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1.
Am J Clin Oncol ; 43(1): 28-34, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693507

RESUMO

BACKGROUND: Both regorafenib and reduced-intensity FOLFOXIRI (riFOLFOXIRI) prolong survival in patients with metastatic colorectal cancer (mCRC). However, the sequence in which they should be administrated first in late-line treatment for refractory mCRC remains unclear. PATIENTS AND METHODS: This study was a single-center retrospective cohort study that reviewed data from patients at Taipei Veterans General Hospital, Taiwan, with mCRC refractory to fluorouracil, irinotecan, oxaliplatin, cetuximab (wild-type RAS), and bevacizumab. Patients were divided into 2 groups: a regorafenib-first group and a riFOLFOXIRI-first group. The Kaplan-Meier method and log-rank test were used to analyze survival, and a Cox proportional hazards model was used for univariate, multivariate, and subgroup analyses. RESULTS: A total of 136 and 55 patients followed a regorafenib-first or riFOLFOXIRI-first treatment strategy, respectively. At baseline, patient characteristics were similar between the groups, except for younger age in the riFOLFOXIRI-first group. The regorafenib-first group had better overall survival (13.8 vs. 10.7 mo, P=0.038), whereas patients in the riFOLFOXIRI-first group had a better partial response rate (P=0.005) but a higher rate of discontinuation due to adverse effects (P=0.004) and cross-over to regorafenib (P<0.001). Thus, no significant difference was observed in progression-free survival (regorafenib-first strategy: 3.17 mo; riFOLFOXIRI-first strategy: 4.97 mo; P=0.624). Regorafenib-first strategy, sex, and pathology were identified as independent prognostic factors. Subgroup analysis indicated that younger age, better performance status, stage IV disease, and mutant RAS gene favored the regorafenib-first strategy. CONCLUSION: Treatment with regorafenib-first followed by riFOLFOXIRI resulted in better overall survival when given as late-line treatment for patients with refractory mCRC.


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Terapia de Salvação , Adenocarcinoma Mucinoso/secundário , Idoso , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano/administração & dosagem , Masculino , Oxaliplatina/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida
2.
J Gastrointest Surg ; 24(5): 1092-1100, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31140063

RESUMO

BACKGROUND OR PURPOSE: To compare the cost-performance between planned short-course radiation and upfront concurrent chemoradiation on metastatic rectal cancer. METHODS: A total of 75 patients with metastatic rectal cancer who underwent planned short-course radiation or upfront concurrent chemoradiation were enrolled. The Kaplan-Meier method was used to compute the survival rates. The χ2 test was used to compare baseline characteristics. The Cox proportional hazards model was applied to determine the prognostic influence of clinicopathological factors. RESULTS: The planned short-course radiation is superior to upfront concurrent chemoradiation in overall survival for the patients with metastatic rectal cancer (34.8 vs. 20.2 months, P = 0.010). The planned short-course radiation was an independent prognostic factor (P = 0.009, HR (95% CI) = 0.319(0.135-0.752)). The efficacy of radiation on downstaging was similar between planned short-course radiation and upfront concurrent chemoradiation. The total cost of concurrent chemoradiation is 4.52-fold more expensive than that of short-course radiation (340,142 vs. 75,106 NT dollars, respectively). CONCLUSIONS: Based on the impressive cost-performance of planned short-course radiation compared with upfront concurrent chemoradiation (better OS, modest downstaging and lower cost), planned short-course radiation should be the preferred radiation approach for managing metastatic rectal cancer.

