Administration of probiotics to healthy volunteers: effects on reactivity of intestinal mucosa and systemic leukocytes.

BACKGROUND: Oral administration of health-promoting bacteria is increasingly used in clinical practise. These bacteria have anti-inflammatory characteristics and modulate the immune system without major reported side effects. The mechanisms of action are not yet fully defined. Our aim was to study systemic effects of probiotics by measurements of leukocytes as well as local effects on rectal mucosal biopsies after adding a standardized inflammatory stimulus in vitro. METHODS: Fourteen healthy subjects were randomized to receive 1010 colony forming units/day orally of the probiotic strain Lactiplantibacillus plantarum 299 (Lp299), n = 7, or Bifidobacterium infantis CURE21 (CURE21), n = 7, for six weeks. Rectal biopsies were taken before and after ingestion of either probiotic strain product, for stimulation in vitro with tumour necrosis factor alpha (TNF-α) at 10 and 100 ng/ml respectively up to 8 h. Blood tests were sampled before and after treatment. Lactate dehydrogenase (LDH) confirmed viable tissue. RESULTS: Composition of the intestinal microbiota was not changed. Systemic leukocytes decreased after administration of CURE21 (P<0.05) and Lp299 (P<0.01). Levels of the pro-inflammatory cytokine IL-6 in rectal mucosa after stimulation with TNF-α were attenuated after ingestion of Lp299. No effect was seen with CURE21. CONCLUSIONS: Administration of these probiotic strains to healthy humans show both a systemic and local reduction of inflammatory response by lowering leukocyte counts, and for Lp299 IL-6 levels in rectal mucosa. Probiotics may play an important role in the reduction of inflammatory responses expected after trauma during surgery or after pelvic irradiation. Trial registration Clinical Trials, registration number NCT01534572, retrospectively registered ( http://www.clinicaltrials.gov ).

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.

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 (ERß) 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 ERß in colorectal cancer (CRC) progression remains unclear. AIM: To investigate the role of ERß 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-ERß antibody. The staining intensity was evaluated using immunohistochemistry. The association of ERß 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 ERß, 182 (58%) had low expression and 132 (42%) had high expression. The Cox multivariate analysis indicated that patients with high ERß 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 ERß expression was significantly correlated with shorter breastfeeding time and longer use of hormone replacement therapy. No association was found between ERß expression and lifestyle indicators. CONCLUSION: Elevated ERß expression is independently associated with a better prognosis and hormone status but not lifestyle indicators in female CRC patients.

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.

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. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9014177329634352.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.