Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer.

Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1ß, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.

Perception of health, well-being, and quality of life in female caregivers: Comparative study of a sample of adult and older women in Spain.

In a study on informal or unpaid care, it is difficult to identify the consequences and effects of care provision on the caregiver's daily life. Thus, it is important to analyze the perceptions of the individual caregiver. This study describes the perceptions of health, well-being, support networks, and quality of life of 13 women aged between 45 and 70 years after completing an intervention program. The data indicate that caregivers' health and quality of life worsen with the intervention, and their well-being and social relations (through new technologies) improve.

The impact of body mass index and nuclear ß-catenin on survival in locally advanced rectal cancer treated with preoperative radiochemotherapy.

BACKGROUND AND OBJECTIVE: We examined the prognostic value of obesity and nuclear ß-catenin in patients with locally advanced rectal cancer. METHODS: We prospectively recruited a total of 98 eligible patients with locally advanced cancer for preoperative radiochemotherapy followed by total mesorectal excision. Patients' height and weight were reaorded before radiochemotherapy, and the immunohistochemical expression of nuclear ß-catenin was analyzed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier method and a Cox regression model was employed for the multivariate analysis. RESULTS: Obese patients were associated with a lower number of recurrences (3.6% vs. 34.3%, P = 0.001), and a higher DFS (95% vs. 53%; HR, 0.09; 95%CI, 0.01-0.64; P = 0.005) than non-obese patients. In the multivariate analysis, body mass index, nuclear ß-catenin expression, and the absence of lymph node metastases showed a significant increase in DFS. CONCLUSIONS: Obesity and nuclear ß-catenin are independent favorable prognostic factors for DFS in locally advanced cancer treated with preoperative radiochemotherapy. J. Surg. Oncol. 2017;115:301-306. © 2017 Wiley Periodicals, Inc.

Preoperative chemoradiotherapy in rectal cancer induces changes in the expression of nuclear ß-catenin: prognostic significance.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the cornerstone of treatment for locally advanced rectal cancer (LARC). Although high local control is achieved, overall rates of distant control remain suboptimal. Colorectal carcinogenesis is associated with critical alterations of the Wnt/ß-catenin pathway involved in proliferation and survival. The aim of this study was to assess whether CRT induces changes in the expression of ß-catenin/E-cadherin, and to determine whether these changes are associated with survival. METHODS: The Immunohistochemical expression of nuclear ß-catenin and membranous E-cadherin was prospectively analysed in tumour blocks from 98 stage II/III rectal cancer patients treated with preoperative CRT. Tumour samples were collected before and after CRT treatment. All patients were treated with pelvic RT (46-50 Gy in 2 Gy fractions) and 5-fluorouracil (5FU) intravenous infusion (225 mg/m2) or capecitabine (825 mg/m2) during RT treatment, followed by total mesorectal excision (TME). Disease-free survival (DFS) was analysed using the Kaplan-Meier method and a multivariate Cox regression model was employed for the Multivariate analysis. RESULTS: CRT induced significant changes in the expression of nuclear ß-catenin (49% of patients presented an increased expression after CRT, 17% a decreased expression and 34% no changes; p = 0.001). After a median follow-up of 25 months, patients that overexpressed nuclear ß-catenin after CRT showed poor survival compared with patients that experienced a decrease in nuclear ß-catenin expression (3-year DFS 92% vs. 43%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.02). In the multivariate analysis for DFS, increased nuclear ß-catenin expression after CRT almost reached the cut-off for significance (p = 0.06). CONCLUSIONS: In our study, preoperative CRT for LARC induced significant changes in nuclear ß-catenin expression, which had a major impact on survival. Finding a way to decrease CRT resistance would significantly improve LARC patient survival.

Differential Composition and Structure of the Microbiota from Active and Inactive Stages of HLA-B27-associated Uveitis by Paired Fecal Metagenomes.

