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1.
Int J Clin Oncol ; 28(3): 400-408, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36637609

RESUMO

BACKGROUND: Advanced lung cancer inflammation index (ALI) is reported to be a prognosticator in various cancer patients with chemotherapy. However, the clinical impact of the ALI on treatment strategies in metastatic colorectal cancer (mCRC) patients remains unclear. METHODS: A total of 356 patients, who received first-line chemotherapy for mCRC between April 2005 and November 2019 in a single institution, were retrospectively enrolled. The association of pretreatment ALI (calculated as follows: BMI × albumin value/neutrophil-to-lymphocyte ratio) status with clinicopathological factors and patient survival outcome was analyzed, using subgroup analysis. RESULTS: The ALI-low cases were significantly associated with female sex, more synchronous metastasis, multiple metastatic sites, less primary tumor resection, less liver resection after chemotherapy, and poor overall survival (OS). A multivariate Cox proportional hazards analysis clarified that the ALI-low status was independently associated with poor OS (HR: 1.78, 95% CI 1.27-2.48, P = 0.001), in addition to right side tumor, multiple metastatic sites, and the non-performance of liver resection after chemotherapy. A subgroup analysis revealed that primary tumor resection and the resection of liver metastases after chemotherapy could not improve the prognosis of ALI-low cases in comparison with ALI-high cases, and the type of first-line chemotherapy did not significantly affect the association between the prognosis and the ALI status. CONCLUSION: ALI comprehensively evaluates the prognostic host status and is a reliable prognosticator for the mCRC patients with chemotherapy. Calculating pretreatment ALI may serve as a cost-effective and easily available tool for constructing treatment strategies.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Inflamação/patologia , Prognóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia
2.
J Surg Oncol ; 125(6): 982-990, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35099817

RESUMO

OBJECTIVE: Using a self-expanding metal stent as a bridge to surgery (BTS) is considered a reasonable strategy for patients with acute malignant large bowel obstruction. Since postoperative complications have a negative impact on patient survival, we aim to clarify the predictors of complications in patients undergoing BTS using a self-expanding metal stent. METHODS: We conducted a retrospective review of 61 patients with colorectal cancer (CRC) who underwent stenting as a BTS at our institution. We analyzed the association of postoperative complications with clinicopathologic, surgical, and patient factors, and with the prestenting or preoperative laboratory data. RESULTS: Both postoperative complications in general and severe complications were significantly associated with a longer stenotic-section length (p = 0.007 and p = 0.003), lower preoperative hemoglobin levels (p < 0.001 and p = 0.081), and lower prestenting hemoglobin levels (p = 0.006 and p = 0.042). Multivariate logistic regression analysis showed that lower prestenting (<13.0 g/dl) and preoperative (<11.5 g/dl) hemoglobin levels were independent predictive factors for postoperative complications (odds ratio [OR]: 4.15; 95% confidence interval [CI]: 1.07-18.90; p = 0.040; and OR: 4.93; 95% CI: 1.35-20.28; p = 0.016). A stenotic-section length of 5.0 cm or greater was predictive of severe complications (OR: 25.67; 95% CI: 1.95-1185.00; p = 0.011). CONCLUSIONS: Our data suggest that lower hemoglobin levels before stenting and a longer length of the stenotic section of bowel might predict postoperative complications in patients with CRC undergoing BTS for obstruction.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Hemoglobinas , Humanos , Obstrução Intestinal/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento
3.
Langenbecks Arch Surg ; 407(5): 2011-2019, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35499587

