Real-world assessment of longitudinal opioid use and healthcare resource utilization in patients undergoing colorectal resection.

Liposomal bupivacaine (LB) has been used in multimodal pain management regimens to improve postsurgical analgesia. This retrospective cohort analysis assessed clinical and economic outcomes of LB vs non-LB analgesia in minimally invasive colorectal resection surgery using real-world patient data from the IQVIA linkage claims databases. Patients who received LB were 1:1 matched to patients who did not receive LB (non-LB) via propensity scores. Outcomes included opioid use during the perioperative (2 weeks before surgery to 2 weeks after discharge), continued (>2 weeks to 3 months after discharge), and persistent (>3 months to 6 months after discharge) periods and healthcare resource utilization (HRU) during the first 3 months after discharge. Mean opioid consumption was lower in the LB (n = 4397) versus non-LB (n = 4397) cohort perioperatively (483 vs 538 morphine milligram equivalents [MMEs]; P = 0.001) and after discharge within ∼3 months (222 vs 328 MMEs; P < 0.0001) and 3-6 months (245 vs 384 MMEs; P < 0.0001). The LB cohort had shorter mean length of stay (5.2 vs 5.7 days; P < 0.0001) and fewer inpatient readmissions (odds ratio [OR], 0.71; P < 0.0001), emergency department visits (OR, 0.78; P < 0.0001), and outpatient/office visits (OR, 0.91; P = 0.028) than the non-LB cohort 3 months after discharge. These data suggest use of LB in minimally invasive colorectal resection surgery may reduce perioperative and postdischarge opioid use as well as HRU. Although additional studies are needed to confirm these findings, this analysis provides valuable real-world data from large claims databases to evaluate clinical and economic outcomes that complement other types of retrospective and prospective studies.

Effects of liposomal bupivacaine on opioid use and healthcare resource utilization after outpatient spine surgery: a real-world assessment.

BACKGROUND CONTEXT: Perioperative pain management affects cost and outcomes in elective spine surgery. PURPOSE: This study investigated the association between liposomal bupivacaine (LB) and outpatient spine surgery outcomes, including perioperative, postoperative, and postdischarge opioid use and healthcare resource utilization. STUDY DESIGN: This was a retrospective comparative study. PATIENT SAMPLE: Eligibility criteria included adults with ≥6 months of continuous data before and after outpatient spine procedures including discectomy, laminectomy, or lumbar fusion. Patients receiving LB were matched 1:3 to patients receiving non-LB analgesia by propensity scores. OUTCOME MEASURES: Outcomes included (1) opioid use in morphine milligram equivalents (MMEs) during the perioperative and postdischarge periods and (2) postdischarge readmission and emergency department (ED) visits up to 3 months after surgery. Generalized linear mixed-effects modeling with appropriate distributions was used for analysis. METHODS: Deidentified data from the IQVIA linkage claims databases (2016-2019) were used for the analysis. This study was funded by Pacira BioSciences, Inc. RESULTS: In total, 381 patients received LB and 1143 patients received non-LB analgesia. Baseline characteristics were well balanced after propensity score matching. The LB cohort used fewer MMEs versus the non-LB cohort before discharge (80 vs 132 MMEs [mean difference, -52 MMEs; p=.0041]). Following discharge, there was a nonsignificant reduction in opioid use in the LB cohort versus the non-LB cohort within 90 days (429 vs 480 MMEs [mean difference, -50 MMEs; p=.289]) and from >90 days to 180 days (349 vs 381 MMEs [mean difference, -31 MMEs; p=.507]). The LB cohort had significantly lower rates of ED visits at 2 months after discharge versus the non-LB cohort (3.9% vs 7.6% [odds ratio, 0.50; p=.015]). Postdischarge readmission rates did not differ between cohorts. CONCLUSIONS: Use of LB for outpatient spine surgery was associated with reduced opioid use at the hospital and nonsignificant reduction in opioid use at all postoperative timepoints examined through 90 days after surgery versus non-LB analgesia. ED visit rates were significantly lower at 60 days after discharge. These findings support reduced cost and improved quality metrics in patients treated with LB versus non-LB analgesia for outpatient spine surgery.

