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BACKGROUND: Preoperative carcinoembryonic antigen (CEA) has yet to be used as a prognostic or adjuvant chemotherapy factor for colorectal cancer (CRC). METHODS: This retrospective cohort study included all stage I-III CRC patients with different preoperative serum CEA levels (≤ 5, 5-10, and > 10 ng/ml) at a single center between 1995 and 2010. Propensity score matching was performed in a 1:1 ratio between the two elevated CEA groups (5-10 ng/ml and > 10 ng/ml) and in a 1:2 ratio between the elevated and non-elevated groups (≤ 5 ng/ml), with a caliper of 0.05. RESULTS: After exclusion and matching, 3857 patients had preoperative CEA levels ≤ 5 ng/ml, 1121 patients had CEA levels between 5 and 10 ng/ml, and 1121 patients had CEA levels > 10 ng/ml. Elevated preoperative CEA showed an increased risk of overall survival (5-10 ng/ml: hazard ratio [HR] 1.376; > 10 ng/ml: HR 1.523; both p < 0.001), cancer-specific survival (5-10 ng/ml: HR 1.404; > 10 ng/ml: HR 1.712; both p < 0.001), and recurrence free interval (5-10 ng/ml: HR 1.190; > 10 ng/ml: HR 1.468; both p < 0.05). Patients with negative lymph node staging (LNs) and CEA > 10 ng/ml, as well as those with positive LNs and CEA ≤ 5 ng/ml, showed similar overall survival (5-year survival: 72% vs. 69%; p = 0.542) and recurrence free intervals (19.9 vs. 21.72 months; p = 0.662). CONCLUSIONS: A preoperative CEA level can be an independent prognostic factor for stage I-III CRC after curative resection. Patients with negative LNs and preoperative CEA level > 10 ng/ml should be considered for intensive follow-up or adjuvant chemotherapy.
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Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/patología , Cirugía Colorrectal/métodos , Cuidados Preoperatorios , Anciano , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Puntaje de Propensión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Local excision (LE) is a feasible treatment approach for rectal cancers in stage pT1 and presents low pathological risk, whereas total mesorectal excision (TME) is a reasonable treatment for more advanced cancers. On the basis of the pathology findings, surgeons may suggest TME for patients receiving LE. This study compared the survival outcomes between LE with/without chemoradiation and TME in mid and low rectal cancer patients in stage pT1/pT2, with highly selective intermediate pathological risk. METHODS: This retrospective study included 134 patients who received TME and 39 patients who underwent LE for the treatment of intermediate risk (pT1 with poor differentiation, lymphovascular invasion, perineural invasion, relatively large tumor, or small-sized pT2 tumor) rectal cancer between 1998 and 2016. RESULTS: Overall survival (OS), disease-free survival (DFS), and cumulative recurrence rate (CRR) were similar between the LE (3-year DFS 92%) and TME (3-year DFS 91%) groups. Following subgrouping into an LE with adjuvant therapy group and a TME without adjuvant therapy group, the compared survival outcomes (OS, DFS, and CRR) were found not to be statistically different. The temporary and permanent ostomy rates were higher in the TME group than in the LE group (p < 0.001). Rates of early and late morbidity following surgery were higher in the TME group (p = 0.005), and LE had similar survival compared with TME. CONCLUSION: For patients who had mid and low rectal cancer in stage pT1/pT2 and intermediate pathological risk, LE with chemoradiation presents an alternative treatment option for selected patients.
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Procedimientos Quirúrgicos del Sistema Digestivo/clasificación , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias del Recto/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: We aim to investigate whether a difference exists between right-sided and left-sided colon cancer at the same disease stage and subsequent liver metastasis and identify whether tumor location can independently influence survival. METHODS: Right-sided colon cancer was defined as malignancy arising from the cecum to the transverse colon; left-sided colon cancer was defined as malignancy arising from the splenic flexure to the sigmoid colon. Clinicopathological features and survival data were collected for analysis. RESULTS: Overall, 1442 patients were included for analysis. The median follow-up time was 58.2 months. Patients with left-sided colon cancer had better 5-year overall survival (75.2% vs 61.7%, P = 0.005), 5-year cancer-specific survival (81.6% vs 73.4%, P = 0.001), and 5-year recurrence-free survival (70.9% vs 66.5%, P = 0.033) compared with patients having right-sided colon cancer. After the presentation of subsequent liver metastasis, patients with primary left-sided colon cancer had better 3-year cancer-specific survival ( P < 0.001). In the multivariate analysis, cancer location was an independent prognostic factor for cancer-specific survival (right vs left, HR: 1.276, 95% CI: 1.002-1.625). CONCLUSIONS: The primary tumor location can serve as a prognostic factor for treatment outcomes either in primary stage III colon cancer or subsequent liver metastasis.
