RESUMO
PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.
Assuntos
Neoplasias Colorretais , Neoplasias Gástricas , Humanos , Masculino , Idoso , Feminino , Neoplasias Gástricas/terapia , Reparo de Erro de Pareamento de DNA , Proteína 1 Homóloga a MutL , Neoplasias Colorretais/patologia , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Pulmonary metastasis (M1-PUL) as first site of dissemination in pancreatic ductal adenocarcinoma (PDAC) is a rare event and may define a distinct biological subgroup. PATIENTS AND METHODS: Arbeitsgemeinschaft Internistische Onkologie-Young Medical Oncologists-Pankreas-0515 study (AIO-YMO-PAK-0515) was a retrospective German multicenter study investigating clinical and molecular characteristics of M1-PUL PDAC patients; 115 M1-PUL PDAC patients from 7 participating centers were included. Clinical characteristics and potential prognostic factors were defined within the M1-PUL cohort. Archival tumor samples were analyzed for Her2/neu, HNF1A and KRT81 expression. Additionally, messenger RNA (mRNA) expression analysis (using a 770-gene immune profiling panel) was carried out in the M1-PUL and in a control cohort (M1-ANY). RESULTS: Median overall survival in the entire M1-PUL cohort was 20 months; the most favorable prognosis (median survival: 28 months) was observed in the subgroup of 66 PDAC patients with metachronous lung metastases after previous curative-intent surgery. The number of metastatic lesions, uni- or bilateral lung involvement as well as metastasectomy were identified as potential prognostic factors. Her2/neu expression and PDAC subtyping (by HNF1A and KRT81) did not differ between the M1-PUL and the M1-ANY cohort. mRNA expression analysis revealed significant differentially expressed genes between both cohorts: CD63 and LAMP1 were among the top 20 differentially expressed genes and were identified as potential mediators of organotropism and favorable survival outcome of M1-PUL patients. CONCLUSION: M1-PUL represents a clinically favorable cohort in PDAC patients. Site of relapse might already be predetermined at the time of surgery and could potentially be predicted by gene expression profiling.
Assuntos
Neoplasias Pulmonares , Neoplasias Pancreáticas , Biologia , Humanos , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Endoscopy has a key role in establishing the diagnosis of eosinophilic esophagitis (EoE), but endoscopic features of EoE might not be well known. METHODS: All patients aged 18 or older who were diagnosed with EoE from 2008 to 2013 were systematically identified retrospectively and findings at esophago-gastro-duodenoscopy (EGD) were reviewed by two experienced endoscopists through a query of the university hospital database. Patients in whom biopsies from the esophagus were lacking or inadequate for histopathological examination were excluded. RESULTS: 23 patients (17 male, 6 female) were included into the study (median age: 38 years, range: 19 to 71 years). Patients presented with the following symptoms: 12 (52â%) had bolus obstruction and 18 (78â%) dysphagia and/or chest pain. At EGD, 22 of 23 (96â%) patients were observed with at least one endoscopic feature of EoE, i.âe., mucosal edema (52â%), longitudinal furrows (57â%), vertical furrows (48â%), or crêpe paper esophagus (52â%). CONCLUSIONS: Typical endoscopic features were present in most patients in whom EoE was diagnosed. Recognizing typical characteristics of EoE is substantial for establishing the diagnosis and for taking biopsies.
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Esofagite Eosinofílica/patologia , Esofagoscopia/métodos , Esôfago/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Proton pump inhibitors (PPI) are widely used in patients with liver diseases. Within the last years, there have been concerns about the PPI use as they may promote infections in patients with cirrhosis. AIM: As there are sparse data of the prognostic relevance of PPI treatment, to perform a prospective study investigating the relation of PPI treatment and overall survival (OS) in cirrhotic individuals. METHODS: Patients with cirrhosis were enrolled and followed prospectively. The primary end point was OS. PPI treatment and additional clinical and laboratory data were assessed at the day of the study inclusion. The time until the end point death was assessed and the individual risks were calculated with Cox regression analyses. RESULTS: A total of 272 patients were included and 213 individuals (78.3%) were on PPI treatment. In multivariate logistic regression analysis, PPI treatment was associated with higher MELD scores (P = 0.027) and ascites (P = 0.039). In a multivariate Cox regression model, PPI use was an independent predictor of mortality (hazard ratio 2.330, 95% confidence interval 1.264-4.296, P = 0.007) in addition to the model of end-stage liver disease (MELD) score, hepatocellular carcinoma and hepatic decompensation. CONCLUSIONS: PPI use is an independent risk factor for mortality in patients with cirrhosis. Although a causative role for increased mortality in patients taking PPI is still missing, the prescription of PPI in cirrhotics should be considered carefully taking into account its potential adverse effects.