Liposomal Bupivacaine Analgesia in Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Retrospective Cohort Study.

Background: Liposomal bupivacaine (LB) can be used for postsurgical analgesia after breast reconstruction. We examined real-world clinical and economic benefits of LB versus bupivacaine after deep inferior epigastric perforator (DIEP) flap breast reconstruction. Methods: This retrospective cohort study used the IQVIA claims databases to identify patients undergoing primary DIEP flap breast reconstruction in 2016-2019. Patients receiving LB and those receiving bupivacaine were compared to assess opioid utilization in morphine milligram equivalents (MMEs) and healthcare resource utilization during perioperative (2 weeks before surgery to 2 weeks after discharge) and 6-month postdischarge periods. A generalized linear mixed-effects model and inverse probability of treatment weighting method were performed. Results: Weighted baseline characteristics were similar between cohorts (LB, n = 669; bupivacaine, n = 348). The LB cohort received significantly fewer mean MMEs versus the bupivacaine cohort during the perioperative (395 versus 512 MMEs; rate ratio [RR], 0.771 [95% confidence interval (CI), 0.677-0.879]; P = 0.0001), 72 hours after surgery (63 versus 140 MMEs; RR, 0.449 [95% CI, 0.347-0.581]; P < 0.0001), and inpatient (154 versus 303 MMEs; RR, 0.508 [95% CI, 0.411-0.629]; P < 0.0001) periods; postdischarge filled opioid prescriptions were comparable. The LB cohort was less likely to have all-cause inpatient readmission (odds ratio, 0.670 [95% CI, 0.452-0.993]; P = 0.046) and outpatient clinic/office visits (odds ratio, 0.885 [95% CI, 0.785-0.999]; P = 0.048) 3 months after discharge than the bupivacaine cohort; other all-cause healthcare resource utilization outcomes were not different. Conclusions: LB was associated with fewer perioperative MMEs and all-cause 3-month inpatient readmissions and outpatient clinic/office visits than bupivacaine in patients undergoing DIEP flap breast reconstruction.

Economic Outcomes and Incidence of Postsurgical Hypotension With Liposomal Bupivacaine vs Epidural Analgesia in Abdominal Surgeries.

Background: Epidural analgesia can be associated with high costs and postsurgical risks such as hypotension, despite its widespread use and value in providing opioid-sparing pain management. We tested the hypothesis that liposomal bupivacaine (LB) might be a reliable alternative to epidural analgesia in this real-world study. Objectives: To compare economic outcomes and hypotension incidence associated with use of LB and epidural analgesia for abdominal surgery. Methods: This retrospective analysis identified records of adults who underwent abdominal surgeries between January 2016 and September 2019 with either LB administration or traditional epidural analgesia using the Premier Healthcare Database. Economic outcomes included length of stay, hospital costs, rates of discharge to home, and 30-day hospital readmissions. Secondary outcomes included incidence of postsurgical hypotension and vasopressor use. Subgroup analyses were stratified by surgical procedure (colorectal, abdominal) and approach (endoscopic, open). A generalized linear model adjusted for patient and hospital characteristics was used for all comparisons. Results: A total of 5799 surgical records (LB, n=4820; epidural analgesia, n=979) were included. Compared with cases where LB was administered, cases of epidural analgesia use were associated with a 1.6-day increase in length of stay (adjusted rate ratio [95% confidence interval (CI), 1.2 [1.2-1.3]]; P<.0001) and $6304 greater hospital costs (adjusted rate ratio [95% CI], 1.2 [1.2-1.3]]; P<.0001). Cost differences were largely driven by room-and-board fees. Epidural analgesia was associated with reduced rates of discharge to home (P<.0001) and increased 30-day readmission rates (P=.0073) compared with LB. Epidural analgesia was also associated with increased rates of postsurgical hypotension (30% vs 11%; adjusted odds ratio [95% CI], 2.8 [2.3-3.4]; P<.0001) and vasopressor use (22% vs 7%; adjusted odds ratio [95% CI], 3.1 [2.5-4.0]; P<.0001) compared with LB. Subgroup analyses by surgical procedure and approach were generally consistent with overall comparisons. Discussion: Our results are consistent with previous studies that demonstrated epidural analgesia can be associated with higher utilization of healthcare resources and complications compared with LB. Conclusions: Compared with epidural analgesia, LB was associated with economic benefits and reduced incidence of postsurgical hypotension and vasopressor use.