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Neoplasias del Colon/patología , Neoplasias Hepáticas/secundario , Anciano , Neoplasias del Colon/mortalidad , Neoplasias del Colon/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Sistema de Registros , Taiwán/epidemiologíaRESUMEN
PURPOSE: The rate of postoperative morbidity and mortality is reportedly high in patients aged ≥ 75 years with colorectal cancer (CRC). In such patients, a comparison of the short-term outcome between open method and laparoscopy has not been clearly defined in Taiwan. We aimed to compare postoperative morbidity and mortality parameters after open method and laparoscopy in CRC patients aged ≥ 75 years. METHODS: We retrospectively analyzed patients who underwent surgery for CRC from February 2009 to September 2015 at the Linkou Chang Gung Memorial Hospital in Taiwan and analyzed their clinicopathological factors. Postoperative morbidity and mortality were analyzed for evaluating if laparoscopic surgery offers more favorable outcomes than open surgery in the elderly. RESULTS: A total of 1133 patients were enrolled and analyzed in this study; they were divided into two groups (open method vs. laparoscopy = 797 vs. 336). The anastomotic leakage rate was significantly higher in the laparoscopy group than in the open method group (3.3 vs. 0.9%, p = 0.003). Overall postoperative morbidity and mortality rates showed no significant difference between these two groups. Postoperative hospital stay was significantly shorter in the laparoscopy group than in the open method group (10.4 ± 8.7 vs. 13.8 ± 13.5 days, p < 0.001). CONCLUSIONS: Our results suggest that laparoscopy in patients aged ≥ 75 years with CRC had higher anastomosis leakage rate compared with open surgery but is acceptable and offers the benefit of a shorter hospital stay over open surgery.
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Fuga Anastomótica , Colectomía , Neoplasias Colorrectales , Complicaciones Posoperatorias , Factores de Edad , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Colectomía/efectos adversos , Colectomía/métodos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Masculino , Selección de Paciente , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Ajuste de Riesgo/métodos , Taiwán/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved. METHODS: A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed. RESULTS: Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07-2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99-1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors. CONCLUSION: The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.
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Toma de Decisiones Clínicas , Neoplasias Colorrectales/patología , Hepatectomía/mortalidad , Neoplasias Hepáticas/secundario , Recurrencia Local de Neoplasia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
AIMS: The purposes of this study were to identify the impact of a case management programme on the related factors of refusing treatment or discontinuing treatment in Taiwanese colorectal cancer patients. BACKGROUND: Side effects of anti-cancer treatments are associated with refusing treatment and discontinuing treatment. DESIGN: This case-control study, longitudinal database and secondary analysis of population-based data was conducted from 2009-2012. METHODS: Logistic regression was used to reveal the factors related to refusing or discontinuing treatment. RESULTS: Of the 68 patients who refused treatment, the top reasons for refusing treatment were patients or their family considered the patients poor physical condition, difficulty in enduring any condition likely to cause physical discomfort from the disease treatment, selected complementary and alternative medicine, patients or their families or friends experienced negative treatment effects and worried about the side effects of treatment, older age, poor family support and lost contact. Of the 278 patients who discontinued treatment, the most common reasons for discontinuing treatment were patients or their families or friends experienced negative treatment effects and worried about the side effects of treatment, inconvenient transportation, patients or their family considered the patients poor physical condition, difficulty in enduring any condition likely to cause physical discomfort from the disease treatment, poor treatment effect and selected complementary and alternative medicine. CONCLUSION: Case managers can provide positive communication and available resources in relation to cancer treatment. A case management programme can help patients cope with the difficulties encountered during the treatment period.
