Podocalyxin-like protein expression in primary colorectal cancer and synchronous lymph node metastases

Aims: Previous studies have shown that membranous expression of podocalyxin-like protein (PODXL) is associated with poor prognosis in colorectal cancer (CRC). In this study, we compared PODXL expression in primary CRC and synchronous lymph node metastases. We further analyzed whether its expression changed in rectal tumours after neoadjuvant radiation therapy. Methods and results: The studied cohort consists of 73 consecutive patients from the South-Swedish Colorectal Cancer Biobank. Immunohistochemical PODXL expression was examined on full-face sections from all primary tumours and all 140 available lymph node metastases from 31 cases. Membranous PODXL expression was denoted in 18/73 (24,7%) primary tumours, with a high concordance between primary and metastatic lesions. While all negative primary tumours had negative metastases, some PODXL positive primaries had a varying proportion of positive and negative metastatic lymph nodes. PODXL expression was also found to be mainly unaltered in pre- and post-irradiation surgically resected tumour specimens in rectal cancer patients (n=16). Conclusions: The findings in this study suggest that analysis of PODXL expression in the primary tumour is sufficient for its use as a prognostic and treatment predictive biomarker in CRC, also in patients with metastatic disease

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

Sexual and functional long-term outcomes following advanced pelvic cancer and reconstruction using vertical rectus abdominis myocutaneous and gluteal myocutaneous flap

Introduction: After extensive pelvic surgery for cancer two flap types are used at Skåne University Hospital (SUS), Sweden for perineal reconstruction: vertical rectus abdominis myocutaneous flap and gluteal flap with or without vaginal reconstruction. The objective was to study the long-term outcomes in patients treated for advanced pelvic cancer receiving a flap. Method: Patients with pelvic cancer subjected to surgery including perineal reconstruction between January 2010 and August 2016 at SUS were included retrospectively. Participating patients were scheduled for an out-patient visit. Questionnaires addressing quality of life, (QLQ-C30 and EQ-5D) and sexual function (FSFI and IIEF) were filled in. Sensitivity test, using monofilaments on the gluteal/posterior thigh area, neovaginal measurements using silicon gauges and muscular functionality tests (timed stands test and stairs test) were performed. Results: Thirty-six (24 women, 12 males) out of 71 invited patients conceded participation. Patients scored a median of 85/100 regarding global health using EQ-5D. All women reported sexual dysfunction and 75% (9/12) of men reported severe erectile dysfunction. Neovaginal measurements showed adequate reconstructions. Sensitivity test implied decreased sensitivity on the operated side compared to the unoperated side in patients with gluteal flap. Both physical tests demonstrated adequate muscular functionality in everyday life activities after reconstructions using gluteal flap. Conclusion: This long-term follow up after extensive surgery treating pelvic cancer with perineal flap reconstruction implies high quality of life, good muscular functionality and adequate neovaginal measurements. However sexual function is impaired among both sexes and sensitivity in the surgical area of the gluteal flap is decreased

Association of the oestrogen receptor beta with hormone status and prognosis in a cohort of female patients with colorectal cancer

Background The oestrogen receptor beta (ERβ) is the predominant oestrogen receptor in the normal colon mucosa and has been reported to exert anti-proliferative and pro-apoptotic effects. However, the role of ERβ in colorectal cancer (CRC) progression remains unclear. Aim To investigate the role of ERβ and its association with hormone status and lifestyle indicators in a female cohort of patients with CRC. Methods Tissue microarrays of primary CRC tumour samples from 320 female patients were conducted with a monoclonal anti-ERβ antibody. The staining intensity was evaluated using immunohistochemistry. The association of ERβ expression with overall survival, disease-free survival, hormone status and lifestyle was evaluated, and effect estimators with 95% confidence intervals (CIs) were reported. Results Among the 314 samples with successfully detected ERβ, 182 (58%) had low expression and 132 (42%) had high expression. The Cox multivariate analysis indicated that patients with high ERβ expression had a decreased risk of overall mortality by 50% (hazard ratio [HR], 0.50; CI, 0.30–0.83) and of cancer recurrence by 76% (HR, 0.24; CI, 0.11–0.52) after adjusting for age, tumour-node-metastasis stage and tumour intravascular invasion. Furthermore, high ERβ expression was significantly correlated with shorter breastfeeding time and longer use of hormone replacement therapy. No association was found between ERβ expression and lifestyle indicators. Conclusion Elevated ERβ expression is independently associated with a better prognosis and hormone status but not lifestyle indicators in female CRC patients