Effectiveness of Liposomal Bupivacaine Compared With Standard-of-Care Measures in Pediatric Cardiothoracic Surgery: A Retrospective Cohort Study.

OBJECTIVE: Effective postsurgical pain management is important for pediatric patients to improve outcomes while reducing resource use and waste. The authors examined opioid consumption and economic outcomes associated with liposomal bupivacaine (LB) or non-LB analgesia use in pediatric patients undergoing cardiothoracic surgery. DESIGN: The authors retrospectively analyzed Premier Healthcare Database records. SETTING: The data extracted from the database included patient records from hospitals across the United States in both rural and urban locations. PARTICIPANTS: The records included data from patients aged 12-to-<18 years. INTERVENTIONS: The records belonged to patients undergoing video-assisted thoracoscopic procedures (VATS) who received LB or non-LB analgesia after surgery. MEASUREMENTS AND MAIN RESULTS: Outcomes included in-hospital postsurgical opioid consumption in morphine milligram equivalents (MMEs), hospital length of stay (LOS), and total hospital costs; the LB and non-LB cohorts were compared using a generalized linear model with inverse probability of treatment weighting to balance the cohorts. For VATS procedures, pediatric patients receiving LB had significant reductions in in-hospital opioid consumption (632 v 991 MMEs; p < 0.0001), shorter LOS (5.1 v 5.6 days; p = 0.0023), and lower total hospital costs ($18,084 v $21,962; p < 0.0001) compared with those receiving non-LB analgesia. CONCLUSIONS: These results support use of LB in multimodal analgesia regimens for managing pain in pediatric patients after cardiothoracic surgery.

Clinical and Economic Outcomes Associated With Use of Liposomal Bupivacaine Versus Standard of Care for Management of Postsurgical Pain in Pediatric Patients Undergoing Spine Surgery.

Background: Approximately 60% of hospitalized children undergoing surgery experience at least 1 day of moderate-to-severe pain after surgery. Pain following spine surgery may affect opioid exposure, length of stay (LOS), and costs in hospitalized pediatric patients. This is a retrospective cohort analysis of pediatric patients undergoing inpatient primary spine surgery. Objectives: To examine the association of opioid-related and economic outcomes with postsurgical liposomal bupivacaine (LB) or non-LB analgesia in pediatric patients who received spine surgery. Methods: Premier Healthcare Database records (January 2015-September 2019) for patients aged 1-17 years undergoing inpatient primary spine surgery were retrospectively analyzed. Outcomes included in-hospital postsurgical opioid consumption (morphine milligram equivalents [MMEs]), opioid-related adverse events (ORAEs), LOS (days), and total hospital costs. A generalized linear model adjusting for baseline characteristics was used. Results: Among 10 189 pediatric patients, the LB cohort (n=373) consumed significantly fewer postsurgical opioids than the non-LB cohort (n=9816; adjusted MME ratio, 0.53 [95% confidence interval (CI), 0.45-0.61]; P<0.0001). LOS was significantly shorter in the LB versus non-LB cohort (adjusted rate ratio, 0.86 [95% CI, 0.80-0.94]; P=0.0003). Hospital costs were significantly lower in the LB versus non-LB cohort overall (adjusted rate ratio, 0.92 [95% CI, 0.86-0.99]; P=0.0227) mostly because of decreased LOS and central supply costs. ORAEs were not significantly different between groups (adjusted rate ratio, 0.84 [95% CI, 0.65-1.08]; P=0.1791). Discussion: LB analgesia was associated with shorter LOS and lower hospital costs compared with non-LB analgesia in pediatric patients undergoing spine surgery. The LB cohort had lower adjusted room and board and central supply costs than the non-LB cohort. These data suggest that treatment with LB might reduce hospital LOS and subsequently health-care costs, and additional cost savings outside the hospital room may factor into overall health-care cost savings. LB may reduce pain and the need for supplemental postsurgical opioids, thus reducing pain and opioid-associated expenses while improving patient satisfaction with postsurgical care. Conclusions: Pediatric patients undergoing spine surgery who received LB had significantly reduced in-hospital postsurgical opioid consumption, LOS, and hospital costs compared with those who did not.

