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Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC). This study elucidated the effect of nutritional support (NS) on survival outcomes among patients with AGC undergoing chemotherapy. We retrospectively evaluated new AGC cases at our institute between January 2015 and January 2021. Inclusion criteria were unresectable or recurrent chemotherapy-treated gastric adenocarcinoma, ECOG performance status (PS) 0-2, and adequate organ function. Time to treatment failure (TTF) and overall survival (OS) were evaluated, and univariate and multivariate analyses identified prognostic factors. A total of 103 eligible patients were separated into groups: 69 patients (67%) into NS and 34 (33%) into routine care (RC). The median follow-up time was 11.0 mo, (0.5-92). NS was offered to patients with poorer PS (p = 0.03), Glasgow prognostic score (GPS) positivity (p = 0.001), and high neutrophil-to-lymphocyte ratios (cut-off ≤ 3, p = 0.02). Median OS and TTF in the RC and NS groups were 11.6 and 10.4 mo, (p = 0.99) and 4.2 and 5.5 mo, (p = 0.07), respectively. Multivariate analyses identified NS (hazard ratio [HR] = 0.53, p = 0.01) and GPS positivity for TTF, and low body mass index (HR = 2.03, p = 0.007) and GPS positivity (HR = 2.25, p = 0.001) for OS as significant prognostic factors. Thus, NS with chemotherapy is a potentially effective intervention for AGC.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Prognóstico , Estudos Retrospectivos , Apoio Nutricional , Adenocarcinoma/patologiaRESUMO
BACKGROUND: Bacterial contamination status may differ under different biliary drainage conditions. The purpose of this study was to determine the impact of qualitative and quantitative biliary bacterial contamination on the incidence of infection complications in patients undergoing pancreatoduodenectomy. METHODS: Patients undergoing pancreatoduodenectomy for periampullary diseases with different biliary drainage conditions, such as external drainage (ED), internal drainage (ID), and no drainage (ND), were included. Bile was collected intraoperatively, and biliary contamination status was qualified and quantified using bacterium-specific ribosomal RNA-targeted reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The impact of biliary contamination status on infection complications was analyzed. RESULTS: A total of 152 patients were included (38 with ED, 40 with ID, and 74 with ND). The positive rate of microorganisms in bile was higher in the ID group (98%) compared with the ED group (82%, p = 0.021) and the ND group (65%, p < 0.001). The number of microorganisms detected in bile samples was higher in the ID group compared with the ED group (median 489,788 vs. 5375 bacteria/mL of bile, p < 0.001). With multivariate analysis, soft pancreas, intraoperative bleeding (> 600 mL), and biliary contamination by Atopobium cluster were identified as independent risk factors for infection complications. Biliary contamination by Atopobium cluster was significantly higher in the ID group compared with the other groups. CONCLUSIONS: Biliary bacterial contamination is more frequently induced by ID than either ED or ND. In addition to the previously known risk factors, biliary contamination with Atopobium cluster may be one of the risk factors of infection complications following pancreatoduodenectomy.
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Infecções Bacterianas , Pancreaticoduodenectomia , Infecções Bacterianas/etiologia , Infecções Bacterianas/microbiologia , Bile/microbiologia , Drenagem/efeitos adversos , Drenagem/métodos , Humanos , Incidência , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/microbiologia , Cuidados Pré-OperatóriosRESUMO
BACKGROUND: The clinical role of peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, partly due to its low sensitivity. This study aimed to develop a new biomarker, defined as peritoneal lavage tumor DNA (ptDNA), using DNAs extracted from peritoneal lavage samples from patients with PDAC. METHODS: Samples were collected intraoperatively from 89 PDAC patients who underwent pancreatectomy between 2012 and 2017. Droplet digital polymerase chain reaction (PCR) was used to measure ptDNA for detection of KRAS mutations. The ptDNA status and clinical characteristics were retrospectively evaluated. RESULTS: Positive ptDNA was found in 41 patients, including all 9 patients positive for CY (CY+) and 32 patients negative for CY (CY-). The mutant allele frequency was significantly higher in the CY+ patients than in the CY- patients. The disease-free survival (DFS) and overall survival (OS) were significantly poorer in the