Clinical effectiveness of adding probiotics to a low FODMAP diet: Randomized double-blind placebo-controlled study.

BACKGROUND: There are various studies showing the relationship between irritable bowel syndrome (IBS) and diet, and some dietary adjustments are recommended to reduce symptoms. In recent years, there is a growing number of studies that show a 4-8 wk low fermentable oligo, di- and mono-saccharides and polyols (FODMAP) diet has a 50%-80% significant effect on symptoms in IBS patients. There is strong evidence suggesting that changes in fecal microbiota have an impact on IBS pathogenesis. Based on this argument, probiotics have been used in IBS treatment for a long time. As is seen, the FODMAP diet and probiotics are used separately in IBS treatment. AIM: To evaluate the effectiveness of adding probiotics to a low FODMAP diet to control the symptoms in patients with IBS. METHODS: The patients who were admitted to the Gastroenterology Clinic of Dokuz Eylul University Hospital and diagnosed with IBS according to Rome IV criteria were enrolled into the study. They were randomized into 2 groups each of which consisted of 50 patients. All patients were referred to a dietitian to receive dietary recommendations for the low FODMAP diet with a daily intake of 9 g. The patients were asked to keep a diary of foods and beverages they consumed. The patients in Group 1 were given supplementary food containing probiotics (2 g) once a day in addition to their low FODMAP diet, while the patients in Group 2 were given a placebo once a day in addition to their low FODMAP diet. Visual analogue scale (VAS), the Bristol Stool Scale and IBS Symptom Severity Scale (IBS-SSS) scores were evaluated before and after the 21 d treatment. RESULTS: The rate of adherence of 85 patients, who completed the study, to the FODMAP restricted diet was 92%, being 90% in Group 1 and 94% in Group 2. The mean scores of VAS and IBS-SSS of the patients in Group 1 before treatment were 4.6 ± 2.7 and 310.0 ± 78.4, respectively, and these scores decreased to 2.0 ± 1.9 and 172.0 ± 93.0 after treatment (both P < 0.001). The mean VAS and IBS-SSS scores of the patients in Group 2 before treatment were 4.7 ± 2.7 and 317.0 ± 87.5, respectively, and these scores decreased to 1.8 ± 2.0 and 175.0 ± 97.7 after treatment (both P < 0.001). The IBS-SSS score of 37 patients (86.04%) in Group 1 and 36 patients (85.71%) in Group 2 decreased by more than 50 points. Group 1 and Group 2 were similar in terms of differences in VAS and IBS-SSS scores before and after treatment. When changes in stool shape after treatment were compared using the Bristol Stool Scale, both groups showed significant change. CONCLUSION: This study is the randomized controlled study to examine the efficiency of probiotic supplementation to a low FODMAP diet in all subtypes of IBS. The low FODMAP diet has highly positive effects on symptoms of all subtypes of IBS. It was seen that adding probiotics to a low FODMAP diet does not make an additional contribution to symptom response and adherence to the diet.

Can Inflammatory and Nutritional Serum Markers Predict Chemotherapy Outcomes and Survival in Advanced Stage Nonsmall Cell Lung Cancer Patients?

