OBJECTIVE To assess the association between erectile dysfunction (ED) and the long-term risk of coronary artery disease (CAD) and the role of age as a modifier of this association. PARTICIPANTS AND ...METHODS From January 1, 1996, to December 31, 2005, we biennially screened a random sample of 1402 community-dwelling men with regular sexual partners and without known CAD for the presence of ED. Incidence densities of CAD were calculated after age stratification and adjusted for potential confounders by time-dependent Cox proportional hazards models. RESULTS The prevalence of ED was 2% for men aged 40 to 49 years, 6% for men aged 50 to 59 years, 17% for men aged 60 to 69 years, and 39% for men aged 70 years or older. The CAD incidence densities per 1000 person-years for men without ED in each age group were 0.94 (40-49 years), 5.09 (50-59 years), 10.72 (60-69 years), and 23.30 (≥70 years). For men with ED, the incidence densities of CAD for each age group were 48.52 (40-49 years), 27.15 (50-59 years), 23.97 (60-69 years), and 29.63 (≥70 years). CONCLUSION ED and CAD may be differing manifestations of a common underlying vascular pathology. When ED occurs in a younger man, it is associated with a marked increase in the risk of future cardiac events, whereas in older men, ED appears to be of little prognostic importance. Young men with ED may be ideal candidates for cardiovascular risk factor screening and medical intervention.
Abstract Objective To: a) identify prognostic factors in patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS), and b) compare ...post-surgical survival between patients treated with NACT/IDS for presumed unresectable disease and stage IIIC/IV patients who underwent suboptimal primary debulking surgery (PDS). Methods This was a retrospective study of consecutive stage IIIC or IV patients undergoing IDS after NACT at Mayo Clinic from January 2007 to December 2013. A subset of patients receiving NACT/IDS for the indication of unresectable disease were matched 1:1 on age and stage to a cohort of patients who underwent suboptimal PDS between 2003 and 2011. Hazard ratios and corresponding 95% confidence intervals were estimated from Cox proportional hazards models. Results We identified 87 patients treated with NACT/IDS: the median OS and PFS following surgery was 2.4 and 1.0 years, respectively. Factors associated with significantly worse OS were older age (adjusted HR 1.60 per 10-year increase in age, 95% CI 1.18, 2.16) and elevated CA-125 before IDS (adjusted HR 2.30 for CA-125 > 35 U/mL, 95% CI 1.25, 4.23). Number of adjuvant chemotherapy cycles administered did not have a significant effect on survival. In the matched cohort analysis of presumed unresectable cases undergoing NACT/IDS vs suboptimal PDS cases (n = 45 each), the NACT/IDS group had a significant OS advantage (HR 0.53; 95% CI 0.32, 0.88), and fewer patients experienced a 30-day postoperative Accordion grade 3/4 complication (11% vs 36%, P = 0.01). Conclusions Younger age and normalization of CA-125 prior to IDS are associated with improved survival with NACT/IDS. For primary EOC where resection to residual disease of 1 cm or less is unlikely, NACT/IDS is associated with improved survival and reduced perioperative morbidity compared to PDS. As these patients are likely best served by NACT/IDS, more reliable predictors of resectability would be valuable.