high-ptDNA group than in the low-ptDNA group (median DFS, 11.0 vs. 18.8 months; p = 0.007; median OS, 28.7 vs not reached; p = 0.001). The survival curves of DFS and OS in the CY+ group were almost equal to those in the CY- and high-ptDNA group. In a multivariable analysis, ptDNA was an independent predictive factor for DFS (p = 0.025) and OS (p = 0.047). The estimated cumulative incidence of peritoneal recurrence was 45.5% in the high-ptDNA group. The ptDNA biomarker had a much higher sensitivity for peritoneal recurrence than CY, whereas CY had higher specificity. CONCLUSIONS: As a promising biomarker, ptDNA may predict poor prognosis and peritoneal recurrence in PDAC, resolving the controversy surrounding CY.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Neoplasias Peritoneais , Biomarcadores , Carcinoma Ductal Pancreático/genética , DNA/genética , Humanos , Recidiva Local de Neoplasia/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Lavagem Peritoneal , Neoplasias Peritoneais/genética , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Occult-bacterial translocation (O-BT) has been reported as the condition in which microorganisms are detected in blood or lymph nodes by a highly sensitive method. However, the clinical impact of preoperative O-BT on postoperative complication is unclear. STUDY DESIGN: A prospective observational study with patients undergoing pancreatoduodenectomy for periampullary diseases was conducted. Blood samples were collected immediately after induction of anesthesia. The status of O-BT was investigated using bacterium-specific ribosomal RNA-targeted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The impact of O-BT on surgical site infection (SSI) was analyzed. RESULTS: A total of 155 patients were included. The positive rate in preoperative blood samples detected by RT-qPCR was significantly higher than that obtained by the culture method (32 of 155 vs 4 of 155, p < 0.001). Preoperative blood samples were contaminated with 1.0 to 19.2 bacterial cells/mL in positive patients, and 30 of the 41 detected microorganisms were obligate anaerobes. No differences in preoperative factors were observed between patients with positive and negative RT-qPCR results. The incidence of any SSI was significantly higher in patients with contaminated preoperative blood (≥1.2 bacterial cells/mL) than in other patients (14 of 27 vs 35 of 128, p = 0.013). Multivariable analysis indicated that contaminated preoperative blood was identified as one of the independent risk factors for SSI (odds ratio 2.71, 95% CI 1.04 to 7.24, p = 0.041). CONCLUSIONS: O-BT, predominantly with obligate anaerobes, was commonly observed in preoperative blood samples. In addition to the previously known risk factors, O-BT may be one of the risk factors for SSI after pancreatoduodenectomy.
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Bacteriemia/complicações , Bactérias Anaeróbias/fisiologia , Translocação Bacteriana , Pancreaticoduodenectomia , Infecção da Ferida Cirúrgica/etiologia , Adulto , Idoso , Bacteriemia/diagnóstico , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Prospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologiaAssuntos
Carcinoma Ductal Pancreático , Neoplasias Primárias Desconhecidas , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/epidemiologia , Carcinoma Ductal Pancreático/terapia , Humanos , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Lavagem Peritoneal , PrevalênciaRESUMO
BACKGROUND/AIM: Epithelial-to-mesenchymal transition (EMT) plays important roles in cancer progression. This study aimed to identify the exosomal miRNA (exo-miRNA) profiles related to the EMT status in pancreatic cancer (PC). MATERIALS AND METHODS: Comprehensive exo-miRNA-expression profiles in the culture media of PC cell lines were analyzed through microarray technology. The identified miRNAs were analyzed to investigate their clinical implication using The Cancer Genome Atlas (TCGA) dataset and clinical samples. RESULTS: We prioritized 291 exo-miRNAs differentially expressed between epithelial and mesenchymal cell types. Among them, survival analysis based on the TCGA dataset revealed that mir-196b and mir-204 significantly stratify the prognosis of PC cases. In addition, analysis of cell lines indicated miR-196b-3p as a mesenchymal marker and miR-204-3p as an epithelial marker. Finally, we demonstrated that miR-196b-3p and miR-204-3p in serum exosomes were differentially expressed among intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and PC. CONCLUSION: Serum exo-miRNA biomarkers potentially identify the pancreatic tumor status through less-invasive methods.
