The impact on clinical outcome of high prevalence of diabetes mellitus in Taiwanese patients with colorectal cancer

BackgroundBoth colorectal cancer (CRC) and diabetes mellitus (DM) are important public health problems worldwide. As there are controversies about survival impact on CRC patients with preexisting DM, the purpose of the present study is to evaluate the incidence and the survival impact of preexisting DM on the long-term outcomes of patients with CRC in Taiwan.MethodsFrom January 2002 to December 2008, 1,197 consecutive patients with histologically proven primary CRC, who received surgical treatment at a single institution, were enrolled. The clinicopathologic features between these patients with and without DM were retrospectively investigated. Moreover, we intended to analyze the impact of DM on overall survival (OS) and cancer-specific survival (CSS) rates.ResultsOf 1,197 CRC patients, 23.6% of patients had either a reported history of DM or were currently taking one or more diabetes-controlling medications. CRC patients with DM were significantly older than those without DM (P < 0.001), and had a higher incidence of cardiac disease and higher body mass index than those without DM (both P < 0.001). There were no significant differences in gender, tumor size, tumor location, histological type, AJCC/UICC cancer stage, vascular invasion, perineural invasion, comorbidity of pulmonary disease or renal disease, and OS, and CSS between two groups. Additionally, DM patients had a higher incidence of second malignancy than patients without DM (9.54% vs 6.01%, P = 0.040).ConclusionsA considerably high prevalence of DM in CRC patients but no significant impact of DM on survival was observed in the single-institution retrospective study, regardless of cancer stages and tumor locations. Therefore, treatment strategies for CRC patients with DM should be the same as patients without DM.

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abstract: Previous studies have documented significant variations in colorectal cancer incidence rates and trends regionally and across countries. However, no study has examined the worldwide pattern using the most recently updated incidence data from the IARC.  We obtained sex-specific colorectal cancer incidence for 1953-57 through 1998-2002 by cancer registry from Cancer Incidence in Five Continents (CI5) databases. For 51 cancer registries with long-term incidence data, we assessed the change in the incidence rates over the past 20 years by calculating the ratio of the incidence rates in 1998-2002 to that in 1983-87.  Colorectal cancer incidence rates for both males and females statistically significantly increased from 1983-87 to 1998-2002 for 27 of 51 cancer registries considered in the analysis, largely confined to economically transitioning countries including Eastern European countries, most parts of Asia, and select countries of South America. These increases were more prominent for men than for women. We also observed substantial variations in colorectal cancer incidence trends within countries such as Japan. Similarly, trends in Israel and Singapore varied significantly according to ethnicity. The United States is the only country where colorectal cancer incidence rates declined in both males and females.  Colorectal cancer incidence rates continue to increase in economically transitioning countries, with incidence rates among men in the Czech Republic and Slovakia exceeding the peak incidence observed in the United States and other long-standing developed nations. Targeted prevention and early detection programs could help reverse the trend in these countries.

title: Alarming Colorectal Cancer Incidence Trends: A Case for Early Detection and Prevention
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title: The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence.
abstract: We conducted a systematic review and a meta-analysis to estimate the magnitude and determinants of association between diabetes and hepatocellular carcinoma (HCC).



MEDLINE searches were conducted for published full studies (between January 1966 and February 2005) that provided risk estimates and met criteria concerning the definition of exposure and outcomes. Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes were obtained or calculated for each study and were synthesized using a random-effects model.



A total of 26 studies met our inclusion and exclusion criteria. Among 13 case-control studies, diabetes was associated significantly with HCC in 9 studies (pooled odds ratio, 2.5; 95% confidence interval, 1.8-3.5). Among 13 cohort studies, diabetes was associated significantly with HCC in 7 studies (pooled risk ratio, 2.5; 95% confidence interval, 1.9-3.2). The results were relatively consistent in different populations, different geographic locations, and a variety of control groups. The significant association between HCC and diabetes was independent of alcohol use or viral hepatitis in the 10 studies that examined these factors. Few studies adjusted for diet and obesity.



Diabetes is associated with an increased risk for HCC. However, more research is required to examine issues related to the duration and treatment of diabetes, and confounding by diet and obesity.

title: Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis.
abstract: To evaluate diabetes mellitus as a risk factor for pancreatic cancer with the consideration that diabetes may also be a consequence of pancreatic cancer.



Pertinent studies of diabetes mellitus and pancreatic cancer published between 1975 and 1994 were identified from a MEDLINE search and from citations in articles and books.



Twenty of a total of 30 case-control and cohort studies met the two inclusion criteria: cases with a duration of diabetes of at least 1 year prior to either pancreatic cancer diagnosis or death and the ability to calculate an appropriate relative risk (RR) estimate and variance.



The pooled RR and 95% confidence interval (CI) of pancreatic cancer for diabetics relative to nondiabetics was 2.1 (1.6 to 2.8). There was a tendency for a higher RR for the nine cohort studies (RR, 2.6; 95% CI, 1.6 to 4.1) than for the 11 case-control studies (RR, 1.8; 95% CI, 1.1 to 2.7). Requiring diabetes duration of at least 5 years resulted in an RR of 2.0 (95% CI, 1.2 to 3.2).



Pancreatic cancer occurs with increased frequency among persons with long-standing diabetes.

title: Antidiabetic therapies affect risk of pancreatic cancer.
abstract: Antidiabetic drugs have been found to have various effects on cancer in experimental systems and in epidemiologic studies, although the association between these therapeutics and the risk of human pancreatic cancer has not been explored. We investigated the effect of antidiabetic therapies on the risk of pancreatic cancer.