PURPOSE: To compare the diversities and abundances of bacterial taxa in the microbiome of patients with HLA B27-positive acute anterior uveitis (AAU) in the active and inactive phases. METHODS: An observational descriptive prospective and comparative study was conducted in ten HLA-B27-positive AAU patients (44.6 ± 13.4 years). The microbiome of the stool samples obtained in the active and inactive stages was analyzed by sequencing the V3 region of the 16S rRNA gene. RESULTS: The differences in the bacteria profile between active and inactive stages in each individual were confirmed (p < 0.0001). Ten OTUs were found exclusively in the active phase of 90% of the individuals, suggesting a proinflammatory association. Blautia OUT_4 and Faecalibacterium OUT_2 abundances showed a direct relationship between abundance and severity of ocular inflammation. Two OTUs were exclusive of the inactive stage, suggesting an anti-inflammatory role. CONCLUSION: The metagenomic profile of the fecal microbiota differs in the acute phase of the AAU compared to when the inflammation subsides, despite being the same individual and a short time-lapse. AAU is a fertile field for studying the connection between subtle rapid changes in microbiota and their systemic consequences.

Impact of nutritional and educational support on home enteral nutrition.

BACKGROUND: Home Enteral Nutrition (HEN) is used to prevent or correct malnutrition in outpatients. Due to the complexity of this process, the indication, follow-up, and results of an educational program of HEN patients was evaluated. METHODS: A prospective, observational, real-life, multicenter study was performed in 21 Spanish Hospital. Patients receiving HEN by nasogastric tube or ostomy were included. The following variables were collected: age, gender, HEN indication, type of formula, nutritional requirements, laboratory variables, complications, and quality standards of the educational program. To calculate the energy and protein requirements, the FAO/WHO/UNU formula was used considering the adjusted weight of the patients. All data were analyzed using SPSS.24. RESULTS: 414 patients were included. Most conditions diagnosed were neurodegenerative diseases (64.8%). 100 (25.3%) were diabetic. The mean weight was 59.3 ± 10.4 kg and BMI 22.6 ± 3.2. Moderate protein-calorie malnutrition was predominant at baseline (46.4%). Improvement in nutritional status at six months was recorded in more than 75% of patients (p < 0.05). Tolerance problems, diarrhea and abdominal distension fell between the 3- and 6-month visits (p < 0.05). Patients who received intermittent EN had fewer tolerance-related effects (OR 0.042; 95% CI 0.006-0.279) and less diarrhoea (OR 0.042; 95% CI 0.006-0.279). At the baseline and 6-month visits, compliance with the educational measures proposed by the prescriber was ≥ 99%. CONCLUSION: The nutritional assessment to prescribe individualized HEN to each patient, together with educational measures and training in the proper use of this treatment for both patients and trainers, improves nutritional status and reduces the onset of adverse events.

Male breast cancer: immunohistochemical subtypes and clinical outcome characterization.

AIM: The aim of this study was to assess the molecular subtype profiles of male breast cancer (MBC) and subsequent clinical outcome using a validated 6-marker immunohistochemical panel. METHODS: A total of 43 cases of MBC were examined retrospectively using a semiquantitative immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (Her2), epidermal growth factor receptor and cytokeratin 5/6. Patients were classified into the following categories: luminal A, luminal B, Her2-positive or basal-like subtypes. RESULTS: The median age of patients was 63 years (r: 32-89). The predominant histology was invasive ductal carcinoma (91%). Only 1 patient had advanced breast cancer at diagnosis. Ninety-three percent were ER-positive and 84% were PR-positive. Two patients had tumors that were ER- and PR-negative. The distribution of tumor molecular subtypes was 19 (44%) luminal A, 22 (51%) luminal B and 2 (5%) basal-like. The Her2-positive tumor subtype was not identified. The clinicopathological characteristics did not differ significantly between tumor subtypes A and B. There were no significant differences in 6-year disease-free survival (74 vs. 82%, p = 0.77) or overall survival (74 vs. 82%, p = 0.69) between luminal A and luminal B subtypes, respectively. CONCLUSION: The most common subtypes in our cohort of MBC were luminal B followed by luminal A, and no differences were found between both tumor subtypes in terms of clinicopathologic characteristics and patient outcome.

The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response.

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.

Urates in uric acid renal calculi.

