Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis.

PURPOSE: The goal of this study was to perform a systematic review and meta-analysis to examine the effect of pre-existing diabetes on breast cancer-related outcomes. METHODS: We searched EMBASE and MEDLINE databases from inception through July 1, 2009, using search terms related to diabetes mellitus, cancer, and prognostic outcome. Studies were included if they reported a prognostic outcome by diabetes status, evaluated a cancer population, and contained original data published in the English language. We performed a meta-analysis of pre-existing diabetes and its effect on all-cause mortality in patients with breast cancer and qualitatively summarized other prognostic outcomes. RESULTS: Of 8,828 titles identified, eight articles met inclusion/exclusion criteria and described outcomes in patients with breast cancer and diabetes. Pre-existing diabetes was significantly associated with all-cause mortality in six of seven studies. In a meta-analysis, patients with breast cancer and diabetes had a significantly higher all-cause mortality risk (pooled hazard ratio [HR], 1.49; 95% CI, 1.35 to 1.65) compared with their nondiabetic counterparts. Three of four studies found pre-existing diabetes to be associated with more advanced stage at presentation. Diabetes was also associated with altered regimens for breast cancer treatment and increased toxicity from chemotherapy. CONCLUSION: Compared with their nondiabetic counterparts, patients with breast cancer and pre-existing diabetes have a greater risk of death and tend to present at later stages and receive altered treatment regimens. Studies are needed to investigate pathophysiologic interactions between diabetes and breast cancer and determine whether improvements in diabetes care can reduce mortality in patients with breast cancer.

Postoperative mortality in cancer patients with preexisting diabetes: systematic review and meta-analysis.

OBJECTIVE: Diabetes appears to increase risk for some cancers, but the association between preexisting diabetes and postoperative mortality in cancer patients is less clear. Our objective was to systematically review postoperative mortality in cancer patients with and without preexisting diabetes and summarize results using meta-analysis. RSEARCH DESIGN AND METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE) for articles published on or before 1 July 2009, including references of qualifying articles. We included English language investigations of short-term postoperative mortality after initial cancer treatment. Titles, abstracts, and articles were reviewed by at least two independent readers. Study population and design, results, and quality components were abstracted with standard protocols by one reviewer and checked for accuracy by additional reviewers. RESULTS: Of 8,828 titles identified in our original search, 20 articles met inclusion criteria for qualitative systematic review. Of these, 15 reported sufficient information to be combined in meta-analysis. Preexisting diabetes was associated with increased odds of postoperative mortality across all cancer types (OR = 1.85 [95% CI 1.40-2.45]). The risk associated with preexisting diabetes was attenuated but remained significant when we restricted the meta-analysis to models that controlled for confounders (1.51 [1.13-2.02]) or when we accounted for publication bias using the trim and fill method (1.52 [1.13-2.04]). CONCLUSIONS: Compared with their nondiabetic counterparts, cancer patients with preexisting diabetes are approximately 50% more likely to die after surgery. Future research should investigate physiologic pathways to mortality risk and determine whether improvements in perioperative diabetes care can reduce postoperative mortality.

Quality of life after open or robotic prostatectomy, cryoablation or brachytherapy for localized prostate cancer.

PURPOSE: Health related quality of life concerns factor prominently in prostate cancer management. We describe health related quality of life impact and recovery profiles of 4 commonly used operative treatments for localized prostate cancer. MATERIALS AND METHODS: Beginning in February 2000 all patients treated with open radical prostatectomy, robot assisted laparoscopic prostatectomy, brachytherapy or cryotherapy were asked to complete the UCLA-PCI questionnaire before treatment, and at 3, 6, 12, 18, 24, 30 and 36 months after treatment. Outcomes were compared across treatment types with statistical analysis using univariate and multivariate models. RESULTS: A total of 785 patients treated between February 2000 and December 2008 were included in the analysis with a mean followup of 24 months. All health related quality of life domains were adversely affected by all treatments and recovery profiles varied significantly by treatment type. Overall urinary function and bother outcomes scored significantly higher after brachytherapy and cryotherapy compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Brachytherapy and cryotherapy had a 3-fold higher rate of return to baseline urinary function compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Sexual function and bother scores were highest after brachytherapy, with a 5-fold higher rate of return to baseline function compared to cryotherapy, open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. All 4 treatments were associated with relatively transient and less pronounced impact on bowel function and bother. CONCLUSIONS: In a study of sequential health related quality of life assessments brachytherapy and cryotherapy were associated with higher urinary function and bother scores compared to open radical prostatectomy and da Vinci prostatectomy. Brachytherapy was associated with higher sexual function and bother scores compared to open radical prostatectomy, robotic assisted laparoscopic radical prostatectomy and cryotherapy.