A hospital-based case-control study was conducted at M. D. Anderson Cancer Center from 2004 to 2008 involving 973 patients with pancreatic adenocarcinoma (including 259 diabetic patients) and 863 controls (including 109 diabetic patients). Information on diabetes history and other risk factors was collected by personal interview. The frequencies of use of insulin, insulin secretagogues, metformin, and other antidiabetic medications among diabetic patients were compared between cases and controls. The risk of pancreatic cancer was estimated using unconditional logistic regression analysis.



Diabetic patients who had taken metformin had a significantly lower risk of pancreatic cancer compared with those who had not taken metformin (odds ratio, 0.38; 95% confidence interval, 0.22-0.69; P = .001), with adjustments for potential confounders. This difference remained statistically significant when the analysis was restricted to patients with a duration of diabetes >2 years or those who never used insulin. In contrast, diabetic patients who had taken insulin or insulin secretagogues had a significantly higher risk of pancreatic cancer compared with diabetic patients who had not taken these drugs.



Metformin use was associated with reduced risk, and insulin or insulin secretagogue use was associated with increased risk of pancreatic cancer in diabetic patients.

title: Diabetes mellitus and risk of endometrial cancer: a meta-analysis
abstract: has been associated with a statistically significantly increased risk of endometrial cancer in most, but not all studies. To provide a quantitative assessment of the association between diabetes and risk of endometrial cancer, we conducted a meta-analysis of case-control studies and cohort studies.Subjects and methodsWe identified studies by a literature search of PubMed and Embase through to January 2007 and by searching the reference lists of relevant articles. Summary relative risks (RRs) with 95% CIs were calculated using random-effects model.ResultsThe analysis of diabetes (largely type 2) and endometrial cancer is based on 16 studies (three cohort and 13 case-control studies), including 96,003 participants and 7,596 cases of endometrial cancer. Twelve of the studies showed a statistically significantly increased risk and four a non-significant increased risk of endometrial cancer. In our meta-analysis we found that diabetes was statistically significantly associated with an increased risk of endometrial cancer (summary RR 2.10, 95% CI 1.75–2.53). The risk estimates were somewhat stronger among case-control (RR 2.22, 95% CI 1.80–2.74) than among cohort studies (RR 1.62, 95% CI 1.21–2.16), stronger among studies adjusting only for age (RR 2.74, 95% CI 1.87–4.00) compared with multivariate adjustment (RR 1.92, 95% CI 1.58–2.33) and slightly lower in studies performed in the USA than in those performed Europe. The analysis of type 1 diabetes and endometrial cancer was based on three studies and found a statistically significant positive association (summary RR 3.15, 95%CI 1.07–9.29).Conclusions/interpretationResults from the meta-analysis support a relationship between diabetes and increased risk of endometrial cancer.

title: Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women.
abstract: The remarkable similarity of lifestyle and environmental risk factors for type 2 (non-insulin-dependent) diabetes mellitus and colon cancer has led to the hypothesis that diabetes may increase the risk of this cancer. We prospectively examined the relationship between diabetes and risk of colorectal cancer in a cohort of 118403 women aged 30 through 55 years who were without previously diagnosed cancer at baseline in 1976.



The women, who were enrolled in the Nurses' Health Study, were assessed for history of diabetes at baseline and during follow-up by use of biennial questionnaires. Self-reported diabetes was validated by information obtained from a supplemental questionnaire on symptoms and treatment and was confirmed by medical record review in a sample of the participants. Incident cases of colorectal cancer were ascertained through medical record review. All reported P values are two-sided.



During 18 years of follow-up (201061 person-years), we documented 892 new cases of colorectal cancer. After adjustment for age, body mass index (weight in kg/height in m2), physical activity, and other covariates, relative risks (RRs) were 1.43 (95% confidence interval [CI] = 1.10-1.87; P = .009) for colorectal cancer, 1.49 (95% CI = 1.09-2.06; P = .01) for colon cancer, 1.11 (95% CI = 0.56-2.21; P = .76) for rectal cancer, 1.56 (95% CI = 1.07-2.28; P = .02) for advanced colorectal cancer, and 2.39 (95% CI = 1.46-3.92; P = .0005) for fatal colorectal cancer.



Our data provide support for the hypothesis that diabetes is associated with an increased risk of colorectal cancer in women.

title: Diabetes mellitus and risk of colorectal cancer: a meta-analysis.
abstract: Diabetes has been associated with an increased risk of colorectal cancer in most, but not all, studies. Findings have also been inconclusive with regard to sex and subsite in the colorectum. To resolve these inconsistencies, we conducted a meta-analysis of published data on the association between diabetes and the incidence and mortality of colorectal cancer.



We identified studies by a literature search of Medline from January 1, 1966, through July 31, 2005, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. All statistical tests were two-sided.



Analysis of 15 studies (six case-control and nine cohort studies), including 2 593 935 participants, found that diabetes was associated with an increased risk of colorectal cancer, compared with no diabetes (summary RR of colorectal cancer incidence = 1.30, 95% CI = 1.20 to 1.40), without heterogeneity between studies (P(heterogeneity) = .21). These results were consistent between case-control and cohort studies and between studies conducted in the United States and in Europe. The association between diabetes and colorectal cancer incidence did not differ statistically significantly by sex (summary RR among women = 1.33, 95% CI = 1.23 to 1.44; summary RR among men = 1.29, 95% CI = 1.15 to 1.44; P(heterogeneity) = .26) or by cancer subsite (summary RR for colon = 1.43, 95% CI = 1.28 to 1.60; summary RR for rectum = 1.33, 95% CI = 1.14 to 1.54; P(heterogeneity) = .42). Diabetes was positively associated with colorectal cancer mortality (summary RR = 1.26, 95% CI = 1.05 to 1.50), but there was evidence for heterogeneity between studies (P(heterogeneity) = .04).



