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1.

Introduction

Diabetes mellitus (DM) has the potential to impact the pathogenesis, treatment, and outcome of pancreatic cancer. This study evaluates the impact of DM on pancreatic cancer survival.

Methods

We conducted a retrospective cohort study from the Veterans Affairs (VA) Central Cancer Registry (VACCR) for pancreatic cancer cases between 1995 and 2008. DM and no-DM cases were identified from comorbidity data. Univariate and multivariable analysis was performed. Multiple imputation method was employed to account for missing variables.

Results

Of 8,466 cases of pancreatic cancer DM status was known in 4728 cases that comprised this analysis. Males accounted for 97.7% cases, and 78% were white. Overall survival was 4.2 months in DM group and 3.6 months in the no-DM group. In multivariable analysis, DM had a HR = 0.91 (0.849–0.974). This finding persisted after accounting for missing variables using multiple imputations method with the HR in DM group of 0.93 (0.867–0.997).

Conclusions

Our data suggest DM is associated with a reduction in risk of death in pancreatic cancer. Future studies should be directed towards examining this association, specifically impact of DM medications on cancer outcome.  相似文献   

2.
Rectal bleeding is considered to be an alarm symptom of colorectal cancer. However, the symptom is seldom reported to the general practitioner and it is often assumed that patients assign the rectal bleeding to benign conditions. The aims of this questionnaire study were to examine whether rectal bleeding was associated with longer patient delays in colorectal cancer patients and whether rectal bleeding was associated with cancer worries. All incident colorectal cancer patients during a 1-year period in the County of Aarhus, Denmark, received a questionnaire. 136 colorectal cancer patients returned the questionnaire (response rate: 42%). Patient delay was assessed as the interval from first symptom to help-seeking and was reported by the patient. Patients with rectal bleeding (N = 81) reported longer patient intervals than patients without rectal bleeding when adjusting for confounders including other symptoms such as pain and changes in bowel habits (HR = 0.43; p = 0.004). Thoughts about cancer were not associated with the patient interval (HR = 1.05; p = 0.887), but more patients with rectal bleeding reported to have been wondering if their symptom(s) could be due to cancer than patients without rectal bleeding (chi2 = 15.29; p<0.001). Conclusively, rectal bleeding was associated with long patient delays in colorectal cancer patients although more patients with rectal bleeding reported to have been wondering if their symptom(s) could be due to cancer than patients without rectal bleeding. This suggests that assignment of symptoms to benign conditions is not the only explanation of long patient delays in this patient group and that barriers for timely help-seeking should be examined.  相似文献   

3.

Objective

To know the effect of age on survival outcome in operated and non-operated patients with colon cancer.

Methods

From the Surveillance, Epidemiology, and End Results database, we identified 123,356 patients with colon cancer who were diagnosed between 1996 and 2005, grouped them as older or younger than 40 years and analyzed their 5-year cancer-specific survival (CSS) data, along with some risk factors, using Kaplan–Meier methods and multivariable Cox regression models.

Results

The younger group had significantly higher pathological grades (P<0.001), more mucinous and signet-ring histology (P<0.001), advanced AJCC stage (P<0.001), and were more likely to undergo surgery (P<0.001). For surgically treated patients, age did not significantly affect 5-year CSS (younger: 66.7%; older: 67.3%; P = 0.86). Further analysis showed that age was an independent prognostic factor in stage I–IV disease (stage I: P = 0.001; P<0.001 for stages II–IV, in both uni- and multivariate analyses), but not for patients with unknown disease stage (P = 0.52). For non-surgically treated patients, age significantly affected 5-year CSS (younger: 16.2%; older: 12.9%; P<0.001) in univariate analysis; and was an independent prognostic factor (P<0.001) in multivariate analysis.

Conclusion

The CSS rate for younger CC patients was at least as high as for older patients, although they presented with higher proportions of unfavorable factors and more advanced disease.  相似文献   

4.

Purpose

To evaluate the prognostic impact of the lymph node ratio (LNR) in ypStage III rectal cancer patients who were treated with neoadjuvant chemoradiotherapy (NCRT).

Materials and Methods

We retrospectively reviewed the data of 638 consecutive patients who underwent NCRT followed by total mesorectal excision, and postoperative adjuvant chemotherapy for rectal cancer from 2004 to 2011. Of these, 125 patients were positive for lymph node (LN) metastasis and were analyzed in this study.