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Neoplasias Colorrectales/terapia , Personal de Salud/psicología , Negativa al Tratamiento/estadística & datos numéricos , Enfermo Terminal/psicología , Enfermo Terminal/estadística & datos numéricos , Negativa del Paciente al Tratamiento/psicología , Negativa del Paciente al Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , TaiwánRESUMEN
PURPOSE: Purpose To assess preoperative serum alkaline phosphatase (ALP) levels in colon adenocarcinomapatients with various clinical features and determine its prognostic value. METHODS: Between 2000 and 2013, 10,800 stage I-IV colon cancer patients who underwent surgery wereretrospectively enrolled. The relationship between ALP level and variables, including age, gender,carcinoembryonic Antigen (CEA) levels, aspartate aminotransferase (AST) level, bilirubin level, tumor size,liver cirrhosis, hepatitis, albumin level, histological type, and TNM-stage, were evaluated. The impact of ALP level elevation on survival was evaluated. RESULTS: Significant elevations in ALP level were found in patients with CEA ≥5 ng/ml (p<0.001); AST |≥43 U/L (p<0.001); total bilirubin ≥1.5 U/L (p<0.001); liver cirrhosis (p<0.001); albumin; <3.5g/dL (p <0.001); and stage IV disease (p=0.03).Patients with elevated ALP levels had significantly worse 5-year overall survival (OS) for colon (5-year OSrate: 71.5% vs. 78.3%, p<0.001; Fig. 1a) and rectal (5-year OS rate: 64.5% vs. 72.3%, p<0.001; Fig. 1b)cancer than patients with normal ALP levels. CONCLUSIONS: Elevated preoperative ALP levels was not only associated with liver disease, but it was alsorelated with advanced tumor status, and indicated a poor survival in colon and rectal cancer patients.
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Adenocarcinoma/sangre , Fosfatasa Alcalina/sangre , Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/sangre , Adenocarcinoma/enzimología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Anciano , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
BACKGROUND: Hepatic metastasectomy for patients with primary colorectal cancer offers better long-term outcome, and chemotherapy can increase the rate of hepatic resectability for patients with initially inoperable disease. The pattern of liver metastasis and status of the primary tumor are rarely discussed in the analysis of long-term outcome. In this report, we evaluate the influence of the pattern of metastasis on clinical features and prognosis. METHODS: One hundred and fifty-nine patients who underwent hepatic metastasectomy with curative intent for liver metastasis of colorectal cancer between October 1991 and December 2006 were enrolled. Patients were grouped according to whether liver metastasis was centrally or peripherally located, based on imaging and operative findings. Patient demographics, characteristics of the primary and metastatic tumors, and surgical outcomes were analyzed for long-term survival. RESULTS: A greater proportion of patients with centrally located metastases were male, as compared with those with peripherally located metastases. Compared with patients with peripherally located metastases, patients with centrally located metastases were more likely to have multiple lesions (P = 0.016), involvement of multiple segments (P = 0.006), large metastases (P < 0.001), and bilobar distribution of metastases (P < 0.001). The estimated 5-year recurrence-free and overall survival rates were 22.4% and 34.2%, respectively. Univariate analysis revealed that centrally located metastasis, primary tumor in the transverse colon, metastasis in regional lymph nodes, initial extrahepatic metastasis, synchronous liver metastasis, multiple lesions, poorly differentiated tumor, and resection margin <10 mm were significant poor prognostic factors for recurrence-free survival and overall survival. Cox regression analysis showed that inadequate resection margin and centrally located liver metastasis were significant predictors of shorter overall survival. CONCLUSIONS: In colorectal cancer, centrally located liver metastasis represents a poor prognostic factor after hepatectomy, and is associated with early recurrence. Neoadjuvant chemotherapy may be used to downstage centrally located liver metastases to improve outcome.
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Neoplasias Colorrectales/cirugía , Hepatectomía/mortalidad , Neoplasias Hepáticas/cirugía , Metastasectomía/mortalidad , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
The abnormal S-nitrosylation induced by the overexpression and activation of inducible nitric oxide synthase (iNOS) modulates many human diseases, such as inflammation and cancer. To delineate the pathophysiological S-nitrosoproteome in cancer patients, we report an individualized S-nitrosoproteomic strategy with a label-free method for the site-specific quantification of S-nitrosylation in paired tumor and adjacent normal tissues from 11 patients with colorectal cancer (CRC). This study provides not only the first endogenous human S-nitrosoproteomic atlas but also the first individualized human tissue analysis, identifying 174 S-nitrosylation sites in 94 proteins. Fourteen novel S-nitrosylation sites with a high frequency of elevated levels in 11 individual patients were identified. An individualized S-nitrosylation quantitation analysis revealed that the detected changes in S-nitrosylation were regulated by both the expression level and the more dramatic post-translational S-nitrosylation of the targeted proteins, such as thioredoxin, annexin A4, and peroxiredoxin-4. These endogenous S-nitrosylated proteins illustrate the network of inflammation/cancer-related and redox reactions mediated by various S-nitrosylation sources, including iNOS, transnitrosylase, or iron-sulfur centers. Given the demonstrated sensitivity of individualized tissue analysis, this label-free approach may facilitate the study of the vastly under-represented S-nitrosoproteome and enable a better understanding of the effect of endogenous S-nitrosylation in cancer.