3.
World J Surg Oncol ; 17(1): 226, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864365

RESUMO

BACKGROUND: Perineal wound complications are a long-lasting issue for abdominoperineal resection (APR) patients. Complication rates as high as 60% have been reported, with the most common complication being delayed perineal wound healing. The aim of this study was to identify risk factors for delayed perineal wound healing and its impact on prolonged hospital stay. METHODS: We included low rectal tumor patients who underwent APR at a referral medical center from April 2002 to December 2017; a total of 229 patients were included. The basic characteristics and surgical outcomes of the patients were analyzed to identify risk factors for delayed perineal wound healing (> 30 days after APR) and prolonged hospital stay (post-APR hospital stay > 14 days). RESULTS: All patients received primary closure for their perineal wound. The majority of patients were diagnosed with adenocarcinoma (N = 213, 93.1%). In the univariate analysis, patients with hypoalbuminemia (albumin < 3.5 g/dL) had an increased risk of delayed wound healing (39.5% vs. 60.5%, P = 0.001), which was an independent risk factor in the multivariable analysis (OR 2.962, 95% CI 1.437-6.102, P = 0.003). Patients with delayed wound healing also had a significantly increased risk of prolonged hospital stay (OR 6.404, 95% CI 3.508-11.694, P < 0.001). CONCLUSIONS: Hypoalbuminemia was an independent risk factor for delayed wound healing, which consequently led to a prolonged hospital stay. Further clinical trials are needed to reduce the incidence of delayed perineal wound healing by correcting albumin levels or nutritional status before APR.


Assuntos
Tempo de Internação , Períneo/cirurgia , Protectomia/métodos , Neoplasias Retais/cirurgia , Cicatrização/fisiologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Hipoalbuminemia/sangue , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/etiologia , Masculino , Pessoa de Meia-Idade , Períneo/patologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Protectomia/efeitos adversos , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
World J Surg ; 43(12): 3207-3215, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31515570

RESUMO

BACKGROUND: Patients with stage II colorectal cancer (CRC) have a higher risk of recurrence when they have certain risk factors, including clinical and pathological patterns. However, as the prognostic role of molecular patterns for stage II disease is still unclear, this study aimed to investigate it. METHODS: A total of 509 patients with stage II CRC were enrolled, and all clinical, pathological, and molecular data were collected. Molecular patterns included microsatellite instability (MSI); elevated microsatellite alterations at selected tetranucleotides (EMAST) status; and expression of RAS/RAF genes, genes of the APC pathway, and other gene mutations. The endpoints were oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local recurrence (LR), and distant recurrence (DR). Cox regression analysis was used. RESULTS: Numerous molecular patterns influenced the oncological outcomes on univariate analysis, but no variable reached significance in LR. On multivariate analysis, a mucinous component (MC) > 50% (P < 0.01) was significant for OS and CSS. Lymphovascular invasion (LVI; P< 0.01), MC > 50% (P < 0.01), and EMAST-H (P = 0.02) significantly influenced DFS, whereas LVI (P < 0.01), MC > 50% (P < 0.01), and TP53 mutation (P = 0.02) were significant for DR. CONCLUSIONS: In this study, MSI, EMAST, and RAS/RAF alterations did not influence the oncological outcomes. Overall, LVI and MC were two significant prognostic factors for DFS and DR. Thus, the histopathology, rather than the genes, plays a major role in the prognosis of patients with stage II CRC.