Real-world analysis of treatment patterns and clinical outcomes in patients with newly diagnosed chronic lymphocytic leukemia from seven Latin American countries.

OBJECTIVE: To describe chronic lymphocytic leukemia (CLL) treatment patterns and patient outcomes in Latin America. METHODS: This chart review study (NCT02559583; 2008-2015)evaluated time to progression (TTP) and overall survival (OS) outcomes among patients with CLL who initiate done (n = 261) to two (n = 96) lines of therapy (LOT) since diagnosis. Differences in TTP and OS were assessed by Kaplan-Meier analysis, with a log-rank test for statistical significance. Association between therapeutic regimen and risk for disease progression or death was estimated using Cox proportional hazard regression. RESULTS: The most commonly prescribed therapies in both LOTs were chlorambucil-, followed by fludarabine- and cyclophosphamide (C)/CHOP-based therapies. Chlorambucil- and C/CHOP-based therapies were largely prescribed to elderly patients (≥65 years) while fludarabine-based therapy was predominantly used by younger patients (≤65 years). In LOT1, relative to chlorambucil-administered patients, those prescribed fludarabine-based therapies had lower risk of disease progression (hazard ratio [HR] and 95% confidence interval [CI] 0.32 [0.19-0.54]), whereas C/CHOP-prescribed patients had higher risk (HR 95%CI 1.88 [1.17-3.04]). Similar results were observed in LOT2. There was no difference in OS between treatments in both LOTs. DISCUSSION: Novel therapies such as kinase inhibitors were rarely prescribed in LOT1 or LOT2in Latin America. The greater TTP observed forfludarabine-based therapies could be attributed to the fact that fludarabine-based therapies are predominantly administered to young and healthy patients. CONCLUSION: Chlorambucil-based therapy, which has limited benefits, is frequently prescribed in Latin America. Prescribing novel agents for fludarabine-based therapy-ineligible patients with CLL is the need of the hour. Trial registration: ClinicalTrials.gov identifier: NCT02559583.

Plasma Estradiol and Testosterone Levels and Ischemic Stroke in Postmenopausal Women.

Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

Multiple myeloma treatment patterns and clinical outcomes in the Latin America Haemato-Oncology (HOLA) Observational Study, 2008-2016.

Limited data are available regarding contemporary multiple myeloma (MM) treatment practices in Latin America. In this retrospective cohort study, medical records were reviewed for a multinational cohort of 1103 Latin American MM patients (median age, 61 years) diagnosed in 2008-2015 who initiated first-line therapy (LOT1). Of these patients, 33·9% underwent autologous stem cell transplantation (ASCT). During follow-up, 501 (45·4%) and 129 (11·7%) patients initiated second- (LOT2) and third-line therapy (LOT3), respectively. In the LOT1 setting, from 2008 to 2015, there was a decrease in the use of thalidomide-based therapy, from 66·7% to 42·6%, and chemotherapy from, 20·2% to 5·9%, whereas use of bortezomib-based therapy or bortezomib + thalidomide increased from 10·7% to 45·5%. Bortezomib-based therapy and bortezomib + thalidomide were more commonly used in ASCT patients and in private clinics. In non-ASCT and ASCT patients, median progression-free survival (PFS) was 15·0 and 31·1 months following LOT1 and 10·9 and 9·5 months following LOT2, respectively. PFS was generally longer in patients treated with bortezomib-based or thalidomide-based therapy versus chemotherapy. These data shed light on recent trends in the management of MM in Latin America. Slower uptake of newer therapies in public clinics and poor PFS among patients with relapsed MM point to areas of unmet therapeutic need in Latin America.

