Malnutrition risk at solid tumor diagnosis: the malnutrition screening tool in a large US cancer institute.

BACKGROUND: In cancer, malnutrition is common and negatively impacts tolerance and outcomes of anti-tumor therapies. The aim of this study was to evaluate the prevalence of malnutrition risk and compare the clinicodemographic features between those with high malnutrition screening tool (MST) scores (i.e., ≥ 2 of 5 = high risk for malnutrition, H-MST) to low scores (L-MST). METHODS: A cohort of 3585 patients (May 2017 through December 2018), who completed the MST at least once at the time of diagnosis of any stage solid tumor, were analyzed. Logistic regression tested for associations between clinicodemographic factors, symptom scores, and H-MST prevalence. RESULTS: The median age was 64 years (25-75 IQR, 55-72), with 62% females and 81% White. Most common tumor primary sites were breast (28%), gastrointestinal (GI) (21%), and thoracic (13%). Most had non-metastatic disease (80%). H-MST was found in 28%-most commonly in upper (58%) and lower GI (42%), and thoracic (42%) tumors. L-MST was most common in breast (90%). Multivariable regression confirmed that Black race (OR 1.9, 95% CI 1.5-2.4, p = < 0.001), cancer primary site (OR 1.6-5.7, p = < 0.001), stage IV disease (OR 1.8, 95% CI 1.4-2.2, p = < 0.001), low BMI (OR 4.2, 95% CI 2.5-6.9 p = < 0.001), and higher symptom scores were all independently associated with H-MST. CONCLUSIONS: Twenty-eight percent of solid tumor oncology patients at diagnosis were at high risk of malnutrition. Patients with breast cancer rarely had malnutrition risk at diagnosis. Significant variation was found in malnutrition risk by cancer site, stage, race, and presence of depression, distress, fatigue, and trouble eating/swallowing.

Early-onset pancreatic cancer: an institutional series evaluating end-of-life care.

PURPOSE: Little is known about the use of palliative and hospice care and their impact on healthcare utilization near the end of life (EOL) in early-onset pancreatic cancer (EOPC). METHODS: Patients with EOPC (≤ 50 years) were identified using the institutional tumor registry for years 2011-2018, and demographic, clinical, and rates of referral to palliative and hospice services were obtained retrospectively. Predictors of healthcare utilization, defined as use of ≥ 1 emergency department (ED) visit or hospitalization within 30 days of death, place of death (non-hospital vs. hospital), and time from last chemotherapy administration prior to death, were assessed using descriptive, univariable, and multivariable analyses including chi-square and logistic regression models. RESULTS: A total of 112 patients with EOPC with a median age of 46 years (range, 29-50) were studied. Forty-four percent were female, 28% were Black, and 45% had metastatic disease. Fifty-seven percent received palliative care at a median of 7.8 weeks (range 0-265) following diagnosis. The median time between last chemotherapy and death was 7.9 weeks (range 0-102). Seventy-four percent used hospice services prior to death for a median of 15 days (range 0-241). Rate of healthcare utilization at the EOL was 74% in the overall population. Black race and late use of chemotherapy were independently associated with increase in ED visits/hospitalization and hospital place of death. CONCLUSIONS: Although we observed early referrals to palliative care among patients with newly diagnosed EOPC, short duration of hospice enrollment and rates of healthcare utilization prior to death were substantial.

We report performance status in oncology-but not nutritional status?

Performance status (PS) scales are used routinely in clinical oncology to evaluate functional status and help direct treatment decisions. PS is also used to determine research protocol eligibility, indicate treatment response, and evaluate toxicity in oncology clinical trials. Malnutrition (like poor PS) is associated with adverse outcomes such as lower tolerance to anti-tumor treatment, poor quality of life, and decreased survival. Nutritional status is therefore arguably as important as PS for cancer outcomes. Despite well-documented adverse consequences for patients, malnutrition also often goes undiagnosed until severe depletion is evident. If the predictive importance of nutritional status is comparable to PS, why is nutritional status not routinely used along with PS to guide treatment decisions? There is compelling evidence to support the predictive abilities of both PS and nutritional status in cancer outcomes and treatment decision-making. Perhaps, PS may be a proxy for nutritional status. Nutritional status might also serve as an effective tool for patient selection and stratification in oncology trials. Together with PS, it might provide important and distinct prognostic information; we propose both should be routinely included in outcome studies. The extent to which impaired PS may be a surrogate for malnutrition warrants investigation. Given its comparable importance to PS, it is inexcusable that nutritional status is not given the prominence it deserves as a key patient-reported outcome.