In endometrial cancer, occult high-risk subtypes (rooted in histomorphologically low-risk disease) with insensitivity to adjuvant therapies impede improvements in therapeutic efficacy. Therefore, we ...aimed to assess the ability of molecular high-risk (MHR) and low-risk (MLR) ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification to profile recurrence in early, low-risk endometrioid endometrial cancer (EEC) and insensitivity to platinum-based chemotherapy or radiotherapy (or both) in high-risk EEC. Using The Cancer Genome Atlas endometrial cancer database, we identified 192 EEC cases with available DNA sequencing and RNA expression data. Molecular parameters were integrated with clinicopathologic risk factors and adverse surveillance events. MHR was defined as high (-H) CCNA2 or E2F1 log2 expression (≥2.75), PPP2R1A mutations (-mu), or FBXW7mu; MLR was defined as low (-L) CCNA2 and E2F1 log2 expression (<2.75). We assessed 164 cases, plus another 28 with POLEmu for favorable-outcomes comparisons. MHR and MLR had significantly different progression-free survival (PFS) rates (P < .001), independent of traditional risk factors (eg, TP53mu), except for stage IV disease. PFS of CCNA2-L/E2F1-L paralleled that of POLEmu. ECPPF status stratified responses to adjuvant therapy in stage III-IV EEC (P < .01) and profiled stage I, grade 1-2 cases with risk of recurrence (P < .001). MHR was associated with CTNNB1mu-linked treatment failures (P < .001). Expression of homologous recombination repair (HR) and cell cycle genes was significantly elevated in CCNA2-H/E2F1-H compared with CCNA2-L/E2F1-L (P<1.0E-10), suggesting that HR deficiencies may underlie the favorable PFS in MLR. HRmu were detected in 20.7%. No treatment failures were observed in high-grade or advanced EEC with HRmu (P = .02). Favorable PFS in clinically high-risk EEC was associated with HRmu and MLR ECPPF (P < .001). In summary, MLR ECPPF and HRmu were associated with therapeutic efficacy in EEC. MHR ECPPF was associated with low-risk, early-stage recurrences and insensitivity to adjuvant therapies.
Abstract Objectives To assess the impact of muscle composition and sarcopenia on overall survival in advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). Methods Women with ...stage IIIC/IV EOC who underwent PDS with curative intent between 1/1/2006 and 12/31/2012 were included. Patient variables and vital status were abstracted. Body composition was evaluated in a semi-automated process using Slice-O-Matic software v4.3 (TomoVision). Skeletal muscle area and mean skeletal muscle attenuation were recorded. Associations with overall survival were evaluated using Cox proportional hazards models and recursive partitioning. Results We identified 296 patients and 132 (44.6%) were classified as sarcopenic. The average mean skeletal muscle attenuation of the entire cohort was 33.4 Hounsfield units (HU). A multivariate model of overall risk of death included histology, residual disease, and mean skeletal attenuation. Among patients without residual disease, overall survival, but not progression free survival was significantly different between patients with low versus high mean skeletal attenuation (median survival, 2.8 vs. 3.3 years). Among patients with residual disease, overall survival was significantly different between patients with low versus high mean skeletal attenuation ≥ 36.40 vs. < 36.40 HU (median survival, 2.0 vs. 3.3 years). Conclusions Sarcopenia and low mean skeletal muscle attenuation are common in women undergoing PDS for advanced EOC. These factors are associated with poorer outcomes, and can be used in preoperative risk stratification and patient counseling. Further research into body composition and whether this risk factor can be altered via nutrition or fitness in this population is warranted.
Abstract Objective To describe the prevalence of nonacute conditions among patients seeking health care in a defined US population, emphasizing age, sex, and ethnic differences. Patients and Methods ...The Rochester Epidemiology Project (REP) medical records linkage system was used to identify all residents of Olmsted County, Minnesota, on April 1, 2009, who had consented to review of their medical records for research (142,377 patients). We then electronically extracted all International Classification of Diseases, Ninth Revision codes noted in the records of these patients by any health care institution between January 1, 2005, and December 31, 2009. We grouped International Classification of Diseases, Ninth Revision codes into clinical classification codes and then into 47 broader disease groups associated with health-related quality of life. Age- and sex-specific prevalence was estimated by dividing the number of individuals within each group by the corresponding age- and sex-specific population. Patients within a group who had multiple codes were counted only once. Results We included a total of 142,377 patients, 75,512 (53%) of whom were female. Skin disorders (42.7%), osteoarthritis and joint disorders (33.6%), back problems (23.9%), disorders of lipid metabolism (22.4%), and upper respiratory tract disease (22.1%, excluding asthma) were the most prevalent disease groups in this population. Ten of the 15 most prevalent disease groups were more common in women in almost all age groups, whereas disorders of lipid metabolism, hypertension, and diabetes were more common in men. Additionally, the prevalence of 7 of the 10 most common groups increased with advancing age. Prevalence also varied across ethnic groups (whites, blacks, and Asians). Conclusion Our findings suggest areas for focused research that may lead to better health care delivery and improved population health.
To evaluate the impact of an evidence-based triage algorithm to decide between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NACT/IDS) for ...advanced epithelial ovarian cancer (EOC).