5.
Oncologist ; 24(12): 1534-1542, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31292272

RESUMO

BACKGROUND: The form of microsatellite instability (MSI) affecting tetranucleotide repeats known as elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has emerged as a new potential biomarker in multiple cancers. In colorectal cancer (CRC), the correlation between EMAST and MSI mutations remain inconclusive. MATERIALS AND METHODS: We evaluated 1,505 patients with CRC using five EMAST markers (D20S82, D20S85, D8S321, D9S242, and MYCL1) and the Bethesda panel of MSI markers. Most commonly, mutations involved in CRCs were identified by MassArray Assay, and DNA repair genes were analyzed by next-generation sequencing. Clinical characteristics and prognostic relevance were correlated with EMAST and MSI. RESULTS: Tumors that were EMAST positive and MSI high (MSI-H) were detected in 159 (10.6%) and 154 (10.2%) of 1,505 patients with CRC. Patients were divided into four groups according to EMAST and MSI status (EMAST-positive and MSI-H, EMAST-positive and microsatellite-stable [MSS], EMAST-negative and MSI-H, and EMAST-negative and MSS). The EMAST-positive and MSI-H group was associated with female predominance, higher prevalence of proximal colon tumors, early stage tumors, poorly differentiated tumors, mucinous histology, and higher incidence of mutations in PI3KCA, BRAF, TGFBR, PTEN, and AKT1 compared with other groups. Furthermore, compared with only EMAST-positive tumors or only MSI-H tumors, tumors that were both EMAST-positive and MSI-H had a higher frequency of MLH1, MSH3, MSH6, PMS2, and EXO1 gene mutations. Finally, the presence of EMAST-positive and MSI-H tumors was a good prognostic indicator in CRC. CONCLUSION: High mutations in several DNA repair genes in EMAST-positive and MSI-H tumors suggest that this subtype of CRC might be more suitable for treatment with immune therapy. IMPLICATIONS FOR PRACTICE: Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is a unique molecular subtype of colorectal cancer (CRC). The current study demonstrated that the EMAST-positive and MSI-high (MSI-H) group was associated with female predominance, higher prevalence of proximal colon tumors, early stage tumors, poorly differentiated tumors, mucinous histology, and higher incidence of mutations in PI3KCA, BRAF, TGFBR, PTEN, and AKT1 compared with other groups. Most importantly, high mutations in DNA repair genes and MSI-related genes in EMAST-positive and MSI-H tumors suggest that this subtype of CRC might be more suitable for treatment with immune therapy compared with MSI-H tumors alone.

6.
Int J Cancer ; 145(8): 2209-2224, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30980673

RESUMO

The dynamic cell-cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell-cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the ß-catenin/Tcf-4-activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA-146a-5p (miR-146a) is the major miRNA in CRCSC exosomes and exosomal miR-146a promotes stem-like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR-146a expression in serum exhibits higher miR-146aHigh /NumbLow CRCSC traits, an increased number of tumor-filtrating CD66(+) neutrophils and a decreased number of tumor-infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome-mediated stemness expansion.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Exossomos/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas rab de Ligação ao GTP/genética , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células HT29 , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Interferência de RNA , Microambiente Tumoral/genética , Proteínas rab de Ligação ao GTP/metabolismo
7.
J Chin Med Assoc ; 82(4): 312-317, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30865106

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second most common and third most fatal cancer in Taiwan. To reduce incidence and mortality rates from cancer, including CRC, the Health Promotion Administration in Taiwan initiated the National Program on Cancer Prevention in 2005. For patients who have a positive fecal occult blood test, colonoscopy is recommended, and double-contrast barium enema (BE) is reserved as an alternative for those who cannot receive colonoscopy. In addition, single-contrast BE is sometimes used in pediatrics to evaluate colonic condition. This study evaluated the usage trends of BE and colonoscopy in Taiwan. METHODS: Data from the National Health Insurance Research Database from 2001 to 2013 were used in this study. Patients who received BE and colonoscopy were identified using the procedure codes of the National Health Insurance program. Age-standardized, yearly rates of BE and colonoscopy procedures were calculated. RESULTS: According to the data, the total number of colonoscopies increased 3.7-fold from 2001 to 2013. The compound annual growth rates for BE and colonoscopy were -5.36% and 10.47%, respectively, during the same period. The compound annual growth rates for BE and colonoscopy were -3.89% and 11.64% from 2005 to 2009, and -11.36% and 9.82% from 2010 to 2013, respectively. BE was conducted significantly more frequently than colonoscopy in patients who were aged <12 years and in female patients. CONCLUSION: Professional association guidelines, national cancer prevention programs, patient and physician preferences, and increasing awareness and knowledge of CRC may all contribute to the increasing use of colonoscopy and the dramatic decline in the use of BE in Taiwan.


