Quality of life and radiotherapy in brain metastasis patients

AimThe primary objective of this study was to assess whether there was an improvement in QoL for patients with brain metastases after radiotherapy treatments.BackgroundAssessment of quality of life (QoL) in brain metastasis patients has become increasingly recognized as an important outcome.Materials and methodsPatients treated for brain metastasis in our department during 2010 were included in our prospective study. QoL assessments were conducted at baseline, 1 month, and 3 months after completion of whole-brain radiotherapy (WBRT). Wilcoxon test for multiple comparisons was calculated to detect significant differences in global QoL scores.ResultsThirty-nine patients with brain metastases completed the EORTC QLQ-C30/BN-20 questionnaire independently. Median age was 59.9 years (from 37 to 81 years). Our results report differences between the baseline and 3 months in worsening of a global health status (p = 0.034) and cognitive function (p = 0.004), as well as drowsiness (p = 0.001), appetite loss (p = 0.031) and hair loss (p = 0.005). There is a tendency for deterioration of physical function (p = 0.004), communication deficit (p = 0.012), and weakness of legs (p = 0.024), between the baseline and 1 month evaluation. There was no difference in a global cognitive status between different evaluations. Median survival time was 3 months (CI 95% 1.85; 4.15).ConclusionsOur findings indicate a small deterioration for a global QoL status, and large deterioration for cognitive function after radiation treatments, as well as worsening of brain metastasis related symptom items. Further research is necessary to refine treatment selection for patients with brain metastases, since it may at least contribute to the stabilization of their QoL status.     

Comparison of neoadjuvant oral chemotherapy with UFT plus Folinic acid or Capecitabine concomitant with radiotherapy on locally advanced rectal cancer

AimTo evaluate the differences in treatment response and the impact on survival with both oral agents (UFT and Capecitabine) as neoadjuvant chemotherapy administered concomitantly with radiotherapy.BackgroundThere are still no studies comparing the use of neoadjuvant oral chemotherapy either with UFT plus Folinic acid or Capecitabine concomitant with radiotherapy in locally advanced rectal cancer (LARC).Materials and methodsA set of 112 patients with LARC were treated preoperatively. GROUP 1 – 61 patients underwent concomitant oral chemotherapy with Capecitabine (825 mg/m² twice daily). GROUP 2 – 51 patients submitted to concomitant oral chemotherapy with UFT (300 mg/m²/d) + Folinic acid (90 mg/d) and radiotherapy. 57.1% of patients were submitted to adjuvant chemotherapy.ResultsGROUP 1: acute toxicity – 80.3%; pathological complete response (pCR) – 10.5%; tumor downstaging (TD) – 49.1%; nodal downstaging (ND) – 76.5%; loco-regional response (LRR) – 71.9%; toxicity to adjuvant chemotherapy – 75%. GROUP 2: acute toxicity – 80.4%; pCR – 28%; TD – 62%; ND – 75.6%; LRR – 78%; toxicity to adjuvant chemotherapy – 56%. There was no difference in survival nor loco-regional control between the groups.ConclusionsPatients treated with neoadjuvant oral UFT + Folinic acid had a higher rate of pathologic complete response than patients treated with Capecitabine concomitant with radiotherapy. There were no differences in downstaging, LRR, toxicity, survival or loco-regional control between both groups. There was a trend to a higher rate of toxicity to adjuvant chemotherapy in the Capecitabine group.     

Incidence of radiation toxicity in cervical cancer and endometrial cancer patients treated with radiotherapy alone versus adjuvant radiotherapy