Our findings strongly support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men.

title: Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms
abstract: The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

title: Colorectal cancer: another complication of diabetes mellitus?
abstract: Delayed stool transit and other gastrointestinal abnormalities are commonly observed in persons with diabetes mellitus and are also known to be associated with colorectal cancer. Previous studies of the contribution of diabetes to colorectal cancer incidence and mortality have been limited by small sample sizes and failure to adjust for covariates. With more than 1 million respondents, the 1959-1972 Cancer Prevention Study provided a unique opportunity to explore whether persons with diabetes (n=15,487) were more likely to develop colorectal cancer during a 13-year follow-up period than were persons without diabetes (n=850,946). After adjustment for colorectal cancer risk factors, such as race, educational level, body mass index, smoking, alcohol use, dietary intake, aspirin use, physical activity, and family history of colorectal cancer, the incidence density ratio comparing colorectal cancer in those with diabetes and those without diabetes was 1.30 (95% confidence interval 1.03-1.65) for men and 1.16 (95% confidence interval 0.87-1.53) for women. However, diabetes was not associated with greater case fatality. Future studies should explore the possibility of a cancer-promoting gastrointestinal milieu, including delayed stool transit and elevated fecal bile acid concentrations, associated with hyperglycemia and diabetic neuropathy.

title: Diabetes and risk of incident colorectal cancer in a prospective cohort of women
abstract: ObjectiveTo determine whether accounting for the time dynamics of diabetes exposure will change the risk estimates for colorectal cancer.MethodsWe analyzed data from the 45, 516 women enrolled in the BCDDP follow-up cohort study. We used proportional hazards regression to obtain multivariable-adjusted risk estimates for incident colorectal cancer for prevalent diabetes at baseline and diabetes as a time-dependent variable.ResultsSubjects with diabetes had a statistically significant increased risk of colorectal cancer compared to subjects without diabetes (RR = 1.60, 95% CI 1.18–2.18). When we defined exposure as duration of diabetes exposure at cohort exit, we found that in the first 4 years after diagnosis risk was essentially the same as in those never having had a diagnosis of diabetes. For those who had been diagnosed between 4 and 8 years previously, however, we observed a RR of 2.36 (95% CI 0.96–5.79), while longer duration of exposure was associated with smaller and then no change in risk compared to those without a diagnosis of diabetes.ConclusionsThese results are consistent with the theory that hyperinsulinemia can explain, at least in part, the association of diabetes with colorectal cancer, but in a time-dependent manner.

title: Type 2 diabetes mellitus and the risk of colorectal cancer.
abstract: Type 2 diabetes mellitus might increase the risk of colorectal cancer on the basis of chronic hyperinsulinemia and hyperglycemia. However, epidemiologic evidence for this association is inconclusive. We conducted a population-based study to clarify this association.



We conducted a case-control study in the United Kingdom General Practice Research Database. Cases included all patients with incident colorectal cancer diagnoses (n = 10,447). Up to 10 control subjects were selected for each case, matching on year of birth, enrollment date, and duration of database follow-up. The exposure of interest was type 2 diabetes mellitus. Odds ratios (ORs) were calculated by using conditional logistic regression.



A prior diagnosis of type 2 diabetes mellitus was associated with a modestly increased risk of colorectal cancer (OR, 1.42; 95% confidence interval [CI], 1.25-1.62). The association between type 2 diabetes mellitus and colorectal cancer was observed in both men (OR, 1.36; 95% CI, 1.16-1.61) and women (OR, 1.38; 95% CI, 1.14-1.67). The risk increase was observed in both colon (OR, 1.45; 95% CI, 1.25-1.70) and rectal (OR, 1.34; 95% CI, 1.08-1.68) cancers.



Type 2 diabetes mellitus is associated with an increased risk of colorectal cancer. The risk increase is present in both sexes, as well as in both colonic and rectal cancers.

title: Diabetes mellitus and subsite-specific colorectal cancer risks in the Iowa Women's Health Study.
abstract: Controversy remains regarding the association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) risk. To clarify and extend the existing data, we prospectively evaluated the association between self-reported type 2 DM (onset at >30 years of age) and incident CRC, overall and by anatomic subsite, among postmenopausal women in the Iowa Women's Health Study (n = 35,230).



After 14 years of follow-up, a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up. CRC risks were estimated using Cox proportional hazards regression models.



After adjusting for age, body mass index and other potential confounding variables, the relative risk (RR) for women with DM versus women without DM was modestly increased at 1.4 [95% confidence interval (95% CI), 1.1-1.8]. By anatomic subsite, the RR for proximal colon cancer was statistically significantly increased (RR, 1.9; 95% CI, 1.3-2.6), whereas the RRs for distal colon (RR, 1.1; 95% CI, 0.6-1.8) and rectal cancer (RR, 0.8; 95% CI, 0.4-1.6) were not statistically different from unity. Analyses that included DM ascertained at baseline and follow-up yielded similar results.



In this large, prospective study of postmenopausal women, the association between DM and incident CRC was found to be subsite specific. If confirmed by others, this finding implies that CRC prevention strategies among type 2 DM patients should include examination of the proximal colon.

title: Prospective study reveals associations between colorectal cancer and type 2 diabetes mellitus or insulin use in men.
abstract: Type 2 diabetes mellitus (DM) is associated with an increased risk of colorectal cancer (CRC); it is not clear if this association varies by sex or other factors. Insulin use might also be associated with CRC risk. We investigated associations of type 2 DM and insulin use with CRC risk.