Results

The median numbers of examined and metastatic LNs were 17 and 2, respectively, and the median LNR was 0.143 (range, 0.02–1). Median follow-up time was 55 months. In multivariate analyses, LNR was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] 2.17, p = 0.041), disease-free survival (DFS) (HR 2.28, p = 0.005), and distant metastasis-free survival (DMFS) (HR 2.30, p = 0.010). When ypN1 patients were divided into low (low LNR ypN1 group) and high LNR (high LNR ypN1 group) according to a cut-off value of 0.152, the high LNR ypN1 group had poorer OS (p = 0.043) and DFS (p = 0.056) compared with the low LNR ypN1 group. And there were no differences between the high LNR ypN1 group and the ypN2 group in terms of the OS (p = 0.703) and DFS (p = 0.831).

Conclusions

For ypN-positive rectal cancer patients, the LNR was a more effective prognostic marker than the ypN stage, circumferential resection margin, or tumor regression grade after NCRT, and could be used to discern the high-risk group among ypN1 patients.  相似文献   

5.

Background

Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab.

Patients and Methods

Patients ≥70 years of age received either capecitabine 1250 mg/m2 bid days 1–14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m2 bid days 1–14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS.

Results

In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR.

Conclusion

This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor.  相似文献   

6.
7.

Background

Laparoscopic surgery for middle and lower rectal cancer remain controversial because anatomical and complex surgical procedures specifically influence oncologic outcomes. This study analyzes the long-term outcomes of laparoscopic versus open surgery for middle and lower rectal cancer.

Methods

Patients (laparoscopic: n = 129, open: n = 152) who underwent curative resection for middle and lower rectal cancer from 2003 to 2008 participated in the study. The same surgical team performed all operations. The mean follow up time of all patients was 74.3 months.

Results

No statistical difference in local recurrence rate (7.8% vs. 7.2%; log-rank = 0.024; P = 0.876) and distant recurrence rate (20.9% vs.16.4%; log-rank = 0.699; P = 0.403) between laparoscopic and open groups were observed within 5 years. The 5-year overall survival rates of the laparoscopic and open groups were 72.9% and 75.7%, respectively; no significant statistical difference was observed between them (log-rank = 0.163; P = 0.686). The 5-year survival rates between groups were not different between stages: Stage I (92.6% vs. 86.7%; log-rank = 0.533; P = 0.465); stage II (75.8% vs. 80.5%; log-rank = 0.212; P = 0.645); and Stage III (63.8% vs. 69.1%, log-rank = 0272;P = 0.602). However, significant statistical difference amongst different stages were observed (log-rank = 1.802; P = 0.003).

Conclusion

Laparoscopic and open surgery for middle and lower rectal cancer offer equivalent long-term oncologic outcomes. Laparoscopic surgery is feasible in these patients.  相似文献   

8.

Purpose

The aim of this study was to build a molecular prognostic model based on gene signatures for patients with completely resected hepatic metastases from colorectal cancer (MCRC).

Methods

Using the Illumina HumanHT-12 gene chip, RNA samples from the liver metastases of 96 patients who underwent R0 liver resection were analyzed. Patients were randomly assigned to a training (n = 60) and test (n = 36) set. The genes associated with disease-specific survival (DSS) and liver-recurrence-free survival (LRFS) were identified by Cox-regression and selected to construct a molecular risk score (MRS) using the supervised principle component method on the training set. The MRS was then evaluated in the independent test set.

Results

Nineteen and 115 genes were selected to construct the MRS for DSS and LRFS, respectively. Each MRS was validated in the test set; 3-year DSS/LRFS rates were 42/32% and 79/80% for patients with high and low MRS, respectively (p = 0.007 for DSS and p = 0.046 for LRFS). In a multivariate model controlling for a previously validated clinical risk score (CRS), the MRS remained a significant predictor of DSS (p = 0.001) and LRFS (p = 0.03). When CRS and MRS were combined, the patients were discriminated better with 3-year DSS/LRFS rates of 90/89% in the low risk group (both risk scores low) vs 42/26% in the high risk group (both risk scores high), respectively (p = 0.002/0.004 for DSS/LRFS).

Conclusion

MRS based on gene expression profiling has high prognostic value and is independent of CRS. This finding provides a potential strategy for better risk-stratification of patients with liver MCRC.  相似文献   