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Neoplasias Colorrectales/metabolismo , Proteínas/análisis , Proteínas/metabolismo , Proteómica/métodos , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Western Blotting , Neoplasias Colorrectales/cirugía , Cisteína/metabolismo , Humanos , Datos de Secuencia Molecular , Óxido Nítrico Sintasa de Tipo II/metabolismo , Medicina de Precisión , Proteínas/química , Valores de Referencia , Reproducibilidad de los Resultados , Albúmina Sérica Bovina/análisis , Espectrometría de Masas en Tándem/métodos , Tiorredoxinas/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Rectal cancer patients have a higher incidence of pulmonary metastases than those with colon cancer. This study aimed to examine the effects of rectal cancer level on recurrence patterns in rectal cancer patients. METHODS: Patients with T3/T4 rectal cancers who underwent surgery between 2002 and 2006 were recruited in this study. All the patients were followed up on until death. Recurrence patterns and survival rates were calculated in relation to clinical variables. RESULTS: There were 884 patients were enrolled in this study. Patients with low-rectal cancer had significantly worse five-year overall survival (OS) and disease-free survival (DFS) rates (47.25% and 44.07%, respectively) than patients with mid-rectal (63.46% and 60.22%, respectively) and upper-rectal cancers (73.91% and 71.87%, respectively). The level of the tumor (P <0.001), nodal status (P <0.001), tumor invasion depth (P <0.001), and tumor differentiation (P = 0.047, P = 0.015) significantly affected the surgical outcomes related to OS and DFS in the univariate and multivariate analyses. Furthermore, the level of the rectal cancer was a significant risk factor (hazard ratio 1.114; 95% CI, 1.074 to 1.161; P <0.001) for local recurrence, lung metastases, bone metastases, and systemic lymph node metastases. Significantly higher incidence rates of bone (53.8%) and brain metastases (22.6%) after initial lung metastases rather than initial liver metastases (14.8% and 2.9%, respectively) were also observed. CONCLUSIONS: For rectal cancer patients who underwent surgical resection, the rectal cancer level significantly affected surgical outcomes including rates and patterns of distant metastases.
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Adenocarcinoma/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Recurrencia Local de Neoplasia/patología , Complicaciones Posoperatorias , Neoplasias del Recto/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Invasividad Neoplásica , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Although liver resection (LR) for colorectal cancer (CRC) hepatic metastasis is the best strategy to improve patient outcomes, there are considerable concerns regarding the recurrence of CRC after LR. In this study, we investigated the prognostic indicators associated with CRC recurrence after LR for hepatic metastasis. METHODS: This is a retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and December 2012. The clinicopathological features and outcome parameters affecting prognosis were analyzed. RESULTS: A total of 332 LRs with curative intent were performed in 278 patients, of whom 168 (60.4%) experienced CRC recurrence after the first LR, and 206 of the 332 LRs (62.0%) developed CRC recurrence. A preoperative serum carcinoembryonic antigen level greater than 100 ng/mL and four or more metastatic tumor nodules were independent prognostic factors for CRC recurrence after LR. The disease-free survival rate after LR was significantly associated with the number of metastatic nodules. The patients who underwent surgical resection for recurrent CRC had favorable outcomes, with a five-year overall survival rate of 65.2%. CONCLUSION: The number of metastatic tumors significantly affects the outcomes of patients who undergo LR for CRC hepatic metastasis, indicating that a novel therapeutic strategy for patients at high risk may be required. However, favorable long-term outcomes are achievable through aggressive treatment with surgical resection of the recurrent CRC.