The Cancer Prevention Study II Nutrition Cohort is a prospective study of cancer incidence. In 1992 or 1993, adult participants (n = 184,194) completed a detailed, self-administered questionnaire. Follow-up questionnaires were sent in 1997 and every 2 years thereafter. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for covariates.



After exclusions, 73,312 men and 81,663 women remained in the final analytic cohort; 1567 men (227 with type 2 DM) and 1242 women (108 with type 2 DM) were diagnosed with colon or rectal cancer by 2007. Among men, type 2 DM was associated with increased risk of incident CRC compared to not having type 2 DM (RR: 1.24; 95% CI: 1.08-1.44); risk was higher for participants with type 2 DM using insulin (RR: 1.36; 95% CI: 1.05-1.78), and participants with type 2 DM not using insulin (RR: 1.22, 95% CI: 1.04-1.45). Among women, type 2 DM and insulin use were not associated with risk of incident CRC (RR: 1.01; 95% CI: 0.82-1.23 and RR: 0.95; 95% CI: 0.64-1.41, respectively).



There is a modest association between type 2 DM and CRC among men, but not women. Insulin use is not associated with a substantially increased risk of CRC.

title: Diabetes mellitus and risk of breast cancer: A meta‐analysis
abstract: Diabetes mellitus has been associated with an increased risk of several types of cancers, but its relationship with breast cancer remains unclear. We conducted a meta‐analysis of case–control and cohort studies to assess the evidence regarding the association between diabetes and risk of breast cancer. Studies were identified by searching MEDLINE (1966–February 2007) and the references of retrieved articles. We identified 20 studies (5 case–control and 15 cohort studies) that reported relative risk (RR) estimates (odds ratio, rate ratio/hazard ratio, or standardized incidence ratio) with 95% confidence intervals (CIs) for the relation between diabetes (largely Type II diabetes) and breast cancer incidence.  RRs were calculated using a random‐effects model. Analysis of all 20 studies showed that women with (versus without) diabetes had a statistically significant 20% increased risk of breast cancer (RR, 1.20; 95% CI, 1.12–1.28). The summary estimates were similar for case–control studies (RR, 1.18; 95% CI, 1.05–1.32) and cohort studies (RR, 1.20; 95% CI, 1.11–1.30). Meta‐analysis of 5 cohort studies on diabetes and mortality from breast cancer yielded a summary RR of 1.24 (95% CI, 0.95–1.62) for women with (versus without) diabetes. Findings from this meta‐analysis indicate that diabetes is associated with an increased risk of breast cancer.

title: Diabetes mellitus and risk of bladder cancer: a meta-analysis
abstract: evidence indicates that individuals with diabetes mellitus have an increased risk of several cancers. We performed a systematic review with meta-analysis to evaluate the association between diabetes and risk of bladder cancer.MethodsPertinent studies were identified by searching MEDLINE (from January 1966 to July 2006) and by reviewing the reference lists of retrieved articles. We included case–control and cohort studies reporting relative risk (RR) estimates with 95% CIs (or data to calculate them) of bladder cancer associated with diabetes. Studies of type 1 diabetes were not included.  RRs were calculated using a random-effects model. total of 16 studies (seven case–control studies, three cohort studies and six cohort studies of diabetic patients) fulfilled the inclusion criteria. Analysis of all studies showed that diabetes was associated with an increased risk of bladder cancer, compared with no diabetes (RR = 1.24, 95% CI 1.08–1.42). There was strong evidence of heterogeneity among these studies (p < 0.0001). Stratification by study design found that diabetes was associated with an increased risk of bladder cancer in case–control studies (RR = 1.37, 95% CI 1.04–1.80, pheterogeneity = 0.005) and cohort studies (RR = 1.43, 95% CI 1.18–1.74, pheterogeneity = 0.17), but not in cohort studies of diabetic patients (RR = 1.01, 95% CI 0.91–1.12, pheterogeneity = 0.35).Conclusions/interpretationFindings from this meta-analysis suggest that individuals with diabetes may have a modestly increased risk of bladder cancer.

title: Impact of diabetes mellitus on outcomes in patients with colon cancer.
abstract: To determine the influence of diabetes mellitus on long-term outcomes and treatment-related toxicity among patients with curatively resected colon cancer.



This study was a cohort study within a large, randomized adjuvant chemotherapy trial of 3,759 patients with high-risk stage II and stage III colon cancer treated between 1988 and 1992 throughout the United States. In the cohort, 287 patients were identified as having diabetes mellitus. With a median follow-up of 9.4 years, we analyzed differences in overall survival (OS) and colon cancer recurrence as well as treatment-related toxicity between patients with diabetes and those without diabetes.



At 5 years, patients with diabetes mellitus, compared with patients without diabetes, experienced a significantly worse disease-free survival (DFS; 48% diabetics v 59% nondiabetics; P <.0001), OS (57% v 66%; P <.0001), and recurrence-free survival (RFS; 56% v 64%, P =.012). Median survival was 6.0 years and 11.3 years for diabetics and nondiabetics, respectively. Compared with patients without a history of diabetes, those with diabetes had a 42% increased risk of death from any cause (P <.0001) and 21% increased risk for recurrence (P =.05) after adjustment for other predictors of colon cancer outcome. Treatment-related toxicities were similar between the two groups, although patients with diabetes experienced an increase in treatment-related diarrhea.