9.
Risk of colorectal cancer (CRC) is considerably higher in men compared to women; however, there is inconclusive evidence of sex differences in CRC prognosis. We aimed to assess and explain sex differences in 5-year relative survival using standard and model-based period analysis among 164,996 patients diagnosed with CRC from 1997 to 2006 and reported to 11 German cancer registries covering a population of 33 million inhabitants. Age-adjusted 5-year relative survival was higher in women (64.5% vs. 61.9%, P<0.0001). A substantial survival advantage of women was confirmed in multivariate analysis after adjusting for CRC stage and subsite in subjects under 65 years of age (relative excess risk, RER 0.86, 95% CI 0.82–0.90), but not in older subjects (RER 1.01, 95% CI 0.98–1.04); this pattern was similar in the 1st and in the 2nd to 5th year after diagnosis. The survival advantage of women varied by CRC stage and age and was most pronounced for localized disease (RERs 0.59–0.88 in various age subgroups) and in patients under 45 years of age (RERs 0.59, 0.72 and 0.76 in patients with localized, regional or advanced disease, respectively). On the contrary, sex differences in survival did not vary by location of CRC. In conclusion, our large population-based study confirmed a survival advantage of female compared to male CRC patients, most notably in young and middle aged patients and patients with localized disease. The effect of sex hormones, either endogenous or through hormonal replacement therapy, might be the most plausible explanation for the observed patterns.  相似文献   

10.

Background

The rising challenge of diabetes requires novel service delivery approaches. In the UK, Local Enhanced Services (LES) have been commissioned for diabetes. Health professionals from general practices (GPs) who signed up to LES were given additional training (and a monetary incentive) to improve management of patients with diabetes. All practices in the PCT were invited to the LES initiative, which ensured avoiding selection bias. The aim of the study was to examine the impact of LES in terms of diabetes Quality Outcome Framework (QOF) indicators: DM23(glycaemia), DM17(lipid) and DM12(blood pressure; BP).

Methods

QOF diabetes indicators were examined using data from 76 general practices for 2009–2010 in a large primary care trust area in Birmingham, UK. Data were extracted from Quality Management Analysis System. The primary outcome was a difference in achievement of QOF indicators between LES and NLES practices. A secondary outcome was the difference between LES and non-LES practices for hospital first and follow-up appointments.

Results

We did not find any difference for DM12(BP) and DM17(lipid) outcomes between LES and NLES practices. However, LES practices were more likely to achieve the DM23(glycaemia) outcome (estimated odds 1.459;95% CI:1.378-1.544; P=0.0001). The probability of achieving satisfactory level of DM23(glycaemia) increased by almost 10% when GPs belonged to LES groups compared with GPs in NLES group. LES practices were less likely to refer patients to secondary care.

Conclusion

Overall, LES practices performed better in the achievement of DM23(glycaemia) and also referred fewer patients to hospital, thereby meeting their objectives. This suggests that the LES approach is beneficial and needs to be further explored in order to ascertain whether the impact exerted was due to LES.  相似文献   

11.

Background

Delayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients.

Patients and Methods

Patients (age ≥66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER–Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples.

Results

4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2–3 months), and 12.3% had delayed chemotherapy (≥3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival).

Conclusion

Although the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation.  相似文献   

12.
In a panel of 18 colon cancer cell lines we found that the thymidylate synthase (TS) genotype was related to TS enzyme activity, but not to TS protein and mRNA levels. In addition, no relation with drug sensitivity was observed. TS genotyping of different tissues from 78 colorectal cancer patients revealed a high level of homology in polymorphic status between normal and malignant tissues and the heterozygous genotype to be the most frequent.  相似文献   

13.
目的:探讨胃大部切除后不同吻合术式对胃癌合并2型糖尿病患者血糖的影响.方法:选择66例在本院行手术治疗的胃癌合并2型糖尿病的患者为研究对象,随机分为毕Ⅰ式组26例,毕Ⅱ式组24例,Roux-en-y组16例.检测和比较三组患者术前和术后随访3月时患者的OGTT空腹及负荷后血糖值、糖化血红蛋白等水平.结果:术前三组OGTT空腹血糖、2h血糖、糖化血红蛋白水平、空腹胰岛素水平、稳态模型评估胰岛素抵抗(HOMA-IR)的比较均无统计学差异(P均>0.05).术后3月,与毕Ⅰ式组比较,毕Ⅱ式组与Roux-en-y组未达2型糖尿病诊断标准的患者百分率显著升高(X2=7.866,P=0.020),OGTT空腹血糖(F=6.472,P=0.005)水平、OGTT 2 h血糖水平(F=3.431,P=0.041)、糖化血红蛋白水平(F=5.456,P=0.009)、空腹胰岛素水平(F=6.120,P=0.008)、HOMA-IR(F=8.091,P<0.001)均显著降低.毕Ⅱ式组与Roux-en-y组之间以上指标比较均无统计学差异(P>0.05).结论:胃癌合并2型糖尿病的患者在消化道重建术后部分可得缓解,采用毕Ⅱ式或Roux-en-y吻合术可能更适宜胃癌合并2型糖尿病的患者.  相似文献   

14.