Colorectal cancer outcomes, recurrence, and complications in persons with and without diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Diabetes 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Patients 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.

The effect of dutasteride on the efficacy of photoselective vaporization of the prostate: results of a randomized, placebo-controlled, double-blind study (DOP trial).

OBJECTIVES: To study the effect of Dutasteride on the efficacy of GreenLight photoselective vaporization of the prostate (PV). Some investigators have suggested that 5 alpha-reductase inhibitors may interfere with PV by reducing intraprostatic blood flow. Dutasteride offers the most complete blockade of the 5 alpha-reductase inhibitors, with minimal increase in side effects. METHODS: This is a prospective, placebo-controlled, randomized, double-blind study. A total of 59 patients were randomized to either dutasteride 0.5 mg or placebo for 3 months before and 12 months after PV. Surgical time, joules used, estimated blood loss, and ease of the procedure were compared. Other clinical end points investigated include postsurgical catheter time, hematuria, dysuria, urinary flow parameters, American Urological Association symptom score, benign prostatic hyperplasia quality of life score, prostate volume, and prostate-specific antigen level. RESULTS: Average surgical time and joules used were 12% (P = .24) and 16% (P = .15) less, respectively, for dutasteride patients compared with placebo. Estimated blood loss was also lower in the treatment group (P = .14). However, these results were not statistically significant. Surgeon-rated ease of the procedure was comparable between the 2 groups. There were no significant differences in catheter time, dysuria, quality of life scores, or urinary flow parameters. Quality of life and urinary parameters markedly improved after PV. CONCLUSIONS: Compared with patients randomized to placebo, patients randomized to dutasteride experienced a trend toward decreased time, joules used, and blood loss during surgery. Although we could not convincingly prove an operative benefit of treatment with dutasteride before surgery, we have demonstrated the efficacy of PV in men receiving dutasteride.

Usefulness of cystatin C and prognosis following admission for acute heart failure.

Cystatin C is a novel marker of renal function that has been found to predict adverse cardiovascular outcomes in ambulatory patients. The aim of this study was to investigate whether this biomarker predicts the length of hospitalization and adverse outcomes in patients hospitalized for heart failure. Two hundred forty consecutive patients aged > or =25 admitted to Johns Hopkins Hospital with exacerbations of heart failure were prospectively enrolled. Cystatin C levels were measured on admission. Patients were followed for 1 year. The primary outcome measure was the length of hospitalization. Secondary outcomes included all-cause mortality and readmission for heart failure. Cystatin C showed no significant association with the length of hospitalization. Patients in the highest quartile (quartile 4) of cystatin C level were at increased risk for death (hazard ratio 2.07 for quartile 4 vs quartiles 1 to 3, p = 0.01) and death or rehospitalization (hazard ratio 1.61 for quartile 4 vs quartiles 1 to 3, p = 0.01). The association between cystatin C and the combined end point of death or rehospitalization during 1-year follow-up remained significant after adjusting for age, race, gender, co-morbidities, and creatinine. Cystatin C was more predictive of these end points than creatinine, and the combination of cystatin C and creatinine was more predictive than either variable alone. In conclusion, cystatin C may be useful in addition to creatinine for predicting outcomes after admission for acute heart failure exacerbations.

Risk factors for type 2 diabetes among women with gestational diabetes: a systematic review.

We conducted a systematic review of studies examining risk factors for the development of type 2 diabetes among women with previous gestational diabetes. Our search strategy yielded 14 articles that evaluated 9 categories of risk factors of type 2 diabetes in women with gestational diabetes: anthropometry, pregnancy-related factors, postpartum factors, parity, family history of type 2 diabetes, maternal lifestyle factors, sociodemographics, oral contraceptive use, and physiologic factors. The studies provided evidence that the risk of type 2 diabetes was significantly higher in women having increased anthropometric characteristics with relative measures of association ranging from 0.8 to 8.7 and women who used insulin during pregnancy with relative measures of association ranging between 2.8 and 4.7. A later gestational age at diagnosis of gestational diabetes, >24 weeks gestation on average, was associated with a reduction in risk of development of type 2 diabetes with relative measures of association ranging between 0.35 and 0.99. We concluded that there is substantial evidence for 3 risk factors associated with the risk of type 2 diabetes in women having gestational diabetes.

Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis.

