Reproducibility of Anterior Scalene Stiffness Measurement with Shear Wave Elastography: An Inter-Examiner Reliability Study.

PURPOSE: Although previous studies have highlighted the clinical relevance of the anterior scalene muscle (AS) in patients with neck pain or nerve compressive syndromes, evidence reporting the diagnostic accuracy of shear wave elastography (SWE) for assessing the AS stiffness properties is lacking. This study aimed to analyze the SWE inter-examiner reliability for calculating the Young's modulus and shear wave speed of the AS muscle in asymptomatic subjects. MATERIALS AND METHODS: Using a linear transducer, ultrasound images of the antero-lateral neck region at the C7 level were acquired in 35 healthy volunteers by one experienced examiner and one novice examiner. After codifying the images to blind the participants' identity, the trial, and the side, Young's modulus and shear wave speed were obtained by an independent experienced rater in randomized order. Intra-class correlation coefficients (ICC), standard error of measurement (SEM), minimal detectable changes (MDC), and coefficient of variation (CV%) were calculated. RESULTS: The assessed AS metrics showed no side-to-side differences (p>0.05). Sex differences were found for muscle size (p=0.002), but muscle brightness and stiffness were similar (p>0.05). Inter-examiner reliability was good for determining the AS muscle stiffness (ICC = 0.881 for Young's modulus and 0.850 for shear wave speed). CONCLUSION: The obtained results suggest that assessing the AS stiffness properties in asymptomatic subjects is a reliable procedure. Further studies should verify the SWE capacity for discriminating healthy and clinical populations and identify potential factors contributing to the variance of measurement errors.

Levator Scapulae Stiffness Measurement Reliability in Individuals with and without Chronic Neck Pain by Experienced and Novel Examiners.

The levator scapulae muscle is a key structure in the etiopathology of neck and shoulder musculoskeletal pain. Although previous studies used shear-wave elastography (SWE) for characterizing this muscle elasticity, limited evidence assessed the inter-examiner reliability of this procedure. This study aimed to analyze the inter-examiner reliability for calculating Young's modulus and shear wave speed in a cohort of participants with and without chronic neck pain. A diagnostic accuracy study was conducted, acquiring a set of SWE images at the C5 level in participants with and without neck pain (n = 34 and 33, respectively) by two examiners (one experienced and one novel). After blinding the participants' identity, examiner involved, and side, the stiffness indicators were calculated by an independent rater in a randomized order. Intra-class correlation coefficients (ICC), standard error of measurement, minimal detectable changes, and coefficient of variation were calculated. Both cohorts had comparable sociodemographic characteristics (p > 0.05). No significant levator scapulae elasticity differences were found between genders, sides, or cohorts (all, p > 0.05). Inter-examiner reliability for calculating Young's modulus and shear wave speed was moderate-to-good for assessing asymptomatic individuals (ICC = 0.714 and 0.779, respectively), while poor-to-moderate in patients with neck pain (ICC = 0.461 and 0.546, respectively). The results obtained in this study support the use of this procedure for assessing asymptomatic individuals. However, reliability estimates were unacceptable to support its use for assessing elasticity in patients with chronic neck pain. Future studies might consider that the shear wave speed is more sensitive to detect real changes in comparison with Young's modulus.

The prognostic effect of neutrophil-to-lymphocyte ratio and De Ritis ratio in glioblastoma multiforme patients.

AIMS: Individuals with a higher De Ritis ratio (aspartate transaminase/alanine transaminase) and neutrophil-to-lymphocyte ratio (NLR) have an inferior survival in varied malignancies. To our knowledge, the prognostic potential of the De Ritis ratio and NLR to predict the survival in nonmetastatic glioblastoma multiforme (GBM) patients remains unclear. In this study, we aimed to explore the prognostic power of the De Ritis ratio and NLR in patients with nonmetastatic glioblastoma multiforme. METHODS: Data of 262 patients with glioblastoma multiforme have been retrospectively analyzed. Their age, gender, tumor characteristics, AST/ALT ratio, NLR and hemogram values, including age at diagnosis and date of diagnosis were recorded. RESULTS: The median survival time of the study group was 21 months (95% CI: 19‒23 months). The first-year and second-year survival rates were 73.0% and 40.5%, respectively. The univariate analysis revealed that the correlation of survival with age, gender, left/right location of tumor, mean platelet volume and De Ritis ratio did not reach the level of significance. The univariate analysis of the prognostic potential of NLR indicated that a 1-unit increase in NLR value translates to a 1.05 times higher risk of death (95% CI: 1.01‒1.09). CONCLUSION: The results of this study lead to the observation that NLR value can serve as an effective prognostic marker in predicting the outcomes of patients with glioblastoma multiforme. It can be positioned as an easily accessible and cost-effective biomarker for establishing appropriate therapeutic strategies (Tab. 2, Fig. 1, Ref. 20).