AimThe study was made to evaluate early and late toxicity in a diversified group of patients receiving definitive or adjuvant radiotherapy in terms of clinical diagnosis and treatment methods.BackgroundRadiotherapy is a standard way of treatment in cervical and endometrial cancer patients, both as definitive and adjuvant therapy. But every radiation treatment may be involved with toxicity.Materials and methodsA detailed analysis was performed of 263 patients with gynaecological cancer treated with definitive (90 patients with cervical cancer received radiochemotherapy or radiotherapy exclusively) and adjuvant radiotherapy (38 with cervical and 135 with endometrial cancer).ResultsAcute reactions were found in 51.3% and late reactions were found in 14.8% of patients. It was stated that early (p < 0.007) and late (p < 0.003) post radiation reaction appear more frequently in women treated with definitive than adjuvant radiotherapy. The analysis of the whole group revealed higher rate of toxicity, both early and late, in the gastrointestinal tract than in the urinary system (p < 0.004). Comparing the subgroups, it was found that intestinal reactions occurred more frequently in the definitive radiotherapy group than in the adjuvant one.The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of radiotherapy. The comparison of the subgroups showed that interruptions occurred more frequently in patients receiving definitive rather than adjuvant radiotherapy (17.7–2.9%).ConclusionsDefinitive radiotherapy compared with adjuvant treatment may by associated with higher percentage of side effects caused by dose of therapy and correlation with chemotherapy.     

Rôle de la TEP au 18F-FDG dans l’évaluation des volumes cibles chez des patients atteints de CBNPC traités par radiochimiothérapie

Currently ¹⁸F-FDG-PET is the gold standard to evaluate tumor response after chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC). PET can also determine the volumes to be treated by radiotherapy, in inoperable patients. The aim of our mixed (prospective and retrospective) study concerned 28 patients with NSCLC, was to quantify the variation of the metabolic activity of lesions and their volumes after chemotherapy. We also studied the impact of change of these volumes on the definition of radiotherapy target volumes. Patients with stage II–IV and inoperable NSCLC were included. Two PET scans were performed: before treatment (PET1), then after two to six courses of chemotherapy (PET2). Of the 28 patients included, we observed complete metabolic response in six patients (21%), partial metabolic response in 13 patients (46%), stable disease in seven patients (25%), and progressive metabolic disease in two patients (7%), according to the PERCIST criteria. We observed significant variation (P < 0.001) of metabolic activity (estimated by SULpeak or SUVmax) for primary tumor as well as for overall lesions between the two PET scans. Thus, the target volumes of radiotherapy decreased significantly (P < 0.01) in PET2. Our results confirm that ¹⁸F-FDG-PET is not only a powerful technique for treatment evaluation but also a useful tool for radiotherapy planning after chemotherapy, in the context of personalized treatments.     

Durability of Effects of Exenatide Treatment on Glycemic Control,Body Weight,Systolic Blood Pressure,C-Reactive Protein,and Triglyceride Concentrations

ObjectiveTo determine (1) whether long-term treatment with exenatide is associated with reductions in C-reactive protein (CRP), systolic blood pressure (BP), and triglyceride concentrations in addition to reductions in body weight and hemoglobin A1c (A1C) levels and (2) whether these beneficial results persist without any loss of effect while exenatide is being used, and whether they reverse after its cessation.MethodsWe conducted a retrospective review of 141 patients with type 2 diabetes mellitus treated with exenatide at a tertiary clinic.ResultsExenatide (mean duration of treatment, 1.4 years) decreased A1C (0.7%), weight (5 kg), systolic BP (8 mm Hg), and triglyceride concentrations (46 mg/dL) (P < .05 for all). Sixty-one patients continued exenatide therapy throughout the study (mean duration of use, 2.4 years). Exenatide treatment reduced their mean weight by 7 kg, systolic BP by 8 mm Hg, triglycerides by 52 mg/dL, A1C by 1.3%, and CRP by 2.4 mg/L (P < .05 for all). Reductions in systolic BP and CRP were not related to weight loss. The reduction in CRP concentration was significantly related to the baseline CRP concentration (r = 0.78; P < .001) and to change in A1C (r = 0.68; P = .02). Patients who stopped taking exenatide had a reversal of the benefits within 6 months after cessation of treatment.Conclusion:Exenatide treatment in patients with type 2 diabetes has durable and persistent beneficial effects on A1C, weight, CRP, systolic BP, and triglyceride concentrations. Cessation of treatment reverses all these beneficial effects within 6 months. There was no evidence of loss of its effects while exenatide treatment was continued. (Endocr Pract. 2011;17:192-200)     

Exenatide Use in the Management of Metabolic Syndrome: A Retrospective Database Study