Assuntos
Enema Opaco/estatística & dados numéricos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Taiwan/epidemiologia , Adulto Jovem
8.
Int J Biol Markers ; 34(1): 47-53, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30854932

RESUMO

PURPOSE: The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC). MATERIALS AND METHODS: A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Right-sided colon cancer was defined as cancers in the cecum, ascending colon, and transverse colon, while LCRC was defined as cancers in the splenic flexure colon, descending colon, sigmoid colon, and rectum. The endpoint was overall survival. The mutations were detected via polymerase chain reaction and MASS array. The prognostic value was determined using the log-rank test and the Cox regression analysis. RESULTS: A total of 407 and 1096 cases were classified as right-sided colon cancer and LCRC, respectively. Compared to patients with LCRC, those with right-sided colon cancer had more mucinous type cancer (7.4% vs. 3.5%), poorly differentiated tumor (11.5% vs. 3.6%), and advanced tumor-node-metastasis stage. The risk for peritoneal tumor seeding was higher in the right-sided colon cancer group (12.8% vs. 5.7%). Overall survival was better in LCRC than in right-sided colon cancer ( P=0.036). CONCLUSIONS: In our study, right-sided colon cancer had a more advanced tumor stage, a higher risk of peritoneal metastasis, and a poorer outcome than LCRC. Moreover, right-sided colon cancer had more gene mutations in BRAF, KRAS, SMAD4, TGF-ß, PIK3CA, PTEN, AKT1, and high microsatellite instability.


Assuntos
Adenocarcinoma Mucinoso/secundário , Adenocarcinoma/secundário , Carcinoma de Células em Anel de Sinete/secundário , Neoplasias Colorretais/patologia , Cirurgia Colorretal/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Peritoneais/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/cirurgia , Idoso , Carcinoma de Células em Anel de Sinete/cirurgia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/cirurgia , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
9.
Am J Gastroenterol ; 114(1): 107-115, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30177785

RESUMO

INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region. METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude. RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn's disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43-1.57). India (9.31; 95% CI: 8.38-10.31) and China (3.64; 95% CI, 2.97-4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01-4.76]) and CD (IRR: 3.28; 95% CI: 1.83-9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10-5.16) and UC (IRR: 2.63; 95% CI: 1.2-5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91-0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05-1.24) was observed for CD incidence in China. This study received IRB approval. CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Adulto , Ásia/epidemiologia , Austrália/epidemiologia , Demografia , Feminino , Humanos , Incidência , Doenças Inflamatórias Intestinais/etiologia , Masculino , Pessoa de Meia-Idade , Ilhas do Pacífico/epidemiologia , Vigilância da População , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
10.
World J Surg Oncol ; 16(1): 128, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29976257

RESUMO

BACKGROUND: The incidence, site distribution, and mortality rates of patients with colorectal cancer differ according to gender. We investigated gene mutations in colorectal patients and wanted to examine gender-specific differences. METHODS: A total of 1505 patients who underwent surgical intervention for colorectal cancer were recruited from March 2000 to January 2010 at Taipei Veterans' General Hospital and investigated for gene mutations in K-ras, N-ras, H-ras, BRAF, loss of 18q, APC, p53, SMAD4, TGF-ß, PIK3CA, PTEN, FBXW7, AKT1, and MSI. RESULTS: There were significant differences between male and female patients in terms of tumor location (p < 0.0001) and pathological stage (p = 0.011). The female patients had significantly more gene mutations in BRAF (6.4 vs. 3.3%, OR 1.985, p = 0.006), TGF-ß (4.7 vs. 2.5%, OR 1.887, p = 0.027), and revealed a MSI-high status (14.0 vs. 8.3%, OR 1.800, p = 0.001) than male patients. Male patients had significantly more gene mutations in N-ras (5.1 vs. 2.3%, OR 2.227, p = 0.012); however, the significance was maintained only for mutations in BRAF (OR 2.104, p = 0.038), MSI-high status (OR 2.003 p = 0.001), and N-ras (OR 3.000, p = 0.010) after the groups were divided by tumor site. CONCLUSION: Gene mutations in BRAF, MSI-high status, and N-ras differ according to gender among patients with colorectal cancer.