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Biomarcadores Tumorais/sangue , Transição Epitelial-Mesenquimal/genética , MicroRNAs/sangue , Neoplasias Pancreáticas/sangue , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Análise em Microsséries , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , PrognósticoRESUMO
Circulating tumor DNA (ctDNA) measurements can be used to estimate tumor burden, but avoiding false-positive results is challenging. Herein, digital next-generation sequencing (NGS) is evaluated as a ctDNA detection method. Plasma KRAS and GNAS hotspot mutation levels were measured in 140 subjects, including 67 with pancreatic ductal adenocarcinoma and 73 healthy and disease controls. To limit chemical modifications of DNA that yield false-positive mutation calls, plasma DNA was enzymatically pretreated, after which DNA was aliquoted for digital detection of mutations (up to 384 aliquots/sample) by PCR and NGS. A digital NGS score of two SDs above the mean in controls was considered positive. Thirty-seven percent of patients with pancreatic cancer, including 31% of patients with stages I/II disease, had positive KRAS codon 12 ctDNA scores; only one patient had a positive GNAS mutation score. Two disease control patients had positive ctDNA scores. Low-normal-range digital NGS scores at mutation hotspots were found at similar levels in healthy and disease controls, usually at sites of cytosine deamination, and were likely the result of chemical modification of plasma DNA and NGS error rather than true mutations. Digital NGS detects mutated ctDNA in patients with pancreatic cancer with similar yield to other methods. Detection of low-level, true-positive ctDNA is limited by frequent low-level detection of false-positive mutation calls in plasma DNA from controls.
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Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Intraductais Pancreáticas/sangue , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Cromograninas/genética , Códon/genética , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
The efficacy of nab-paclitaxel combined with gemcitabine (GnP) and of chemoradiotherapy (CRT) for unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) is still unclear. We previously conducted a phase I study of CRT using GnP and determined the recommended dose and have now designed a phase II trial to evaluate the efficacy of CRT incorporating GnP for UR-LA PDAC. Eligibility criteria are chemotherapy-naïve patients with UR-LA PDAC as defined by the NCCN guidelines version 2. 2016. Study patients will receive 100 mg/m2 nab-paclitaxel and 800 mg/m2 gemcitabine on Days 1, 8, and 15 per 4-week cycle with concurrent radiation therapy (total dose of 50.4 Gy in 28 fractions of 1.8 Gy per day, 5 days per week). Treatment will be continued until disease progression or surgery, which is to be performed only for patients in whom the disease is well-controlled at 8 months from beginning the protocol treatment. Primary endpoint is 2-year overall survival rate and co-primary endpoint is resection rate. Secondary endpoints are overall survival, progression free survival, time to treatment failure, response rate, disease control rate, early tumor shrinkage, depth of response, reduction of SUV-max on PET-CT, serum tumor markers, relative dose intensity, safety, and Quality of life. This study will show the efficacy and safety of chemoradiotherapy combined with GnP.
Assuntos
Albuminas/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Carcinoma Ductal Pancreático/mortalidade , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem , GencitabinaRESUMO
BACKGROUND AND AIM: A reliable classification for predicting postoperative prognosis and perioperative risk of hepatocellular carcinoma (HCC) patients is required to make a precise decision for HCC treatment. In the present study, we assessed the perioperative and prognostic importance of indocyanine green (ICG) testing, tumor-node-metastasis (TNM) stage, albumin-bilirubin (ALBI) grade, and ALBI-TNM (ALBI-T) score using consecutive resected HCC cases. METHODS: Between 1998 and 2011, 273 consecutive patients who underwent primary and curative hepatectomy for HCC were identified. Among these 273 cases, 235 Child-Pugh class A patients were enrolled in the present study. RESULTS: Correlation analysis showed that the value of linear predictor for ALBI grade was significantly correlated with ICG 15-minute retention rates (r = 0.51, P < 0.0001). Survival analysis for both recurrence-free survival (RFS) and overall survival (OS) showed there were significant differences between the two groups stratified by stage or ALBI-T score (stage, RFS: P = 0.01, OS: P = 0.003; ALBI-T, RFS: P < 0.0001, OS: P < 0.0001). In addition, Cox proportional hazard model identified ALBI-T score was a significant predictor for both RFS and OS (RFS, P = 0.001; OS, P = 0.004). Furthermore, ALBI-T score could predict perioperative risk in hepatectomy such as longer operation time and excessive intraoperative blood loss. CONCLUSIONS: This study showed a robust association of ALBI-T score with postoperative HCC patient survival and perioperative risk in hepatectomy. ALBI-T score can be used as a simple and powerful tool for assessing HCC patients with further study.