Patients with diabetes mellitus and high-risk stage II and stage III colon cancer experienced a significantly higher rate of overall mortality and cancer recurrence, even after adjustment for other predictors of colon cancer outcome. These results underscore the need for further research to understand the mechanism that underlies this relation.

title: Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults.
abstract: Several studies have suggested that diabetes mellitus may alter the risk of developing a variety of cancers, and the associations are biologically plausible. To learn more about the relation between diabetes and cancer mortality, the authors examined associations with selected cancers in a large, prospective US cohort of 467,922 men and 588,321 women who had no reported history of cancer at enrollment in 1982. After 16 years of mortality follow-up, diabetes was significantly associated with fatal colon cancer in men (multivariate relative risk (RR) = 1.20, 95% confidence interval (CI): 1.06, 1.37) and women (RR = 1.24, 95% CI: 1.07, 1.43) and with pancreatic cancer in men (RR = 1.48, 95% CI: 1.27, 1.73) and women (RR = 1.44, 95% CI: 1.21, 1.72). For men, diabetes was significantly associated with liver cancer (RR = 2.19, 95% CI: 1.76, 2.72) and bladder cancer (RR = 1.43, 95% CI: 1.14, 1.80). In addition, diabetes was significantly associated with breast cancer in women (RR = 1.27, 95% CI: 1.11, 1.45). These associations were not explained by high body mass. Our findings suggest that diabetes is an independent predictor of mortality from cancer of the colon, pancreas, female breast, and, in men, of the liver and bladder.

title: Diabetes mellitus negatively impacts survival of patients with colon cancer, particularly in stage II disease
abstract: PurposeThis retrospective study aimed to determine the effects of diabetes on overall survival (OS) and cancer-specific survival (CSS) in patients with newly diagnosed colon cancers, with particular focus on the impact of diabetes on survival at each stage of colon cancer.MethodsFrom January 1999 to January 2008, 2762 consecutive patients diagnosed with colon cancer in Taipei Veterans General Hospital were enrolled. The general characteristics as well as presence of diabetes prior to colon cancer diagnosis were identified. Cox proportional hazard analyses were used for prognostic factors determination; and survival was analyzed using the Kaplan–Meier method with log-rank test. total of 469 patients (17%) had diabetes at diagnosis of colon cancer. Patients with diabetes had baseline characteristics comparable to those without diabetes with the exception that the patients with diabetes were older (>65 years). Diabetes significantly and negatively impacted OS and CSS in multivariate analyses. After adjusting for possible confounding factors, the prognostic impact of diabetes on OS and CSS was particularly significant in patients with stage II colon cancer.ConclusionsDiabetes is a poor prognostic factor in patients with newly diagnosed colon cancer, and it may directly impact the tumor behavior of stage II disease. Further study is required to elucidate the underlying pathophysiologic mechanisms.

title: Diabetes mellitus and outcomes of colorectal cancer
abstract: Patients with diabetes mellitus have an increased risk of colorectal cancer. However, there is limited information on the outcome for diabetic patients diagnosed with this type of cancer.  The health records of all 1 194 patients treated for colorectal adenocarcinoma at Levanger Hospital from 1980 – 2004 were reviewed. Diabetes status and prognostic factors were registered. Primary endpoints were cancer specific survival and overall survival.  There were no significant differences between diabetic patients and non-diabetic patients concerning stage, grade, treatment, infective or non-infective postoperative complications, hospital stay, or 30 days mortality after laparotomy. After a curative resection, the estimated 5-year cancer specific survival in 97 diabetic patients was 73% (95% CI 60–87) and 79% (95% CI 75–82) in 1097 non-diabetic patients (not significant). The estimated overall 5-year survival in patients treated with curative intent was 46% (95% CI 33–59) in diabetic patients and 65% (95% CI 62–69) in non-diabetic patients (p<0.001). The diabetic patients were significantly older and more frequently had cardiac diseases.  Diabetes mellitus did not affect the short-term survival or the cancer specific survival. A shorter overall survival was associated with cardiac diseases and higher age.

title: AJCC Cancer Staging Manual
abstract: General Information on Cancer Staging and End-Results  Purposes and Principles of Cancer Staging.- Cancer Survival Analysis.- Head and Neck.- Lip and Oral Cavity.- Pharynx.- Larynx.- Nasal Cavity and Paranasal Sinuses.- Major Salivary Glands.- Thyroid.- Mucosal Melanoma of the Head and Neck.-  Small Intestine.- Colon and Rectum.- Anus.- Gastrointestinal Stromal Tumor.- Neuroendocrine Tumors.- Liver.- Intrahepatic Bile Ducts.- Gallbladder.- Perihilar Bile Ducts.- Distal Bile Duct.- Ampulla of Vater.- Exocrine and Endocrine Pancreas.- Thorax.- Lung.- Pleural Mesothelioma.- Musculoskeletal Sites.- Bone.- Soft Tissue Sarcoma.- Skin.- Cutaneous Squamous Cell Carcinoma and Other Cutaneous Carcinomas.- Merkel Cell  Melanoma of the Skin.- Breast.- Breast.- Gynecologic Sites.- Vulva.- Vagina.- Cervix Uteri.- Corpus Uteri.- Ovary and Primary Peritoneal Carcinoma.- Fallopian Tube.- Gestational Trophoblastic Tumors.- Genitourinary Sites.- Penis.- Prostate.- Testis.- Kidney.- Renal Pelvis and Ureter.- Urinary Bladder.- Urethra.- Adrenal.- Ophthalmic Sites.- Carcinoma of the Eyelid.- Carcinoma of the Conjunctiva.- Malignant Melanoma of the Conjunctiva.- Malignant Melanoma of the Uvea.- Retinoblastoma.- Carcinoma of the Lacrimal Gland.- Sarcoma of the Orbit.- Ocular Adnexal Lymphoma.- Central Nervous System.- Brain and Spinal Cord.- Lymphoid Neoplasms.- Lymphoid Neoplasms.