Purpose. To determine the values of prognostic nutritional and inflammatory markers in chemotherapy outcomes and survival in the patients with advanced nonsmall cell lung cancer (NSCLC) and also in the secondary malnutrition and cachexia. Methods. Twenty-five patients with diagnosis of aNSCLC were registered for the prospective study. Malnutrition was determined by the Subjective Global Assessment (SGA) and performance status by criteria of the Eastern Cooperative Oncology Group (ECOG). Before treatment, serum levels of albumin, prealbumin, vitamin D, zinc (Zn), C-reactive protein (CRP), IL-6, IL-1 ß, TNF-α, lipoprotein lipase (LPL), and the Glasgow Prognostic Score (GPS) were recorded. Patients were followed prospectively for treatment outcomes and survival. Results. Due to the deaths of 18 patients during the 4-month follow-up period, no adequate measurements of inflammatory and nutritional markers could be performed. However, seven patients completed the treatment period and evaluations of these markers could be performed during the three periods. Eighty-four percent of patients were male with a mean age of 63.3 ± 8.7 years. Evaluation of the malnutrition by SGA showed that 5 (20%) patients were well nourished (A), 12(48%) were moderately malnourished (B), and 8(32%) were severely malnourished (C). Low levels of serum albumin (<3.5g/dl), prealbumin (<20 mg/ml), 25-hydroxycholecalciferol (<30 ng/ml), and Zn (<70mg/ml) were detected in 15(60%), 17(68%), 24 (96%), and 22 (88%) patients, respectively. Elevated levels of CRP (≥10 mg/L), IL6 (≥18pg/ml), TNF-α (≥24pg/ml), IL-1ß (≥10pg/ml), and LPL (<12pg/ml) were found in 24 (96%), 11(44%), 9(36), 13(52%), and 11(44%) patients, respectively. Moderate and severe malnutrition, acute phase response, and reduced survival were determined in patients with NCSLC. In 7 patients that completed the treatment period, there was an association between elevated serum levels of IL-6, IL-1ß, TNF-α, CRP, and LPL and also the reduced serum levels of albumin, prealbumin, Zn, vitamin D, and GPS, respectively. Similarly, Friedman analysis indicated that prealbumin significantly increased (p=0.007) in the follow-up period. But the serum levels of CRP (mean 37.3±22.3; Wilcoxon test P=0.368) in the seven patients were lower than those of the 18 patients that expired (mean 75.82±56.2). Conclusion. Malnutrition and cachexia negatively influence oncological outcomes in patients with NSCLC. These nutritional/inflammatory markers may be useful for selection of high risk and reduced survival in patients with aNSCLC undergoing adjuvant chemotherapy.

Evaluation of sarcopenia, sarcopenic obesity, and phase angle in geriatric gastrointestinal cancer patients: before and after chemotherapy

Background/aim: The purpose of this study was to determine sarcopenia, sarcopenic obesity and phase angle (PA) and the influence of chemotherapy (CT) on anthropometric measurements and and the PA in in geriatric patients with gastrointestinal (GI) cancer. Materials and methods: The anthropometric measurements, calf circumference (CC), upper midarm circumference (UMAC), and hand grip strength (HGS), have been measured to understand muscle function of 153 patients (mean age of 70.5 ± 5.6 years, 28.8% female, 71.2% male). Sarcopenia and PA measurements have been evaluated by bioelectrical impedance analyses. The same evaluations were checked again after 1 cycle of CT (min: 4, max: 6 weeks). Results: Patient population consisted of colorectal (51,6%), gastric (26.8%), pancreas (11.8%), liver (7.2%), and biliary tract cancer (2%). UMAC (28.5 ± 4.4 before, 28.1 ± 4.9, P = 0.034 after CT), and HGS measurements (27.5 ± 8.6 before, 26.8 ± 8.8 after CT, P = 0.007) have significantly decreased after CT. CC measurement < 31 cm at first visit was seen in 13.1% of patients, but the ratio raised to 20.3% after CT (χ², P = 0.003). Severe sarcopenia was determined in 33% of all patients, and 30.0% of them have been considered as sarcopenic obese. Conclusion: Sarcopenia and sarcopenic obesity were prevalent in this group patients. The CT caused a decrease in muscle functions, UMAC, and CC. Patients should be followed up carefully for sarcopenia, sarcopenic obesity, and nutritional aspect and it would be proper to intervene before sarcopenia has not occurred yet.

The effect of chemotherapy on nutritional status and weakness in geriatric gastrointestinal system cancer patients.

OBJECTIVES: Malnutrition is common in patients with geriatric gastrointestinal system (GIS) cancer. This study aimed to evaluate patients with geriatric GIS cancer in terms of nutritional status and weakness and determine the changes caused by chemotherapy (CT). METHODS: Patients with geriatric GIS cancer who received CT were included in the study. Their nutritional status was assessed with the Mini Nutritional Assessment, and weakness was assessed with the handgrip strength/body mass index ratio. After CT (minimum 4 wk and maximum 6 wk later), patients were assessed for the same parameters. RESULTS: A total of 153 patients aged ≥65 y (mean age, 70.5 ± 5.6 y; 44 female and 109 male) were evaluated. The population consisted of patients who were diagnosed with colorectal (51.6%), gastric (26.8%), pancreatic (11.8%), hepatic (7.2%), biliary tract (2%), and esophageal (0.7%) cancer. Of these patients, 37.9% were malnourished, 34.6% were at risk of malnutrition, and 27.5% were well nourished. After one course of CT, the frequency of malnutrition increased to 46.4% (P = 0.001). The patient groups with the highest rates of weakness were those who were diagnosed with biliary tract, hepatic, and colorectal cancer (33.3%, 27.3%, and 20%, respectively). Weakness was significantly increased after one course of CT in patients who received CT before (P = 0.039). CONCLUSIONS: Malnutrition and weakness were common in patients with geriatric GIS cancer, and even one course of CT worsened the nutritional status of the patients. Patients who have received CT previously should be carefully monitored for weakness.