OBJECTIVES: To investigate the presence of calcium urate, sodium, potassium and calcium in 'pure' uric acid calculi. METHODS: Ten spontaneously passed uric acid urinary calculi have been examined by stereoscopic microscopy, infrared spectroscopy, scanning electron microscopy and energy dispersive X-Ray analysis. RESULTS: The analysis of selected uric acid calculi revealed the presence of a near-pure calcium urate in two cases and of calcium enriched urate zones in all of the samples. Furthermore, in some cases complex urates containing sodium, potassium and calcium in different proportions appeared on the surface of the uric acid calculi studied, potassium being generally predominant. Ammonium urate was not detected. CONCLUSIONS: Most urinary uric acid calculi are not pure in composition. 'Complex urates', sodium, potassium and calcium were found together in various proportions in many areas of uric acid stones.

Effectiveness of an oral diabetes-specific supplement on nutritional status, metabolic control, quality or life, and functional status in elderly patients. A multicentre study.

BACKGROUND & AIMS: The purpose of this study was to assess nutritional status, quality of life (QoL) and function in malnourished or at risk for malnutrition community-dwelling (CD) and nursing home-dwelling (NHD) elderly patients with type 2 diabetes mellitus (DM2), receiving treatment with a diabetes-specific oral nutritional supplement (DSONS). METHODS: A prospective, multicentre, observational study was conducted. A DSONS (high-calorie, high-protein, with slow-digestible carbohydrate and high monounsaturated fatty acid - MUFA-content - Glucerna® 1.5 Cal) had been prescribed the week before inclusion. The following assessments were undertaken at baseline (BL), at week 6 (V1) and at month 3 (FV): body mass index (BMI), glycosylated haemoglobin (HbA1c), nutritional status (Mini Nutritional Assessment - MNA), QoL (EQ-5D questionnaire), and functional status (Katz Index - KI of Independence in Activities of Daily Living). The data were reported in the overall population (OP) and in the CD and NHD groups. RESULTS: A total of 402 patients aged 80.8 ± 8.5 years were evaluable (44.5% men), including 61.7% CD and 38.3% NHD. BMI (kg/m2) increased in the OP from 22.0 ± 3.5 at BL to 22.5 ± 3.6 at V1 (p < 0.001) and 23.0 ± 3.7 at the FV (p < 0.001). BMI also increased in the CD group (p < 0.001) and in the NHD group (p < 0.001). HbA1c decreased in the OP from 7.3 ± 1.1% at BL to 7.2 ± 1.0% at V1 and 7.0 ± 0.9% at the FV (p < 0.001), in both the CD (p < 0.001) and the NHD groups (p = 0.020). The mean overall MNA score increased in the OP from 13.1 ± 4.8 at BL to 17.0 ± 4.7 at V1 and 18.6 ± 5.1 at the FV (p < 0.001). The mean overall MNA score also increased in the CD (p < 0.001) and the NHD groups (p < 0.001). The mean overall EQ-5D score improved in the OP from 46.0 ± 18.0 at BL to 54.8 ± 17.5 at V1 and 59.7 ± 18.8 at the FV (p < 0.001). The mean overall EQ-5D score also improved in the CD (p < 0.001) and the NHD groups (p < 0.001). Gastrointestinal adverse events were seen in only 2% of patients. Treatment compliance was 94.4%. CONCLUSIONS: In this study, conducted in routine, multicentre, clinical settings, the treatment with the high-calorie, high-protein, with slow-digestible carbohydrate, and high MUFA content DSNOS - Glucerna® 1.5 Cal-, was associated with improvements in HbA1c, nutritional status, BMI and QoL following 6 weeks and 3 months of treatment in both institutionalised and non-institutionalised elderly patients with diabetes who were malnourished or at risk for malnutrition. A slight improvement in functional status was also observed at 12 weeks. As this is an observational effectiveness study, a randomized controlled trial would be necessary to establish a causal relationship between the DSNOS and the described events.

Spanish consensus for the management of sinonasal tumors. / Consenso español para el tratamiento de los tumores nasosinusales.

Sinonasal tumors are rare neoplasms with distinctive clinical, aetiological and pathological features. The diagnosis and treatment of these tumours is challenging because of their low incidence, histological diversity and production of non-specific symptoms in the early stages. They have a variable prognosis depending on their histology, origin and staging. Their location, close to neurocritical structures, which are of special relevance to surgery and postoperative treatment, makes their treatment difficult and complex, leading to high morbidity and mortality. Surgery followed by radiotherapy is the mainstay of treatment. To provide the best possible care, patients with sinonasal cancer should be treated in clinical referral centres specializing in skull-base pathologies. Such centres should include a multidisciplinary team led by otolaryngologist surgeons. This article outlines a consensus protocol for the management of these tumours devised by the Spanish Society of Otolaryngology in collaboration with the Spanish Society of Medical Oncology and the Spanish Society for Radiation Oncology.