ObjectiveTo evaluate the effect of exenatide therapy on cardiometabolic risk factors and anthropometric parameters in patients with metabolic syndrome.MethodsFrom June 2005 to June 2007, we performed a retrospective analysis of data extracted from the records of adult patients with metabolic syndrome being treated with exenatide. Diagnosis of any type of diabetes mellitus was exclusionary. Patients were initiated on exenatide therapy, 5 mcg, 1 hour before their morning and evening meals for the first month and were instructed to titrate up to 10 mcg. Cardiometabolic risk factors (total cholesterol, high-denssity lipoprotein cholesterol, triglycerides, calculated low- density lipoprotein cholesterol, and blood pressure) and anthropometric parameters (absolute body weight, body mass index, and abdominal girth) were measured at baseline and at 16 ± 4 weeks after initiating exenatide therapy. Data collected also included age, sex, metabolic syndrome diagnosis, and other concomitant medication used in the management of endocrine disorders.ResultsThe study population consisted of 299 patients (259 women, 40 men) with an age range of 18 to 74 years. Exenatide treatment was associated with significant reductions in mean body weight (P < .001) and body mass index (P < .001). Weight loss in 76.6% of patients was concomitant with a significant reduction in mean abdominal girth (P < .001). Further analysis revealed significant decreases in mean triglycerides (P < .001), total cholesterol (P < .01), and both systolic (P < .01) and diastolic blood pressure (P < .03). Approximately 60.2% of patients used metformin concomitantly, and half either decreased or discontinued metformin therapy.ConclusionsThis is the first report examining the effect of exenatide on patients with metabolic syndrome. We observed a significant improvement in cardiometabolic risk factors and anthropometric parameters as a result of exenatide over the treatment interval. (Endocr Pract. 2008;14:993-999)     

Clinical Outcomes Using Long-Term Combination Therapy with Insulin Glargine and Exenatide in Patients with Type 2 Diabetes Mellitus

ObjectiveTo examine the long-term effects of combination insulin glargine/exenatide treatment on glycemic control.MethodsWe conducted a 24-month retrospective US chart review of patients with inadequately controlled type 2 diabetes (T2DM) and hemoglobin A_1c (A1C) levels > 7.0% for whom glargine and exenatide were coprescribed in differing order (glargine added after exenatide [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]). Treatment order groups were combined to form a pooled treatment group. Changes from baseline in A1C, patients with A1C ≤ 7.0%, body weight, glargine/exenatide daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated.ResultsTreatment groups were similar at baseline; however, patients in the glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3). Overall, baseline A1C was 8.8 ± 1.3% and weight was 109.5 ± 25.3 kg. Significant A1C reductions emerged at month 6 and persisted throughout 24 months (vs baseline) in both treatment groups (pooled: –0.7 ± 1.6; P < .001), and 33.0% of patients achieved an A1C level ≤ 7.0%. After 24 months of exenatide/glargine, body weight remained unchanged (0.7 ± 8.3 kg; P = .640). With glargine/exenatide, body weight decreased (–2.5 ± 6.7 kg; P = .001). At month 24, daily glargine dose was 0.40 ± 0.23 units/kg for the exenatide/glargine group and 0.47 ± 0.30 units/kg for the glargine/exenatide group. Hypoglycemia frequency was similar in both treatment groups.ConclusionsRegardless of treatment order, long-term combined therapy with glargine and exenatide for up to 24 months in patients with inadequately controlled T2DM suggests reduction of A1C without significant weight gain or increased hypoglycemia risk. (Endocr Pract. 2012;18:17-25)     

Pituitary Hormone Dysfunction After Proton Beam Radiation Therapy in Children with Brain Tumors