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BACKGROUND: Identification of gastric cancer-related molecules is necessary to elucidate the pathological mechanisms of this heterogeneous disease. The purpose of this study was to identify novel genes associated with aggressive phenotypes of gastric cancer. METHODS: Global expression profiling was conducted using tissues from four patients with metastatic gastric cancer to identify genes overexpressed in gastric cancer. Fifteen gastric cell lines and 262 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. The contribution of the candidate gene on gastric cancer cell proliferation, invasion, adhesion, and migration were evaluated using small interfering RNA. RESULTS: DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12) was identified as a candidate gene by transcriptome analysis. In clinical samples, DNAJC12 mRNA levels were higher in gastric cancer tissues compared with normal adjacent tissues. Patients with high DNAJC12 expression showed significantly shorter overall survival in our cohort and in the extra-validation cohort analyzed by a published microarray dataset. High DNAJC12 expression in gastric cancer tissues was significantly associated with lymphatic involvement, infiltrative growth type, lymph node metastasis, and advanced stage and was identified as an independent prognostic factor for overall survival in multivariable analysis. Increased expression of DNAJC12 was found in 12 of 14 examined gastric cancer cell lines. Knockdown of DNAJC12 expression significantly decreased the proliferation and invasion abilities of gastric cancer cells. CONCLUSIONS: Our findings support DNAJC12 as a candidate gene associated with aggressive phenotypes of gastric cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Adesão Celular , Estudos de Coortes , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Proteínas Repressoras/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: The detection of molecules and mechanisms affecting the malignant phenotype of gastric cancer cells may contribute to the identification of biomarkers for metastasis and recurrence, and such molecules may serve as targets of therapy. For this purpose, in this study transcriptome analysis was performed using surgically resected specimens from patients with gastric cancer with synchronous metastasis. We identified homeobox C10 (HOXC10) as the most highly expressed gene in gastric cancer tissues compared with the adjacent noncancerous gastric mucosa. METHODS: Polymerase chain reaction (PCR) array analysis was performed to identify genes coordinately expressed with HOXC10. The effects of inhibiting HOXC10 on malignant phenotype was evaluated using HOXC10 knockout gastric cancer cell lines, and antibody array analysis was performed to assess the effect of HOXC10 knockout on intracellular signaling. We used a mouse subcutaneous xenograft model to evaluate the tumorigenicity. HOXC10 expression was determined in gastric cancer tissues acquired from 300 patients with gastric cancer. RESULTS: PCR array analysis revealed that the levels of HOXC10 messenger RNA positively correlated with those of FGFBP1 and SOX10. The phosphorylation of ERK1/2 was decreased in HOXC10 knockout cells. HOXC10 knockout significantly suppressed proliferation by increasing apoptosis and reducing the migration and invasiveness of gastric cancer cells. Mouse xenograft models revealed that the tumorigenicity of HOXC10 knockout cells was attenuated compared with the parental cells. The relatively high expression levels of HOXC10 in gastric cancer tissues were significantly associated with hepatic and peritoneal recurrence, as well as worse prognosis. CONCLUSIONS: Our results indicated that HOXC10 enhances the malignant phenotype of gastric cancer cells. The expression levels of HOXC10 may therefore serve as a prognostic biomarker and the products of HOXC10 may provide targets of therapy.
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Biomarcadores Tumorais/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Gástricas/mortalidade , Idoso , Apoptose , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Fenótipo , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Identification of biomarkers to accurately predict the risk of recurrence and survival following curative esophageal resection is required to improve patient outcomes. The copine 5 (CPNE5) gene encodes a calciumdependent lipidbinding intracellular protein. Copine proteins interact with diverse target proteins that are components of pathways that aberrantly regulate the phenotypes of malignant cells. However, limited information is available on the role of CPNE5 in cancer. The present study investigated whether CPNE5 may serve as a predictive marker of the prognosis of patients with ESCC following curative resection. CPNE5 mRNA expression levels and the methylation status of the CPNE5 promotor region were measured in 11 ESCC cell lines. CPNE5 mRNA expression levels in 106 pairs of surgically resected specimens were measured, and their associations with clinicopathological characteristics were analyzed. The CPNE5 mRNA expression levels in 9 ESCC cell lines were decreased compared with those of the non-tumorigenic esophageal mucosa cell line Het1A. Bisulfite sequencing detected the methylation of the CPNE5 promotor region in all cell lines tested, including Het1A. Furthermore, analysis of tissues revealed that CPNE5 mRNA expression was significantly lower in ESCC cells compared with cognate non-cancerous adjacent mucosal cells. KaplanMeier analysis revealed that patients with low CPNE5 expression experienced significantly shorter overall survival. Multivariable analysis identified low CPNE5 expression to be an independent prognostic factor of OS. Analysis of recurrence patterns revealed that significantly more patients with local recurrence expressed lower levels of CPNE5 mRNA. These findings indicated that CPNE5 expression in ESCC tissues may serve as an informative biomarker for predicting ESCC recurrence, particularly in patients with local recurrence, and may help to ensure that patients receive optimal treatment and followup.