Assuntos
Neoplasias Colorretais , Mutação , Proteínas Proto-Oncogênicas B-raf , Neoplasias Colorretais/genética , Feminino , Genes ras/genética , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Fatores Sexuais
11.
Am J Surg ; 216(5): 1022-1027, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29859628

RESUMO

BACKGROUND: Laparoscopic surgery has become a well-established technique for management of various surgical problems. A more efficient training methods are of upmost importance for current surgery residents. METHODS: This is a prospective, randomized, 3-arm trial to compare the training efficient of the naked-eye box trainer, training box games and conventional video-based box trainer in training laparoscopic suturing skill. RESULTS: The three training models were well acceptable and all could improve the acquisition of laparoscopic suturing and knotting skill in novices. The completion time was 604 ±â€¯298 s in the box trainer games, 617 ±â€¯335 s in the naked-eye training module, and 491 ±â€¯334 s in the video-based box trainer (p = 0.322). Using the structured procedure-specific checklist, there was no significant difference in scores between these three groups (p = 0.977). CONCLUSIONS: Naked-eye box trainer and training box games produce similar training effect as the conventional video-based box trainer. The naked-eye box trainer may serve as a convenient way for novice trainees to acquire laparoscopic suturing technique skills before video-based simulation.


Assuntos
Laparoscopia/educação , Treinamento por Simulação/métodos , Técnicas de Sutura/educação , Competência Clínica , Feminino , Humanos , Masculino , Estudos Prospectivos , Jogos de Vídeo
12.
PLoS One ; 13(5): e0197681, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795620

RESUMO

Recent studies suggest that aberrant DNA methylation might occur early and commonly in colorectal tumorigenesis. In 111 normal subjects, the mean LINE-1 methylation level of peripheral blood was 81.0 ± 5.7%. Of 143 colorectal cancer (CRC) patients, the mean level of LINE-1 methylation was 60.5 ± 12.5%. We defined below 60% as cut-off value of LINE-1 hypomethylation, and 93 cases (65.0%) had LINE-1 hypomethylation in the tumor tissue. LINE-1 hypomethylation was not associated with any other clinical features. There was a trend that LINE-1 hypomethylation tumors were associated with advanced disease, but it did not reach statistical significance. There was no significant association between mutations of 12 genes, MSI-high, EMAST, and LINE-1 hypomethylation level. The median follow-up was 61.2 months. Five-year disease-free survival (DFS) and overall survival curves of patients with LINE-1 hypomethylation tumors were significantly lower than those of patients with normal LINE-1 methylation tumors (p = 0.032 and 0.001, respectively). Multivariate analysis showed that only TNM staging was an independent prognostic factor for CRC patients including DFS and overall survival (OS). LINE-1 did not impact patients' outcomes in multivariate analysis including DFS and OS. In conclusion, LINE-1 hypomethylation is marginally related to advanced stage CRC and impacts patients' outcomes in univariate analysis.


Assuntos
Neoplasias Colorretais/patologia , Metilação de DNA , Elementos Nucleotídeos Longos e Dispersos/genética , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Taxa de Sobrevida
13.
Intest Res ; 15(4): 487-494, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29142516

