RESUMO
The identification of immune cell profiles (ICP) involved in anti-tumor immunity is crucial for immunotherapy. Therefore, we herein investigated cholangiocarcinoma patients (CCA) who received adoptive T-cell immunotherapy (ATI). Eighteen unresectable or recurrent CCA received ATI of αß T cells alone or combined with chemotherapy. ICP were evaluated by flow cytometry. There were 14 patients with intrahepatic cholangiocarcinoma (iCCA) and four with distal cholangiocarcinoma (dCCA). After one course of treatment, nine iCCA and four dCCA had progressive disease (PD), while five iCCA had stable disease (SD). Median overall survival (OS) was prolonged to 21.9 months. No significant differences were observed in OS between the PD and SD groups of iCCA. The frequency of helper T cells (HT) in iCCA decreased from 70.3% to 65.5% (P = .008), while that of killer T cells (KT) increased from 27.0% to 30.6% (P = .005). dCCA showed no significant changes of immune cells. OS was prolonged in iCCA with increased frequencies of CD3+ T cells (CD3) (P = .039) and αß T cells (αß) (P = .039). dCCA showed no immune cells associated with OS. The frequencies of CD3+ T cells and αß T cells in the PD group for iCCA decreased from 63.5% to 53% (P = .038) and from 61.6% to 52.2% (P = .028), respectively. In the SD group, the frequency of HT decreased from 65.8% to 56.9% (P = .043), whereas that of KT increased from 30.1% to 38.3% (P = .043). In conclusions, ATI affected ICP and prolonged OS. Immune cells involved in treatment effects differed according to the site of cholangiocarcinoma.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/terapia , Prognóstico , Imunoterapia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologiaRESUMO
Patients infected with hepatitis C virus (HCV) have an increased risk of developing type 2 diabetes. HCV infection is linked to various liver abnormalities, potentially contributing to this association. We show that HCV infection increases the levels of hepatic selenoprotein P (SeP) mRNA (SEPP1 mRNA) and serum SeP, a hepatokine linked to insulin resistance. SEPP1 mRNA inhibits type I interferon responses by limiting the function of retinoic-acid-inducible gene I (RIG-I), a sensor of viral RNA. SEPP1 mRNA binds directly to RIG-I and inhibits its activity. SEPP1 mRNA knockdown in hepatocytes causes a robust induction of interferon-stimulated genes and decreases HCV replication. Clinically, high SeP serum levels are significantly associated with treatment failure of direct-acting antivirals in HCV-infected patients. Thus, SeP regulates insulin resistance and innate immunity, possibly inducing immune tolerance in the liver, and its upregulation may explain the increased risk of type 2 diabetes in HCV-infected patients.
Assuntos
Proteína DEAD-box 58/antagonistas & inibidores , Hepatite C/patologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , RNA Mensageiro/metabolismo , Selenoproteína P/biossíntese , Humanos , Receptores ImunológicosRESUMO
BACKGROUND: FOLFIRINOX (FFX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have recently been available for treating pancreatic ductal adenocarcinoma (PDAC). We investigated trends in characteristics, treatment and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. METHODS: We retrospectively reviewed the medical records of 1085 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in the Hokuriku area between January 2009 and July 2015. RESULTS: The incidence of pathologically proven PDAC had increased from 18.7% in 2009 to 56.2% in 2015. Oncological therapy was administered to 779 patients (71.8%): chemotherapy (n = 675), chemo-radiotherapy (n = 92) or radiotherapy (n = 12); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 30.7% of the 75 patients diagnosed in 2015 received FFX, 25.3% GnP, 22.7% GEM and 17.3% S-1. The objective response rates of patients treated with FFX, GnP and GEM were 14.9%, 35.0% and 5.5%, respectively and the OS 10.3, 9.9 and 7.5 months after FFX, GnP and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 70.2%, 70.0% and 18.8% of the patients treated with FFX, GnP and GEM, respectively. The reasons for treatment discontinuation were adverse events in 9.8%, 26.7% and 24.1% of the patients treated with FFX, GnP and GEM, respectively. CONCLUSION: Chemotherapeutic protocols changed dramatically between 2009 and 2015. Continuous collection and analysis for our cohort with longer follow-up provides useful information about treatment selection and prediction of outcome.
Assuntos
Neoplasias Pancreáticas/cirurgia , Padrões de Prática Médica , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 29-year-old man with ulcerative colitis presented to the hospital complaining of persistent back pain. Pancreatic enzymes and tumor markers were elevated; imaging showed diffuse narrowing of the main pancreatic duct associated with diffuse pancreatic enlargement. We therefore performed an endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy of the pancreas using a 19-gauge needle. Histopathology revealed interlobular fibrosis, neutrophil infiltration in the intralobular ducts and acini, and very few immunoglobulin G4-positive cells. The patient was diagnosed with type 2 autoimmune pancreatitis and started on oral steroids; subsequently, we observed an improvement in the pancreatic enlargement and duct narrowing. Histologically proven type 2 autoimmune pancreatitis is rare in Japan.