Diet and nutrition information on nine national cancer organisation websites: A critical review.

INTRODUCTION: National Cancer Organisations (NCO) provide web-based diet and nutrition information for patients with all types and stages of cancer. We examined diet and nutrition information provided by nine NCO in English-speaking countries. METHODS: Diet and nutrition information was examined under four headings: disease phases, treatment modalities, nutrition impact symptoms and cancer primary sites. We also examined the degree of concordance between NCO websites and appraised the readability of materials. RESULTS: Nine NCO websites from six English-speaking countries were included: Australia, Canada, Ireland, New Zealand, the United Kingdom and the United States. All provided general healthy eating advice. Information at diagnosis and pre-treatment was inadequate, but well-addressed for survivorship. Specific treatment modalities such as biological and hormone therapy were largely ignored. Symptom management was well-addressed, with some exceptions. Cancer site-specific advice was readily available. All recommended consultation with a dietitian/healthcare professional for personalised guidance. Only one met the universal health literacy standard. CONCLUSIONS: NCO websites provided important general diet and nutrition information for cancer patients. The information was reliable and safe, but more in-depth, evidence-based and health-literate information is required. There is an urgent need for an international consensus for consistent cancer diet and nutrition advice.

Clinical significance of weight changes at diagnosis in solid tumours.

PURPOSE: Weight changes occur throughout the cancer trajectory. Most research has focused on changes during or after treatment, so clinical significance of change at diagnosis remains unclear. This study aimed to determine prevalence, predictors and prognostic significance of weight changes at diagnosis in outpatients with solid tumours presenting to a tertiary academic medical centre. METHODS: A retrospective study of the electronic medical record was conducted (n = 6477). Those with weight recorded within 6 months of cancer diagnosis (pre-diagnosis, T0) and 2 subsequent weights (diagnosis, T1; final visit, T2) were identified (n = 4258). Percentage weight change was categorised into four bands (0.1-2.4%; 2.5-5%; 5.01-9.9%; ≥ 10%) for gain and loss. A stable category was also included. RESULTS: Mean age is 61 ± 12.5 years. Common tumour sites: breast (17%; n = 725), prostate (16%; n = 664), lung (14%; n = 599). 15% (n = 652) had metastatic disease at T1. 98% (n = 4159) had weight change at T1. Head & neck and upper gastrointestinal cancers were significantly associated with weight loss (p < 0.001). Worst survival occurred with ≥ 10% weight gain or ≥ 10% weight loss. Overweight or obese body mass index with any percentage weight change band was associated with better overall survival. CONCLUSIONS: Most had evidence of clinically significant weight changes at diagnosis. Weight loss at diagnosis was associated with a higher risk of further weight loss. A detailed weight history at cancer diagnosis is essential to identify and intervene for those most at risk of weight change-related early mortality.

The Effect of the Pain Symptom Cluster on Performance in Women Diagnosed with Advanced Breast Cancer: The Mediating Role of the Psychoneurological Symptom Cluster.

BACKGROUND: Pain, depression, anxiety, sleep disturbances, and constipation were reported in different symptom clusters at different stages of breast cancer. Managing symptom clusters rather than individual symptoms can improve performance status. AIM: The study examined the effect of pain symptom cluster (pain and constipation) on performance when mediated by the psychoneurological symptom cluster (depression, anxiety, and sleep disturbances) using age as a moderator. DESIGN: A secondary analysis. SETTINGS: Palliative care center at a tertiary medical center in northeast Ohio. PARTICIPANTS: Eighty-six women diagnosed with advanced breast cancer. METHOD: A quantitative cross-sectional approach. RESULTS: Ordinal logistic regression showed that pain symptom cluster did not have a significant mediation effect on performance. Odds ratio indicated that subjects with pain symptom cluster were 63% more likely to be bedridden (odds ratio = 1.63, confidence interval = .69-3.84). Women who reported pain symptom cluster were 5% more likely to have psychoneurological symptom cluster (odds ratio = 1.05, confidence interval = .400-2.774). Stratified analysis of age showed no differences in performance. Post-hoc analysis showed that the components of pain symptom cluster had a significant effect on psychoneurological symptom cluster (odds ratio: 3 [1.18-7.62]). CONCLUSIONS: Pain, constipation, depression, anxiety, and sleep disturbances were highly prevalent in women with advanced breast cancer. However, they tended to cluster in different symptom clusters. Although some findings were not significant, they all supported the direction of the tested hypotheses. Variations in symptom clusters research, including methodology, instruments, statistical tests, and chosen symptom cluster correlation coefficient, should be addressed.