CONTEXT: Diabetes mellitus appears to be a risk factor for some cancers, but the effect of preexisting diabetes on all-cause mortality in newly diagnosed cancer patients is less clear. OBJECTIVE: To perform a systematic review and meta-analysis comparing overall survival in cancer patients with and without preexisting diabetes. DATA SOURCES: We searched MEDLINE and EMBASE through May 15, 2008, including references of qualifying articles. STUDY SELECTION: English-language, original investigations in humans with at least 3 months of follow-up were included. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Of 7858 titles identified in our original search, 48 articles met our criteria. DATA EXTRACTION: One reviewer performed a full abstraction and other reviewers verified accuracy. We contacted authors and obtained additional information for 3 articles with insufficient reported data. RESULTS: Studies reporting cumulative survival rates were summarized qualitatively. Studies reporting Cox proportional hazard ratios (HRs) or Poisson relative risks were combined in a meta-analysis. A random-effects model meta-analysis of 23 articles showed that diabetes was associated with an increased mortality HR of 1.41 (95% confidence interval [CI], 1.28-1.55) compared with normoglycemic individuals across all cancer types. Subgroup analyses by type of cancer showed increased risk for cancers of the endometrium (HR, 1.76; 95% CI, 1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95% CI, 1.24-1.41). CONCLUSIONS: Patients diagnosed with cancer who have preexisting diabetes are at increased risk for long-term, all-cause mortality compared with those without diabetes.

Fatness and fitness: how do they influence health-related quality of life in type 2 diabetes mellitus?

OBJECTIVE: We examined whether adiposity and fitness explain the decrease in health-related quality of life (HRQOL) associated with type 2 diabetes mellitus. METHODS: This was a cross-sectional study using baseline data from two exercise training interventions. One study enrolled people with and the other without type 2 diabetes. We assessed aerobic fitness ("fitness") as peak oxygen uptake during treadmill testing, adiposity ("fatness") as percentage of total body fat by dual-energy x-ray absorptiometry, and HRQOL by the Medical Outcomes Study SF-36. Bivariate and multivariate linear regression analyses were used examine determinants of HRQOL were used to examine determinants of HRQOL. RESULTS: There were 98 participants with and 119 participants without type 2 diabetes. Participants with type 2 diabetes had a mean hemoglobin A1c of 6.6% and, compared with participants without diabetes had lower HRQOL on the physical component summary score (P = 0.004), role-physical (P = 0.035), vitality (P = 0.062) and general health (P < 0.001) scales after adjusting for age, sex and race. These associations of HRQOL with type 2 diabetes were attenuated by higher fitness, even more than reduced fatness. Only general health remained positively associated with type 2 diabetes after accounting for fatness or fitness (P = 0.003). There were no significant differences between participants with and without diabetes in the mental component score. CONCLUSION: Improved fitness, even more than reduced fatness, attenuated the association of type 2 diabetes with HRQOL. The potential to improve HRQOL may motivate patients with type 2 diabetes to engage in physical activity aimed at increasing fitness. Findings from this cross-sectional analysis will be addressed in the ongoing trial of exercise training in this cohort of participants with type 2 diabetes. TRIAL REGISTRATION: NCT00212303.

Therapeutic management, delivery, and postpartum risk assessment and screening in gestational diabetes.

OBJECTIVES: We focused on four questions: What are the risks and benefits of an oral diabetes agent (i.e., glyburide), as compared to all types of insulin, for gestational diabetes? What is the evidence that elective labor induction, cesarean delivery, or timing of induction is associated with benefits or harm to the mother and neonate? What risk factors are associated with the development of type 2 diabetes after gestational diabetes? What are the performance characteristics of diagnostic tests for type 2 diabetes in women with gestational diabetes? DATA SOURCES: We searched electronic databases for studies published through January 2007. Additional articles were identified by searching the table of contents of 13 journals for relevant citations from August 2006 to January 2007 and reviewing the references in eligible articles and selected review articles. REVIEW METHODS: Paired investigators reviewed abstracts and full articles. We included studies that were written in English, reported on human subjects, contained original data, and evaluated women with appropriately diagnosed gestational diabetes. Paired reviewers performed serial abstraction of data from each eligible study. Study quality was assessed independently by each reviewer. RESULTS: The search identified 45 relevant articles. The evidence indicated that: Maternal glucose levels do not differ substantially in those treated with insulin versus insulin analogues or oral agents. Average infant birth weight may be lower in mothers treated with insulin than with glyburide. Induction at 38 weeks may reduce the macrosomia rate, with no increase in cesarean delivery rates. Anthropometric measures, fasting blood glucose (FBG), and 2-hour glucose value are the strongest risk factors associated with development of type 2 diabetes. FBG had high specificity, but variable sensitivity, when compared to the 75-gm oral glucose tolerance test (OGTT) in the diagnosis of type 2 diabetes after delivery. CONCLUSIONS: The evidence suggests that benefits and a low likelihood of harm are associated with the treatment of gestational diabetes with an oral diabetes agent or insulin. The effect of induction or elective cesarean on outcomes is unclear. The evidence is consistent that anthropometry identifies women at risk of developing subsequent type 2 diabetes; however, no evidence suggested the FBG out-performs the 75-gm OGTT in diagnosing type 2 diabetes after delivery.