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Neoplasias Colorrectales/cirugía , Hepatectomía/mortalidad , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is an adult intestinal stem cell marker frequently detected in human colorectal cancers (CRCs). However, the value of Lgr5 level in CRC prognosis and treatment prediction has not been well characterized. METHODS: We examined Lgr5 expression in 384 formalin-fixed paraffin-embedded CRC specimens from 296 CRC patients, including 64 patients treated with 5-fluorouracil (5-FU)-based chemotherapy. The effects of Lgr5 on cell proliferation, survival, and drug resistance were examined in cultured CRC cells. RESULTS: Elevated expression of Lgr5 was observed in CRC tissues, and Lgr5 protein levels were significantly correlated with an advanced American Joint Committee on Cancer stage (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and distant metastasis (P < 0.001). High expression levels of Lgr5 were significantly associated with shorter disease-free survival (P < 0.001) and shorter cancer-specific survival (P = 0.007) in CRC patients. Among the chemotherapy-treated subgroups, patients with low Lgr5 level showed a better response rate (65 %) than patients with high Lgr5 level (37 %) towards 5-FU-based treatment (P = 0.025). In cultured CRC cell lines, knocking down Lgr5 suppressed cell proliferation and colony formation ability, while it enhanced apoptosis and rendered cells more sensitive to chemotherapeutic agents. In contrast, overexpression of Lgr5 increased cell proliferation and enhanced chemoresistance. CONCLUSION: These results suggest that elevated Lgr5 level is associated with CRC progression and treatment response and has the potential to serve as a therapeutic target in CRC patients.
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Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos , Fluorouracilo/uso terapéutico , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Fluorouracilo/farmacología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Análisis de Regresión , Resultado del TratamientoRESUMEN
We developed a multiplexed label-free quantification strategy, which integrates an efficient gel-assisted digestion protocol, high-performance liquid chromatography tandem MS analysis, and a bioinformatics alignment method to determine personalized proteomic profiles for membrane proteins in human tissues. This strategy provided accurate (6% error) and reproducible (34% relative S.D.) quantification of three independently purified membrane fractions from the same human colorectal cancer (CRC) tissue. Using CRC as a model, we constructed the personalized membrane protein atlas of paired tumor and adjacent normal tissues from 28 patients with different stages of CRC. Without fractionation, this strategy confidently quantified 856 proteins (≥2 unique peptides) across different patients, including the first and robust detection (Mascot score: 22,074) of the well-documented CRC marker, carcinoembryonic antigen 5 by a discovery-type proteomics approach. Further validation of a panel of proteins, annexin A4, neutrophils defensin A1, and claudin 3, confirmed differential expression levels and high occurrences (48-70%) in 60 CRC patients. The most significant discovery is the overexpression of stomatin-like 2 (STOML2) for early diagnostic and prognostic potential. Increased expression of STOML2 was associated with decreased CRC-related survival; the mean survival period was 34.77 ± 2.03 months in patients with high STOML2 expression, whereas 53.67 ± 3.46 months was obtained for patients with low STOML2 expression. Further analysis by ELISA verified that plasma concentrations of STOML2 in early-stage CRC patients were elevated as compared with those of healthy individuals (p < 0.001), suggesting that STOML2 may be a noninvasive serological biomarker for early CRC diagnosis. The overall sensitivity of STOML2 for CRC detection was 71%, which increased to 87% when combined with CEA measurements. This study demonstrated a sensitive, label-free strategy for differential analysis of tissue membrane proteome, which may provide a roadmap for the subsequent identification of molecular target candidates of multiple cancer types.
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Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/diagnóstico , Proteínas de la Membrana/metabolismo , Proteoma/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Anexina A4/metabolismo , Biomarcadores de Tumor/química , Proteínas Sanguíneas/biosíntesis , Antígeno Carcinoembrionario/sangre , Claudina-3 , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/sangre , Proteínas de la Membrana/química , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Análisis Multivariante , Péptidos/química , Pronóstico , Modelos de Riesgos Proporcionales , Proteoma/química , Curva ROC , Espectrometría de Masas en Tándem/métodos , alfa-Defensinas/metabolismoRESUMEN
BACKGROUND: This retrospective study evaluated the prognostic factors of chemotherapy in stage III colorectal cancer after curative resection. METHODS: From 1996 to 2001, 1,054 patients with primary single colorectal cancer underwent curative resection. Seven hundred sixteen patients received various 5-fluorouracil (FU)-based adjuvant chemotherapy regimens, including oral and intravenous treatments. The chemotherapy-related parameters examined included therapeutic duration, frequency, route of administration, composition of combination therapies, and postoperative time interval from the operation to the start of chemotherapy. RESULTS: The therapeutic duration and postoperative time interval of starting therapy were independent prognostic factors, in addition to clinicopathological factors. The 8-year cancer-specific/overall survival rates in patients who received chemotherapy for >4 months (63.0/58.6%) were significantly higher than the rates in patients who received no chemotherapy (56.7/37.7%, P < 0.01) and those who remained on chemotherapy for 1-4 months (49.4/41.9%, P < 0.05). The 8-year cancer-specific/overall survival rates in patients who waited 1-5 weeks after surgery to receive chemotherapy (62.9/58.5%) were significantly higher versus rates in those who did not receive chemotherapy (56.7/37.7%) and those who did not receive chemotherapy until >5 weeks after surgery (52.3/45.9%) (both P < 0.05). Survival rates did not differ between patients who did not undergo chemotherapy, those for whom chemotherapy lasted 1-4 months, and patients who did not receive chemotherapy until >5 weeks after surgery. CONCLUSIONS: The appropriate duration of therapy and early chemotherapy after surgery were 2 of the most important factors in eradicating occult cancer and effecting long-term survival benefits in patients with stage III colorectal cancer.