Objectiveo characterize endocrine dysfunction in pediatric patients with brain tumors who received proton beam (PB) radiation therapy and to compare those treated with PB radiotherapy only versus combined conventional and PB irradiation.MethodsA retrospective review of medical records of patients ≤ 18 years of age who received PB radiation therapy for a brain tumor between 2000 and 2008 was performed. Variables analyzed included patient demographics, tumor type, therapeutic modalities, radiation doses, and types and timing of endocrine dysfunction.ResultsThirty-eight patients were identified, of whom 31 (19 boys and 12 girls; mean age, 11.9 ± 3.3 years) had undergone endocrine evaluation. Of these patients, 19 received PB radiotherapy only and 12 received conventional plus PB irradiation. Before irradiation, a cranial surgical procedure was performed in 28 study subjects, and 22 received chemotherapy. The mean duration of follow-up after radiation therapy was 1.8 ± 0.8 years. Nine patients (47%) in the PB only group and 4 (33%) in the conventional plus PB group developed endocrine dysfunction (no significant difference) after cranial irradiation. Children with endocrine sequelae treated with PB irradiation alone received fewer cobalt gray equivalents than those treated with conventional plus PB irradiation (5,384 ± 268 versus 5,775 ± 226, respectively; P < .02), and pituitary hormone deficiencies were detected later during follow-up in those who received PB radiotherapy only versus conventional plus PB irradiation (1.17 ± 0.4 years versus 0.33 ± 0.11 year, respectively; P < .01).ConclusionA high rate of endocrine sequelae was seen in our study. Children with brain tumors treated with conventional plus PB irradiation developed endocrine dysfunction faster and received a higher radiation dose than those receiving PB radiotherapy only. Prior surgical treatment and chemotherapy were additional risk factors. Large prospective studies are needed to evaluate further the incidence of endocrine sequelae after PB irradiation in children. (Endocr Pract. 2011;17:891-896)     

Neoadjuvant chemotherapy with or without oxaliplatin after short-course radiotherapy in high-risk rectal cancer: A subgroup analysis from a prospective study

AimTo evaluate the role of oxaliplatin in neoadjuvant chemotherapy delivered after short-course irradiation.BackgroundUsing oxaliplatin in the above setting is uncertain.Patients and methodsA subgroup of 136 patients managed by short-course radiotherapy and 3 cycles of consolidation chemotherapy within the framework of a randomised study was included in this post-hoc analysis. Sixty-seven patients received FOLFOX4 (oxaliplatin group) while oxaliplatin was omitted in the second period of accrual in 69 patients because of protocol amendment (fluorouracil-only group).ResultsGrade 3+ acute toxicity from neoadjuvant treatment was observed in 30% of patients in the oxaliplatin group vs. 16% in the fluorouracil-only group (p = 0.053). The corresponding proportions of patients having radical surgery or achieving complete pathological response were 72% vs. 77% (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.39–1.98; p = 0.75) and 15% vs. 7% (OR = 2.25; 95% CI: 0.83–6.94; p = 0.16), respectively. The long-term outcomes were similar in the two groups. Overall and disease-free survival rates at 5 years were 63% vs. 56% (p = 0.78) and 49% vs. 44% (p = 0.59), respectively. The corresponding numbers for cumulative incidence of local failure or distant metastases were 33% vs. 38% (hazard ratio [HR] = 0.89; 95% CI: 0.52–1.52; p = 0.68) and 33% vs. 33% (HR = 0.78; 95% CI: 0.43–1.40; p = 0.41), respectively.ConclusionOur findings do not support adding oxaliplatin to three cycles of chemotherapy delivered after short-course irradiation.     

Nasopharyngeal carcinoma in Slovenia, 1990–2003 (results of treatment with conventional two-dimensional radiotherapy)