Serum levels of endocan correlate with the presence and severity of pre-eclampsia.

BACKGROUND: Endocan, a cysteine-rich dermatan sulfate proteoglycan expressed by endothelial cells, is seemed to be a new biomarker for endothelial dysfunction. Pre-eclampsia (PE) is characterized by the new onset of hypertension, proteinuria after 20 weeks of gestation, placental vascular remodeling, systemic vascular inflammation and endothelial dysfunction. The aim of this study was to investigate the relationship of PE and its severity with serum endocan levels. METHODS: A cross-sectional study was performed. Serum was collected from women with PE and normotensive controls. Serum endocan and tumor necrosis factor alpha (TNF-α) concentrations were measured by a specific enzyme linked immunosorbent assay. RESULTS: Patients with PE had significantly higher median (interquartile range) endocan and mean TNF-α concentrations than controls [20.04 (12.26) ng/mL vs 15.55 (6.19) ng/mL, p < 0.001 for endocan; 26.49 ± 12.14 pg/mL vs 14.62 ± 5.61 pg/mL, p < 0.001 for TNF-α; respectively]. Serum endocan concentrations were positively correlated with systolic blood pressure (r = 0.618, p < 0.001), diastolic blood pressure (r = 0.608, p < 0.001), the amount of 24-h proteinuria (r = 0.786, p < 0.001) and TNF-α (r = 0.474, p < 0.001) in women with PE. In subgroup analysis, patients with severe PE had significantly higher endocan concentrations than those with mild PE. Receiver operating characteristic analysis of endocan was used to identify the patients with PE and also discriminating between mild and severe PE. CONCLUSION: Serum endocan concentrations were significantly elevated in women with PE versus normotensive controls, and concentrations seem to be associated with the severity of the disease.

Circulating irisin levels reflect visceral adiposity in non-diabetic patients undergoing hemodialysis.

BACKGROUND: Recent evidence suggests that increased visceral adiposity is a strong independent risk factor for cardiovascular death and all-cause mortality in hemodialysis (HD) patients. Irisin, which is a novel myokine, can play critical roles in diabetes and adiposity. The purpose of our study was to investigate whether serum irisin levels are associated with body mass index, waist circumference (WC), and total fat mass in non-diabetic patients undergoing maintenance HD. METHODS: This cross-sectional study included 108 non-diabetic HD patients and 40 age- and sex-matched apparently healthy subjects. Serum irisin concentrations were determined using an enzyme-linked immunosorbent assay. Body fat composition (TBF-410 Tanita Body Composition Analyzer) was measured and calculated. RESULTS: Serum irisin levels did not differ between HD patients and the healthy controls (523.50 ± 229.32 vs. 511.28 ± 259.74, p = 0.782). Serum irisin levels were associated with age (r = 0.314; p =0.006), HOMA-IR (r = 0.472; p = 0.003), WC (r = 0.862; p < 0.001), and total fat mass (r = 0.614; p < 0.001). In multivariate regression analysis, WC (ß = 1.240, p < 0.001) and total fat mass (ß = 0.792, p = 0.015) were the variables that were significantly associated with irisin concentrations (R(2 )=( )0.684, p < 0.001) after adjusting for confounding factors (age and HOMA-IR). CONCLUSIONS: These results suggest that serum irisin levels are related to visceral adiposity in non-diabetic HD patients.

Association of plasma GDF-9 or GDF-15 levels with bone parameters in polycystic ovary syndrome.

We aimed to determine plasma levels of growth and differentiation factor (GDF)-9 and GDF-15, and their possible association with bone turnover parameters and bone mineral density (BMD), in patients with polycystic ovary syndrome (PCOS). Forty-two obese PCOS women aged 25-35 years, 23 women with idiopathic hirsutism (IH) and 20 healthy controls matched for age and body mass index were enrolled. Anthropometric, metabolic and hormonal patterns, plasma GDF-9 and GDF-15 concentrations, bone turnover markers and BMD were measured. No significant differences were observed in bone turnover markers, BMD measurements, plasma GDF-9 and GDF-15 levels in subjects with PCOS compared with the other two groups. In the combined population of all three groups, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.317, p < 0.01). Analysis of PCOS patients showed a significant correlation of GDF-15 concentrations with age and homeostasis model assessment index (r = 0.319, p < 0.05, and r = 0.312, p < 0.05, respectively). In addition, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.395, p < 0.01) and positively correlated with urine deoxypyridinoline (r = 0.353, p < 0.05). GDF-9 did not correlate with bone markers and BMD measurements. In conclusion, plasma GDF-9 and GDF-15 levels as well as bone turnover markers and BMD measurements in subjects with PCOS (25-35 years of age) were comparable with those either in subjects with IH or in healthy controls with similar anthropometric and metabolic profiles. GDF-15 might be a marker of a crossregulation between bone and energy metabolism.

The psychometric properties of cancer multisymptom assessment instruments: a clinical review.

PURPOSE: Various instruments are used to assess both individual and multiple cancer symptoms. We evaluated the psychometric properties of cancer multisymptom assessment instruments. METHODS: An Ovid MEDLINE search was done. All searches were limited to adults and in English. All instruments published from 2005 to 2014 (and with at least one validity test) were included. We excluded those who only reported content validity. Instruments were categorized by the three major types of symptom measurement scales employed as follows: visual analogue (VAS), verbal rating (VRS), and numerical rating (NRS) scales. They were then examined in two areas: (1) psychometric thoroughness (number of tests) and (2) psychometric strength of evidence (validity, reliability, generalizability). We also assigned an empirical global psychometric quality score (which combined the concepts of thoroughness and strength of evidence) to rank the instruments. RESULTS: We analyzed 57 instruments (17 original, 40 modifications). They varied in types of scales used, symptom dimensions measured, and time frames evaluated. Of the 57, 10 used VAS, 28 VRS, and 19 NRS. The Edmonton Symptom Assessment System (ESAS), ESAS-Spanish, Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Symptom Distress Scale (SDS), M.D. Anderson Symptom Inventory (MDASI)-Russian, and MDASI-Taiwanese were the most comprehensively tested for validity and reliability. The ESAS, ESAS-Spanish, ASDS-2, Memorial Symptom Assessment Scale (MSAS)-SF, POMS, SDS, MDASI (and some translations), and MDASI-Heart Failure all showed good validity and reliability. CONCLUSIONS: The MDASI appeared to be the best overall from a psychometric perspective. This was followed by the ESAS, ESAS-Spanish, POMS, SDS, and some MDASI translations. VRS-based instruments were most common. There was a wide range of psychometric rigor in validation. Consequently, meta-analysis was not possible. Most cancer multisymptom assessment instruments need further extensive validation to establish the excellent reliability and validity required for clinical utility and meaningful research.

First trimester interleukin-6 levels help to predict adverse pregnancy outcomes in both thyroid autoantibody positive and negative patients.

AIM: The aim of the present study is to compare pregnancy outcomes among patients with and without thyroid antibodies and/or subclinical hypothyroidism and investigate whether there is an association between first trimester maternal plasma interleukin-6 (IL-6) levels and adverse pregnancy outcomes. METHODS: A case-control study was carried out including 83 pregnant women (40 thyroid antibody positive and 43 healthy controls). The predictive value of first trimester maternal plasma IL-6 levels on adverse pregnancy outcomes were investigated. The optimal cut-off points of IL-6 for determining maternal and fetal outcomes were evaluated by receiver operating characteristic analyses. RESULTS: Compared with the control, median IL-6 levels were significantly higher in thyroid antibody positive pregnancies (median 1.58 vs 1.63 pg/mL; P = 0.047). IL-6 levels were found to be significantly higher in women who had suffered a miscarriage (P = 0.002), preterm delivery (P < 0.001), intrauterine growth restriction (P = 0.047), preterm premature rupture of membranes (P = 0.043) and overall prenatal complications (P < 0.001). A statistically significant negative correlation between gestational week at birth and IL-6 levels was also determined among all participants involved in the study (r = -0.385, P < 0.001). CONCLUSION: IL-6 levels are significantly increased in thyroid antibody positive patients and predictive for future adverse outcomes, irrespective of thyroid autoimmunity. Increased first trimester IL-6 levels independently predict adverse pregnancy outcomes, regardless of subclinical hypothyroidism.