Endogenous sex hormones and colorectal cancer survival among men and women.

Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone-binding globulin (SHBG) with CRC-specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S. cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. We identified 174 deaths (83 CRC-specific deaths) in men and 106 deaths (70 CRC-specific deaths) in women. In men, higher circulating level of free testosterone was associated with lower risk of overall (the highest vs. lowest tertiles, HR = 0.66, 95% CI, 0.45-0.99, ptrend = 0.04) and possibly CRC-specific mortality (HR = 0.73, 95% CI, 0.41-1.29, ptrend = 0.27). We generally observed nonsignificant inverse associations for other sex steroids, and a positive association for SHBG with CRC-specific mortality among male patients. In women, however, we found a suggestive positive association of estrone with overall (HR = 1.54, 95% CI, 0.92-2.60, ptrend = 0.11) and CRC-specific mortality (HR = 1.96, 95% CI, 1.01-3.84, ptrend = 0.06). Total estradiol, free estradiol and free testosterone were generally suggestively associated with higher risk of mortality among female patients, although not statistically significant. These findings implicated a potential role of endogenous sex hormones in CRC prognosis, which warrant further investigation.

Interaction between Nonsteroidal Anti-inflammatory Drugs and Low-fat Dietary Intervention on Colorectal Cancer Incidence; the Women's Health Initiative (WHI) Dietary Modification Trial.

BACKGROUND: The Women's Health Initiative (WHI) Dietary Modification (DM) trial did not show that reductions in dietary fat accompanied by increases in vegetable and fruit consumption decrease the incidence of colorectal cancer. Secondary analyses suggested that aspirin use may modify the intervention effects of DM on colorectal cancer development, although a recent reanalysis including the postintervention period confirmed no main effect of the intervention on reducing colorectal cancer incidence Methods: We analyzed data from 48,834 postmenopausal women who were randomized into the low-fat DM (N = 19,540) or comparison (N = 29,294) group for an average 8.1 years and followed for an additional 9.4 years through August 31, 2014. Exposure to specific class(es) or strength(s) of nonsteroidal anti-inflammatory drugs (NSAIDs) was modeled at baseline and as time-dependent use through the 9-year clinic visit. A Cox proportional hazard model was employed to assess the association of the DM, medication use, and their interaction with colorectal cancer events. RESULTS: A total of 906 incident cases of colorectal cancer were identified during the intervention and postintervention periods. By both exposure models, we found that colorectal cancer incidence was not different in the DM from the comparison group among any type of NSAID users. None of the interactions with any category of NSAID use was statistically significant; however there was most modest evidence for an interaction (p = 0.07) with aspirin use at baseline (hazard ratio [HR] = 0.81, 95% confidence interval [CI], 0.60-1.11 for users; HR = 1.12, 95% CI, 0.97-1.30 for nonusers). Strength and duration of aspirin use at baseline did not alter the associations. CONCLUSION: Extended follow-up of women in the WHI DM trial did not confirm combined protective effects of aspirin and low-fat diet on colorectal cancer risk among the postmenopausal women.

Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts.

BACKGROUND: Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. OBJECTIVE: In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. DESIGN: Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses' Health Study. RESULTS: During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. CONCLUSION: Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer.

Association between plasma adiponectin levels and colorectal cancer risk in women.

BACKGROUND: Adiponectin, an adipocyte-secreted hormone, has insulin-sensitizing characteristics. It remains unclear whether adiponectin may influence colorectal cancer development. METHODS: To determine whether prediagnostic levels of adiponectin were associated with risk of incident colorectal cancer in the Women's Health Study, we conducted a nested case-control study of 275 colorectal cancer cases and 275 matched controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Multivariable logistic regression with adjustment for colorectal cancer risk factors was used to estimate the odds ratio (OR) and 95 % confidence interval (CI) for risk of colorectal cancer incidence and mortality by adiponectin quartiles based on the control distribution. RESULTS: Median plasma adiponectin level was similar in cases versus controls (6.00 vs. 6.24 µg/mL). In multivariable-adjusted logistic regression models, high plasma adiponectin levels were not significantly associated with risk of colorectal cancer [quartile 4 (Q4) vs. quartile 1 (Q1): OR (95 % CI) 0.86 (0.48-1.56), p trend = 0.63]. CONCLUSIONS: These results suggest no appreciable association between plasma adiponectin and risk of colorectal cancer in women. Confirmation of these observations in larger studies is needed.