Understanding the Psychophysiological and Sensitization Mechanisms Behind Fibromyalgia Syndrome: A Network Analysis Approach.

OBJECTIVE: Current evidence suggests that fibromyalgia syndrome (FMS) involves complex underlying mechanisms. This study aimed to quantify the multivariate relationships between clinical, psychophysical, and psychological outcomes in women with FMS by using network analysis to understand the psychobiological mechanisms driving FMS and generating new research questions for improving treatment strategies. METHODS: Demographic (age, height, weight), clinical (pain history, pain intensity at rest and during daily living activities), psychophysical (widespread pressure pain thresholds [PPT]), sensory-related (PainDETECT, S-LANSS, Central Sensitization Inventory [CSI]) and psychological (depressive and anxiety levels) variables were collected in 126 women with FMS. Network analysis was conducted to quantify the adjusted correlations between the modeled variables and to assess their centrality indices (i.e., the connectivity with other symptoms in the network and the importance in the system modelled as network). RESULTS: The network showed several local associations between psychophysical and clinical sensory-related variables. Multiple positive correlations between PPTs were observed, being the strongest weight between PPTs on the knee and tibialis anterior muscle (ρ: 0.33). PainDETECT was associated with LANSS (ρ: 0.45) and CSI (ρ: 0.24), whereas CSI was associated with HADS-A (ρ: 0.28). The most central variables were PPTs over the tibialis anterior (the highest Strength centrality) and CSI (the highest Closeness and Betweenness centrality). CONCLUSION: Our findings support a model where clinical sensory-related, psychological, and psycho-physical variables are connected, albeit in separate clusters, reflecting a nociplastic condition with a relevant role of sensitization. Clinical implications of the findings, such as developing treatments targeting these mechanisms, are discussed.

Inter-Examiner Disagreement for Assessing Cervical Multifidus Ultrasound Metrics Is Associated with Body Composition Features.

Ultrasound imaging (US) is a biosensing technique that is widely used in several healthcare disciplines (including physiotherapy) for assessing multiple muscle metrics, such as muscle morphology and quality. Since all biosensors need to be tested in order to demonstrate their reliability, accuracy, sensitivity, and specificity, identifying factors that affect their diagnostic accuracy is essential. Since previous studies analyzed the impact of sociodemographic but not body composition characteristics in US errors, this study aimed to assess whether body composition metrics are associated with ultrasound measurement errors. B-mode images of the lumbar multifidus muscle at the L5 level were acquired and analyzed in 47 healthy volunteers by two examiners (one experienced and one novice). The cross-sectional area, muscle perimeter, and mean echo intensity were calculated bilaterally. A correlation analysis and a multivariate linear regression model were used for assessing the inter-examiner differences with respect to body composition metrics. The results demonstrated good-to-excellent reliability estimates for the cross-sectional area, muscle perimeter, aspect ratio, roundness, circularity, and mean brightness metrics (all ICC > 0.85). However, solidity showed unacceptable reliability (ICC < 0.7). Age, height, total lean mass, trunk lean mass, and water volume were associated with inter-examiner disagreement on mean echo intensity. Cross-sectional area, perimeter, and roundness measurement errors were associated with lean mass and water volume.

Convergent Validity between Electromyographic Muscle Activity, Ultrasound Muscle Thickness and Dynamometric Force Measurement for Assessing Muscle.