title: Colorectal Cancer Outcomes, Recurrence, and Complications in Persons With and Without Diabetes Mellitus: A Systematic Review and Meta-Analysis
abstract: BackgroundDiabetes mellitus increases the risk of incident colorectal cancer, but it is less clear if pre-existing diabetes mellitus influences mortality outcomes, recurrence risk, and/or treatment-related complications in persons with colorectal cancer.MethodsWe performed a systematic review and meta-analysis comparing colorectal cancer mortality outcomes, cancer recurrence, and treatment-related complications in persons with and without diabetes mellitus. We searched MEDLINE and EMBASE through October 1, 2008, including hand-searching references of qualifying articles. We included studies in English that evaluated diabetes mellitus and cancer treatment outcomes, prognosis, and/or mortality. The initial search identified 8,208 titles, of which 15 articles met inclusion criteria. Each article was abstracted by one author using a standardized form and re-reviewed by another author for accuracy. Authors graded quality based on pre-determined criteria.ResultsWe found significantly increased short-term perioperative mortality in persons with diabetes mellitus. In the meta-analysis of long-term mortality, persons with diabetes mellitus had a 32% increase in all-cause mortality compared to those without diabetes mellitus (95% CI: 1.24, 1.41). Although data on other outcomes are limited, available studies suggest that pre-existing diabetes mellitus predicts increased risk of some post-operative complications as well as 5-year cancer recurrence. In contrast, there is little evidence that diabetes confers increased risk for long-term cancer-specific mortality.ConclusionsPatients with colorectal cancer and pre-existing diabetes mellitus have an increased risk of short- and long-term mortality. Future research should determine whether improvements in prevention and treatment of diabetes mellitus will improve outcomes for colorectal cancer patients.

title: Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer
abstract: Diabetes is associated with alterations in liver metabolism and immune response that may influence post-operative recovery and long-term survival after hepatectomy for cancer. Patients with type I or type II diabetes mellitus submitted to a potentially curative hepatic resection for metastatic colorectal cancer were identified from the prospective database, and compared with patients with hepatic colorectal metastases submitted to resection during the same time interval, but without diabetes mellitus. Data on operative morbidity and mortality and long-term survival were analyzed. Between December 1990 and July 1999, a total of 727 patients underwent hepatic resection, 61 of whom (8.1%) had type I and type II diabetes mellitus. Operative mortality in the diabetic patients was significantly greater than in nondiabetic patients (8% vs. 2%, P < 0.02). Among patients with diabetes mellitus, four of the five perioperative deaths were due to liver failure after major hepatic resection (lobectomy or greater). All four of these patients had significant parenchymal abnormality (three with steatosis). Long-term survival was identical to that in nondiabetic control subjects. We conclude that the presence of diabetes is associated with a higher incidence of perioperative mortality. In patients with diabetes mellitus and parenchymal steatosis, major hepatic resection should be undertaken with caution.

title: Comorbid diabetes mellitus and risk of death after diagnosis of colorectal cancer: a population-based study.
abstract: The few studies that have examined the association between comorbid diabetes mellitus (DM) and survival after diagnosis of colorectal cancer have involved small numbers of patients with DM, and cause of death was not examined.



All 542 African American (black) and 8,853 white Connecticut residents diagnosed with colorectal cancer in 1994-1999 were identified from the population-based statewide Connecticut cancer registry. Comorbid DM was defined as an inpatient hospital admission (prior to or around the time of colorectal cancer diagnosis) that included DM as one of up to 10 discharge diagnoses.



Comorbid DM, identified for 1014 (10.8%) of the 9395 patients, was associated with a statistically significantly elevated risk of death from any cause (hazard ratio or HR=1.38, 95% confidence interval 1.27-1.49), in a proportional hazards regression model that included age, sex, race and extent of disease at diagnosis. This finding was due to an elevated risk of death from causes of death other than colorectal cancer.



Studies are needed on quality of care for comorbid DM and its complications among colorectal cancer patients.

title: Therapeutic strategy of emergency surgery for colon cancer in 71 patients over 70 years of age in Japan.
abstract: The prognosis for colon cancer is poorest in cases of emergency situation in the elderly not only in Japan, but worldwide. The aim was to design a therapeutic approach used for colon cancer in the elderly.



Seventy-one patients, who were all older than 70 years, with colon carcinoma in an emergency situation were examined. Lethality, surgical procedure, risk of comorbidity, multiple organ system failure and the effect of endotoxin absorption were examined.



Any increase in comorbidity was associated with a higher clinical lethality in the lungs, heart, kidney, and diabetes. The highest postoperative mortality rate was recorded in patients who underwent primary resection after perforation, while the lowest postoperative mortality rate was recorded in patients who underwent primary resection after obstruction. Postoperative failure of the lungs and heart and renal failure were associated with a significantly higher mortality rate. Twenty-five septic patients received an endotoxin adsorption due to blood filtration and 8 patients survived. Of the eight survivors, the endotoxin concentration was significantly decreased by an endotoxin absorption.



In cases of ileus, the resection may be performed positively. In cases of perforation, we may safely say now that stoma and resection is to be recommended. Endotoxin absorption due to blood filtration may be an effective additional therapy for post-operative septic shock.

title: Effects of diabetes mellitus on prognosis of the patients with colorectal cancer undergoing resection: a cohort study with 945 patients.
abstract: Diabetes mellitus plays an important role in cancer prevalence and outcomes. The aim of this study was to evaluate the influence of DM on stages and outcomes among patients with colorectal cancer.



The study enrolled 945 patients who were diagnosed as having colorectal carcinoma from August 1994 to December 2002. In the cohort, 26 patients were diagnosed as having DM. With a median follow-up of 45.8 months, differences in overall survival and disease-free survival between the diabetes and non-diabetes groups were analyzed.