RESUMO

PURPOSE: Main lymph node metastasis (LNM) dissection of transverse colon (TC) cancer is a difficult surgical procedure. Nonetheless, the main LNM ratio and the benefit of main lymph node (LN) dissection in TC cancer were unclear. This study aimed to identify high-risk patients for LNM and to evaluate the benefit of LN dissection in TC cancer. METHODS: Data for 26,552 colorectal cancer patients between 2007 and 2011 were obtained from the JSCCR database. Of these, 871 stage I-III TC cancer patients underwent surgery with radical LN dissection. These patients were evaluated using the index of estimated benefit from lymph node dissection (IEBLD), where IEBLD = (LNM ratio of each LN station) × (5-year overall survival (OS) rate of the patients with LNM) × 100. RESULTS: None of the patients with depth of invasion pT1-2 had main LNM. The presence of main LNM was associated with depth of invasion pT4, CEA-4H (carcinoembryonic antigen 4 times higher than preoperative cutoff value), or type 3, and 323 patients (37.1%) who had these factors were high-risk patients for main LNM. In these high-risk patients, the LNM ratio, 5-year OS rate of patients with LNM and IEBLD values, respectively, were 43.9%, 70.3%, and 30.5 for the pericolic LN; 20.3%, 66.0%, and 15.1 for the intermediate LN; and 9.6%, 58.5%, and 5.6 for the main LN. CONCLUSION: Main LNM is associated with depth of invasion pT4, CEA-4H, or type 3. The IEBLD for the main LN of high-risk TC cancer patients was over 5.


Assuntos
Colo Transverso , Neoplasias do Colo , Antígeno Carcinoembrionário , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estudos Retrospectivos
4.
Ann Surg Oncol ; 28(1): 167-174, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32588261

RESUMO

BACKGROUND: The usefulness of quantitating tumor lesion glycolysis (TLG) from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings as a tool for determining the effect of neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC) has not yet been established. METHODS: The cohort of this retrospective study comprised 46 patients who had undergone NAC and subsequent esophagectomy for locally advanced ESCC between January 2008 and December 2017. PET/CT was conducted before and after NAC to assess its therapeutic effect. Associations between changes in TLG values during NAC and clinicopathological findings, pathological tumor regression grade (TRG), and prognosis were assessed. RESULTS: Most patients received two courses of DCF (Docetaxel, Cisplatin, and Fluorouracil) as NAC. The mean TLG value of the primary tumor decreased significantly after NAC. The median follow-up period was 41 months. The Kaplan-Meier method, analyzed by log-rank test, showed that low TLG ratio (≤ 0.4) and low SUVmax ratio (≤ 0.6) were associated with favorable survival outcomes (P = 0.0073 and P = 0.032, respectively). Univariate and multivariate analysis revealed that TLG ratio and achievement of pathological cure were independent prognostic factors for overall survival. TLG ratio was also associated with pathological TRG (TRG 0-1a vs 1b-3) (P = 0.0016). CONCLUSIONS: TLG ratio before and after NAC is clinically useful in predicting both histological response and survival outcome after NAC and subsequent esophagectomy in patients with ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fluordesoxiglucose F18 , Glicólise , Humanos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral
5.
Int J Cancer ; 147(2): 532-541, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32191346

RESUMO

Tertiary lymphoid structures (TLSs) provide an immunological antineoplastic effect. Recent evidences link a unique 12-chemokine (CCL2, -3, -4, -5, -8, -18, -19, -21, CXCL9, -10, -11, -13) signature status from tumor tissue and the TLS expression. However, the potential significance of 12-chemokine signature status for clinical use is unknown. We aimed to evaluate the association of 12-chemokine signature status with patient outcomes in colorectal cancer (CRC). We used integrated data of resected 975 CRC cases within three independent cohorts from France, Japan and the United States (GSE39582, KUMAMOTO from Kumamoto university hospital and TCGA). The association of 12-chemokine signature status with clinicopathological features, patient outcome, TLS expression status and key tumor molecular features was analyzed. Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11-2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33-10.08, p = 0.0087). High 12-chemokine signature status had significant associations with right-sided tumor, high tumor-localized TLS expression, BRAF mutant, CIMP-high status and MSI-high status. Furthermore, RNA-seq based analysis showed that high 12-chemokine signature status was strongly associated with inflammation-related, immune cells-related and apoptosis pathways (using gene set enrichment analysis), and more tumor-infiltrating immune cells, such as cytotoxic T lymphocytes and myeloid dendritic cells (using MCP-counter analysis). We investigated a promising effect of 12-chemokine signature status in CRC patients who underwent resection. Our data may be helpful in developing novel immunological treatment strategies for CRC.