Adherence and tolerance as key in brake on weight loss in cancer patients with nutritional risk after intervention with a high calorie nutritional and specific hyperproteic supplement / Adherencia y tolerancia como claves en la detención de la pérdida de peso en pacientes oncológicos sometidos a radioterapia mediante una estrategia de suplementación precoz con una fórmula enteral hipercalórica e hiperproteica específica

Background: In patients with nutritional risk, the European Society for Clinical Nutrition and Metabolism (ESPEN) recommends nutritional supplements during cancer treatment to prevent weight loss. Objectives: Our goal is to determine the acceptability, compliance and tolerance of a hyperproteic, high-calorie, omega-3 enriched supplement in cancer patients. Methods: Unicentric, prospective observational study in cancer patients with hyperproteic, high-calorie, rich in omega 3 and low volume nutritional supplement. Thirty patients with malnutrition or risk of malnutrition were included. Supplementation lasted six days. Compliance (packaging used), acceptability (Madrid scale), anthropometric variables and gastrointestinal adverse events (AEs) were evaluated. Results: Seventy per cent were men, with an average age of 60 years (range 32-79), with lung (43.3%), ENT (26.7%) and breast neoplasms (13.3%), stage III-IV (56.7%), and treated with radiotherapy (93.3%), chemotherapy (60%) and surgery (16.7%). The product was accepted by all patients. A compliance rate of 100% was observed. Gastrointestinal AE (grade II) related to the supplement was observed in two patients (6.7%). Both subjects had previous gastrointestinal diseases. The median weight, body mass index (BMI) and protein intake increased during supplementation (0.2 kg, 0.1 kg/m2 and 6.2 g). No differences were observed regarding calorie, fat and carbohydrates intake. Conclusion: The high acceptance and compliance with the specific nutritional supplement was associated with an improved nutritional status for cancer patients, and reversed the weight loss without severe gastrointestinal problems, or producing intake displacement.

Introducción: en pacientes con riesgo nutricional, la Sociedad Europea de Clínica y Metabolismo (ESPEN) y Parenteral recomienda suplementos nutricionales durante el tratamiento oncológico para prevenir la pérdida de peso involuntaria. Objetivos: nuestro objetivo es conocer el cumplimiento, la aceptabilidad y la tolerancia de un suplemento hiperproteico, hipercalórico, rico en omega 3 en pacientes oncológicos. Métodos: estudio unicéntrico, observacional y prospectivo en pacientes oncológicos con un suplemento nutricional hiperproteico, hipercalórico, rico en omega 3 y de bajo volumen. Fueron incluidos 30 pacientes con desnutrición o en riesgo de desnutrición. La suplementación duró seis días. Se evaluaron el cumplimiento (envases utilizado), la aceptabilidad (escala Madrid), las variables antropométricas y los acontecimientos adversos (AA) gastrointestinales. Resultados: el 70% fueron hombres, con una edad media de 60 años (rango: 32 a 79) y con neoplasias de pulmón (43,3%), ORL (26,7%) y mama (13,3%), en estadio III-IV (56,7%), tratados con radioterapia (93,3%), quimioterapia (60%) y cirugía (16,7%). El producto fue aceptado por todos los pacientes. Se observó un cumplimiento del 100%. En dos pacientes (6,7%) se observaron AA gastrointestinales (grado II) relacionados con el suplemento; ambos sujetos presentaban patologías gastrointestinales previas. La mediana del peso, índice de masa corporal (IMC) y proteínas ingeridas aumentó durante la suplementación (0,2 kg, 0,1 kg/m2 y 6,2 g). No se observaron diferencias respecto a la ingesta de calorías, lípidos y carbohidratos. Conclusión: la elevada aceptación y cumplimiento del suplemento nutricional específico se asoció con la mejora nutricional de los pacientes oncológicos, pues revirtió la pérdida de peso, sin presentar problemas gastrointestinales severos ni producir desplazamiento de la ingesta.