AimTo review the treatment results and identify prognostic factors for disease control and survival in a cohort of nasopharyngeal carcinoma (NPC) patients from a non-endemic population in Slovenia, diagnosed between 1990 and 2003.BackgroundIn Caucasians, nasopharyngeal carcinoma is a rare malignant tumor. Its diagnosis and treatment are complex and have been dramatically impacted by recent technological advances.Materials and methodsIn the Cancer Registry of Slovenia database, a total of 126 patients with NPC were identified, 93 of whom were available for analysis. All patients were treated with conventional two-dimensional radiotherapy (RT) and 29.3% underwent chemotherapy (ChT).ResultsThe median follow-up time for those alive at the last follow-up examination was 74.5 months. Disease recurred locally in 17 patients, regionally in 4 patients and at distant sites in 18 patients, resulting in 5-year locoregional control (LRC), distant failure-free survival (DFFS) and disease-free survival (DFS) of 73.7%, 78.6% and 59.3%, respectively. Disease-specific survival at 5 years was 59% and overall survival (OS) was 49.7%. In a multivariate analysis, LRC was favorably affected (P < 0.05) by an undifferentiated histology (hazard ratio [HR] = 2.86), DFFS through the absence of neck metastases (HR = 0.28), DFS by younger age (HR = 0.46), and more intensive RT (expressed as the isoeffective dose, EQD_2,T; HR = 2.08). The independent prognosticator for OS was age (≤55 years vs. >55 years, HR = 0.39); in the ≤55 years subgroup, an improved OS was connected to a more intensive RT regimen of EQD_2,T ≥ 66 Gy (HR = 4.17).ConclusionsOur results confirm an independent and favorable effect from an undifferentiated histology, the absence of neck metastases, a younger patient age at diagnosis, and more intensive RT regimens for disease control and survival.     

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects

IntroductionObesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD).Methods22 severe obese subjects (Median Body Mass Index (BMI): 44.5 kg/m²) were included in a dietary intervention study of 6 month, consisting of a very low calorie formula diet phase (VLCD: 800 kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR).ResultsMean body weight reduction by VLCD accounted to 21.7 kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (r_S = −0.642, p = 0.001) and HOMA (r_S = −0.419, p = 0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p = 0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p = 0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (r_S = −0.650, p = 0.022) during intervention.ConclusionAnti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.     

Ghrelin and peptide YY increase with weight loss during a 12-month intervention to reduce dietary energy density in obese women

Reducing dietary energy density (ED) promotes weight loss; however, underlying mechanisms are not well understood. The purpose of this study was to determine if low-ED diets facilitate weight loss through actions on ghrelin and peptide YY (PYY), independent of influences of psychosocial measures. Seventy-one obese women (BMI 30–40 kg/m²) ages 22–60 years received counseling to reduce ED. Fasting blood samples were analyzed for total ghrelin and total PYY by radioimmunoassay at months 0, 3, 6, and 12. Restraint, disinhibition, and hunger were assessed by the Eating Inventory. Body weight (−7.8 ± 0.5 kg), BMI (−2.9 ± 0.2 kg/m²), body fat (−3.0 ± 0.3%), and ED (−0.47 ± 0.05 kcal/g or −1.97 ± 0.21 kJ/g) decreased from months 0 to 6 (p < 0.05) after which no change occurred from months 6 to 12. Ghrelin increased in a curvilinear fashion (month 0: 973 ± 39, month 3: 1024 ± 37, month 6: 1109 ± 44, and month 12: 1063 ± 45 pg/ml, p < 0.001) and PYY increased linearly (month 0: 74.2 ± 3.1, month 3: 76.4 ± 3.2, month 6: 77.2 ± 3.0, month 12: 82.8 ± 3.2 pg/ml, p < 0.001). ED, body weight, and hunger predicted ghrelin, with ED being the strongest predictor (ghrelin = 2674.8 + 291.6 × ED − 19.2 × BW − 15 × H; p < 0.05). There was a trend toward a significant association between ED and PYY (PYY = 115.0 − 43.1 × ED; p = 0.05). Reductions in ED may promote weight loss and weight loss maintenance by opposing increases in ghrelin and promoting increases in PYY.     

Influence of patient,physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer

PurposeInflammatory breast cancer (IBC) is an aggressive subtype of breast cancer for which treatments vary, so we sought to identify factors that affect the receipt of guideline-concordant care.MethodsPatients diagnosed with IBC in 2004 were identified from the Breast and Prostate Cancer Data Quality and Patterns of Care Study, containing information from cancer registries in seven states. Variation in guideline-concordant care for IBC, based on National Comprehensive Cancer Network (NCCN) guidelines, was assessed according to patient, physician, and hospital characteristics.ResultsOf the 107 IBC patients in the study without distant metastasis at the time of diagnosis, only 25.8% received treatment concordant with guidelines. Predictors of non-concordance included patient age (≥70 years), non-white race, normal body mass index (BMI 18.5–25 kg/m²), patients with physicians graduating from medical school >15 years prior, and smaller hospital size (<200 beds). IBC patients survived longer if they received guideline-concordant treatment based on either 2003 (p = 0.06) or 2013 (p = 0.06) NCCN guidelines.ConclusionsTargeting factors associated with receipt of care that is not guideline-concordant may reduce survival disparities in IBC patients. Prompt referral for neoadjuvant chemotherapy and post-operative radiation therapy is also crucial.     