Assuntos
Proteínas de Transporte/genética , Regulação para Baixo , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Recidiva Local de Neoplasia/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Metilação de DNA , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras GenéticasRESUMO
OBJECTIVES: This study aimed to clarify the correlation between image classification and the pathological degree of portal system invasion (PSI) and to evaluate the prognostic impact of PSI in pancreatic cancer (PC). METHODS: Pancreatic cancer patients with surgical resections (head, n = 244; body and tail, n = 80) were enrolled in this study. RESULTS: Based on imaging findings, portal vein (PV) invasion was classified as type A (absent), B (unilateral narrowing), C (bilateral narrowing), or D (stenosis or obstruction with collaterals). Splenic vein (SPV) invasion was classified as type α (absent), ß (stenosis), or γ (obstruction). The pathological grade of venous invasion was classified as grade 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima). In PV and SPV invasions, image classification and pathological grade showed significant correlation (PV: ρ = 0.696; SPV: ρ = 0.681). Patients with PV invasion deeper than type B exhibited significantly poorer survival than type A (P < 0.0001). In contrast, there was no difference in survival among types α, ß, and γ. CONCLUSIONS: Image classification was correlated with the pathological grade of PSI in PC. Although not applicable for SPV invasion, image classification of PV invasion is a robust indicator for PC prognosis.
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Neoplasias Pancreáticas/patologia , Sistema Porta/patologia , Veia Porta/patologia , Veia Esplênica/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Neoplasias Pancreáticas/cirurgia , Sistema Porta/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Prognóstico , Veia Esplênica/diagnóstico por imagem , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodosRESUMO
Hepatic recurrence of gastric cancer (GC) is uncontrollable. Discovery of causative oncogenes and the development of sensitive biomarkers to predict hepatic recurrence are required to improve patients' outcomes. In this study, recurrence pattern-specific transcriptome analysis of 57 749 genes was conducted to identify mRNAs specifically associated with hepatic metastasis of patients with stage III GC who underwent curative resection. GC cell lines were subjected to mRNA expression analysis, PCR array analysis, and siRNA-mediated knockdown. The expression levels of primary cancer tissues from 154 patients with resectable GC were determined and correlated with clinicopathological variables. Among 21 genes significantly overexpressed specifically in patients with hepatic recurrence, Sushi domain containing 2 (SUSD2) was selected as a promising target. PCR array analysis revealed that SUSD2 mRNA levels positively correlated with those of FZD7, CDH2, TGFB1, SPARC, ITGA5, and ZEB1. Functional analysis revealed that knockdown of SUSD2 significantly reduced the proliferation, migration, and invasiveness GC cell lines. Patients with high SUSD2 expression were more likely to experience shorter disease-free and overall survival. Analysis of the relation between disease recurrence pattern and SUSD2 levels revealed that significantly more patients with hepatic metastases expressed higher levels of SUSD2 mRNA. The cumulative incidence of hepatic recurrence was greater in patients with high SUSD2 expression. In conclusion, SUSD2 likely contributes to the malignant potential of GC and may serve as a novel biomarker that predicts hepatic recurrence after curative resection.