Circulating Vitamin D Levels and Risk of Colorectal Cancer in Women.

Observational data on the association between circulating 25(OH)D and colorectal cancer risk are limited in women. To determine whether prediagnostic levels of 25(OH)D were associated with risk of incident colorectal cancer in the Women's Health Study (WHS), we conducted a nested case-control study using 274 colorectal cases and 274 controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Conditional logistic regression was used to estimate the OR and 95% confidence interval (CI) for colorectal cancer by 25(OH)D quartiles. Mean plasma 25(OH)D was lower in cases versus controls (21.9 vs. 23.9 ng/mL, P = 0.01). In multivariable-adjusted logistic regression models, plasma 25(OH)D was significantly and inversely associated with odds of colorectal cancer (quartile 4 [Q4] vs. quartile 1 [Q1]: OR, 0.45; 95% CI, 0.25-0.81; Ptrend 0.02). In addition, we observed a somewhat lower risk of colorectal cancer-related mortality after adjustment for matching variables, randomization treatment and other risk factors (Q4:Q1 OR, 0.40; 95% CI, 0.17-0.97; Ptrend 0.05). In this cohort of healthy women, we found a significant inverse association between prediagnostic 25(OH)D levels and risk of incident colorectal cancer, and a borderline significant inverse association between prediagnostic 25(OH)D levels and colorectal cancer-related mortality. These results support a possible association between plasma 25(OH)D and risk of colorectal cancer in women.

Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study.

BACKGROUND: Soy intake is associated with a lower risk of breast cancer. However, it is unclear whether the same reduction in risk associated with high soy intake is also applicable to familial or genetic breast cancer. OBJECTIVE: The aim of this study was to assess the dietary factors among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study (KOHBRA). DESIGN: The KOHBRA Study is an ongoing project composed of affected breast cancer patients and familial members of breast cancer cases with BRCA mutations. To assess the association between dietary diversity and breast cancer risk, an HR was estimated by comparing affected subjects with their familial nonaffected members. To assess the interaction between the combination of BRCA mutation and diet diversity, the case-only OR (COR) was estimated by comparing BRCA mutation carriers and noncarriers only in affected subjects. RESULTS: Soy product intake was associated with a lower risk of breast cancer in carriers (HR: 0.39; 95% CI: 0.19, 0.79 for the highest quartile). The highest quartile of meat intake was associated with a higher risk of breast cancer regardless of BRCA mutation in carriers (HR: 1.97; 95% CI: 1.13, 3.44) and noncarriers (95% CI: 1.41; 1.12, 1.78). The associations of meat intake and soybean intake for breast cancer were more prominent in BRCA2 mutation carriers. In the analysis with only cases, the highest quartile of soy intake, but not meat intake, was associated with BRCA-related breast cancer (COR: 0.57; 95% CI: 0.36, 0.91). CONCLUSION: Our study suggests that soy product consumption is associated with lower breast cancer risk and it had an interaction with BRCA mutation.

Association between sex hormones and colorectal cancer risk in men and women.