Cellular and nephrotoxicity of selenium species

ProjectBeside its useful functions at very low concentrations, selenium including supplementary Se sources pose a potential toxicological risk. The toxicity of selenium species was tested in HaCaT cell culture and related nephrotoxicity in mice.ProcedureThe apoptotic shrinkage and necrotic expansion of cells were measured by time-lapse image microscopy. Acute nephrotoxicity was estimated upon administration of various selenium species to mice for two weeks. To confirm or to refute the accumulation of Se in the kidney and its potential chronic effect, Se concentration in kidney tissue and histopathlology were tested.ResultsThe comparison of selenium species showed that organic lactomicroSe did not affect cell growth at 5 ppm, but inorganic nanoSe severely hampered it at lower concentration (1 ppm). The in vivo Se treatment (0.5, 5, 50 ppm, corresponding to 4, 40 and 400 μg/kg) was misleading as it did neither affect the outward appearance nor the weight of the kidney. Se accumulation was observed after selenate, selenite, SelPlex, selenite and nanoSe administration, while lactomicroSe caused no traceable accumulation. In vivo, ex vivo and in vitro experiments reflected this order of selenium toxicity: selenate > selenite > SelPlex = nanoSe > lactomicroSe.ConclusionWithin the tested species lactomicroSe was the only non-nephrotoxic selenium source recommended for nutritional Se supplementation.     

Effect of Astragalus polysaccharides on expression of TNF-α, IL-1β and NFATc4 in a rat model of experimental colitis

AimAstragalus membranaceus is a Chinese medicinal herb and has been shown to improve hapten-induced experimental colitis. One of its major components is polysaccharides. We investigated the effect of Astragalus polysaccharides (APS) on expression of TNF-α, IL-1β and NFATc4 in a rat model of experimental colitis.MethodsThe experimental colitis model was induced by TNBS. Forty five rats were divided into five groups (n = 9): Normal control group, receiving ethanol vehicle with no TNBS during induction and IP saline injection during treatment; TNBS colitis model group (TNBS + IP saline), receiving only IP saline vehicle treatment; APS low dose group (TNBS + L-APS), receiving APS 100 mg/kg; APS high dose group (TNBS + H-APS), receiving APS 200 mg/kg; and positive control group (TNBS + Dexm), receiving dexamethasone 0.3 mg/kg. The clinical features, macroscopic and microscopic scores were assessed. The expressions of TNF-α, IL-1β and NFATc4 were measured by real-time PCR and ELISA assays.ResultsCompared to normal control rats, TNBS + IP saline had significant weight loss, increased macroscopic and microscopic scores, higher disease activity index (DAI) up-regulation of TNF-α, IL-1β and NFATc4 mRNA expression and up-regulation of TNF-α and IL-1β protein expression. Compared to TNBS + IP saline, treatment with APS or dexamethasone significantly reduced DAI, partially but significantly prevented TNBS colitis-induced weight loss and improved both macroscopic and microscopic scores; high dose APS or dexamethasone significantly down-regulated TNF-α and IL-1β expressions (both mRNA and protein) and up-regulated NFATc4 mRNA and protein expression. The effect of high dose APS and dexamethasone is comparable.ConclusionsAPS significantly improved experimental TNBS-induced colitis in rats through regulation of TNF-α, IL-1β and NFATc4 expression.     