[Nitrogenous content in parenteral nutrition: a four-year experience in a general hospital. Critically-ill patient specificity].

INTRODUCTION: There have been several studies focusing on caloric intake during the last years, while protein content relevance has been underestimated. Some recent evidence has shown that protein deficiency has also an impact on patient outcomes. We have studied the nitrogen (N) content in parenteral nutrition (PN) bags administered to adult patients in a Spanish tertiary level hospital for four years. MATERIAL AND METHODS: Patients who received parenteral nutrition in the general ward and Intensive Care Unit (ICU) were recorded. Caloric and protein content were registered and adjusted to weight and length of stay. Data were compared among three group of patients: those in the general ward, those in the ICU and those requiring renal replacement therapy (RRT). The one-factor analysis of variance (ANOVA) test was used after checking data normality and homoscedasticity. RESULTS: There was an increase in the mean g N/stay year after year (p < 0.01) from 14 to 15.5 g, with a decrease in non-protein caloric content (p < 0.001) from 111.6 to 101.8 kcal/g N. The range was established from 4.1 to 32.6 g. PN diets with ≥ 18 g N% ranged from 12.8% (2010) to 19.6% (2013). There were significant differences among the groups when comparing the variable g N/stay (p < 0.0001): 13.5 general ward vs15.9 ICU patients vs17.6 ICU with RRT, also when referring to adjusted weight. CONCLUSIONS: According to most recent recommendations nitrogen has been provided in higher amounts than previously, especially in critical care patients with RRT.

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

BACKGROUND AND PURPOSE: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. MATERIAL AND METHODS: A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. RESULTS: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. CONCLUSIONS: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.

Computational Synteny Block: A Framework to Identify Evolutionary Events.

MOTIVATION: The identification and accurate description of large genomic rearrangements is crucial for the study of Evolutionary Events among species and implicitly defining breakpoints. Although there is a number of software tools available to perform this task, they usually either a) require a collection of pre-computed non-conflicting High-scoring Segment Pairs (HSPs) and gene annotations; or b) involve working at protein level (what excludes non-coding regions) ; or c) need many parameters to adjust the software behaviour and performance; or d) imply working with duplications, repeats and tandem repeats, which complicates the identification of rearrangements task. Although there are many programs specialized in the detection of these repetitions, they are not designed for the identification of main genomic rearrangements.

Evaluation of the utilization of external radiotherapy in the treatment of localized prostate cancer in Andalusia, Spain.

BACKGROUND: Around 27,000 new cases of prostate cancer are diagnosed every year in Spain and 5400 die from this disease. Radiotherapy (RT), alone or combined, has proven to be effective as initial treatment in patients with localized disease. Our objective was to evaluate the use of external beam RT (EBRT) in our region, comparing the indication rate and irradiation rate and examining variability in its application among hospitals. METHODS: We conducted a review of RT guidelines and indication studies for prostate cancer (% expected irradiation). Data were gathered from all twelve public healthcare centers in Andalusia (Spain) on RT-treated prostate cancer patients during 2013 (% actual irradiation) and from nine of the centers on RT discharge reports. Information was classified according to type of hospital, tumor risk category and RT treatment (technique, dosage, volume, toxicity). RESULTS: The estimated RT rate was 67 % (1289/1917), 43 % were aged > 70 years, 44.7 % had ECOG performance status of 0); 44.7 % had high-risk tumors; 57 % underwent RT associated with hormone therapy; 70 % of patients receiving RT were treated with 3D planning (30 % IGRT); and doses were 70-76 Gy in 70 % of cases and >76 Gy in 10.7 %. Acute gastrointestinal and genitourinary toxicities were < grade 2 in 79 and 89 % of patients, respectively. An irradiation rate significantly below the mean for the study was found in four provinces. There was a significant difference among provinces in the distribution of risk groups. CONCLUSIONS: Underutilization of EBRT was estimated to be around 30 % in prostate cancer patients, with an elevated variability in irradiation rates among hospitals related to differences in available technology and in the distribution of patients with different risk levels. These data should be a matter of concern to regional health managers, given the negative and measurable impact on the survival of patients.