Kaplan and Meier analysis showed that there were no significant differences between the two groups in overall survival rates at 3 years or 5 years. At 5 years, patients with DM, compared with patients without diabetes, experienced a significantly lower disease-free survival rate (34.2% diabetics vs. 55.1% non-diabetics; P = 0.025).



DM was associated with an increased risk of recurrence in patients with colorectal cancer.

title: The impact of diabetes process and outcome quality measures on overall survival in patients with co-morbid colorectal cancer
abstract: PurposeTo evaluate the effect of prevalent diabetes mellitus (DM) and quality of diabetes process and outcome measures on overall survival in colorectal cancer (CRC) patients.Patient and MethodsWe conducted a retrospective cohort study among patients newly diagnosed with CRC. Kaplan-Meier analyses and Cox proportional hazard regression models were performed. Quality of diabetes process and outcomes measures in the year prior to CRC diagnosis were compared with those in the year after CRC diagnosis.ResultsFour hundred and seventy CRC patients were identified during the study period, including 122 (26%) patients with DM. Survival between diabetic and non-diabetic were not significantly different after stratifying by stage. In a multivariable model, only age (HR 1.04), stage 2 and 3 (HR 1.88), stage 4 (HR 4.26), and Deyo comorbidity score (HR 1.14) were significantly associated with increased risk of death. Overall, patients in this CRC cohort with DM had good to excellent diabetes quality of care in the year prior to diagnosis as evidenced by primary care and eye clinic visits, number of times diabetes intermediate outcomes were measured, and level of cholesterol (95.5 ± 29.74) and hemoglobin A1c (7.2% + 1.4) control. After CRC diagnosis, there was no significant change in these quality of care indices compared to the year prior.ConclusionsPrevalent DM did not affect overall survival in this cohort of VA patients diagnosed with CRC. The quality of diabetes care prior to CRC diagnosis, which persisted after diagnosis, may have moderated the mortality effect of diabetes in this CRC cohort.

title: Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment
abstract: BackgroundThe aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC) undergoing surgical treatment.MethodsBetween January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely.ResultsOf 1367 CRC patients, there were seven hundred and fifty-seven males (55.4%) and 610 (44.6%) females. The median follow-up period was 60 months (range, 3–132 months). A multivariate analysis identified that low serum albumin level (P = 0.011), advanced UICC stage (P < 0.001), and high carcinoembryonic antigen (CEA) level (P < 0.001) were independent prognostic factors of cancer-specific survival. Meanwhile, a multivariate analysis showed age over 65 years (P < 0.001), advanced UICC stage (P < 0.001), and high CEA level (P < 0.001) were independent prognostic factors of overall survival. Furthermore, combination of UICC stage, serum CEA and albumin levels as predictors of cancer-specific survival showed that the poorer the prognostic factors involved, the poorer the cancer-specific survival rate. Likewise, combination of UICC stage, age and serum CEA level as predictors of overall survival showed that the poorer the prognostic factors involved, the poorer the overall survival rate. Of these prognostic factors, preoperative serum CEA level was the only significant prognostic factor for patients with stage II and III CRCs in both cancer-specific and overall survival categories.ConclusionPreoperative serum albumin level, CEA level and age could prominently affect postoperative outcome of CRC patients undergoing surgical treatment. In addition to conventional UICC staging system, it might be imperative to take these additional characteristics of factors into account in CRC patients prior to surgical treatment.

title: Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.
abstract: Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance.



The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care.



Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC).

title: Colorectal Carcinoma: Diagnostic, Prognostic, and Molecular Features
abstract: Surgical resection is the primary treatment modality for colorectal cancer, and the pathologic assessment of the resection specimen provides data that is essential for patient management, including the estimation of postoperative outcome and the rationale for adjuvant therapy. The essential elements of the pathological assessment of colorectal cancer resection specimens include the pathologic determination of TNM stage, tumor type, histologic grade, status of resection margins, and vascular invasion. The prognostic and/or predictive value of these elements, as well as guidelines for their derivation and interpretation, are reviewed in detail. Other tissue-based prognostic factors that are strongly suggested by existing data to have stage-independent prognostic value or to predict response to adjuvant therapy but that have not yet been validated for routine patient care are also reviewed. These include perineural invasion, tumor border configuration, host immune response to tumor, and molecular features such as microsatellite instability or loss of heterozygosity of chromosome 18. The need for high-quality, reproducible pathologic data in the care of the colorectal cancer patient, and the dependence of that data on standardization of all aspects of pathological assessment, is emphasized.

title: Prognostic significance of lymphovascular invasion in surgically cured rectal carcinoma.
abstract: Surgery is considered curative in Dukes' B rectal cancer; however, many patients present with early relapse. To identify additional staging information, venous and lymphatic invasion were evaluated as potential prognostic factors.



Patients with Dukes' B or C rectal disease treated between 1976 and 2001 at a single institution were compared. Patient and treatment characteristics and vascular invasion were documented. The impact of vessel invasion was determined using Cox proportional hazards model.



There were 256 Dukes' B patients and 74 Dukes' C cases without vascular invasion. Five-year survival was 76.5% for Dukes' B and 57.1% for Dukes' C patients. Vessel involvement increased the risk of recurrence (hazard ratio [HR] = 3.27, P = .0003) and death (HR = 3.11, P = .002) in B2 patients. The magnitude of these associations were comparable to that of C1 patients for recurrence (HR = 2.81, P = .004) and death (HR = 3.05, P = .005), as well as C2 patients for recurrence (HR = 3.45, P = .0008) and death (HR = 3.87, P = .0005).



