A clinical response was observed initially, but symptoms recurred following cessation of medication. The chemotherapeutic agent was changed to paclitaxel (PTX), since the therapeutic response to PLD was reduced and the total dose reached the maximum dose of 500 mg/m2. The patient had a good response to PTX and tolerated the medication well. Symptoms did not recur after completing 8 courses of chemotherapy. PTX should be considered as an alternative agent in treating KS when there are problems with the use of PLD.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Paclitaxel/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Doxorrubicina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , PolietilenoglicóisRESUMO
We encountered a case of plasmablastic extramedullary plasmacytoma with multiple myeloma. Histological findings revealed that the extramedullary plasmacytoma of this patient was of the plasmablastic type, which was positive for λ-stain and EBV-encoded RNA. In contrast, bone marrow aspiration demonstrated a common-type multiple myeloma, which was positive for λ-stain and negative for EBV-encoded RNA. This was a rare case of plasmablastic extramedullary plasmacytoma associated with Epstein-Barr virus arising in an immunocompetent patient with multiple myeloma.