Assuntos
Neoplasias Hepáticas/secundário , Glicoproteínas de Membrana/genética , Recidiva Local de Neoplasia/secundário , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Regulação para CimaRESUMO
BACKGROUND: The association between neoadjuvant therapy (NAT) and nutritional status in pancreatic cancer (PC) is unknown. OBJECTIVE: The aim of this study was to assess the impact of NAT on nutritional status. METHODS: Overall, 161 patients who underwent pancreatoduodenectomy for PC between August 2010 and March 2017 were enrolled and were divided into two groups: the neoadjuvant group (NAG; n = 67) and the control group (CG; n = 94). Based on relative dose intensity (RDI), patients in the NAG group were further divided into RDI ≥ 80% (n = 39) and RDI < 80% (n = 19). Changes in nutritional index, inflammatory index, and inflammation-based prognostic scores during NAT and the perioperative period were assessed. RESULTS: Retinol-binding protein, prealbumin, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutrition index significantly worsened in the NAG after NAT (p = 0.007, p = 0.03, p = 0.04, p = 0.007, and p = 0.004, respectively). The recovery of rapid turnover proteins after postoperative day 5 was significantly worse in the NAG compared with the CG (p < 0.05), but tended to be more prompt in the RDI ≥ 80% group among the NAG. There was no significant difference in the incidence of postoperative complications, length of hospital stay, and time to postoperative adjuvant therapy between the NAG and the CG. CONCLUSIONS: NAT for PC could aggravate nutritional status and hamper its postoperative recovery. Furthermore, malnutrition might decrease tolerance of NAT. These findings suggest the importance of nutritional support for patients with NAT in PC.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mediadores da Inflamação/metabolismo , Desnutrição/etiologia , Terapia Neoadjuvante/efeitos adversos , Estado Nutricional , Neoplasias Pancreáticas/tratamento farmacológico , Pancreaticoduodenectomia/efeitos adversos , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Desnutrição/patologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , PrognósticoRESUMO
OBJECTIVES: The aims of the study were to compare survival outcomes between patients with pancreatic ductal adenocarcinoma (PDAC) and invasive intraductal papillary mucinous neoplasms (IPMN) and to determine candidates for adjuvant chemotherapy. METHODS: A total of 579 consecutive patients, including 375 PDAC and 204 IPMN patients, were reviewed. Stage-matched comparisons of survival data were conducted using the Cox proportional hazards model and propensity analysis. To evaluate prognostic factors, univariate and multivariate Cox regression analyses were performed. RESULTS: The overall survival for invasive IPMN was significantly longer than that for PDAC (hazard ratio, 2.34; P = 0.0001). When the analysis was limited to stage I patients, the 5-year overall survival rate of invasive IPMN patients was significantly better than that of PDAC patients (100% vs 74.1%, P = 0.0092); however, no difference was observed between stage II patients with invasive IPMN and PDAC (hazard ratio, 1.49; P = 0.09). The Cox proportional hazards model and propensity analysis demonstrated no difference in stage-matched survival. Multivariate analysis revealed that only T (≥3) was an independent prognostic factor for invasive IPMN. CONCLUSIONS: Stage-matched analysis did not show a significant survival difference between invasive IPMN and PDAC patients, and T3 or higher was an independent prognostic factor for invasive IPMN.
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Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Papilar/terapia , Idoso , Carcinoma Ductal Pancreático/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Neoplasias Pancreáticas/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher LOXL2 expression was observed in cell lines from mesenchymal type PC than in those from epithelial type PC. A significant correlation between LOXL2 expression and the EMT status defined based on the expression of E-cadherin and vimentin was observed in surgical specimens (P < 0.01). The disease-free survival and overall survival rates among patients with low LOXL2 expression were significantly better than those among patients with high LOXL2 expression (P < 0.001). According to the multivariate analysis, high LOXL2 expression (P = 0.03) was a significant independent prognostic factor for patients with PC. Additionally, LOX inhibition significantly decreased PC cell proliferation, migration, and invasion in vitro. In conclusion, LOXL2 expression is potentially associated with PC progression, and LOXL2 expression represents a biomarker for predicting the prognosis of patients with PC who have undergone complete resection.
Assuntos
Aminoácido Oxirredutases/metabolismo , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal , Regulação Enzimológica da Expressão Gênica , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoácido Oxirredutases/genética , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND: Ultrasensitive detection of low-abundance DNA point mutations is a challenging molecular biology problem, because nearly identical mutant and wild-type molecules exhibit crosstalk. Reliable ultrasensitive point mutation detection will facilitate early detection of cancer and therapeutic monitoring of cancer patients. OBJECTIVE: The objective of this study was to develop a method to correct errors in low-level cell line mixes. MATERIALS AND METHODS: We tested sample mixes with digital-droplet PCR (ddPCR) and next-generation sequencing. RESULTS: We introduced two corrections: baseline variant allele frequency (VAF) in the parental cell line was used to correct for copy number variation; and haplotype counting was used to correct errors in cell counting and pipetting. We found ddPCR to have better correlation for detecting low-level mutations without applying any correction (R2 = 0.80) and be more linear after introducing both corrections (R2 = 0.99). CONCLUSIONS: The VAF correction was found to be more significant than haplotype correction. It is imperative that various technologies be evaluated against each other and laboratories be provided with defined quality control samples for proficiency testing.