Recherche de facteurs de risque de la thrombopénie induite par le 177Lu-DOTATATE dans le bilan de suivi standard

PurposeThe thrombocytopenia induced by the ¹⁷⁷Lu-DOTATATE is one of its frequent, adverse effects. Its persistence causing problems in the subsequent management of patients, especially when the disease progression occurs, predicting it is a major issue. Due to the lack of knowledge about this subject, we searched to determine the existence of predisposing factors concerning the platelet toxicity in the standard follow-up.Material and methodsThis monocentric retrospective study included 20 patients with gastroenteropancreatic neuroendocrine tumors. Various parameters were analyzed, including: the standard blood analysis, the osteomedullary invasion factor, the spleen's volume and the estimated activity in the bone marrow or the spleen 24 hours post-injection.ResultsFour patients had a persistent grade 2 thrombocytopenia, one year after the last treatment. A decrease in platelet count after the first treatment above 30% and an osteomedullary invasion factor above 30% were highlighted as risk factors odds-ratio = ∞ (P = 0.0379) and odds-ratio = ∞ (P = 0.003) respectively. The initial platelet count, splenic length and estimated activity in the spleen after 24 h were correlated with platelet nadir value r = 0.5459 (P = 0.0128); r = − 0,8105 (P < 0,0001) and r = − 0.467; (P < 0.0001) respectively.ConclusionThis study has shown that the decrease of platelet's count after the first round of treatment and the scale of osteomedullary invasion are risk factors for thrombocytopenia and has brought to light that the spleen acts as a factor impacting the severity of this thrombocytopenia.     

Non-closure of peritoneum after abdominal hysterectomy for uterine carcinoma does not increase late intestinal radiation morbidity

Background/AimTo evaluate whether non-closure of the visceral peritoneum after total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) in patients with uterine corpus carcinoma influences the volume of the small intestine within the irradiated volume during adjuvant radiotherapy or late radiation intestinal toxicity.Materials and methodsA total of 152 patients after TAH + BSO with adjuvant pelvic radiotherapy were studied. The state of peritonealization was retrospectively evaluated based on surgical protocols. The volume of irradiated bowels was calculated by CT-based delineation in a radiotherapy planning system. The influence of visceral peritonealization upon the volume of the small intestine within the irradiated volume and consequent late morbidity was analyzed.ResultsVisceral peritonealization was not performed in 70 (46%) of 152 studied patients. The state of peritonealization did not affect the volume of the irradiated small intestine (p = 0.14). Mean volume of bowels irradiated in patients with peritonealization was 488 cm³ (range 200–840 cm³, median 469 cm³); mean volume of bowels irradiated in patients without peritonealization was 456 cm³ (range 254–869 cm³, median 428 cm³). We did not prove any significant difference between both arms. Nor did we observe any influence of non-peritonealization upon late intestinal morbidity (p = 0.34).ConclusionNon-closure of the visceral peritoneum after hysterectomy for uterine corpus carcinoma does not increase the volume of the small intestine within the irradiated volume, with no consequent intestinal morbidity enhancement.     

The effect of radiotherapy and chemotherapy on osmotic fragility of red blood cells and plasma levels of malondialdehyde in patients with breast cancer

BackgroundGamma radiation effects on the erythrocyte membrane from three different functional parts, lipid bilayer, cytoskeleton and protein components. When the red cell membrane is exposed to radiation, it loses its integrity and hemoglobin leaks out. In addition, irradiation leads to lipid peroxidation and the products of this process, leading to hemolysis. The aim of the present study was to measure osmotic fragility (OF) of red blood cells and malondialdehyde (MDA) levels as a marker of oxidative injury in breast cancer patients treated with radiation and chemotherapy.Materials and MethodsThe OF test was performed using different concentrations of a salt solution. The measurement of MDA was done with chemical methods.¹¹ The sampling was taken during three stages of treatment: first sample was taken before starting chemotherapy, the second sample was taken before radiation therapy and the third sample was taken after radiotherapy.ResultsNo statistically significant differences between levels of MDA in these three stages of treatment were observed. However, the comparison of mean levels of MDA showed an increase after radiotherapy. The OF rate did not show significant difference (P > 0.05) during the stages of treatment.ConclusionIn a standard treatment program of radiotherapy and chemotherapy lipid peroxidation level and OF do not significantly increase.