Assuntos
Biomarcadores Tumorais/genética , Quimiocinas/genética , Neoplasias Colorretais/cirurgia , Estruturas Linfoides Terciárias/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Bases de Dados Genéticas , Feminino , França , Regulação Neoplásica da Expressão Gênica , Humanos , Japão , Masculino , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Estados Unidos
6.
Ann Surg ; 271(3): 494-501, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-29995687

RESUMO

OBJECTIVE: To elucidate the clinical value of mean corpuscular volume (MCV) for prognostic prediction in patients with esophageal cancer who underwent radical esophagectomy. BACKGROUND: High MCV is suggested to be relevant to the incidence and prognosis of several malignancies. However, few studies investigating the correlation between MCV and survival outcome of esophageal cancer have been conducted. METHODS: This study included 570 patients with esophageal cancer who underwent radical esophagectomy between April, 2005 and December, 2017. Patients were divided into 2 groups according to the standard value of pretreatment MCV: normal (83-99 fL) and high (>99 fL) groups. Clinical backgrounds, short-term outcomes, and prognostic outcomes postesophagectomy were retrospectively compared between the groups. RESULTS: Of all patients, 410 (71.9%) had normal MCV, and 160 (28.1%) had high MCV. High MCV was significantly associated with lower body mass index, higher frequency of habitual alcohol and tobacco use, and higher incidence of multiple primary malignancies other than esophageal cancer. High MCV also correlated with higher incidence of postoperative morbidity of the Clavien-Dindo classification ≥II and pulmonary morbidity. Overall survival was significantly worse in patients with high MCV. Multivariate analysis suggested that high MCV was an independent risk factor for worse survival outcome (hazard ratio 1.54, 95% confidence interval 1.098-2.151, P = 0.012). CONCLUSIONS: Patients with high MCV have various disadvantages in clinical background that can adversely affect both short-term and long-term outcomes after esophagectomy. MCV can become a predictive marker to estimate survival outcome after esophagectomy for esophageal cancer.


Assuntos
Índices de Eritrócitos , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/cirurgia , Esofagectomia , Idoso , Volume Sanguíneo , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
7.
Ann Surg Oncol ; 27(7): 2402-2411, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32215755

RESUMO

BACKGROUND: Identification of a key person for supporting patients with activities of daily living after esophagectomy can contribute to patients' nutrition, rehabilitation, mental status, and determination of treatments for cancer. It may also affect the patients' prognostic outcomes. PATIENTS AND METHODS: This retrospective study included 504 patients who underwent three-incisional esophagectomy for esophageal cancer between June 2005 and June 2018 at the Kumamoto University Hospital. The association between the type of key person identified and overall survival (OS) was investigated. The impact of the key person on postoperative nutrition and survival after recurrence was also examined. RESULTS: Clinical backgrounds in patients with and without wife as their key person were equivalent. OS among male patients who identified their wife as their key person was significantly better than that in those without their wife as key person (P = 0.0035). Cox regression analysis showed that absence of a wife was an independent risk factor for worse survival outcomes (hazard ratio, 0.62; 95% confidence interval, 0.393-0.987; P = 0.044) along with age, clinical stage, severe postoperative morbidity, and pathological curability. Presence of a wife did not affect postoperative nutritional status. Incidence of death due to other causes and OS after recurrence were better in male patients with a wife than in those without; however, this difference was not significant. CONCLUSIONS: Among males with esophageal cancer, their wives may be a significant contributor to extension of survival after surgery, via various support mechanisms.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Cônjuges , Atividades Cotidianas , Neoplasias Esofágicas/psicologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/psicologia , Feminino , Humanos , Japão , Masculino , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Cônjuges/psicologia , Taxa de Sobrevida
8.
Ann Surg Oncol ; 27(9): 3534-3541, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32648180