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Cirrose Hepática/mortalidade , Inibidores da Bomba de Prótons/efeitos adversos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/epidemiologia , Feminino , Alemanha , Humanos , Incidência , Cirrose Hepática/epidemiologia , Cirrose Hepática/microbiologia , Hepatopatias/microbiologia , Hepatopatias/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
Soluble CD163 (sCD163), a marker for macrophage activation, was found to be associated with the severity of liver cirrhosis. The aim of the current study was to investigate whether serum sCD163 levels correlate with liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection. In a retrospective cohort study, serum sCD163 levels were assessed by ELISA together with clinical and laboratory data in 186 patients with chronic HBV infection and 15 healthy controls. The relation between parameters for liver fibrosis and necroinflammation and sCD163 levels was analysed. Additionally, sCD163 was quantified in a subset of follow-up serum samples after initiation of antiviral treatment. sCD163 levels differed among phases of chronic HBV infection (P < 0.0001), and sCD163 concentrations were associated with inflammatory activity and fibrosis in the liver. sCD163 levels ≥ 1961 ng/l had a high specificity in the identification of subjects with substantial fibrosis (F ≥ 2). sCD163 concentrations decreased significantly after initiation of antiviral treatment. The correlation of sCD163 levels with necroinflammation and fibrosis and the sCD163 decline under treatment indicates that macrophage activation plays a role in HBV-related liver pathogenesis.
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Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Biomarcadores/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Receptores de Superfície Celular/sangue , Adolescente , Adulto , Idoso , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B Crônica/imunologia , Humanos , Cirrose Hepática/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Vitamin D is involved in many biological processes. The role of vitamin D in patients with hepatocellular carcinoma (HCC) remains inconclusive, although there is evolving evidence that vitamin D may modulate cancer development and progression. AIM: To evaluate serum vitamin D as prognostic parameter in HCC, we performed a prospective cohort study. METHODS: HCC patients were prospectively recruited and 25-hydroxyvitamin D3 (25(OH)D3 ) levels were determined. 25(OH)D3 levels were compared to stages of cirrhosis and HCC stages with nonparametric Kruskal-Wallis tests and Spearman correlations in 200 HCC patients. The association of the 25(OH)D3 levels and overall survival (OS) was assessed in uni- and multivariate Cox regression models. RESULTS: Two-hundred patients with HCC were included. The mean follow-up time was 322 ± 342 days with a range of 1-1508 days. Nineteen patients underwent liver transplantation and 60 patients died within the observation time. The mean serum 25(OH)D3 concentration was 17 ± 13 ng/mL with a range of 1-72 ng/mL. 25(OH)D3 serum levels negatively correlated with the stage of cirrhosis as well as with stages of HCC. Patients with severe 25(OH)D3 deficiency had the highest mortality risk (hazard ratio 2.225, 95% confidence interval 1.331-3.719, P = 0.002). Furthermore, very low 25(OH)D3 levels were associated with mortality independently from the MELD score and high alpha-Fetoprotein levels (>400 ng/mL) in a multivariate Cox regression model. CONCLUSIONS: We conclude that 25(OH)D3 deficiency is associated with advanced stages of hepatocellular carcinoma and it is a prognostic indicator for a poor outcome.