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer.

BACKGROUND: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells. METHODS: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels. RESULTS: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 µM and 100 µM. CONCLUSION: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells.

Perspectives and practical applications of medical oncologists on defensive medicine (SYSIPHUS study): a study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

Defensive medicine occasionally indulges unnecessary treatment requests to defend against lawsuits for medical errors and the use of unapproved medical applications. This study determines the attitudes and orientations of medical oncologists on defensive medicine. A cross-sectional survey was sent by e-mail to medical oncologists. The survey was designed to determine the participants' demographic characteristics and defensive medicine practices. The survey measured the attitudes about defensive medicine practices of the oncologists based on a five-point Likert scale (never, rarely, sometimes, often, and always). One hundred and forty-six of a total of 402 physicians serving in oncology were fully filled, and the rate of return invitation was 36 %. The majority of participants were male, with a duration of between 7 and 9 years of work as university hospital officials, and the mean age was 46 ± 9 (years). International guidelines were followed in the most common is NCCN, and the majority of respondents felt that the application of these guidelines improves their defensive medicine. All participants of defensive medicine who stand on the basis of the definition were found to be more afraid of complaints by patients' relatives. Physicians of 45 % was noted that applying defensive medicine. Among the participants were the most frequent checkups of positive defensive approach is defined as increasing or shortening the follow-up period, while avoiding high-risk patients were detected as described in the definition of negative defensive medicine. Both professional groups in both the positive and negative defensive medicine approach defensive medicine approach, academic tasks, work experience and job time, there was a significant correlation between the location. Made in single- and multi-variable analyses, positions were identified both positive and negative defensive medicine is an independent risk factor for direction. Improving the working conditions of young physicians to protect against medical error may require additional educational opportunities.

The Perspective of Non-oncologist Physicians on Patients with Metastatic Cancer and Palliative Care (ALONE Study): A Study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

The aim of our study was to determine the perspective of non-oncologist physicians regarding their attitudes and beliefs associated with palliative care for patients with metastatic cancer. The study was planned as a cross-sectional survey, and non-oncologist physicians were reached via e-mail and social networking sites. The first part of the questionnaire involved demographic properties, the second part inquired as to the perspectives of participants regarding metastatic disease, and the third part was used to determine beliefs and attitudes about palliative care. All of the questions were five-point Likert-type questions. A total of 1734 physicians completed the questionnaire. The majority of participants were general surgeons or internal medicine specialists (21 and 18%, respectively), were male (61%), were younger than 50 years of age (54%), worked in the town center (67%), had more than 11 years of professional experience (57%), and worked in a hospital without an active oncology service (86%). A total of 71% of participants identified all patients with metastatic cancer as being terminal stage, 62% were unaware of palliative care techniques, 64% did not know about common supportive care options, 59% were against hospice, and 63% had no opinion on resuscitation. We determined that non-oncologist physicians believed that all patients with metastatic cancer are at the terminal stage and that palliative/supportive care is the oncologist's task. These data suggest that non-oncologist physicians would benefit from additional graduate and postgraduate courses on these topics.

Determination of Knowledge and Behavior of Women Working at a Hospital on Breast Cancer Early Detection Methods, and Investigation of Efficiency of Planned Education.

OBJECTIVE: This study aimed to evaluate knowledge and attitude of women working in the hospital on breast cancer, their behaviors related to early diagnostic methods, and to determine the effectiveness of training in order to increase awareness on breast cancer. MATERIALS AND METHODS: The study group consisted of women working in the Dokuz Eylül University Hospital. The data of this cross-sectional study were collected by a questionnaire. Within the scope of this study, a training program on breast cancer was organized. The effectiveness of this training was evaluated by a preliminary survey and a final survey. Data were expressed as number and percentage, and paired t test and chi-square test were used for comparison. RESULTS: 161 women participated in the study with a mean age of 35 ± 8. It was determined that 81.4% of women knew early diagnosis and screening methods for breast cancer. 49.1% of women stated that they perform breast self-examination, but only 6.2% practiced it once a month. 32.9% of women had clinical breast examination, 22.4% had a breast ultrasound, and 22.3% had mammography. Most of the women did not perform any of these methods. The average knowledge level of women was significantly increased after completion of the planned training as compared to pre-training levels (p <0.001). CONCLUSION: It was determined that the majority of women were informed on breast cancer early diagnosis and screening methods, but did not practice these methods on themselves. Information and awareness of women against breast cancer have increased with the use of planned training programs on breast cancer, early detection and screening methods.

Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis.

BACKGROUND: The aim of the study was to investigate preventive effects of glutamine (Gln), omega-3 fatty acids (FA) on erythrocyte deformability (EDEF) in rat model of indomethacin-induced enterocolitis. METHODS: Nineteen Wistar albino male rats were divided into three groups: control group, colitis induced by indomethacin and were fed with a standard laboratory diet (group 1), and colitis induced by indomethacin and were also fed with Gln, omega-3 FA (group 2). An investigation was performed in a rat model of experimental colitis induced by subcutaneous injections of 2 mL intdomethacine solution applied at 24 and 48 hours intervals to male Wistar rats for 14 days. Gln and omega-3 FA were added to the daily standard diets of the animals during 14 days of injections. During the study, changes in body weight were evaluated. The intestines were examined, and colitis was macroscopic and histologically scored. The circulating tumor necrosis factor alpha (TNF-α) and interleukine-1ß (IL-1ß), erythrocyte transit time (ETT) and thiobarbituric acid reactive substances (TBARS) levels were determined in addition to calculation of EDEF indices in all groups. RESULTS: No significant differences in body weight changes could be determined between the standard diet and special diet groups at the end of the experiment. After macroscopic and microscopic scoring, in all of the groups that colitis was found induced, the lowest microscopic score was observed in the group 2. But Gln and omega-3 FA supplemented diet did not change the mean macroscopic and histological scores in all rats. The proliferating cell nuclear antigen (PCNA) levels were significantly higher in group 1 and group 2 compared to the control group. Effects of the diet on circulating TNF-α and IL-1ß levels were found correlated with inflammation but statistically significant differences were not found in the group 1 and group 2 (P < 0.05). The ETT and TBARS levels in standard and special diet groups were significantly increased (P < 0.05). However, EDEF indices which are an important parameter of the study were decreased in indomethacin-induced enterocolitis groups that fed with standard and special diet. CONCLUSIONS: Increases in ETT and TBARS levels did not return to normal by addition of Gln and omega-3 FA to diet. Our results suggest that determination of effective optimal doses and route of administration for these nutrients may play an important role in reducing EDEF and microvascular changes.

Mast cell leukemia associated with undefined morphology and chronic basophilic leukemia.

BACKGROUND: Mast cell leukemia (MCL) is rare type of neoplasia with an incidence of 1% in a large series of 342 adult patients with systemic mastocytosis (SM). Chronic basophilic leukemia (CBL) is an extremely rare type of leukemia with appearance of 7 cases in the literature. CASE PRESENTATION: A 73 year-old female patient who presented with weaknes, had a prolonged duration of hematologic remission after treatment of her CBL by hydroxyurea (HU). Evolution of SM occurring as a second neoplasia concurrently with relapse of de novo CBL was demonstrated by mast cells (MCs) infiltration in the bone marrow (BM) biopsy and smear and increase in tryptase level. Transformation to MCL with simultaneous occurrance of accelerated phase of CBL were documented by the appearance of MCs in both BM and peripheral blood (PB) smears, antigen expressions detected by flow cytometry and spesific stains. Sequence analysis of c-kit gene revealed c-kit exon 11 K550N mutation. Undefined associations of MCL with different mast cell morphology, increase in IL-6 level and accelerated phase of de novo CBL was described. CONCLUSION: Elevations in CRP and IL-6 levels occurring with increases in basophil counts to high levels revealed that febrile episodes with abdominal pain seen in our patient were induced by increase in IL-6 levels released from neoplastic basophils. Neoplastic basophils with diffuse and coarse basophilic granules possibly mimic neutrophils with toxic granules and cause wrong characterization of neoplastic basophils as neutrophils by the automated blood cell counters and misleaded physicians.

New paraneoplastic syndrome in chronic basophilic leukemia.