RESUMO

BACKGROUND: Liver fibrosis influences liver regeneration and surgical outcomes, and several noninvasive models based on laboratory data have been developed to predict liver fibrosis. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, a noninvasive fibrosis marker, can predict the prognosis in patients with colorectal liver metastases (CRLM) undergoing hepatectomy. METHODS: This retrospective study involved 193 consecutive patients with CRLM who underwent hepatectomy. The FIB-4 index was calculated by laboratory data and age before hepatectomy and before preoperative chemotherapy. The FIB-4 cut-off was determined using survival classification and regression tree analysis. Patients were divided into two groups (high and low FIB-4 index), and post-hepatectomy overall survival (OS) and recurrence-free survival (RFS) were investigated. RESULTS: In total, 193 patients were evaluated. Chemotherapy before hepatectomy was performed in 105 (54.4%) patients. A high FIB-4 index (> 2.736) was found in 39 (20.2%) patients. OS was significantly shorter in patients with a high FIB-4 index than those with a low FIB-4 index in the univariate (45.9 vs. 74.4 months, log-rank p = 0.007) and multivariate analysis (hazard ratio 2.28, 95% confidence interval 1.39-3.74; p = 0.001). Among patients who received chemotherapy before hepatectomy, those with a high FIB-4 index had significantly shorter RFS (6.9 vs. 45.3 months, log-rank p = 0.047) and OS (23.9 vs. 55.0 months, log-rank p = 0.003) than those with a low FIB-4 index. This association was also confirmed by multivariate analysis (hazard ratio 4.28, 95% confidence interval 1.46-12.6; p = 0.008). CONCLUSION: Both the preoperative and prechemotherapy FIB-4 index can predict long-term outcomes after hepatectomy in patients with CRLM.


Assuntos
Neoplasias Colorretais , Hepatectomia , Cirrose Hepática , Neoplasias Hepáticas , Índice de Gravidade de Doença , Fatores Etários , Idoso , Biomarcadores/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Feminino , Fibrose/sangue , Fibrose/diagnóstico , Hepatectomia/mortalidade , Humanos , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
9.
Biochim Biophys Acta Rev Cancer ; 1868(2): 439-448, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28939182

RESUMO

Colorectal cancer (CRC) is a heterogeneous disease with distinct molecular and clinical features, which reflects the wide range of prognostic outcomes and treatment responses observed among CRC patients worldwide. Our understanding of the CRC epigenome has been largely developed over the last decade and it is now believed that among thousands of epigenetic alterations present in each tumor, a small subgroup of these may be considered as a CRC driver event. DNA methylation profiles have been the most widely studied in CRC, which includes a subset of patients with distinct molecular and clinical features now categorized as CpG island methylator phenotype (CIMP). Major advances have been made in our capacity to detect epigenetic alterations, providing us with new potential biomarkers for diagnostic, prognostic and therapeutic purposes. This review aims to summarize our current knowledge about epigenetic alterations occurring in CRC, underlying their potential future clinical implications in terms of diagnosis, prognosis and therapeutic strategies for CRC patients.


Assuntos
Neoplasias Colorretais/genética , Metilação de DNA , Instabilidade Cromossômica , Neoplasias Colorretais/terapia , Ilhas de CpG , Humanos , MicroRNAs/fisiologia , Instabilidade de Microssatélites , Fenótipo
10.
J Surg Oncol ; 122(2): 344-349, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32346880

RESUMO

OBJECTIVE: We retrospectively evaluated the impact of postoperative complications on long-term outcomes after curative resection for colorectal cancer (CRC), using propensity-score analysis (PSA). PATIENTS AND METHODS: We reviewed data from 673 consecutive patients with stage I to III CRC, who underwent curative resections between 2005 and 2017. Patients were divided into the complication group (Clavien-Dindo [CD] grade ≥ 3) and the control group (others). We performed PSA to obtain unbiased estimates of the effects of the oncological background on each outcome. RESULTS: We matched for sex, age, American Society of Anesthesiologists grade, location (right colon/left colon/rectum), histology (tub1/tub2/por), pathological tumor depth, and lymph node metastases. Eighty-five patients (12.6%) developed postoperative complications with CD grade ≥ 3. After PSA, 81 patients were included in each group. The complication group showed significantly worse relapse-free survival (RFS) than the control group (5-year RFS rate: 62% vs 77%; P = .047). In multivariate analysis with inverse probability of treatment weights, the complication group had a higher risk of relapse or death than the control group (hazard ratio: 2.08, 95% confidence interval:1.3-3.3; P = .018). CONCLUSIONS: Postoperative complications (CD grade ≥ 3) could cause poor long-term outcomes in patients with stage I to III CRC; their presence requires appropriate adjuvant chemotherapy and follow-up.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Int J Clin Oncol ; 25(4): 651-659, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31834556

RESUMO

BACKGROUND: Serum anti-p53 antibody is used clinically as a tumor marker of colorectal cancer. However, its prognostic significance in patients with metastatic colorectal cancer (mCRC) remains unclear. KRAS status may influence the host immune response against tumor progression. In the present study, we investigated the prognostic significance of serum anti-p53 in mCRC patients with wild-type KRAS and mutant KRAS treated with systemic chemotherapy. METHODS: A retrospective study of 150 mCRC patients in whom serum anti-p53 antibody was measured before first-line chemotherapy was conducted. The patients were divided into two groups, high p53 and low p53, based on their serum anti-p53 antibody levels. Associations between serum anti-p53 level and clinical outcomes were evaluated in conjunction with KRAS status. RESULTS: There were 97 (64.7%) patients with wild-type KRAS and 53 (35.3%) with mutant KRAS. In an analysis of all patients, there was no significant difference in overall survival (OS) between the high p53 and low p53 groups. In patients with mutant KRAS, those in the high p53 group exhibited significantly longer OS than those in the low p53 group (p = 0.017, log-rank test). In the multivariate analysis, serum p53 antibody level was an independent predictor of OS in mCRC patients (high vs. normal; hazard ratio 0.438, 95% confidence interval 0.178-0.974, p < 0.05). CONCLUSIONS: Serum anti-p53 antibody level may be an independent predictor of OS in mCRC patients with KRAS mutant tumors.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/sangue , Neoplasias Colorretais/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Proteína Supressora de Tumor p53/imunologia
12.
Surg Today ; 50(6): 597-603, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31844988

RESUMO

PURPOSE: To investigate the effect of old age on the perioperative, short-term, and long-term surgical outcomes of elderly patients undergoing curative surgery for colorectal cancer (CRC). METHODS: The subjects of this retrospective study were 526 patients who underwent curative resections for stage I-III CRC between March 2005 and March 2016. We divided the patients into a young group (< 75 years old, n = 361) and an elderly group (≥ 75 years old, n = 165) and compared the clinicopathological factors and prognoses of the two groups. We performed a propensity score-matched (PSM) analysis with inverse probability of treatment weighting (IPTW) to avoid confounding bias. RESULTS: The elderly group had more right-sided tumors and more comorbidities than the young group. After PSM, there were 148 patients in each group. Although the elderly group had significantly shorter overall survival than the young group, the two groups did not differ significantly in cancer-specific survival (CSS; P = 0.136) or recurrence rate (RR; P = 0.317). Multivariate analysis with IPTW also revealed no significant difference in CSS (P = 0.171) or RR (P = 0.284) between the young and elderly groups. Our findings were limited by the study's retrospective single-institute conditions, and the inclusion of only patients who underwent radical resections. CONCLUSION: Primary tumor resection is appropriate for elderly patients with CRC.


Assuntos
Neoplasias Colorretais/cirurgia , Fatores Etários , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos do Sistema Digestório , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
13.
Int J Cancer ; 145(8): 2082-2090, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30856283

RESUMO

AMP-activated protein kinase (AMPK) is a key sensor of energy homeostasis and regulates cell metabolism, proliferation and chemotherapy/radiotherapy sensitivities. This study aimed to explore the relationship between the AMPK pathway-related single nucleotide polymorphisms (SNPs) and clinical outcomes in patients with metastatic colorectal cancer (mCRC). We analyzed a total of 884 patients with mCRC enrolled in three randomized clinical trials (TRIBE, MAVERICC and FIRE-3: where patients were treated with FOLFIRI, mFOLFOX6 or FOLFOXIRI combined with bevacizumab or cetuximab as the first-line chemotherapy). The association between AMPK pathway-related SNPs and clinical outcomes was analyzed across the six treatment cohorts, using a meta-analysis approach. Our meta-analysis showed that AMPK pathway had significant associations with progression-free survival (PFS; p < 0.001) and overall survival (OS; p < 0.001), but not with tumor response (TR; p = 0.220): PRKAA1 rs13361707 was significantly associated with favorable PFS (log HR = -0.219, SE = 0.073, p = 0.003), as well as PRKAA1 rs10074991 (log HR = -0.215, SE = 0.073, p = 0.003), and there were suggestive associations of PRKAG1 rs1138908 with unfavorable OS (log HR = 0.170, SE = 0.083, p = 0.041), and of UBE2O rs3803739 with unfavorable PFS (log HR = 0.137, SE = 0.068, p = 0.042) and OS (log HR = 0.210, SE = 0.077, p = 0.006), although these results were not significant after false discovery rate adjustment. AMPK pathway-related SNPs may be predictors for chemotherapy in mCRC. Upon validation, our findings would provide novel insight for selecting treatment strategies.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Bevacizumab/administração & dosagem , Biomarcadores Tumorais/genética , Camptotecina/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fluoruracila , Humanos , Leucovorina/administração & dosagem , Metástase Neoplásica , Prognóstico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Transdução de Sinais/genética
15.
Gastric Cancer ; 21(2): 204-212, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28656485

RESUMO

BACKGROUND: Controlling Nutritional Status (CONUT), as calculated from serum albumin, total cholesterol concentration, and total lymphocyte count, was previously shown to be useful for nutritional assessment. The current study investigated the potential use of CONUT as a prognostic marker in gastric cancer patients after curative resection. METHODS: Preoperative CONUT was retrospectively calculated in 416 gastric cancer patients who underwent curative resection at Kumamoto University Hospital from 2005 to 2014. The patients were divided into two groups: CONUT-high (≥4) and CONUT-low (≤3), according to time-dependent receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. RESULTS: CONUT-high patients were significantly older (p < 0.001) and had a lower body mass index (p = 0.019), deeper invasion (p < 0.001), higher serum carcinoembryonic antigen (p = 0.037), and higher serum carbohydrate antigen 19-9 (p = 0.007) compared with CONUT-low patients. CONUT-high patients had significantly poorer overall survival (OS) compared with CONUT-low patients according to univariate and multivariate analyses (hazard ratio: 5.09, 95% confidence interval 3.12-8.30, p < 0.001). In time-dependent ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 5-year OS than the neutrophil lymphocyte ratio, the Modified Glasgow Prognostic Score, or pStage. When the time-dependent AUC curve was used to predict OS, CONUT tended to maintain its predictive accuracy for long-term survival at a significantly higher level for an extended period after surgery when compared with the other markers tested. CONCLUSIONS: CONUT is useful for not only estimating nutritional status but also for predicting long-term OS in gastric cancer patients after curative resection.


Assuntos
Colesterol/sangue , Contagem de Linfócitos , Albumina Sérica/análise , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Intervalo Livre de Doença , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Resultado do Tratamento
16.
World J Surg ; 42(4): 1085-1091, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28887635

RESUMO

BACKGROUND: Several studies have examined controlling nutritional status (CONUT), which is one of the useful biomarkers for predicting patients' prognosis following cancer treatment. The aim of this study was to evaluate the value of CONUT as a postoperative prognostic marker in patients with intrahepatic cholangiocarcinoma (ICC) following curative hepatectomy. METHODS: We retrospectively analyzed 71 patients who underwent curative hepatectomy for ICC between May 2002 and November 2016. Patients were divided into two groups according to their preoperative CONUT score (i.e., CONUT â‰§ 2 or CONUT < 2). RESULTS: The number of patients assigned to the normal, mild, moderate, or severe malnutrition groups was 40, 28, two, and one, respectively. The high CONUT group (CONUT â‰§ 2) consisted of 31 patients (43.7%) and had a poor prognosis with regard to overall survival (OS) (p = 0.0149). A high CONUT score is also identified as one of the independent predictors of poor prognosis in OS (hazard ratio 3.02; 95% confidence interval 1.4-6.8; p = 0.007). However, in the current study, a high CONUT score was not associated with postoperative complications (Clavien-Dindo classification â‰§ III or more). CONCLUSIONS: CONUT may be useful for the preoperative assessment of prognosis in patients with ICC who have undergone curative hepatectomy.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia , Desnutrição/diagnóstico , Avaliação Nutricional , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos
17.
Surg Today ; 48(7): 667-672, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29468435

RESUMO

PURPOSE: Surgery remains the curative treatment of choice for colorectal cancer (CRC). However, to our knowledge, no report has addressed the usefulness of additional regional lymph node dissection for primary CRC that has invaded another colon region. METHODS: We reviewed the clinicopathological characteristics and outcomes of eight patients who underwent surgery between March, 2005 and August, 2014, for CRC that invaded another region of the colon. RESULTS: Five patients underwent additional regional lymph node dissection in the area of the invaded colon and one patient had lymph node metastasis in the region. Two of three patients who did not undergo additional regional lymph node dissection were found to have regional lymph node recurrences in the area during the follow-up period. Although there was no statistical correlation between extra-regional lymph node metastasis and clinicopathological or operative factors, the patients with extra-regional lymph node metastasis or recurrence had primary regional lymph node metastasis. CONCLUSION: For curative intent, surgeons may need to perform additional regional lymph node dissection for primary CRC invading another colon region.


Assuntos
Colo/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Excisão de Linfonodo , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico por imagem , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento
18.
HPB (Oxford) ; 20(10): 939-948, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29759640

RESUMO

BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulates tumor malignancy by gene silencing via histone methylation. In this study we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC). METHODS: The influence of EZH2 on tumor angiogenesis was examined by bioinformatics analysis of a public database. We also assessed the correlation between EZH2 and vasohibin 1 (VASH1) expression in 47 patients with ICC by immunohistochemical (IHC) staining and in vitro gene silencing assays. The prognostic significance of EZH2 and VASH1 expression by IHC was also examined in the ICC cohort. RESULTS: Bioinformatics analysis showed that EZH2 was associated with several angiogenesis gene sets in the public database. EZH2 suppressed VASH1 expression in in vitro assays and IHC studies. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P = 0.019) and poor overall survival (P = 0.0055). CONCLUSION: The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC.


Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Recidiva Local de Neoplasia , Neovascularização Patológica , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Progressão da Doença , Intervalo Livre de Doença , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Regulação Neoplásica da Expressão Gênica , Hepatectomia , Humanos , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Transdução de Sinais , Fatores de Tempo
19.
Esophagus ; 15(4): 301-303, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30090963

RESUMO

Anastomotic stricture is often observed after esophagectomy. Surgical treatment is considered for refractory stricture to conservative treatments. However, it is not established what type of surgery is safe and effective. In this report, we present a novel approach, percutaneous transluminal plasty, for refractory anastomotic stricture reconstructed via the subcutaneous route in esophagectomy. We believe that the effectiveness and safety of this technique is considerably good and can become a good alternative for refractory stricture after esophagectomy.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/cirurgia , Esofagectomia/efeitos adversos , Endoscopia/métodos , Neoplasias Esofágicas/patologia , Estenose Esofágica/etiologia , Estenose Esofágica/patologia , Humanos , Masculino , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento
20.
Int J Colorectal Dis ; 32(1): 99-106, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27726014

RESUMO

BACKGROUND: Controlling nutritional status (CONUT) score, calculated from serum albumin and total cholesterol concentrations and total lymphocyte count, is reportedly valuable for nutritional assessment. This study investigated whether CONUT score was predictive of outcomes in colorectal cancer (CRC) patients undergoing surgical resection. METHODS: Preoperative CONUT scores were retrospectively evaluated in 417 CRC patients who underwent potentially curative resection at Kumamoto University Hospital from March 2005 to August 2014. Patients were divided into four groups based on preoperative CONUT scores: normal, light, moderate, and severe. The associations of CONUT score with clinicopathological factors, patient survival, and postoperative complications were examined. RESULTS: CONUT score correlated significantly with age (P < 0.001), body mass index (P = 0.005), carcinoembryonic antigen (P = 0.002), and carbohydrate antigen 19-9 (P = 0.005) concentrations. Overall survival (OS) rate was significantly lower in patients with moderate/severe than light or normal CONUT scores. CONUT score was independently prognostic of OS [moderate/severe vs. normal, hazard ratio = 5.92, 95 % confidence interval (CI) 2.30-14.92; P < 0.001)]. Patients with moderate/severe CONUT scores were at greater risk for complications, especially for severe complications. Multivariate analysis showed that CONUT score was independently predictive of severe complications (moderate/severe vs. normal, odds ratio = 4.51, 95 % CI 1.89-10.74; P < 0.001). CONCLUSIONS: CONUT score may predict survival and postoperative severe complications in CRC patients undergoing potentially curative resection. Management of CRC patients may need consideration of host nutritional status.


Assuntos
Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Estado Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Modelos Logísticos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Albumina Sérica/metabolismo , Resultado do Tratamento , Adulto Jovem
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