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Quimioterapia Adyuvante , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: To evaluate outcome and prognostic factors of patients with anorectal melanoma. METHODOLOGY: Twenty-two consecutive patients with anorectal melanoma received operation from 1993 through 2011 were reviewed. The definitions of stage I, II and III are local disease, locoregional lymphadenopathy and metastatic disease, respectively. RESULTS: The patients included 8 men and 14 women, aged from 36 to 83 years (mean, 58.4 years). At the end of the follow-up period, 19 patients died of disease and only 3 patients were alive with disease. Only two patients were alive longer than 5 years after operation. For stage I and II tumors that underwent clinical curative resection (n=17), stage II (p=0.04), tumor size >3 cm (p=0.008) and invasion depth to muscle (p=0.021) all showed poorer prognosis in overall survival. Though wide local excision (WLE) were performed in the patients with earlier tumors, there was no statistical difference in overall (p=0.063) and disease-free survival (p=0.333) between WLE and radical surgery. Furthermore, patients with WLE had more chance of local recurrence than radical surgery (6/7 vs. 3/10, p=0.050). Four salvage radical operations could be performed after local recurrence in WLE group. CONCLUSIONS: WLE increases the chance of local recurrence more than radical surgery. Care should be taken to avoid microseeding during performed WLE.
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Neoplasias del Ano/cirugía , Melanoma/cirugía , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/mortalidad , Neoplasias del Ano/patología , Femenino , Humanos , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patologíaRESUMEN
BACKGROUND/AIMS: Long course concurrent chemoradiotherapy provides potential tumor downstaging. When local recurrent rectal cancer without distant metastases is diagnosed, a potentially curative resection can be performed. The aim of this study was to assess the outcome of concurrent chemoradiotherapy in treating isolated local recurrent rectal cancer. METHODOLOGY: Patients (n=102) with isolated local recurrent rectal cancer within the pelvis were scheduled for concurrent chemoradiotherapy, consisting of pelvic irradiation with a total dose of 50.4 Gy in 28 fractions. Chemotherapy was administered concurrently and included 85 mg/m2 oxaliplatin by venous infusion over 2 h on day 1, followed by 1,200 mg*m-2*day-1 of continuous venous infusion for 2 days. This regimen was repeated every 2 weeks for 6 cycles. The overall survival rate, responses, disease-free interval and toxicities were assessed. RESULTS: A total of 96 patients completed planned concurrent chemoradiation. Complete clinical responses were found in 13 of the 96 patients (14%), partial responses in 59 (61%), stable disease in 21 (22%) and disease progression in 3 (3%). The overall survival and disease-free survival rates in all the 96 patients were 45% and 14%, respectively. CONCLUSIONS: The treatment of locally recurrent rectal cancer is complicated. Concurrent chemoradiation can increase disease-free survival and overall survival by increasing complete resection rate of locally recurrent tumors and even complete response of the tumors. Ongoing treatment strategies aim to enhance response rates and to accurately assess the extent of local recurrent tumor response to concurrent chemoradiation.