Chronic basophilic leukemia (CBL) is an extremely rare disorder. A female patient presented with recurrent attacks of chills, fever and abdominal pain was found to have simultaneous cyclic oscillation in leukocyte counts and C-reactive protein values. She was initially diagnosed with familial Mediterranean fever and treated with colchicine. Diagnosis of CBL was established by morphologic studies of peripheral blood and bone marrow. Her febrile attacks recurred with marked elevation in serum interleukin-6 (IL-6) level when basophil counts climbed to peak levels during cyclic oscillation. Molecular studies by real-time PCR showed IL-6 gene expression in neoplastic basophils separated by magnetic-activated cell sorting infiltrating the bone marrow, suggesting that IL-6 is released by neoplastic basophils of an underlying CBL, resulting in a new paraneoplastic syndrome that mimics autoinflammatory disorders.

Chemopreventive efficacies of rosiglitazone, fenretinide and their combination against rat mammary carcinogenesis.

INTRODUCTION: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and retinoic acid receptors (RAR/RXR) belong to the nuclear steroid receptor family. In vitro studies have suggested that PPAR-gamma ligands are highly effective in preventing mammary tumours and these effects are enhanced by some retinoids. However, in vivo anti-initiator and anti-promoter efficacies of this combination are not clear. AIM AND METHODS: The present study aimed to investigate the chemopreventive efficacies of the PPAR-gamma ligand rosiglitazone (200 microg/kg/day), synthetic retinoid fenretinide (0.3 mg/kg/day) and their combination on a DMBA-induced rat mammary carcinogenesis model. RESULTS: In the rosiglitazone group, no malignant tumour developed, apart from the lowest proliferative mammary lesions. In the fenretinide group, 30% developed a malignant tumour but there were no benign tumours. Cancer incidences were 61.5% and 10% in the control and combination groups respectively. CONCLUSIONS: Our results showed that the PPAR-gamma ligand rosiglitazone and synthetic retinoid fenretinide have potent chemopreventive properties against in vivo mammary carcinogenesis; however, the efficacies were not enhanced by their combination.

Effects of selenium supplementation on antioxidant defense and glucose homeostasis in experimental diabetes mellitus.

The objective of this study was to investigate the effects of different forms of Se supplementation on the antioxidant defense and glucose homeostasis in experimental diabetes. Sodium selenate (SS) or selenomethionine (SM) were administered (2 micromol Se kg(-1) day(-1)) via orogastric route to streptozotocine (STZ)-induced diabetic rats in addition to basal diet for 12 weeks. Glucose levels in whole blood, glutathione peroxidase (GSH-Px) activity in erythrocytes, Se and fructosamine levels in plasma were evaluated monthly. Plasma Se levels increased significantly in all diabetic groups compared to basal measurements, being more prominent in SM group [p(SM(3)/SM(0)) = 0.018]. The increase in GSH-Px activities was significant at the end of the second month in SS [p(SS(2)/SS(0)) = 0.028], whereas at the end of the third month in SM the value was lower [p(SM3/SM0) = 0.018] and the unsupplemented diabetic control (DC) groups, p(DC(3)/DC(0)) = 0.012. Glucose increased significantly only in DC group. Fructosamine increased gradually in all diabetic groups, being significant in DC and SS groups. At the end of the third month, highest fructosamine levels were observed in SS group, which were significantly higher than the SM group [p(SM/SS) = 0.010]. In conclusion, Se augmented the antioxidant defense by increasing GSH-Px activity and this effect was more prominent when Se was supplemented as SM, which exerted positive effects also on glucose homeostasis.

Does antioxidant supplementation alter the effects of acute exercise on erythrocyte aggregation, deformability and endothelium adhesion in untrained rats?

This study aimed to determine whether high-dose antioxidant supplementation had an impact on the acute exercise effects related to erythrocyte membrane mechanics. Experimental animals (n=32) were divided into four groups as control, exercised, supplemented, and supplemented + exercise. Four-week antioxidant supplementation (vitamin C, vitamin E, and zinc) was applied to experimental animals. Following acute exercise on a motor-driven rodent treadmill, erythrocyte aggregation and deformability, erythrocyte adhesion to endothelial cells, superoxide dismutase (SOD), and glutathione peroxidase activities of the erythrocytes were analyzed. In both supplemented and non-supplemented exercised groups, there was a significant decrease in SOD activities and erythrocyte aggregation, and an increase in adhesion to endothelial cell although there was no change on erythrocyte deformability. There were no differences in the responses to the exercise of supplemented and nonsupplemented rats. The data suggested that high-dose antioxidant supplementation did not alter the effects of acute exercise on erythrocyte membrane mechanics.

Toxicity induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene and the protective effects of selenium in Wistar rats.

7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 microg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA-Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA-Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA-Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA.