Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer.</p> <p>Methods</p> <p>TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term) preoperative RT and 21 patients 25 × 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test.</p> <p>Results</p> <p>RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0.001-0.021) and with increased s-creatinine concentrations assessed prior to surgery (P = 0.041).</p> <p>Conclusions</p> <p>The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.</p

Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study

Background: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC). Results: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p < 0.01 for men and 9.2 %, p < 0.01 for women), whereas no association was observed with the rest of the MetS components as well as with MetS overall (per 10 nmol/L: OR = 1.42, 95 % CI = 0.85-2.39 for men and OR = 1.38, 95 % CI = 0.79-2.43). Conclusions: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS

Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: A randomized controlled trial.

OBJECTIVE: This study aimed to clarify the microbial change in the intestinal microbiota in patients, with cardiovascular disease, consuming a drink with high numbers of live Lactobacillus plantarum. METHODS: Sixteen males, with atherosclerotic plaque on the carotid wall, were randomly selected from a larger cohort and included in this double blind, placebo controlled study. Colonic biopsies, taken before and after four weeks of probiotic treatment, were analysed with Terminal Restriction Fragment Length Polymorphism, including digestion with MspI and HaeIII. Microbial diversity was calculated, short-chain fatty acids in faeces, and blood markers were analysed. RESULTS: Consumption of one probiotic strain of L. plantarum (DSM 9843) increased intestinal microbial diversity. The probiotic group had an increased diversity after consumption of the probiotic drink compared to the change in the placebo group when Shannon and Weaner diversity index (MspI and HaeIII, p=0.026) and Simpson index of diversity (MspI, p=0.044 and HaeIII, p=0.026) were calculated. The fermentation pattern of short-chain fatty acids in faeces were unaffected for most acids, but the probiotic group had decreased concentration of isovaleric acid (p=0.006) and valeric acid (p=0.029). Viable count of lactobacilli increased in the probiotic group (p=0.001), but no significant changes in blood markers were observed. CONCLUSION: Administration of a single-strain probiotic increases the bacterial diversity in the gut, and affects the concentration of some short-chain fatty acids. Consumption of the single strain L. plantarum DSM 9843 might be a strategy to favour a diverse intestinal microbiota, which is beneficial for the host

Patients' Perception of Information and Health-Related Quality of Life 1 Month After Discharge for Colorectal Cancer Surgery.

The aim of this study was to investigate how patients perceive information and their health-related quality of life 1 month after discharge for colorectal cancer surgery. The aim was also to compare these results with the first 2 weeks at home and to identify factors related to the perception of information. One hundred patients from three surgical clinics in the south of Sweden were included in this study. Perception of information was assessed with EORTC QLQ-INFO25, health-related quality of life with QLQ-C30 and QLQ-CR38, classification of physical status with American Society of Anaesthesiologists (ASA) and sense of coherence with SOC-13. Patients in this study did not receive enough information, and this had not changed significantly since the first 2 weeks at home. Only one subscale about disease information (p = 0.01) had improved since the first 2 weeks at home, while health-related quality of life had improved significantly during the same period. Poorer physical status and living alone were related to a perception of having received less information after discharge. Patients did not receive sufficient information to prepare them for the period at home after discharge, and their perception of information remained during the first month at home. Patients with a poorer preoperative physical status and who live alone constitute a vulnerable group in need of more information at discharge. This enhances the need to individualize the information and to offer multiple ways of accessing information after discharge

Perceived information after surgery for colorectal cancer - an explorative study.

Aim: With fast track surgery and shorter hospital stay, discharge from hospital after cancer surgery is becoming more challenging for the individual patient. The aim of this study was to explore how patients perceive information after surgery for colorectal cancer, what their information needs are and to determine factors affecting received information. Method: One hundred patients filled in the questionnaires EORTC QLQ-C30, CR38, INFO25, ECOG and SOC and provided written comments within the first two weeks after discharge following surgery for colorectal cancer. The questionnaires were analyzed using hierarchical cluster analysis and a multiple linear regression analysis. The written comments were analysed using content analysis. Results: Forty-nine percent of the patients expressed a need for more information. In the written comments they specified these areas of information: they lacked information concerning their surgery, how to handle symptoms and problems at home, someone to contact after discharge and prognostic information about their future. Patients reported most received information in areas of medical tests and disease but less on other services and support in outpatient care. The variation in INFO25 was best explained by gender (p=0.045) and preoperative health status (ASA 3 p=0.022). Conclusion: The results from this study indicate that women and patients with a poorer preoperative health status scored less on information received and would need more time and support to prepare for discharge. The patients expressed a desire for more information about the surgery, how to handle symptoms at home and prognostic information about their future

Lactobacillus plantarum 299v reduces colonisation of Clostridium difficile in critically ill patients treated with antibiotics

Background: The incidence of Clostridium difficile-associated disease (CDAD) in hospitalised patients is increasing. Critically ill patients are often treated with antibiotics and are at high risk of developing CDAD. Lactobacillus plantarum 299v (Lp299v) has been found to reduce recurrence of CDAD. We investigated intensive care unit (ICU) patients regarding the impact of Lp299v on C. difficile colonisation and on gut permeability and parameters of inflammation and infection in that context. Methods: Twenty-two ICU patients were given a fermented oatmeal gruel containing Lp299v, and 22 received an equivalent product without the bacteria. Faecal samples for analyses of C. difficile and Lp299v were taken at inclusion and then twice a week during the ICU stay. Other cultures were performed on clinical indication. Infection and inflammation parameters were analysed daily. Gut permeability was assessed using a sugar probe technique. Main Results: Colonisation with C. difficile was detected in 19% (4/21) of controls but in none of the Lp299v-treated patients (p < 0.05). Conclusions: Enteral administration of the probiotic bacterium Lp299v to critically ill patients treated with antibiotics reduced colonisation with C. difficile. Trial registration: Current Controlled Trials ISRCTN8565554

Short-term outcomes following beyond total mesorectal excision and reconstruction using myocutaneous flaps : A retrospective cohort study

Introduction: Beyond total mesorectal excision (bTME) offers long-term survival in patients with advanced pelvic malignancy. At Skåne University Hospital (SUS) Malmö in Sweden, the vertical rectus abdominis musculocutaneous (VRAM) and gluteal maximus (GM) flap have been used for perineal reconstruction to promote healing and functional outcomes after significant tissue loss. This study aims to examine 90-day overall and flap-specific complications in patients with advanced pelvic cancer treated with bTME and perineal flap reconstruction. Method: This retrospective study conducted at SUS included patients undergoing surgery between January 01, 2010 and August 01, 2016. Patients’ data were gathered through medical chart reviews. The Clavien-Dindo (CD) classification system was used to classify surgical and medical postoperative complications. Flap-specific complications were evaluated regardless of CD classification. Results: One hundred five patients (51 men, 54 women) underwent bTME surgery with perineal reconstruction, with VRAM flaps used in 27 (26%) patients, GM flaps in 51 (49%) patients and GM flaps with vaginal reconstruction in 27 (26%) patients. The 90-day mortality rate was one (1%), despite surgical CD ≥ III and/or medical CD ≥ II complications affecting 51 (48%) patients. Partial perineal dehiscence was noted in 45 (43%) patients, mostly treated conservatively. At the first outpatient postoperative visit (median, 42 days), flap healing was complete in 47 (45%) patients. Conclusion: bTME surgery in pelvic cancer patients with perineal flap reconstruction using VRAM or GM flaps results in high overall and flap complication rates, but low mortality. Most complications can be conservatively treated