Muscle fatigue is defined as a reversible decline in performance after intensive use, which largely recovers after a resting period. Surface electromyography (EMG), ultrasound imaging (US) and dynamometry are used to assess muscle activity, muscle morphology and isometric force capacity. This study aimed to assess the convergent validity between these three methods for assessing muscle fatigue during a manual prehension maximal voluntary isometric contraction (MVIC). A diagnostic accuracy study was conducted, enrolling 50 healthy participants for the measurement of simultaneous changes in muscle thickness, muscle activity and isometric force using EMG, US and a hand dynamometer, respectively, during a 15 s MVIC. An adjustment line and its variance (R2) were calculated. Muscle activity and thickness were comparable between genders (p > 0.05). However, men exhibited lower force holding capacity (p < 0.05). No side-to-side or dominance differences were found for any variable. Significant correlations were found for the EMG slope with US (r = 0.359; p < 0.01) and dynamometry (r = 0.305; p < 0.01) slopes and between dynamometry and US slopes (r = 0.227; p < 0.05). The sample of this study was characterized by comparable muscle activity and muscle thickness change between genders. In addition, fatigue slopes were not associated with demography or anthropometry. Our findings showed fair convergent associations between these methods, providing synergistic muscle fatigue information.

The prognostic role of epidermal growth factor receptor mutation in completely resected ampullary adenocarcinoma.

The aim of this study is to make a differential diagnosis and prognosis of the ampullary adenocarcinoma subtypes. We also investigated the role of prognostic markers PD-1 and PD-L1, and epidermal growth factor receptor (EGFR). Local or locally advanced stage ampullary adenocarcinoma patients who had undergone pancreaticoduodenectomy at the time of diagnosis were included. MUC1, MUC2, MUC5AC, CDX2, CK7, CK20, PD-1, and PDL-1 were analysed immunohistochemically, and EGFR was analysed by real-time polymerase chain reaction. According to histopathological and immunohistochemical evaluation, we found 27 patients as pancreatobiliary type and 56 patients as intestinal type adenocarcinoma. The median survival of patients with intestinal and pancreatobiliary type adenocarcinoma was 23 months and 76 months ( p = 0.201), respectively. When the survival of PD1-positive ( n = 23) and PD-L1-positive ( n = 18) patients were compared with the patients with negative staining ( n = 60, n = 65), no significant difference was found. Epidermal growth factor receptor mutation was detected in a total of 6 patients, and 5 of these 6 mutations were shown in intestinal type tumours and one in a pancreatobiliary type tumour. A significant difference was determined in terms of overall survival for the patients with EGFR mutations compared to those without ( p = 0.008). In conclusion, we could reveal the prognostic significance of EGFR mutation, which is also a target molecule.

Acoustic Environmental Conditions (Do Not?) Affect the Static Posturography Diagnostic Accuracy: A Test-Retest Reliability Study.

Static posturography assessed with force platforms is a procedure used to obtain objective estimates related to postural adjustments. However, controlling multiple intrinsic and extrinsic factors influencing the diagnostic accuracy is essential to obtain reliable measurements and recommend its use with clinical or research purposes. We aimed to analyze how different environmental acoustic conditions affect the test−retest reliability and to analyze the most appropriate number of trials to calculate a valid mean average score. A diagnostic accuracy study was conducted enrolling 27 healthy volunteers. All procedures were taken considering consistent device settings, posture, feet position, recording time, and illumination of the room. Three trials were recorded in a silent environment (35−40 dB) and three trials were recorded in a noisy environment (85−90 dB). Results showed comparable reliability estimates for both acoustic conditions (ICC = 0.453−0.962 and 0.621−0.952), but silent conditions demonstrated better sensitivity to changes (MDC = 13.6−76%). Mean average calculations from 2 and 3 trials showed no statistically significant differences (p > 0.05). Cross-sectional studies can be conducted under noisy or silent conditions as no significantly different scores were obtained (p > 0.05) and ICC were comparable (except oscillation area). However, longitudinal studies should consider silent conditions as they demonstrated better sensitivity to real changes not derived from measurement errors.

Echo-intensity, fatty infiltration, and morphology ultrasound imaging assessment in healthy and whiplash associated disorders populations: an observational study.

BACKGROUND: Although changes in muscle morphology and quality in deep neck flexors seem to be clear in patients with whiplash-associated disorders (WAD), evidence for deep neck extensors is heterogeneous. In addition, most studies have used magnetic resonance imaging or computer tomography, which is not available for regular practice. OBJECTIVES: To assess differences in deep neck extensors morphology and quality between patients with WAD and controls with ultrasound imaging (US) and to assess the association of imaging findings with clinical features. METHODS: One hundred and sixty brightness-mode images at C4/C5 level were acquired in 41 patients with WAD and 39 pain-free controls. Muscle morphology and quality characteristics of the cervical multifidus (CM) and short rotators (SR), clinical pain features and pressure pain thresholds (PPT) were assessed in a blinded design. RESULTS: Between-groups differences in both CM and SR were observed for fatty infiltration percentage (mean: 4.9%; P < 0.001; mean: 3.5%; P < 0.05, respectively) and mean EI (mean: 4.1; P < 0.001; mean: 3.2; P < 0.05, respectively): patients exhibited higher fatty infiltration than controls. The intensity of neck pain was negatively associated with multifidus CSA and perimeter (P < 0.001); symptoms duration was negatively associated with CM morphology (P < 0.001), CM mean EI (P < 0.05) and SR morphology (P < 0.05); pain-related disability was associated with CM morphology (P < 0.001) and SR mean EI (P < 0.05); and PPTs was associated with CM mean EI (P < 0.01) and FI (p < 0.05) and SR morphology (P < 0.001). No significant effect of gender was found in any analysis. CONCLUSION: US assessment of deep cervical extensors revealed greater fatty infiltration, but no differences in muscle morphology, between WAD patients and pain-free controls.

Chemotherapy-induced sarcopenia in newly diagnosed cancer patients: Izmir Oncology Group (IZOG) study.

BACKGROUND: Sarcopenia is associated with physical disability, increased post-operative complications, poorer tolerance to chemotherapy, and reduced survival outcome. However, little is known about the changes in body composition during chemotherapy treatment. We aimed to determine whether adjuvant or palliative chemotherapy causes the development of sarcopenia in newly diagnosed cancer patients and to reveal the relationship of sarcopenia with the duration of chemotherapy. METHODS: The study included newly diagnosed cancer patients who underwent curative surgery for primary tumor and also cancer patients who were metastatic at diagnosis. Body composition and handgrip strength were assessed by bio-electric impedance analysis (BIA) and handgrip dynamometer tools, respectively. Measurement tests were performed prior to chemotherapy, in the third and sixth months of chemotherapy. RESULTS: The median age of a total of 276 patients was 57.5 years (range 18-83), and majority of them (55.8%) were women. Among the pre-chemotherapy factors that could be associated with sarcopenia, male gender ≥ 65 years of age, body mass index (BMI) < 25, and nutritional risk screening 2002 score < 3 were found to be positively associated with sarcopenia (p < 0.001, p = 0.036, p < 0.001, and p < 0.001, respectively). In the multivariate analysis, male gender (p < 0.001) and BMI < 25 (p = 0.047) were found to be significant. Of 276 patients, 14.5% were sarcopenic prior to chemotherapy. After chemotherapy, 21.4% of them were sarcopenic at the end of the third month and 23.9% were sarcopenic at the end of the sixth month. CONCLUSION: The incidence of sarcopenia was found to be increased with chemotherapy itself and its duration in both non-metastatic and metastatic cancer patients which has to be evaluated in detail in disease-specific prospective and randomized studies.

Prevalence and related factors of sarcopenia in newly diagnosed cancer patients.

INTRODUCTION: Sarcopenia is defined as the loss of muscle mass and muscular functioning. Although sarcopenia prevalence is highly variable in the literature, pre-chemotherapy sarcopenia prevalence was not well studied in newly diagnosed cancer patients. In this context, the present study aims to determine the prevalence of sarcopenia and its related factors in this population. MATERIAL AND METHODS: Prospectively, newly diagnosed cancer patients were evaluated for body composition measurement and muscle strength by employing the bioelectric impedance analysis method and handgrip dynamometer tool. RESULTS: A total of 461 patients were included in the study. The median age of patients was 59 years (range 18-83) and 258 patients (56%) were women. Sarcopenia was present in 77 patients (16.7%) and was at significantly higher frequencies in men (p = 0.015), advanced age (≥ 65 years, p = 0.014), lower body mass index (BMI < 25, p = < 0.001), and poor performance status (ECOG status > 0, p = 0.026). In multivariate analyses, advanced age (over 65 years), gender (men), and lower body mass index (BMI < 25) were significantly associated with sarcopenia (p values 0.033, < 0.001, and < 0.001, respectively). CONCLUSIONS: Our study is the first prevalence study conducted with bioelectric impedance analysis on Turkish cancer patients and sarcopenia was detected to be notably prevalent among our patients with newly diagnosed cancer. Given the likely negative outcomes of sarcopenia reported in the literature (treatment failure, increased complications, and impaired survival), it is important to know the presence of sarcopenia before treatment and take preventive precautions.

The role of inflammation in adjuvant chemotherapy-induced sarcopenia (Izmir Oncology Group (IZOG) study).

INTRODUCTION: Although the chemotherapy-induced sarcopenia has some explanatory presence in clinical practice, the mechanisms underlying this phenomenon have not been clearly distinguished in patients with cancer. Therefore, we aimed with this study to investigate the role of inflammation by examining the inflammatory markers in the physiopathology of adjuvant chemotherapy-induced sarcopenia in patients with gastrointestinal tract cancer. MATERIAL AND METHOD: To detect the presence of sarcopenia, patients' body composition measurements were assessed using the BIA, and their muscular strength was assessed with a handgrip dynamometer in both pre- and post-adjuvant chemotherapy. At the same time, we examined the baseline and post-adjuvant chemotherapy anthropometric measurements and inflammatory markers in serum (Hs-CRP, IL8, and TNF-α). Patients were divided in three groups. Group 1 consisted of patients who presented post-treatment sarcopenia although they did not have it prior to the treatment, group 2 included the patients who had no pre- or post-treatment sarcopenia, and group 3 was comprised of patients who presented pre-treatment sarcopenia. Each group included 30 patients. RESULTS: A total of 90 patients were included in the study. Fifty-one of them were female patients. Median age was 60.5 (range 27-83). The patients consisted of cases with colorectal and gastric cancers. In group 1, Wilcoxon signed-rank test revealed a significant difference between scores of IL-8 (pg/mL), TNF-α (pg/mL) and Hs-CRP (mg/dL) given for the post-chemotherapy compared with the pre-chemotherapy ((Z 3.61, p < 0.001), (Z 3.254, p = 0.001), (Z 3.319, p = 0.001)). The post-chemotherapy median scores of IL-8 (pg/mL), TNF-α (pg/mL), and Hs-CRP were 76.31, 7.34, and 1.55, respectively, which remained on the levels of 12.25, 1.6, and 0.51 for the pre-chemotherapy. For group 2, a Wilcoxon signed-rank test indicated no significant difference between scores of the same markers given for the post-chemotherapy compared with the pre-chemotherapy. In all patients (including groups 1, 2, and 3), a comparison of the patients with pre-treatment sarcopenia (n = 30) and non-sarcopenic patients (n = 60) in terms of baseline IL-8, TNF-α, and Hs-CRP mean levels, IL-8 and Hs-CRP were found to be statistically different (146.02 (SD 311.96) vs. 47.24 (SD 66.3) (p = 0.009), 3.91 (SD 4.26) vs. 0.75 (SD 1.08) (p < 0.001), respectively). CONCLUSIONS: The present prospective observational study suggested an association of chemotherapy-induced sarcopenia with inflammatory markers Hs-CRP, IL8, and TNF-α. Inflammation may play a role in chemotherapy-induced sarcopenia in newly diagnosed non-metastatic patients.

BRCA genes: BRCA 1 and BRCA 2.

BRCA1 and BRCA2 are the genes related with breast and ovarian cancer. They have function in DNA repair processes and thus they are tumor suppressor genes. There are hundreds of mutations identified in these genes. Functional deficiencies due to these mutations impair DNA repair and cause irregularities in the DNA synthesis. The standard method for the laboratory assessment of these BRCA genes includes comprehensive sequencing and testing of broad genomic rearrangements. Members of the families with BRCA mutations have an increased risk for early onset of breast cancer and ovarian cancer occurring at any age. Surveillance of patients with mutations in BRCA 1/2 is done by yearly mammography and breast MRI and by transvaginal ultrasonography and serum CA-125 levels every 6-12 months for ovarian cancer.

Is adjuvant chemotherapy necessary for Luminal A-like breast cancer?

PURPOSE: Patients with breast cancer with Luminal-A subtype have a better prognosis but poor chemotherapy response. Chemotherapy is controversial in lymph node-positive patients with Luminal-A subtype. In this retrospective study, we aimed to evaluate the efficacy and benefit of chemotherapy in the Luminal A-like subtype of breast cancer. METHODS: Patients diagnosed with breast cancer within 2006 and 2011 were retrospectively evaluated. Patients with pathologically confirmed Luminal A-like breast cancer were analyzed , and were divided in those receiving taxane-based adjuvant chemotherapy and those who did not. RESULTS: A total of 136 patients with Luminal-A type were included in the study. The 10-year cumulative disease-free survival (DFS) was 85.6 vs 96.7% (p=0.230) for the chemotherapy and non-chemotherapy groups, and overall survival (OS) was 88.6 vs 100%, respectively (p=0.242). The 10-year cumulative DFS was 80 vs 98.1% for the taxane-based chemotherapy group and taxane-free chemotherapy group (p=0.501), while the OS was 87.5 vs 95.2%, respectively (p=0.391). There was a positive correlation between relapse status and lymph node involvement in the multivariate analysis (p=0.031). CONCLUSION: Adjuvant chemotherapy in Luminal-A showed no significant difference for DFS and OS. Taxane-based chemotherapy did not demonstrate any benefit for OS and DFS with relatively more advanced stage and lymph node involvement. We believe that adjuvant chemotherapy plays a minor role in a significant proportion of Luminal-A subtype of breast cancer.

Evaluation of prognostic factors in localized high-grade undifferentiated pleomorphic sarcoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology.

Most data on prognostic factors for patients with high-grade undifferentiated pleomorphic sarcoma (HGUPS) is obtained from analyses of soft tissue sarcomas. The purpose of this study was to evaluate the clinicopathologic features and their impact on outcomes specifically in patients diagnosed with HGUPS. In this multicenter trial, we retrospectively analyzed 112 patients who were diagnosed and treated at 12 different institutions in Turkey. We collected data concerning the patients, tumor characteristics, and treatment modalities. There were 69 males (61.6 %) and 43 females (38.4 %). Median age was 56 years (19-90). The most common anatomic site of tumor origin was the upper extremity. Pleomorphic variant was the predominant histological subtype. Median tumor size was 8.2 cm (0.6-30 cm). Tumors were mainly deeply seated (57.1 %). Fifty-seven patients (50.9 %) were stage II and the remainder were stage III at the time of diagnosis. Median follow-up was 30 months (2-160). The primary site of distant metastasis was the lung (73.5 %) and the second most common site was the liver (11.7 %). The 5-year overall survival, distant metastasis-free survival, and local recurrence-free survival rates were 56.3, 53.4, and 67.2 %, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of II (p = 0.033), deep tumor location (p = 0.000), and development of distant metastasis (p = 0.004) were negatively correlated with overall survival, and perioperative radiotherapy and negative microscopic margins were significant factors for local control rates (p = 0.000 for each). Deep tumor location (p = 0.003) was the only adverse factor related to distant metastasis-free survival. Deep tumor location, ECOG performance score of II, and development of distant metastasis carry a poor prognostic implication on overall survival. These will aid clinicians in predicting survival and treatment decision.

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study.

BACKGROUND: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. METHODS: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. RESULTS: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. CONCLUSION: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Patients with Neuroendocrine Tumors: An Izmir Oncology Group Study.

BACKGROUND: Several studies evaluating the prognostic factors of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) have been published. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been accepted as prognostic factors for cancer patients. MATERIALS AND METHODS: This study included 132 patients diagnosed with GEP-NETs. Peripheral blood samples were collected before the pretreatment period. RESULTS: NLR and PLR were increased as the grade increased in NETs. The embryonic origin analysis revealed higher NLR and PLR rates in NETs of foregut origin. NLR and PLR were also higher in pancreatic NET patients compared to the gastroenteric NET patients. Analysis of NETs by TNM indicated that an advanced stage was accompanied by significantly higher NLR and PLR. We found a strong negative correlation between progression-free survival and NLR and PLR. CONCLUSION: The study verified that NLR and PLR are simple laboratory findings that can be used to identify NETs with a worse outcome.

Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with breast cancer.

PURPOSE: Cytotoxic treatment may cause weight gain and important alterations in the metabolic status of breast cancer (BC) patients. The aim of this study was to investigate the changes in metabolic and anthropometric parameters of patients with BC who received adjuvant chemotherapy. METHODS: All consecutive women treated with adjuvant TAC (docetaxel 75 mg/m(2), doxorubicine 50 mg/m(2), cyclophosphamide 500 mg/m(2)) chemotherapy for node-positive breast carcinoma at our Institution between 2008 and 2010 were included. RESULTS: Among 104 patients, 84 of them were stage II and 20 of them were stage III. When we compared the measurements between 1(st) and 6(th) adjuvant chemotherapy, we observed statistically significant increases in weight and serum triglyceride levels, and decreases in high density lipoprotein, apolipoprotein A-1, transferrin, albumin and prealbumin levels. An elevation of follicle stimulating hormone, luteinizing hormone together with the decrease of estradiol was detected. Waist-to-hip ratio has also increased significantly. In subgroup analyses, we observed dramatic changes in body mass index in pre-menopausal women whereas no significant change was seen in the post-menopausal group. CONCLUSIONS: Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with BC and these changes are more profound in pre-menopausal patients.

Serum apelin levels and body composition changes in breast cancer patients treated with an aromatase inhibitor.

PURPOSE: The adipose tissue plays a role in carcinogenesis with the adipokines it generates. Apelin is an anti-obesigenic adipokine, and assumes roles in both vascularization and tumor cell proliferation. The present study aimed to investigate changes in apelin levels, in postmenopausal breast cancer (BC) patients receiving aromatase inhibitors (AIs). METHODS: Forty early-stage postmenopausal BC patients treated with AIs with no history of chemotherapy administration were included in the study. At the beginning, we measured serum apelin levels in postmenopausal BC patients who were receiving AIs and healthy women of similar age and normal body mass index (BMI) (control group). We evaluated changes in the body composition, serum lipid profile and serum apelin levels at the beginning and the 12th month through anthropometric measurements and bioelectric impedance analysis. RESULTS: Forty subjects with postmenopausal BC had a median age of 57 years (range 44-82)). BC patients exhibited significantly higher apelin levels and body mass index (BMI) scores compared to the control group (p=0.0001, p=0.0001, respectively). The 12th month's measurements indicated reduced apelin levels in 24 patients (60%) and increased apelin levels in 16 patients (40%) compared to the initial figures. With respect to the parameters, the patients with reduced apelin levels had significantly different waist-to-hip ratio (WHR) and fat mass scores compared to those with higher apelin levels (p=0.008, p=0.047, respectively). CONCLUSION: This study showed that postmenopausal BC patients had high levels of apelin and high BMI scores. This finding suggests that apelin promoted carcinogenesis particularly in obese individuals. The massive and metabolic changes observed in the fat tissues of the postmenopausal BC patients receiving AIs will especially affect the BC-associated outcome.

Zoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell lines.

Our aim was to investigate the possible synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and zoledronic acid (ZA), in PC-3 hormone-refractory prostate cancer cells (HRPC), as well as their docetaxel-resistant sublines. We established a docetaxel-resistant cell line (PC-3R) from PC-3 prostate cancer cells, by intermittent exposure to increasing concentrations of docetaxel in vitro. We then examined the effect of ZA and docetaxel on cell proliferation in both PC-3 and PC-3R prostate cancer cells. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 enzyme activity were measured to verify apoptosis. According to our results, docetaxel and ZA were found to be synergistically cytotoxic and apoptotic in both PC-3 and docetaxel-resistant PC-3R cells, in a dose- and time-dependent manner. Combined treatment with docetaxel and ZA synergistically inhibited PC-3 cell growth in vitro through an enhanced induction of cell death, compared with either agent alone; this result was also evident on PC-3R cells. Moreover, we have also demonstrated that apoptosis was induced in prostate cancer cells exposed to these drugs by a concentration-dependent increase in DNA fragmentation and caspase 3/7 enzyme activity. We concluded that ZA, either with docetaxel or not, might still exert some cytotoxicity even in docetaxel-resistant cells. From the clinical perspective, when the clinician decided to change the treatment in the post-docetaxel setting, continuing or combination with ZA may be an effective therapeutic approach for the treatment of HRPC patients.