RESUMO

Background/Aims: In Taiwan, due to budget limitations, the National Health Insurance only allows for a limited period of biologics use in treating moderate to severe Crohn's disease (CD). We aimed to access the outcomes of CD patients following a limited period use of biologics, specifically focusing on the relapse rate and remission duration; also the response rate to second use when applicable. Methods: This was a multicenter, retrospective, observational study and we enrolled CD patients who had been treated with adalimumab (ADA) according to the insurance guidelines from 2009 to 2015. Results: A total of 54 CD patients, with follow-up of more than 6 months after the withdrawal of ADA, were enrolled. The average period of treatment with ADA was 16.7±9.7 months. After discontinuing ADA, 59.3% patients suffered a clinical relapse. In the univariate analysis, the reason for withdrawal was a risk factor for relapse (P=0.042). In the multivariate analysis, current smoker became an important risk factor for relapse (OR, 3.9; 95% CI, 1.2-14.8; P=0.044) and male sex was another risk factor (OR, 2.9; 95% CI, 1.1-8.6; P=0.049). For those 48 patients who received a second round of biologics, the clinical response was seen in 60.4%, and 1 anaphylaxis occurred. Conclusions: Fifty-nine percent of patients experienced a relapse after discontinuing the limited period of ADA treatment, and most of them occurred within 1 year following cessation. Male sex and current smoker were risk factors for relapse. Though 60.4% of the relapse patients responded to ADA again.

14.
Intest Res ; 15(3): 266-284, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28670225

RESUMO

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic mucosal inflammation of the colon, and the prevalence and incidence of UC have been steadily increasing in Taiwan. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of UC taking into account currently available evidence and the expert opinion of the committee. Accurate diagnosis of UC requires thorough clinical, endoscopic, and histological assessment and careful exclusion of differential diagnoses, particularly infectious colitis. The goals of UC therapy are to induce and maintain remission, reduce the risk of complications, and improve quality of life. As outlined in the recommended treatment algorithm, choice of treatment is dictated by severity, extent, and course of disease. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to immunosuppressive treatment, especially with steroids and biologic agents, and should be regularly monitored for reactivation of latent infection. These consensus statements are also based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of UC in Taiwan.

15.
Intest Res ; 15(3): 285-310, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28670226

RESUMO

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.

16.
Int J Mol Sci ; 18(7)2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28678173

RESUMO

We compared the clinicopathological and molecular profiles between different age groups of sporadic colorectal cancer (CRC) patients (age <50, 56-60, 60-70, 70-80, and >80); 1475 CRC patients were enrolled after excluding 30 individuals with Lynch syndrome. The mutation spectra for APC, TP53, KRAS, PIK3CA, FBXW7, BRAF, NRAS, HRAS, TGFbR, Akt1, and PTEN were analyzed using polymerase chain reaction (PCR), followed by MassArray and microsatellite (MSI-high) analysis by performing genotyping. Male patients (74.1%) were significantly predominant to females (25.9%) in the older age group (70-80, >80). There was an insignificantly linear trend between TNM staging and age-onset of CRC diagnosis. Patients aged < 50 had 58.7% diseases in the advanced stages (Stage III: 36.5% and IV: 22.2% respectively), while this decreased to 40.2% (Stage III: 26.2% and IV; 14.0% respectively) in patients >80. The distributions of mutation frequency were similar in majority of the genes studied among different age groups. Additionally, patients aged <50 had significantly higher frequency of MSI-high, PTEN, and HRAS mutations than those of other groups. Age-onset at diagnosis significantly affected overall survival (HR = 1.46; 95% CI: 1.35-1.58), but not cancer-specific survival (HR = 1.08; 95% CI: 0.99-1.18) in multivariate analysis. In conclusion, molecular and clinicopathological differences were not as significant among different age groups of CRC patients as previously suspected.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
17.
Oncotarget ; 8(8): 13805-13817, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28099153