BACKGROUND & AIMS: There is observational and clinical evidence that indicates that sex hormones affect development of colorectal cancer in men and women. However, the relationship between endogenous sex hormone levels and colorectal cancer is unclear. METHODS: We collected data on lifestyle, medical history, and diet (through 2008), along with blood samples, from the Nurses' Health Study, the Women's Health Study, the Health Professional Follow-up Study, and the Physicians' Health Study II. We measured plasma levels of estrone, estradiol, testosterone, sex hormone binding globulin (SHBG), and C-peptide among 730 women (293 cases of colorectal cancer and 437 healthy individuals as controls) and 1158 men (439 colorectal cancer cases and 719 controls) and used unconditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals. All statistical tests were 2-sided. RESULTS: Total testosterone, SHBG, and the ratio of estradiol to testosterone were associated with colorectal cancer in men after adjustments for matching and risk factors for colorectal cancer, including body mass index and plasma levels of C-peptide. The RRs in the highest relative to the lowest quartile were 0.62 for testosterone (95% confidence interval, 0.40-0.96), 0.65 for SHBG (95% confidence interval, 0.42-0.99), and 2.63 for the ratio (95% confidence interval, 1.58-4.36) (P values for trend ≤ .02). However, in women, only the ratio of estradiol to testosterone was (inversely) associated with colorectal cancer after adjustments for all factors (RR, 0.43; 95% confidence interval, 0.22-0.84; P value for trend = .03). CONCLUSIONS: On the basis of combined data from 4 population studies, there appears to be an association between levels of sex hormones and colorectal cancer risk in men. There also appears to be an inverse association between the ratio of estradiol to testosterone and colorectal cancer in postmenopausal women.

A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts.

BACKGROUND: The adipocyte-secreted hormone adiponectin has insulin-sensitizing and anti-inflammatory properties. Although development of pancreatic cancer is associated with states of insulin resistance and chronic inflammation, the mechanistic basis of the associations is poorly understood. METHODS: To determine whether prediagnostic plasma levels of adiponectin are associated with risk of pancreatic cancer, we conducted a nested case-control study of 468 pancreatic cancer case subjects and 1080 matched control subjects from five prospective US cohorts: Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. Control subjects were matched to case subjects by prospective cohort, year of birth, smoking status, fasting status, and month of blood draw. All samples for plasma adiponectin were handled identically in a single batch. Odds ratios were calculated with conditional logistic regression, and linearity of the association between adiponectin and pancreatic cancer was modeled with restricted cubic spline regression. All statistical tests were two-sided. RESULTS: Median plasma adiponectin was lower in case subjects versus control subjects (6.2 vs 6.8 µg/mL, P = .009). Plasma adiponectin was inversely associated with pancreatic cancer risk, which was consistent across the five prospective cohorts (P (heterogeneity) = .49) and independent of other markers of insulin resistance (eg, diabetes, body mass index, physical activity, plasma C-peptide). Compared with the lowest quintile of adiponectin, individuals in quintiles 2 to 5 had multivariable odds ratios ([ORs] 95% confidence intervals [CIs]) of OR = 0.61 (95% CI = 0.43 to 0.86), OR = 0.58 (95% CI = 0.41 to 0.84), OR = 0.59 (95% CI = 0.40 to 0.87), and OR = 0.66 (95% CI = 0.44 to 0.97), respectively (P (trend) = .04). Restricted cubic spline regression confirmed a nonlinear association (P (nonlinearity) < .01). The association was not modified by sex, smoking, body mass index, physical activity, or C-peptide (all P (interaction) > .10). CONCLUSIONS: In this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer.

The aromatase gene (CYP19A1) variants and circulating hepatocyte growth factor in postmenopausal women.

