RESUMO
BACKGROUND: The impact of preoperative body composition as independent predictor of prognosis for esophageal cancer patients after esophagectomy is still unclear. The aim of the study was to explore such a relationship. METHODS: This is a multicenter retrospective study from a prospectively maintained database. We enrolled consecutive patients who underwent Ivor-Lewis esophagectomy in four Italian high-volume centers from May 2014. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), and subcutaneous fat area (SFA) were determined based on CT images. Perioperative variables were systematically collected. RESULTS: After exclusions, 223 patients were enrolled and 24.2% had anastomotic leak (AL). Sixty-eight percent of patients were sarcopenic and were found to be more vulnerable in terms of postoperative 90-day mortality (p = 0.028). VFA/TAMA and VFA/SFA ratios demonstrated a linear correlation with the Clavien-Dindo classification (R = 0.311 and 0.239, respectively); patients with anastomotic leak (AL) had significantly higher VFA/TAMA (3.56 ± 1.86 vs. 2.75 ± 1.83, p = 0.003) and VFA/SFA (1.18 ± 0.68 vs. 0.87 ± 0.54, p = 0.002) ratios. No significant correlation was found between preoperative BMI and subsequent AL development (p = 0.159). Charlson comorbidity index correlated significantly with AL (p = 0.008): these patients had a significantly higher index (≥ 5). CONCLUSION: Analytical morphometric assessment represents a useful non-invasive tool for preoperative risk stratification. The concurrent association of sarcopenia and visceral obesity seems to be the best predictor of AL, far better than simple BMI evaluation, and potentially modifiable if targeted with prehabilitation programs.
Assuntos
Neoplasias Esofágicas , Sarcopenia , Humanos , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Estudos Retrospectivos , Composição Corporal , Neoplasias Esofágicas/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaAssuntos
Pancreatectomia , Neoplasias Pancreáticas , Humanos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Fístula Pancreática/diagnóstico por imagem , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Medição de Risco , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Fatores de Risco , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgiaRESUMO
INTRODUCTION: Liver steatosis (LS) has been increasingly described in preoperative imaging of patients undergoing pancreaticoduodenectomy (PD). The aim of this study was to assess the impact of preoperative LS on complications after PD and identify possible contributors to LS development in this specific cohort. METHODS: Pancreatic head adenocarcinoma (PDAC) patients scheduled for PD, with preoperative CT-imaging available were included in the study. LS was defined as mean liver density lower than 45 Hounsfield units. Patients showing preoperative LS were matched for patient age, gender, BMI, ASA score, neoadjuvant treatment, and vascular and multivisceral resections, based on propensity scores in a 1:2 ratio to patients with no LS. The primary outcome was postoperative complication severity at 90 days as measured by the comprehensive complication index (CCI) RESULTS: Overall, 247 patients were included in the study. Forty-three (17%) patients presented with LS at preoperative CT-scan. After matching, the LS group included 37 patients, whereas the non-LS group had 74 patients. LS patients had a higher mean (SD) CCI, 29.7 (24.5) versus 19.5 (22.5), p = 0.035, and a longer length of hospital stay, median [IQR] 12 [8-26] versus 8 [7-13] days, p = 0.006 compared with non-LS patients. On multivariate analysis, variables independently associated with CCI were: LS (16% increase, p = 0.048), male sex (19% increase, p = 0.030), ASA score ≥ 3 (26% increase, p = 0.002), fistula risk score (FRS) (28% increase for each point of FRS, p = 0.001) and vascular resection (20% increase, p = 0.019). CONCLUSION: Preliminary evidence suggests that preoperative LS assessed by CT-scan influences complication severity in patients undergoing PD for PDAC.