RESUMO

We developed a series of models to predict the likelihood of recurrence and the response to chemotherapy for the personalized treatment of stage I and II colorectal cancer patients. A recurrence prediction model was developed from 235 stage I/II patients. The model successfully distinguished between high-risk and low-risk groups, with a hazard ratio of recurrence of 4.66 (p < 0.0001). More importantly, the model was accurate for both stage I (hazard ratio = 5.87, p = 0.0006) and stage II (hazard ratio = 4.30, p < 0.0001) disease. This model performed much better than the Oncotype and ColoPrint commercial services in identifying patients at high risk for stage II recurrence. And unlike the commercial services, the robust model included recurrence prediction for stage I patients. As stage I/II CRC patients usually do not receive chemotherapy, we generated chemotherapy efficacy prediction models with data from 358 stage III patients. The predictions were highly accurate: the hazard ratio of recurrence for responders vs. non-responders was 4.13 for those treated with FOLFOX (p < 0.0001), and 3.16 (p = 0.0012) for those treated with fluorouracil. We have thus created a prognostic model that accurately identifies patients at high risk for recurrence, and the first accurate chemotherapy efficacy prediction model for individual patients. In the future, complete personalized treatment plans for stage I/II patients may be developed if the drug prediction models generated from stage III patients are verified to be effective for stage I and II patients in prospective studies.


Assuntos
Neoplasias Colorretais/patologia , Simulação por Computador , Recidiva Local de Neoplasia/epidemiologia , Medicina de Precisão/métodos , Idoso , Área Sob a Curva , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade
18.
Oncotarget ; 8(22): 36707-36715, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27888621

RESUMO

Ascites related to metastatic colorectal cancer (mCRC) reduces patient survival and quality of life, and systemic chemotherapy is largely ineffective for managing ascites. Here, we examined the clinical efficacy of intraperitoneal (IP) ziv-aflibercept for managing refractory ascites in 15 mCRC patients who did not respond to standard chemotherapy. Fifty or 100 mg of ziv-aflibercept in 100 mL of saline solution were infused through a pigtail catheter and retained for 24 h. When the ascites drainage volumes were subsequently monitored, 73.3% of patients showed an objective response (OR) to IP ziv-aflibercept treatment. Patients with low Eastern Cooperative Oncology Group (ECOG) performance status or with serum ascites albumin gradients (SAAG) less than 1.1 g/dL had better responses to treatment, and 4 patients with SAAG less than 1.1 g/dL showed rapid objective responses (rOR). These findings indicate that intraperitoneal ziv-aflibercept therapy may be a highly effective means of treating refractory ascites in mCRC patients, and that SAAG may be predictive of a rapid response to this treatment.


Assuntos
Antineoplásicos/administração & dosagem , Ascite/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Gerenciamento Clínico , Feminino , Humanos , Injeções Intraperitoneais , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Razão de Chances , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
20.
Intest Res ; 14(3): 248-57, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27433147

RESUMO

BACKGROUND/AIMS: With the recent progress in medical treatment, surgery still plays a necessary and important role in treating ulcerative colitis (UC) patients. In this study, we analyzed the surgical results and outcomes of UC in Taiwan in the recent 20 years, via a multi-center study through the collaboration of Taiwan Society of IBD. METHODS: A retrospective analysis of surgery data of UC patients from January 1, 1995, through December 31, 2014, in 6 Taiwan major medical centers was conducted. The patients' demographic data, indications for surgery, and outcome details were recorded and analyzed. RESULTS: The data of 87 UC patients who received surgical treatment were recorded. The median post-operative follow-up duration was 51.1 months and ranged from 0.4 to 300 months. The mean age at UC diagnosis was 45.3±16.0 years and that at operation was 48.5±15.2 years. The 3 leading indications for surgical intervention were uncontrolled bleeding (16.1%), perforation (13.8%), and intractability (12.6%). In total, 27.6% of surgeries were performed in an emergency setting. Total or subtotal colectomy with rectal preservation (41.4%) was the most common operation. There were 6 mortalities, all due to sepsis. Emergency operation and low pre-operative albumin level were significantly associated with poor survival (P=0.013 and 0.034, respectively). CONCLUSIONS: In the past 20 years, there was no significant change in the indications for surgery in UC patients. Emergency surgeries and low pre-operative albumin level were associated with poor survival. Therefore, an optimal timing of elective surgery for people with poorly controlled UC is paramount.

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