BACKGROUND: Estrogen and androgen have been linked to the regulation of circulating hepatocyte growth factor (HGF), an adipose tissue-derived cytokine. It is possible that the CYP19A1 gene which alters sex hormones production may influence HGF levels. We examined the association between the CYP19A1 gene variants and plasma HGF concentrations. DESIGN: We evaluated 45 common and putative functional variants of CYP19A1 and circulating levels of HGF among 260 postmenopausal women who later developed colorectal cancer from the Women's Health Initiative Observational Cohort. As the distribution of HGF levels was highly skewed, we transformed HGF concentrations for all women into a log-, ranked-, or normal score-scale value. Multiple linear regression with adjustment for age was used to evaluate the associations. RESULTS: We observed an association between the rs7172156, rs1008805, rs6493494, rs749292, and rs11636639 variants and HGF levels in ranked and normal score scales (corrected p values ≤0.02), although the association of these 5 SNPs with log-scale HGF was not significant (corrected p values ≥0.16). The associations remained unchanged after additional adjustment for hormone therapy use and estradiol levels. These 5 SNPs, which were in linkage disequilibrium (pairwise D'≥97%, r(2)≥56%), constituted a block with 2 common haplotypes accounting for 82% frequency. The most common haplotype, TCCCA, was associated with lower ranked- or normal score-transformed HGF levels (corrected p values ≤0.001), whereas the second most common haplotype, CTTCA, was associated with higher ranked- or normal score-transformed HGF levels (corrected p values ≤0.02). CONCLUSION: Our findings of a potential association between the CYP19A1 variants and circulating HGF levels warrant confirmation in studies with larger sample size.

Surgical delay of the nipple-areolar complex: a powerful technique to maximize nipple viability following nipple-sparing mastectomy.

OBJECTIVES: Nipple-sparing mastectomy (NSM) improves cosmetic outcome of mastectomy, but many patients are not candidates for this procedure because of concerns about nipple-areolar viability. Surgical delay is a technique that has been used for more than 400 years to improve survival of skin flaps. We used a surgical delay procedure to improve nipple viability in patients who were identified to be at high risk for nipple necrosis following NSM. METHODS: Patients at high risk for nipple necrosis following NSM underwent a surgical delay procedure 7-21 days prior to mastectomy. Subareolar biopsy and sentinel node biopsy, if indicated, were performed at the time of the delay procedure. Nipple viability was assessed before and after NSM. If the subareolar biopsy revealed malignancy, the NAC was removed at the time of mastectomy. RESULTS: 31 NAC in 20 patients underwent surgical delay. All of the NAC subjected to a surgical delay survived following the delay procedure. In 2 patients, the subareolar biopsy was positive and 3 NAC were removed at the time of mastectomy (1 for purposes of symmetry). Of the 28 delayed NAC left at the time of NSM, all survived the post-mastectomy course. CONCLUSION: A procedure to surgically delay the NAC 7-21 days prior to NSM is demonstrated to ensure viability of NAC in patients previously thought to be at high risk for nipple loss.

Postmenopausal hormone therapy is associated with a reduced risk of colorectal cancer lacking CDKN1A expression.

Experimental studies have shown that estrogen- or progesterone-activated signaling leads to growth inhibition effects on colon cancer cells through the upregulation of several cell-cycle regulators. However, epidemiologic studies evaluating hormone therapy use and colorectal cancer risk by the status of cell-cycle regulators are lacking. In this study, we used data from the prospective Nurses' Health Study to evaluate whether the association between hormone therapy use and colorectal cancer risk differs by the molecular pathologic status of microsatellite instability (MSI) and expression of cell-cycle-related tumor biomarkers, including CDKN1A (p21, CIP1), CDKN1B (p27, KIP1), and TP53 (p53) by immunohistochemistry. Duplication Cox regression analysis was used to determine an association between hormone therapy use, cancer risk, and specific tumor biomarkers in 581 incident colon and rectal cancer cases that occurred during 26 years of follow-up among 105,520 postmenopausal women. We found a difference between hormone therapy use and colorectal cancer risk according to CDKN1A expression (P(heterogeneity) = 0.01). Current hormone therapy use was associated with a reduced risk for CDKN1A-nonexpressed [multivariate relative risk (RR), 0.61; 95% confidence interval (CI), 0.46-0.82] but not for CDKN1A-expressed (RR, 1.32; 95% CI, 0.76-2.31) tumors. The lower risk for CDKN1A-nonexpressed but not for CDKN1A-expressed cancers was also present among current users of estrogen-alone therapy. We found no significant difference in the relations between hormone therapy use and cancer risk according to MSI, CDKN1B, or TP53 status. Together, our molecular pathological epidemiology findings suggest a preventive effect of hormone therapy against colorectal carcinogenesis that depends, in part, on loss of cyclin-dependent kinase inhibitor CDKN1A.