Assuntos
Adenocarcinoma , Fígado Gorduroso , Neoplasias Pancreáticas , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Humanos , Masculino , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias PancreáticasRESUMO
PURPOSE: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020-December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. RESULTS: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1-18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6-96.9), a specificity of 95.6% (95% CI: 90.6-98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3-92.3), a negative PV of 97.1% (95% CI: 74.6-96.9) and an accuracy of 94.2% (95% CI: 89.6-97.2) in predicting PMD/PNX (AUC:0.924). CONCLUSIONS: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.
Assuntos
COVID-19 , Enfisema Mediastínico , Pneumotórax , Síndrome do Desconforto Respiratório , Estudos de Casos e Controles , Humanos , Enfisema Mediastínico/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem , SARS-CoV-2RESUMO
Chronic hepatitis C virus (HCV) infection is the most frequent cause of progressive liver disease and liver cancer in the West. The p53 tumor suppressor gene is known to play an important role in carcinogenesis of different tissues being involved in gene transcription, DNA synthesis and repair and somatic mutations of p53 are common in primary liver cancer. The p53 gene displays a common genetic Arg/Pro polymorphism at codon 72 with functional significance, that has been investigated as risk factor in several cancer models. We analyzed p53 codon 72 polymorphism in a group of 340 HCV-infected subjects at different stages of disease, including 84 hepatocellular carcinoma patients. No association between codon 72 genotypes and disease severity or liver cancer was observed.
Assuntos
Carcinoma Hepatocelular/genética , Genes p53/genética , Hepacivirus/patogenicidade , Hepatite C/complicações , Cirrose Hepática/genética , Polimorfismo Genético , Idoso , Carcinoma Hepatocelular/virologia , Códon/genética , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Hepatite C/genética , Humanos , Cirrose Hepática/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Hepatitis C virus (HCV) shows remarkable genetic variation in both populations and individuals, in whom it circulates as quasispecies (QS). Sequence variation within an infected host has adaptive significance and reflects the modes and intensity of selection mechanisms operating on the virus. We investigated the sequence diversity of hypervariable region 1 of HCV in liver transplant recipients and correlated it with the recurrence of hepatitis. Twenty-six patients were considered during a 2-year period; all had graft reinfection, and 14 patients developed hepatitis recurrence. Cloned sequences were obtained from sera collected before or within 1 month after orthotopic liver transplantation (OLT) and at 3 and 24 months thereafter. Sequence diversity within single sera and over consecutive samples was analyzed quantitatively by matrix comparison and phylogenetic analysis. Propagation of viral QS in the graft was markedly dependent on individual factors. Viral QS in post-OLT sera were less complex and evolved slower compared with immunocompetent subjects with chronic hepatitis. Sequence variation was greater during the first 3 months post-OLT than during the remaining period. Genetic diversity within single samples was not related to hepatitis recurrence or other clinical features. Conversely, sequence diversity over consecutive samples was reduced in patients who experienced hepatitis recurrence, in particular, in those infected with genotype 1b and with an HLA-DR mismatched graft. Selection of viral sequences was markedly impaired in liver transplant recipients and tended to be greater early after OLT. Reduced sequence turnover correlated negatively with the outcome of graft reinfection.
Assuntos
Hepacivirus/genética , Hepatite C Crônica/cirurgia , Hepatite C Crônica/virologia , Transplante de Fígado , Proteínas Virais/genética , Adulto , Clonagem Molecular , Feminino , Hepacivirus/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Complicações Pós-Operatórias/virologia , Recidiva , Replicação ViralRESUMO
BACKGROUND/AIMS: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5alpha-reductase type II (SRD5A2), cytochrome P450c17alpha (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease. METHODS: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category. RESULTS: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2%, odds ratio (OR): 2.29, P: 0.05). Females mostly contributed to this association (OR: 4.95, P: 0.01) and OR values increased in post-menopausal women (OR: 6.00, P: 0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms. CONCLUSIONS: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.
Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Hepatite C/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Esteroide 17-alfa-Hidroxilase/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Adulto , Idoso , Catecol O-Metiltransferase/genética , Estudos Transversais , Feminino , Genótipo , Heterozigoto , Humanos , Cirrose Hepática/genética , Masculino , Menopausa/genética , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Caracteres SexuaisRESUMO
Cancer risk can be influenced by the exposure to endogenous or environmental toxins. Polymorphic enzymes involved in the metabolic activation/detoxification of carcinogens may account for individual variations of risk. We studied the polymorphisms of five enzymes of the P450 superfamily, CYP1A1, CYP1A2, CYP2D6, CYP2E1 and CY3A4, as risk factors for liver disease progression and cancer in hepatitis C virus-infected patients. CYP genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism or allele-specific PCR. Different stages of disease were considered, as follows: 90 asymptomatic carriers and 87 chronic hepatitis, 92 cirrhosis and 91 hepatocellular carcinoma (HCC) cases. Reference allele frequencies were obtained from 99 blood donors. Allele distributions among categories were compared using the chi(2) test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to express relative risks. Independent associations were modeled by correspondence analysis and logistic regression. Frequencies of the CYP1A1 highly inducible alleles, MspI m2 and Val, were increased in liver disease patients compared with carriers; no specific association with HCC was found. The high-activity CYP2E1 c2 allele was underrepresented among HCC patients with respect to other HCV categories, including cirrhosis. CYP2D6 poor metabolizer (PM) genotypes were significantly more frequent in healthy subjects (7.1%) and carriers (11.1%) than in hepatitis/cirrhosis (4.6%) and HCC (1.2%) patients. This was confirmed by multivariable analysis. PM genotypes protected against progressive disease as ORs reduced proportionally to stage. The age at diagnosis for HCC was anticipated in non-PM individuals. No differences were seen for CYP1A2 and CYP3A4 genes. Polymorphic variants of CYP genes may contribute to the progression of liver disease and HCC risk in HCV-infected subjects.
Assuntos
Carcinoma Hepatocelular/enzimologia , Sistema Enzimático do Citocromo P-450/genética , Hepatite C Crônica/enzimologia , Cirrose Hepática/enzimologia , Neoplasias Hepáticas/enzimologia , Polimorfismo Genético/genética , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Predisposição Genética para Doença/genética , Genótipo , Hepacivirus/patogenicidade , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Factors influencing the progression of liver disease and the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection are poorly understood. Inherited variations of drug-metabolizing enzyme (DME) activities may affect liver damage and cancer risk by modifying individual susceptibility to endogenous or exogenous toxic compounds. We investigated the association of liver disease severity with common alleles of microsomal epoxide hydrolase (mEH), an enzyme involved in the metabolism of highly reactive epoxide intermediates. Three polymorphisms (Tyr113His, His139Arg, and -613C/T) were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphisms (RFLPs) in 394 patients at different stages of disease, including 92 asymptomatic carriers, 109 patients with chronic hepatitis, 100 patients with cirrhosis, and 93 patients with HCC. Reference allele frequencies were obtained from 99 healthy blood donors. Allele distributions between categories were compared using the chi(2) test; odds ratios (ORs) and 95% CI were calculated to express relative risks. Allele frequencies among 99 healthy controls were as follows: 15.1% for 113His/His, 4.0% for 139Arg/Arg, and 46.5% for -613C/T. mEH 113His/His homozygotes were overrepresented in advanced stages of disease, in particular among HCC patients (27.9%; P =.03; OR, 2.2; 95% CI, 1.0-4.6). Differences were more pronounced among men and between extreme patient categories. When mEH genotypes were combined to express a metabolic phenotype, very slow metabolizers were highly prevalent among cirrhotic and HCC patients (18% vs. 3.3% in carriers; P <.001). In conclusion, mEH gene polymorphisms were significantly associated with HCV-related liver disease severity and HCC risk. Men were at higher risk than women; this might be explained by hormonal regulation of gene expression or by differential exposure to environmental toxins.