Association of ambulatory arterial stiffness index with sEPCR in newly diagnosed hypertensive patients.

AIM: Increased arterial stiffness is strongly associated with cardiovascular diseases, while thrombotic events are more common than hemorrhagic events in hypertensive patients. Markers of a hypercoagulable state may also predict future cardiovascular events in hypertensive patients. Here, we speculated that increased arterial stiffness might lead to the development of a hypercoagulable state that can play a role in the thrombotic complications of hypertension. Soluble endothelial protein C receptor (sEPCR) is one such marker of hypercoagulation. The ambulatory arterial stiffness index (AASI) could be accepted as a non-invasive measure of arterial stiffness. The aim of this study was to investigate association of AASI with levels of sEPCR in newly diagnosed hypertensive patients. MATERIALS AND METHODS: The study included 263 newly diagnosed essential hypertensive patients and 55 healthy normotensive controls. All subjects underwent 24 h ambulatory blood pressure monitoring (ABPM); the AASI was derived from ABPM tracings. Plasma sEPCR was measured by ELISA. RESULTS: Hypertensive patients (n = 263) had higher AASI, C-reactive protein (CRP) and sEPCR versus the normotensive healthy group (n = 55). Univariate analysis showed that AASI was positively associated with age (r = 0.212, p < 0.001) body mass index (r = 0.412, p < 0.001), pulse pressure (r = 0.350, p < 0.001), plasma sEPCR (r = 0.894, p < 0.001), 24-h heart rate (r = 0.176, p = 0.001) and inversely related to high-density lipoprotein (HDL) (r = -0.293, p < 0.001). Multivariate analyses revealed that sEPCR and HDL are independently correlated to AASI. CONCLUSION: We suggest that increased AASI is associated with elevated sEPCR. It might be responsible for subsequent thrombotic events in newly diagnosed hypertensive patients.

Higher levels of circulating CXCL-9 and CXCL-11 in euthyroid women with autoimmune thyroiditis and recurrent spontaneous abortions.

BACKGROUND: We aimed to measure serum CXCL-9 and CXCL-11 levels in patients with autoimmune thyroiditis (AIT) and recurrent spontaneous abortions (RSA). METHODS: Forty-one euthyroid, non-pregnant women with AIT and a history of unexplained first trimester RSA, 35 euthyroid women with AIT, and 29 healthy controls matched for age and body mass index were enrolled. Serum CXCL-9 and CXCL-11 were measured. RESULTS: Serum CXCL-9 and -11 levels were significantly higher (p < 0.001 for both) in the antibody-positive women with a history of abortions than in both control groups. Additionally, CXCL-9 levels were higher in patients with AIT without RSA than in healthy controls. No significant differences were found in CXCL-9 and -11 levels in subjects with a history of RSA in relation to the number of previous abortions. In multiple linear regression analyses, abortions were significantly related to CXCL-9 (ß-coefficient = 0.174, p < 0.001), CXCL-11 (ß-coefficient = 0.490, p < 0.001). CONCLUSION: Higher circulating levels of CXCL-9 and -11 have been shown in non-pregnant AIT patients with a history of RSA as compared to both control groups, suggesting that this subgroup produce a more dominant Th-1 cytokine profile.

Increased total Renin levels but not Angiotensin-converting enzyme activity in obese patients with polycystic ovary syndrome.

OBJECTIVE: To investigate the renin-angiotensin-aldosterone system and angiotensin-converting enzyme (ACE) activity in patients with polycystic ovarian syndrome (PCOS). SUBJECTS AND METHODS: In this case-control study, 41 obese (PCOS) women and 29 healthy controls, matched for age and body mass index, were enrolled. Anthropometric, metabolic, and hormonal patterns, including plasma aldosterone, plasma renin, and ACE activity, were measured in each subject. RESULTS: Plasma renin levels were significantly higher in PCOS patients (19.7 ± 14.5 µg/ml) compared with controls (12.9 ± 9.0 µg/ml, p < 0.05). ACE activity and aldosterone levels did not significantly differ between both groups (p = 0.15 and p = 0.18, respectively). Analysis of PCOS patients showed a significant correlation of fasting insulin levels with levels of renin (r = 0.305, p < 0.01) and free testosterone (r = 0.384, p = 0.001). Similarly, homeostasis model assessment index was positively correlated with total renin concentrations (r = 0.366, p < 0.01) and free testosterone (r = 0.352, p < 0.01). CONCLUSION: Obese PCOS women had higher total renin levels, but not ACE activity and aldosterone levels, related to insulin resistance compared with controls.