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Calcifediol/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Deficiência de Vitamina D/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Humanos , Cirrose Hepática/complicações , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Deficiência de Vitamina D/epidemiologia , alfa-Fetoproteínas/metabolismoRESUMO
miR-122 is a liver-specific microRNA, which also circulates in the blood. The levels of miR-122 in serum and plasma correlate with hepatic necroinflammation in patients with hepatitis B virus (HBV) infection. Here, we investigated whether miR-122 levels correlate with surrogate markers for viral replication and translation. Furthermore, we examined whether miR-122 levels differ in the different groups of HBV-infected patients and whether miR-122 levels may be useful to identify patients with higher or lower risk for liver disease progression. Therefore, RNA was extracted from sera of therapy-naïve patients with HBV infection (n = 89) and from healthy volunteers (n = 19). The concentration of miR-122 was assessed by quantitative real-time reverse-transcription PCR. HBs antigen and HBV DNA levels were quantified as surrogate parameters for HBV replication and translation. Liver biopsies were examined according to the histological activity index and the degree of fibrosis was assessed. We found that the miR-122 serum concentration correlated with the level of ALT, HBV DNA and HBs antigen (r = 0.259, P < 0.05; r = 0.225, P < 0.05; r = 0.508, P < 0.001, respectively). The miR-122 serum levels discriminated the different patient groups infected with HBV from healthy subjects (P < 0.001), and inactive carrier patients with high (>3500 IU/mL) or low (<3500 IU/mL) levels of HBs antigen could be differentiated by the miR-122 serum concentration (P < 0.05). As serum miR-122 levels strongly correlated with HBs antigen, it might be an indicator for viral translation. Furthermore, serum miR-122 levels discriminated HBV carrier patients with high or low risk for disease progression and may, thus, be an additional marker for risk stratification.
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Biomarcadores/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/fisiopatologia , MicroRNAs/sangue , Adulto , Biópsia , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/patologia , Histocitoquímica , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Soro/químicaRESUMO
Granulocytic sarcoma (GS) occurs in patients with chronic myeloproliferative disorders as well as in patients with acute myeloid leukemia (AML). These tumorous masses can occur anywhere in the body and have to be differentiated from lymphoma, carcinoma or infectious processes. We report the results of fine-needle aspiration cytology (FNAC) in 26 patients with GS. Seventeen patients suffered from AML and 9 from chronic myeloid leukemia (CML) blast crisis. In 5 patients with AML, GS was the initial presentation of hematological malignancy, in the remaining 21 patients, FNAC confirmed relapse of AML or extramedullary blast crisis of CML. In 8 patients, GS was located in the skin, in 17 in the lymph node and in another patient in the spinal canal. This study demonstrates the clinical utility and diagnostic accuracy of FNAC in the evaluation of GS from multiple sites.
Assuntos
Biópsia por Agulha , Leucemia Mieloide/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Crise Blástica/diagnóstico , Carcinoma/diagnóstico , Diagnóstico Diferencial , Estudos de Avaliação como Assunto , Feminino , Humanos , Leucemia Mieloide/patologia , Leucemia Mieloide de Fase Acelerada/diagnóstico , Linfonodos/patologia , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva , Neoplasias Cutâneas/diagnóstico , Canal MedularRESUMO
OBJECTIVE: Extramedullary plasmacytoma is a rare plasma cell neoplasm. It can occur as the sole manifestation of plasma cell neoplasm, as a metastasis from another extramedullary plasmacytoma, as a solitary plasmacytoma of the bone or as a consequence of multiple myeloma. These plasma cell tumors can occur anywhere and have to be differentiated from other neoplasms, infectious processes and chloroma. STUDY DESIGN: We report the findings of fine needle aspiration cytology (FNAC) in 18 patients with extramedullary plasmacytoma. In six patients extramedullary plasmacytoma was the initial presentation of plasma cell neoplasm. In the remaining 12 patients the tumors occurred under or after treatment of plasma cell disease. RESULTS: Eleven lesions were located in the skin, seven in the lymph nodes, one in the liver and another in the spleen. Two patients with known diagnoses of plasma cell disease were thought, before FNAC, to have an infection, and two had a histologic diagnosis of non-Hodgkin's lymphoma. In 13 of 18 patients, cytologic smears showed anaplastic plasma cells. CONCLUSION: FNAC is a front-line investigative procedure in diagnosing extramedullary plasmacytoma.