Background

To investigate the impact of pre-treatment lactate dehydrogenase (LDH) levels on the outcome of patients with metastatic colorectal cancer treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase III prospective multicentre randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial.

Methods

Three hundred and seventy patients enrolled onto the ITACa first-line trial were considered for this study, 176 receiving chemotherapy (either FOLFIRI or FOLFOX) plus bevacizumab and 194 receiving chemotherapy only. Pre-treatment LDH levels were evaluated to identify a potential correlation with progression-free survival (PFS), overall survival (OS) and objective response rate.

Results

Information on pre-treatment LDH levels was available for 344 patients. High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population. In the chemotherapy plus bevacizumab group, median PFS was 9.1 and 9.8 months in patients with high LDH and low LDH, respectively (p= 0.073), whereas in the chemotherapy-only arm it was 6.9 and 9.1 months, respectively (p < 0.0001). In patients with high LDH, the addition of bevacizumab to chemotherapy led to a reduction in the rate of progressive disease (16.4 vs. 30.5%, p= 0.081) and to a prolonged PFS (p= 0.028).

Conclusion

A high LDH value was confirmed as a marker of poor prognosis. Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.

Trial Registration

NCT01878422 ClinicalTrials.gov  相似文献   

15.

Background

Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC).

Methods

We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.

Results

One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS) or overall survival (OS) associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5%) after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009). Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194–3.619; p = 0.010) was independently associated with OS.

Conclusions

Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC.  相似文献   

16.
17.
赵明  习阳  步世忠 《生命科学研究》2016,(4):365-370,376
国内外的流行病学研究表明,2型糖尿病与结直肠癌的发病率逐年升高,且两者可能存在相关性。现主要从两者共有的危险因素,如性别差异、不良的生活方式、疾病家族史和胰岛素的治疗情况等,及疾病发生的分子机制如胰岛素样生长因子、高胰岛素血症、慢性炎症和氧化应激、长链非编码RNA及细胞自噬等角度阐述糖尿病与结直肠癌之间的关系。  相似文献   

18.
PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I) as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001) and PFS (P < .001) than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001) and PFS (P = .001). PFS (P < .001) in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049). CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.  相似文献   

19.

Objective

To explore genes of the killer-cell immunoglobulin-like receptor (KIR) and of the HLA ligand and their relationship with the outcome of metastatic colorectal cancer (mCRC) patients treated with first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI).

Methods

A total of 224 mCRC patients were screened for KIR/HLA typing. The determination of the KIR/HLA combinations was based upon the gene content and variants. Genetic associations with complete response (CR), time to progression (TTP) and overall survival (OS) were evaluated by calculating odds and hazard ratios. Multivariate modeling with prognostic covariates was also performed.

Results

For CR, the presence of KIR2DL5A, 2DS5, 2DS1, 3DS1, and KIR3DS1/HLA-Bw4-I80 was associated with increased CR rates, with median ORs ranging from 2.1 to 4.3, while the absence of KIR2DS4 and 3DL1 was associated with increased CR rates (OR 3.1). After univariate analysis, patients that underwent resective surgery of tumor, absence of KIR2DS5, and presence of KIR3DL1/HLA-Bw4-I80 showed a significant better OS (HR 1.5 to 2.8). Multivariate analysis identified as parameters independently related to OS the type of treatment (surgery; HR 2.0) and KIR3DL1/HLA-Bw4-I80 genotype (HR for T-I80 2.7 and for no functional KIR/HLA interaction 1.8). For TTP, no association with KIR/HLA genes was observed.

Conclusion

This study, for the first time, evidences that the genotyping for KIR-HLA pairs are found predictive markers associated with complete response and improves overall survival prediction of FOLFIRI treatment response in metastatic colorectal cancer. These results suggest a role of the KIR/HLA system in patient outcome, and guide new research on the immunogenetics of mCRC through mechanistic studies and clinical validation.  相似文献   

20.
目的:评价中国地区糖尿病对乳腺癌患者预后的影响,为临床工作提供依据。方法:检索万方、中国知网、维普、Medline、Pubmed、Embase数据库有关糖尿病对乳腺癌患者预后影响的文章,收集数据,进行meta 分析,以合并OR 值作为效应指标。结果:meta 分析共纳入11 篇文献,总共有28589 个病例;合并糖尿病对乳腺癌患者5 年无病生存率有影响[OR=2.48,95%CI(1.81~3.40);I2=0%,P(Q)=0.42];合并糖尿病对乳腺癌患者5 年总生存率有影响[OR=2.40,95%CI(1.75~3.29);I2=81.67%,P(Q)<0.01]。结论:糖尿病对乳腺癌患者预后有影响,造成生存率降低。  相似文献   

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