Application of the 2011 international consensus cancer cachexia classification in routine oncology dietetic practice: An observational study.

BACKGROUND: Cancer cachexia (CC) is highly prevalent and associated with significant morbidity and mortality, yet underrecognized. In 2011, an international cachexia consensus (ICC) proposed a definition, assessment framework, and stages for classification: cancer precachexia, cachexia, and refractory cachexia. The authors anticipated that a "more practical classification approach for clinical practice" would be required, which we interpreted as a bedside assessment based on clinical data. We investigated whether the ICC classification could be employed in routine dietetic practice without access to objective muscle mass measures. METHODS: Data from 200 consecutive patients with solid tumors were collected as part of clinical practice by oncology dietitians in five tertiary referral hospitals. Dietitians used information gathered during their routine assessment and applied the ICC framework to assign a stage. When the dietitian was unable to assign a stage, the reason was noted. RESULTS: Based on available data, classification was possible in 177 (88%); 23 (12%) could not be staged. The reasons cited were as follows: unknown C-reactive protein (n = 14), complex clinical situation (n = 5), unknown weight loss (n = 2), and acute illness (n = 2). Thirty (17%) of the 177 participants were judged to be noncachectic.  One hundred twelve (83%) met the criteria for 1 of the 3 ICC stages: 92 (52%) were cachectic; 35 (20%) precachectic, and 20 (11%) refractory. CONCLUSIONS: CC staging based on the ICC classification was feasible and practical in routine dietetic practice even without access to objective muscle mass measures. Once validated and operationalized, expert clinical assessment by a dietitian could be a cost-effective means to identify and stage CC, with more resource-intensive means used when there is clinical doubt.

Intensifying Iodine Deficiency Throughout Trimesters of Pregnancy in a Borderline Iodine-Sufficient Urban Area, Ankara, Turkey.

Iodine has long been recognized as an essential micronutrient for maternal thyroid function, as well as fetal growth and development during pregnancy. The current study aimed to evaluate thyroid hormone status, urinary iodine concentration (UIC), thyroid volume, and nodularity in pregnant women, throughout trimesters, in a borderline iodine sufficient, urban area with mandatory table salt iodization. Two-hundred-sixty-five pregnant women ranging from 17 to 45 years participated in this prospective longitudinal study. Thyroid function tests, thyroid volume, nodule growth, and UIC were recorded throughout the first, second, and third trimesters with no intervention. Median UIC was 96, 78, and 60 µg/L in the first, second, and third trimester of pregnancy, respectively (p < 0.001). Mean TSH values increased significantly (i.e. 0.65 mIU/ml, 1.1 mIU/ml, and 1.3 mIU/ml in the first, second, and third trimesters, respectively) (p < 0.001). Mean ± s.d. thyroid volume was significantly higher in the third trimester (14.72 ± 6.8 ml) compared with the first trimester (13.69 ± 5.31 ml) (p < 0.001). An intensifying iodine deficiency (ID) was reported throughout trimesters in this cohort of pregnant women from Ankara. A significant percentage of pregnant women from a borderline iodine sufficient, urban area in Turkey were iodine deficient during all trimesters, and the deficiency increased throughout the pregnancy. Pregnant women should receive iodine supplementation, besides consuming iodized salt in borderline iodine sufficient areas.

The Effects of Diet and Exercise on Endogenous Estrogens and Subsequent Breast Cancer Risk in Postmenopausal Women.