Vascular invasion may be useful in characterizing patients with aggressive Dukes' B disease, who might benefit the most from adjuvant systemic therapy.

title: American Joint Committee on Cancer prognostic factors consensus conference
abstract: The American Joint Committee on Cancer (AJCC), which regularly reviews TNM staging systems, established a working party to develop recommendations for colorectal carcinoma.

title: Effect of diabetes mellitus on the epidemiology and outcomes of colon cancer
abstract: ObjectivesTo assess the effect of diabetes mellitus (DM) on the pathogenesis and outcomes from colon cancer.MethodsA retrospective chart review was conducted on 1853 patients with colon cancer. higher percentage of males than females with colon cancer had DM (16.2% vs 11.3%; p<0.01). Males had a slightly lower risk of dying from colon cancer (RR−0.88; p=0.08). There was no difference in the median age of diagnosis of colon cancer in patients with and without DM, but a larger proportion of patients with diabetes mellitus were ≥70 yr at diagnosis (50% vs 43%) (p=0.0004). No significant relationship was noted between stage of colon cancer or survival and presence of DM.ConclusionsDM did not affect either the stage at diagnosis, or outcomes from colon cancer. More males with colon cancer tended to have DM and a larger proportion of patients with DM were ≥70 yr at the time of diagnosis.

title: Effect of Diabetes Mellitus on Outcomes of Colorectal Cancer
abstract: Many studies have revealed that diabetes mellitus (DM) increases a person's lifetime risk of colorectal cancer and that DM is associated with a worse outcome of colon cancer, but this association is controversial. In this study, we intended to examine the relationship between DM and the long-term outcomes of colorectal cancer.  A retrospective analysis was conducted on 657 patients who underwent surgery due to colorectal cancer between 1997 and 2004 at Korea Cancer Center Hospital. The operations were done by a single surgeon. With a median follow-up of 4.7 years, we analyzed differences in recurrence-free survival (RFS) and overall survival (OS) between patients with DM and those without DM.  Of the 657 patients, 374 (57%) were males and 67 (10%) had DM. There was no difference in age at diagnosis, sex and pathologic stage of colorectal cancer according to the presence of DM. There were no difference in the RFS and the OS of colon cancer between the patients with DM and those without DM. At 5 years, the RFS was 71.3% in diabetic patients vs. 70.4% in non-diabetic patients (P = 0.480), and the OS was 68.8% in diabetic patients vs. 75.0% in non-diabetic patients (P = 0.498). There was no difference in the median survival between the groups (9.6 years in the diabetic group vs. 10.6 years in the non-diabetic group; P = 0.495).  In this study, we did not find any relation between the presence of DM and either the recurrence or the survival in cases of colorectal cancer. More studies to elucidate whether the influence of DM is directly related to a higher rate of cancer recurrence or survival are needed.

title: Elevated HbA1c Is an Independent Predictor of Aggressive Clinical Behavior in Patients with Colorectal Cancer: A Case-Control Study
abstract: The aim of this study was to seek an association between the control of type 2 diabetes mellitus (T2DM), as determined by hemoglobin A1c (HbA1c) levels, and the outcome of colorectal cancer (CRC).  We performed a retrospective review of patients with T2DM who had CRC diagnosed between 1997 and 2001. We defined well-controlled T2DM as HbA1c < 7.5% and poorly controlled T2DM as HbA1c ≥ 7.5%. A group of age- and gender-matched patients who had CRC without T2DM were used as controls. Forty clinical factors were reviewed, and those associated with poor clinical outcome in each group were examined by univariate analysis (UA) and by the maximum likelihood analysis of logistic regression to determine the independent predictors of cancer outcome.  We identified 155 patients with T2DM and CRC, and 114 control patients who had CRC without T2DM. We found no significant differences in any clinical factor by UA between the patients with well-controlled T2DM and the patients who had CRC without T2DM. Compared to both of those patients groups, in contrast, the patients with poorly controlled T2DM had more right-sided CRCs (P = 0.04, OR = 2, 95% CI = 1–4.1), more advanced CRCs (P = 0.02, OR = 2.1, 95% CI = 1–4.4), a younger age of presentation (P = 0.05), greater use of exogenous insulin (P = 0.002), and a poorer 5-year survival (P = 0.001) by UA. Logistic regression showed that poorly controlled T2DM independently predicted the early onset of CRC, a more advanced stage at the time of presentation, poorer 5-year survival, and an increased incidence of right-sided CRCs.  In patients with T2DM who have CRC, poor glycemic control is associated with a clinically aggressive course for the cancer.

title: Less aggressive treatment and worse overall survival in cancer patients with diabetes: A large population based analysis
abstract: The purpose of this study was to document the prevalence of diabetes among newly diagnosed cancer patients and to evaluate the influence of diabetes on stage at diagnosis, treatment and overall survival. We performed a population‐based analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by hospital medical records review. Follow‐up of all patients was completed until January 1, 2005. Nine percent of all cancer patients had diabetes at the time of cancer diagnosis. The prevalence of diabetes was highest among patients with cancer of the pancreas (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast and ovarian cancer patients with diabetes were more often diagnosed with a higher tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus, colon, breast and ovary were treated less aggressively compared to those without diabetes (p < 0.05). During the follow‐up period 3,902 of 5,555 cancer patients with diabetes died and 29,909 of 52,943 cancer patients without diabetes died. For all cancers combined, in a multivariate cox‐regression model, adjusting for age, gender, stage, treatment and cardiovascular disease, patients with diabetes experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40–1.49), ranging however from 0 to 40% for different types of cancer, compared to those without diabetes. In conclusion, diabetic cancer patients frequently were treated less aggressively and had a worse prognosis compared to those without diabetes.