Assuntos
Doenças Autoimunes/patologia , Pancreatite/patologia , Adulto , Doenças Autoimunes/tratamento farmacológico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Masculino , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
We report the case of an 80-year-old female suffering from pancreatic cancer who developed severe non-alcoholic steatohepatitis (NASH) resulting in fatal hepatic failure after anti-cancer chemotherapy with gemcitabine. Hepatic encephalopathy appeared 1 year after the chemotherapy, and the patient developed progressive liver failure and eventually died. Radiological examination showed severe fatty liver. Histopathological examination of a liver needle necropsy showed almost panlobular macrovesicular fatty change. Ballooning degeneration and necrosis of hepatocytes accompanying neutrophil infiltration, Mallory bodies, and a few bile plugs were found in zone 3. Marked perivenular and pericellular/perisinusoidal fibrosis and extensive bridging fibrosis were also found. Together, these findings indicated steatohepatitis at a precirrhotic stage. Because the patient had no history of drinking in excess, we made a diagnosis of NASH, in particular, chemotherapy-associated steatohepatitis (CASH). Gemcitabine is a pyrimidine nucleoside antimetabolite with anti-cancer activity. A few reports have mentioned fatal hepatotoxicity caused by gemcitabine, but, to our knowledge, this is the first report of steatohepatitis, possibly associated with gemcitabine. Physicians treating patients with this drug should be aware of the possibility of steatohepatitis.
RESUMO
We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically.
Assuntos
Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Ductos Pancreáticos , Pancreatite/sangue , Pancreatite/diagnóstico , Adulto , Idoso , Anticorpos Antinucleares/sangue , Doenças Autoimunes/terapia , Estudos de Casos e Controles , Doença Crônica , Constrição Patológica/sangue , Constrição Patológica/diagnóstico , Constrição Patológica/terapia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pancreatite/terapia , Resultado do Tratamento , gama-Globulinas/metabolismoRESUMO
We treated a patient with recurrent ovarian cancer with cancerous peritonitis by weekly paclitaxel (w-TXL) therapy (65 mg/m2). Abdominocentesis was not performed to eliminate ascites, in order to maintain higher quality of life (QOL), and critical adverse reaction was not seen for 12 months. We measured the TXL concentration in blood plasma and ascites after TXL infusion by HPLC method. The TXL titer in plasma was 427 ng/ml after infusion, 23 ng/ml after 24 hours and under 10 ng/ml after 48 hours. The TXL titer in ascites was 41 ng/ml after infusion, 37 ng/ml after 6 hours, 18 ng/ml after 12 hours, 10 ng/ml after 24 hours and under 10 ng/ml after 48 hours. TXL transportation from blood to ascites was good. This result suggested that intravenous infusion of TXL was effective for cancerous peritonitis treatment.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Peritonite/tratamento farmacológico , Adenocarcinoma/metabolismo , Antineoplásicos Fitogênicos/farmacocinética , Líquido Ascítico/química , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacocinética , Qualidade de VidaRESUMO
It is well known that neuropathy, myelopathy, and arthropathy are specific adverse effects induced by paclitaxel administration. Parkinson's disease is neural degenerative disease, and the influence of paclitaxel administration on patients with Parkinson's disease is unknown. We have successfully treated an ovarian cancer patient with Parkinson's disease by paclitaxel/CBDCA combined chemotherapy after surgery. The patient was a 57-year-old woman with solid and cystic ovarian tumor. Among the tumor markers CA125, CA19-9, and SLX, only SLX was elevated. We operated and made a pathological diagnosis of the ovarian tumor as clear cell adenocarcinoma (FIGO stage Ic). After surgery, the patient was treated with paclitaxel (260 mg [175 mg/m2]) and CBDCA (600 mg [AUC = 5]) combined chemotherapy for 5 courses. Her status is complete remission. During chemotherapy, she had felt the decreased efficacy of her Parkinson's disease medication. We could continue chemotherapy by increasing the dose of the Parkinson's drug. There is only one case report on the influence of paclitaxel on Parkinson's disease, in which the course was similar to the present case.
Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Doença de Parkinson/complicações , Adenocarcinoma de Células Claras/complicações , Adenocarcinoma de Células Claras/cirurgia , Antiparkinsonianos/administração & dosagem , Área Sob a Curva , Carboplatina/administração & dosagem , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Ovariectomia , Paclitaxel/administração & dosagem , Doença de Parkinson/tratamento farmacológicoRESUMO
Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis, and the development of new therapeutic strategies is necessary. Here we report the efficacy of combination chemotherapy in our biochemical modulation. Synergistic effects of interferon-alpha-2b on 5-fluorouracil or cisplatin were demonstrated in Huh7 cells. The efficacy of methotrexate-5-fluorouracil, cisplatin, and interferon-alpha-2b combination therapy was demonstrated in 34 patients with HCC complicated by major portal vein thrombosis. Among the 29 patients eligible for the study, there were 3 complete responders and 10 partial responders with an overall response rate of 45%. The 2-year survival of the 34 patients was 15%, and the median survival of complete and partial responders was 11 months. There was severe transient hematological toxicity. Eight patients suffered from renal insufficiency, and 4 of them underwent hemodialysis. Although a control study is clearly necessary, our combination therapy induced a good response in the patients with advanced HCC. On the basis of our results, intensive chemotherapy should be attempted in advanced HCC complicated by major portal vein invasion.