Endogenous estrogens have been associated with overall breast cancer risk, particularly for postmenopausal women, and ways to reduce these estrogens have served as a primary means to decrease overall risk. This narrative review of clinical studies details how various nutritional and exercise lifestyle interventions have been used to modify estrogen levels and metabolism to provide a protective impact against breast cancer incidence. We also summarized the evidence supporting the efficacy of interventions, outcomes of interest and identified emerging research themes. A systematic PubMed MEDLINE search identified scholarly articles or reviews published between 2000-2020 that contained either a cohort, cross-sectional, or interventional study design and focused on the relationships between diet and/or exercise and overall levels of different forms of estrogen and breast cancer risk and occurrence. Screening and data extraction was undertaken by two researchers. Data synthesis was narrative due to the heterogeneous nature of studies. A total of 1625 titles/abstracts were screened, 198 full texts reviewed; and 43 met eligibility criteria. Of the 43 studies, 28 were randomized controlled trials, and 15 were observational studies. Overall, studies that incorporated both diet and exercise interventions demonstrated better control of detrimental estrogen forms and levels and thus likely represent the best strategies for preventing breast cancer development for postmenopausal women. Some of the strongest associations included weight loss via diet and diet + exercise interventions, reducing alcohol consumption, and consuming a varied dietary pattern, similar to the Mediterranean diet. More research should be done on the effects of specific nutritional components on endogenous estrogen levels to understand the effect that the components have on their own and in combination within the diet.

Symptom clusters: myth or reality?

Clinical experience suggests that many symptoms occur together. In this paper, we examine the rationale and evidence base for symptom clusters in different medical fields, particularly the cluster phenomenon in cancer. Cancer symptom clusters are a reality. Various symptoms that cluster clinically have also been verified statistically. Specific clusters such as nausea-vomiting, anxiety-depression, and cough-dyspnea are evident on both clinical observation and in research investigation. Fatigue-pain and fatigue-insomnia-pain have also been demonstrated statistically as clusters. Another proposed cluster 'depression-fatigue-pain' seems relevant to clinical practice. Other clusters may serve only as theoretical models that illustrate possible common biological etiologies in cancer; they need to be validated in future research. Analysis of the literature is complicated by considerable inconsistencies across studies. Discrepancies between clinically defined and statistically obtained clusters raise important questions. We must consider the analytical techniques used, and how methodology might influence cluster occurrence and composition. Further research is warranted to establish universally accepted statistical methods and assessment tools for symptom cluster research.

Symptom severity and distress in advanced cancer.

We determined the relationship between symptom severity and distress for multiple cancer symptoms, and examined patient demographic influences on severity and distress in advanced cancer. A Cochran-Armitage trend test determined whether symptom distress increased with severity. Chi-square, Fisher's exact test and logistic regression analysis examined moderate/severe ('clinically important') and distressful symptoms by age (65), gender, primary site group, and ECOG performance status. Forty-six symptoms were analyzed in 181 individuals. More than 50% of individuals with clinically important symptoms rated them as distressful. The median percentage of individuals with mild but still distressful symptoms was 25%, with a range of 0% (bad dreams) to 73% (sore mouth). In both univariate and multivariate analysis, younger (

Systematic bias in cancer patient-reported outcomes: symptom 'orphans' and 'champions'.

INTRODUCTION: Patient-reported outcomes are an integral part of modern healthcare. We report a comparison of symptom item content from several validated cancer instruments to that of a published checklist, and identify the important differences this revealed. METHODS: We defined orphans as any symptom not assessed in any of the six selected instruments; champions, in contrast, were present in all six. An empirically derived cancer multisymptom checklist was used.Three symptom categories were identified Orphan-absent from all 6,Champion-present in all 6,Intermediate-underreported. The contents of each validated instrument were cross-referenced against the checklist. RESULTS: Eighteen (39%) checklist symptoms were orphans. Five (11%) were champions: fatigue, pain, anorexia, dyspnoea and nausea. Of the 46 checklist symptoms, 23 (50%) were inconsistently recorded. All 18 orphan symptoms were clinically important checklist symptoms. Common gastrointestinal and neuropsychological symptoms that pose great clinical management challenges were among the orphan symptoms. CONCLUSIONS: Of 46 checklist cancer symptoms, over a third were orphans. All orphan symptoms were rated as clinically important and distressing by checklist. Only 5 checklist symptoms were champions: fatigue, pain, anorexia, dyspnoea and nausea. Important-but usually omitted-symptoms included early satiety (6 of 6) and weight loss (5 of 6). The bias appears to disproportionately affect gastrointestinal and neuropsychiatric symptoms. Symptom studies should specifically report the limitations and account for the inherent item bias of any instrument used.