Single center experience with third-generation cryosurgery for management of organ-confined prostate cancer: critical evaluation of short-term outcomes, complications, and patient quality of life.

BACKGROUND AND PURPOSE: Technical refinements such as improved ultrasonographic localization and the routine use of urethral warmers and small-gauge needle delivery systems have renewed interest in cryosurgical treatment as a minimally invasive option for selected patients with localized prostate cancer. Only three reports of quality of life (QoL) in prostate cryoablation exist, and none report on patients treated with third-generation cryoablative technology. We critically examine our initial series of consecutive patients at a single institution undergoing primary third-generation cryosurgical treatment of localized prostate cancer with respect to treatment outcome, morbidity profile, and QoL parameters. To our knowledge, this is the first QoL report on third-generation cryoablation of the prostate. PATIENTS AND METHODS: We retrospectively review the records of 89 consecutive patients with median followup of 11 months (1-32) who have undergone third-generation cryosurgical ablation of the prostate as primary treatment for localized prostate cancer with intention to cure. Patients were risk stratified according to preprocedural parameters of prostate-specific antigen (PSA), clinical stage, and Gleason score. PSA trends were recorded and treatment effectiveness was observed using different definitions of biochemical failure. Charts were reviewed for postprocedure complications. Quality of life was measured prospectively using the University of California, Los Angeles, Prostate Cancer Index as well as American Urological Association symptom scores. We compare a percent of baseline score (%BS) for various domains between our series of patients treated with primary cryoablation with a series of patients undergoing brachytherapy for localized prostate cancer. RESULTS: Treatment success was defined by achievement of a PSA nadir of < or =0.1 ng/mL and by biochemical disease-free survival (BDFS) assessed with both a PSA threshold of < or =0.4 ng/dL over time and the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of three consecutive rises in PSA. According to risk stratification, 86%, 81.5%, and 78% of low-, intermediate-, and high-risk patients, respectively, achieved a PSA nadir of < or =0.1 ng/mL. Overall, at 12 months follow-up, 94% of patients achieved BDFS using ASTRO criteria while 70% achieved BDFS using a PSA threshold of < or =0.4 ng/mL. With risk stratification, 74%, 70%, and 60% of low-, intermediate-, and high-risk patients, respectively, achieved BDFS defined by PSA threshold of < or =0.4 ng/mL. Complications were rare. The response rate for Health Related Quality of Life (HRQoL) questionnaires was 71% for cryoablation patients and 51% for brachytherapy patients. At 12 months follow-up, patients undergoing cryoablation on average achieved urinary and bowel domain scores comparable to baseline, but sexual domains remained well below baseline. When compared with a brachytherapy series with better baseline sexual function (P = 0.04) and urinary function (P = 0.03), cryotherapy patients experienced more negative impact on sexual function steadily for up to 12 months (P = 0.02). Urinary function was similar between the groups until 18 months, at which time cryoablation patients fared better (P = 0.01); this was sustained up to 24 months (P = 0.04). CONCLUSIONS: Treatment success with cryosurgery varies with definition; however, our results are comparable to other series with regard to short-term cancer control. Complication rates in this series of third-generation cryosurgical patients are low. QoL characteristics of third-generation cryoablation are similar to those described in second-generation cryoablation series. Compared with brachytherapy, cryotherapy results in less irritative and obstructive voiding symptoms in the early post-treatment period and may improve urinary function up to 24 months after treatment. In a small group of older patients with baseline erectile dysfunction undergoing cryoablation, sexual function returns to 20% of its baseline value with up to 12 months follow-up.

Lifetime weight patterns in male physicians: the effects of cohort and selective survival.

OBJECTIVE: The natural history of lifetime weight change is not well understood because of conflicting evidence from cross-sectional and longitudinal studies. Cross-sectional analyses find that adult weight is highest at approximately 60 years of age and lower thereafter. Longitudinal analyses have not found this pattern. Our objective was to test whether cohort effects and selective survival may explain the differences observed between cross-sectional and longitudinal studies. RESEARCH METHODS AND PROCEDURES: We analyzed data on white men from the Johns Hopkins Precursors Study (n = 1197). Weight and height were measured at enrollment during medical school. The Precursors Study collected subsequent weight measurements by self-report and follows all participants for mortality. RESULTS: In preliminary analyses that ignored cohort and survival effects, average weight increased 0.16 kg/yr to age 65 (p < 0.001) and declined 0.10 kg/yr thereafter (p = 0.002). When controlling for differing rates of weight change by cohort and survival group, the apparent decline after 65 years of age was mostly explained. DISCUSSION: These data suggest that, in white men, weight increases steadily until age 65 and then plateaus. These findings emphasize the necessity of longitudinal rather than cross-sectional data to describe lifetime weight patterns.