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Quimioradioterapia , Recurrencia Local de Neoplasia/terapia , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Recto/mortalidadRESUMEN
BACKGROUND: Colorectal cancer (CRC) is still among the most lethal and prevalent malignancies in the world. Despite continuous efforts, the diagnosis and prognosis of CRC have never been satisfying, especially the non-invasive assays. METHODS: Our study comprised three independent cohorts of 835 qualified stool samples. From 46 literature-identified miRNA candidates, four miRNA ratios were selected and developed into a miRNA-based signature after applied to the training and test sets. The clinical performances of this signature were further evaluated in the prospective cohorts. RESULTS: Four miRNA ratios with significant alterations and the highest discriminating power between the CRC and control groups in the training set were successfully validated in the test set. In the training dataset, combining these four miRNA ratios using a logistic regression model improved the area under the curve value to 0.821 and obtained a sensitivity of 73.6% and specificity of 78.9%. This miRNA signature showed consistent performances in the other two sample cohorts, with the highest sensitivity of 85.7% in the prospective cohort. Additionally, the higher miRNA signature was associated with worse disease-free survival (hazard ratio = 2.27) and overall survival (hazard ratio = 1.83) of CRC patients. For fecal immunochemical test (FIT)-positive populations, the positive predictive value for CRC detection in miRNA-positive subjects was 3.43-fold higher in the prospective cohort, compared to FIT alone. CONCLUSION: This stool miRNA signature is highly associated with poor outcome of CRC and can be added to FIT tests to help identify the most at-risk group to receive prompt colonoscopy examination.
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Neoplasias Colorrectales , MicroARNs , Humanos , MicroARNs/genética , Estudios Prospectivos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Pronóstico , Modelos LogísticosRESUMEN
BACKGROUND: Local excision has become an alternative for radical resection in rectal cancer for selected patients. The purpose of this study was to assess the clinicopathologic factors determining lymph node metastasis (LNM) in patients with T1-2 rectal cancer. METHODS: Between January 1995 and December 2009, a total of 943 patients with pT1 or pT2 rectal adenocarcinoma received radical resection at a single institution. Clinicopathologic factors were evaluated by univariate and multivariate analyses to identify risk factors for LNM. RESULTS: A total of 943 patients (544 men and 399 women) treated for T1-2 rectal cancer were included in this study. LNM was found in 188 patients (19.9%). In multivariate analysis, lymphovascular invasion (LVI; P < 0.001, hazard ratio 11.472), poor differentiation (PD; P = 0.007, hazard ratio 3.218), and depth of invasion (presence of pT2; P = 0.032, hazard ratio 1.694) were significantly related to nodal involvement. The incidence for LNM lesions in the presence of LVI, PD, and pT2 was 68.8, 50.0, and 23.1%, respectively, while that for pT1 carcinomas with no LVI or PD was 7.5%. CONCLUSIONS: LVI, PD, and pT2 are independent risk factors predicting LNM in pT1-2 rectal carcinoma.
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Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Ganglios Linfáticos/patología , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Literatura de Revisión como Asunto , Tasa de Supervivencia , Adulto JovenRESUMEN
PURPOSE: We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) on disease-free survival in patients with stages I to III colorectal cancer (CRC). METHODS: There were 3857 patients identified from our database. We used receiver operating characteristic (ROC) analysis to identify the best cutoff value of NLR. A 5-year disease-free survival was used as end point. Survival analysis was used to assess the NLR effect, after stratification by several clinopathologic factors. RESULTS: In the ROC analysis, NLR = 3 had the highest sensitivity and specificity. Elevated NLR (>3) in colon cancer seemed to accompany larger tumor size (~5 cm) and more advanced T stage. By multivariate analysis, elevated NLR in colon cancer was associated with an increased risk of disease progression or cancer death [hazard ratio (HR) 1.377, 95 % confidence interval 1.104-1.717, P = 0.014]. However, elevated NLR in rectal cancer lost its significance in multivariate analysis (HR 1.121, 95 % confidence interval 0.941-1.336, P = 0.200). Patients with elevated NLR had worse outcome, especially for colon cancer. CONCLUSIONS: Preoperative NLR influenced the disease-free survival in patients with stages I to III CRC. Elevated NLR (>3) was associated with worse outcome (5-year disease-free survival 66.3 % vs. 78.9 % in colon cancer, P < 0.001; 60. 5 % vs. 66.2 % in rectal cancer, P = 0.008). The difference was larger in colon cancer than in rectal cancer. NLR should be considered as a prognostic factor for stages I to III CRC patients after curative surgery.
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Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/cirugía , Procedimientos Quirúrgicos Electivos , Linfocitos/patología , Neutrófilos/patología , Neoplasias Colorrectales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.