Surgical morbidity and mortality (M/M) after PDS for stage IIIC-IV EOC at Mayo Clinic after implementation of the triage algorithm (contemporary cohort, 2012-July 2016) were compared to that of a historic PDS cohort (2003−2011).
Mean age of the 232 women who met inclusion criteria in the contemporary cohort was 63.9 years. We observed a 71% decrease in 90-day mortality from 8.9% to 2.6% (P = 0.002) between the contemporary and historic cohorts. Accordion grade 3+ postoperative complications within 30 days after surgery decreased from 22.3% to 18.3% (P = 0.19). Among those with a grade 3+ complication, 90-day mortality rates decreased from 28.3% in the historic cohort to 2.4% in the contemporary cohort (P < 0.001) suggesting patients were better able to tolerate complex surgery. When compared to the historic PDS cohort, oncologic outcomes were also improved in the contemporary PDS cohort. Complete as well as optimal (residual disease ≤1 cm) cytoreduction rates increased (45.5% vs. 62.5% and 84.5% vs. 95.3%, respectively, P < 0.001), and the proportion of women starting chemotherapy within 42 days of surgery increased (57.4% vs. 69.8%, P = 0.001). Three-year overall survival was 53% in the historic cohort and 66% in the contemporary cohort (P < 0.001).
Use of the Mayo triage algorithm for EOC was associated with reduced 90-day mortality after PDS and improved oncologic outcomes. Surgical risk assessment is a critical aspect of treatment planning in the primary management of EOC and should be incorporated into practice.
•Both primary debulking (PDS) & neoadjuvant chemotherapy (NACT) are ideal approaches for different ovarian cancer patients•Choice between NACT and PDS should be based on risk of surgical morbidity and mortality•Use of our triage algorithm to choose between PDS and NACT reduces 90 day mortality after PDS•Use of our triage algorithm also improved residual disease and ability to start chemotherapy within 42 days of surgery.
To determine what proportion of a geographically defined population who receive new opioid prescriptions progresses to episodic or long-term patterns of opioid prescribing and to explore the clinical ...characteristics associated with patterns of opioid prescribing.
Population-based drug prescription records for the population of Olmsted County between January 1 and December 31, 2009, were obtained using the Rochester Epidemiology Project medical records linkage system (N=142,377). All medical records were reviewed for a random sample of 293 patients who had a new ("incident") prescription for an opioid analgesic in 2009. Patients were followed through their medical records for 1 year after their initial prescription date, with patterns of opioid prescribing categorized as short-term, episodic, or long-term.
Overall, 293 patients received 515 new opioid prescriptions in 2009. Of these, 61 (21%) progressed to an episodic prescribing pattern and 19 (6%) progressed to a long-term prescribing pattern. In multivariable logistic regression analyses, substance abuse was significantly associated (P<.001) with a long-term opioid prescribing pattern as compared with an short-term opioid prescribing pattern. Past or current nicotine use (P=.03) and substance abuse (P=.04) were significantly associated with an episodic or long-term prescribing pattern as compared with a short-term prescribing pattern.
Knowledge of the clinical characteristics associated with the progression of a short-term to an episodic or long-term opioid prescribing pattern could aid in the identification of at-risk patients and provide the basis for developing targeted clinical interventions.
Abstract Objectives To assess clinicopathologic outcomes between two nodal assessment approaches in patients with endometrioid endometrial carcinoma and limited myoinvasion. Methods Patients with ...endometrial cancer at two institutions were reviewed. At one institution, a complete pelvic and para-aortic lymphadenectomy to the renal veins was performed in select cases deemed at risk for nodal metastasis due to grade 3 cancer and/or primary tumor diameter > 2 cm (LND cohort). This is a historic approach at this institution. At the other institution, a sentinel lymph node mapping algorithm was used per institutional protocol (SLN cohort). Low risk was defined as endometrioid adenocarcinoma with myometrial invasion < 50%. Macrometastasis, micrometastasis, and isolated tumor cells were all considered node-positive. Results Of 1135 cases identified, 642 (57%) were managed with an SLN approach and 493 (43%) with an LND approach. Pelvic nodes (PLNs) were removed in 93% and 58% of patients, respectively (P < 0.001); para-aortic nodes (PANs) were removed in 14.5% and 50% of patients, respectively (P < 0.001). Median number of PLNs removed was 6 and 34, respectively; median number of PANs removed was 5 and 16, respectively (both P < 0.001). Metastasis to PLNs was detected in 5.1% and 2.6% of patients, respectively (P = 0.03), and to PANs in 0.8% and 1.0%, respectively (P = 0.75). The 3-year disease-free survival rates were 94.9% (95% CI, 92.4–97.5) and 96.8% (95% CI, 95.2–98.5), respectively. Conclusions Our findings support the use of either strategy for endometrial cancer staging, with no apparent detriment in adhering to the SLN algorithm. The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy is yet to be determined.
To estimate lower extremity lymphedema prevalence in patients surgically treated for endometrial cancer, identify predictors of lymphedema, and evaluate the effects of lymphedema on quality of life.
...One thousand forty-eight consecutive patients who were operated on between 1999 and 2008 at the Mayo Clinic were mailed a survey, which included our validated 13-item lymphedema screening questionnaire and two validated quality-of-life measures. Logistic regression models were fit to identify factors associated with prevalent lymphedema; a multivariable model was obtained using stepwise and backward variable selection methods. The relationship between lymphedema and obesity with each quality-of-life score was evaluated separate multivariable linear models.
There were 591 responders (56%) after exclusions. Our questionnaire revealed a previous self-reported lymphedema diagnosis in 103 (17%) patients and identified undiagnosed lymphedema in 175 (30%) (overall prevalence 47.0%, median 6.2 years follow-up). Lymphedema prevalence in patients treated with hysterectomy alone compared with lymphadenectomy was 36.1% and 52.3%, respectively (attributable risk 23%). Lymphedema risk was not associated with the number of nodes removed or the extent of lymphadenectomy after adjusting for other factors. On multivariable analysis, higher body mass index, congestive heart failure, performance of lymphadenectomy, and radiation therapy were associated with prevalent lymphedema. Multiple quality-of-life scores were worse in women with lymphedema.
The attributable risk of developing lower extremity lymphedema was 23% for patients with endometrial cancer who underwent lymphadenectomy compared with hysterectomy alone with an overall prevalence of 47%. Lymphedema was associated with reductions in multiple quality-of-life domains.
II.
We aimed to examine the interplay between frailty and nutritional status on 90-day mortality after primary cytoreductive surgery (PCS) for ovarian cancer (OC).
Patients with OC who underwent PCS from ...1/2/2006–4/30/2018 at a single institution were identified. Frailty index (FI) includes 30 items and is calculated summing across all the item scores and dividing by the total; frailty was defined as FI ≥0.15. Nutritional status was considered impaired when preoperative serum albumin was <3.5 g/dL. Logistic regression was used to analyze the association between FI (continuous) and albumin status (binary) and 90-day postoperative mortality.
A total of 533 patients (mean age, 64.4 years) were included, the majority were stage IIIC disease and serous histology. Albumin was <3.5 g/dL in 87 patients (16.3%) and 113 patients (21.2%) were considered frail. Median FI was 0.07 (IQR 0.03, 0.13).
Postoperative 90-day mortality occurred in 24 patients (4.5%). Mortality within 90 days was higher amongst patients with low albumin (12/87, 13.8%), regardless of frailty status (13.8% 9/65 non-frail and 13.6% 3/22 frail patients). Ninety-day mortality in patients with normal albumin (n = 446) was over twice as likely in frail versus non-frail patients (5.5% 5/91 vs. 2.0% 7/355, respectively, p = 0.08). A model to assess 90-day mortality that included both FI and low albumin significantly improved the overall discrimination compared to low albumin alone (AUC 0.76 vs. 0.68 p = 0.03).
Our findings suggest that frailty and nutrition are both related to 90-day mortality. Preoperative interventions to improve functional and nutritional characteristics are needed.
•Albumin is a strong predictor of poor outcomes after surgery for advanced ovarian cancer irrespective of frailty status.•Patients who are either frail or nutritionally impaired are at risk for 90-day mortality after cytoreductive surgery.•Individualized prehabilitation strategies should be investigated to improve preoperative patient status.
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