Summary
Summary
Barrett's oesophagus (BO) and gastro‐oesophageal reflux disease (GERD) are precursors of oesophageal adenocarcinoma (OAC). There is an oesophageal biofilm, which changes in disease, ...but its role in aetiopathogenesis remains unclear.
Aim
To define the oesophageal microbiota of patients with GERD, BO and OAC compared with controls and to investigate mucosal responses related to the microbiota.
Methods
Cultural analysis identified the dominant bacterial species from a subset of each disease group. Based on this, molecular techniques were used to define the cohort. Host responses were analysed in tissues and co‐culture experiments.
Results
A total of 111 species belonging to 26 genera were isolated. There was a significant decrease in bacterial counts in the GERD and BO groups for all genera except Campylobacter, which colonised GERD and Barrett's patients in increasing numbers. Campylobacter concisus was the dominant species. This relationship was not seen in the cancer group. Significant increases in IL‐18 were seen in GERD and BO colonised by Campylobacter.
Conclusions
This study defines differences in the oesophageal biofilm in disease states, revealing the emergence of C. concisus as the dominant new colonist in the refluxed oesophagus. We also associate the presence of these bacteria with increased expression of cytokines related to carcinogenesis.
Aliment Pharmacol Ther 2010; 32: 872–883
Summary
Background Crohn’s disease is an inflammatory illness in which the immune response against gut microorganisms is believed to drive an abnormal immune ...response. Consequently, modification of mucosal bacterial communities, and the immune effects they elicit, might be used to modify the disease state.
Aim To investigate the effects of synbiotic consumption on disease processes in patients with Crohn's disease.
Methods A randomized, double‐blind placebo‐controlled trial was conducted involving 35 patients with active Crohn's disease, using a synbiotic comprising Bifidobacterium longum and Synergy 1. Clinical status was scored and rectal biopsies were collected at the start, and at 3‐ and 6‐month intervals. Transcription levels of immune markers and mucosal bacterial 16S rRNA gene copy numbers were quantified using real‐time PCR.
Results Significant improvements in clinical outcomes occurred with synbiotic consumption, with reductions in both Crohn's disease activity indices (P = 0.020) and histological scores (P = 0.018). The synbiotic had little effect on mucosal IL‐18, INF‐γ and IL‐1β; however, significant reductions occurred in TNF‐α expression in synbiotic patients at 3 months (P = 0.041), although not at 6 months. Mucosal bifidobacteria proliferated in synbiotic patients.
Conclusion Synbiotic consumption was effective in improving clinical symptoms in patients with active Crohn's disease.
Most studies involving prebiotic oligosaccharides have been carried out using inulin and its fructo-oligosaccharide (FOS) derivatives, together with various forms of galacto-oligosaccharides (GOS). ...Although many intestinal bacteria are able to grow on these carbohydrates, most investigations have demonstrated that the growth of bifidobacteria, and to a lesser degree lactobacilli, is particularly favoured. Because of their safety, stability, organoleptic properties, resistance to digestion in the upper bowel and fermentability in the colon, as well as their abilities to promote the growth of beneficial bacteria in the gut, these prebiotics are being increasingly incorporated into the Western diet. Inulin-derived oligosaccharides and GOS are mildly laxative, but can result in flatulence and osmotic diarrhoea if taken in large amounts. However, their effects on large bowel habit are relatively minor. Although the literature dealing with the health significance of prebiotics is not as extensive as that concerning probiotics, considerable evidence has accrued showing that consumption of GOS and FOS can have significant health benefits, particularly in relation to their putative anti-cancer properties, influence on mineral absorption, lipid metabolism, and anti-inflammatory and other immune effects such as atopic disease. In many instances, prebiotics seem to be more effective when used as part of a synbiotic combination.
Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has ...been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system.
We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics.
We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = 21.7% - 39.9%, p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636).
Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.
•Implementation of ERAS gynecologic oncology guidelines results in significant clinical improvements and cost savings.•Use of an audit system allows measurement of compliance to the individual ERAS recommendations.•ERAS teams should strive to improve compliance to guidelines as this translates into improved outcomes.
Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal ...microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is no clear evidence for a single transmissible agent being involved in IBD aetiology. Although marked alterations occur in faecal and mucosal bacterial communities in IBD, it is unclear whether they are responsible for causing disease, or are due to changes in the gut environment that result from inflammatory reactions and extensive tissue destruction. Despite the involvement of microorganisms in inflammatory processes, antibiotic therapy has generally been unsuccessful in IBD. However, recent studies involving the use of probiotics, prebiotics and synbiotics suggest that there is potential for controlling these diseases through manipulation of the composition of the gut microbiota, and direct interactions with the gut immune system.
Objectives. The aim of this study was to compare peri-operative morbidity and recurrence-free survival of early-stage cervical cancer patients treated by laparoscopic-assisted radical vaginal ...hysterectomy (LARVH) with time-matched radical abdominal hysterectomy (RAH) controls at our center.
Methods. Since July 1984, all patients with FIGO stage IA/IB cervical cancer undergoing radical surgery by members of our division have been entered into a prospective database. Since November 1996, one surgeon at our center has performed LARVH on all surgically appropriate patients. Non-parametric tests were used. Differences between medians were compared using Wilcoxon Rank Sum test. Statistical analysis used the Kaplan–Meier method to calculate disease-free survival. Differences between survival curves were compared with the log rank test. Statistical significance was defined as
P < 0.05.
Results. Between November 1996 and December 2003, 71 and 205 patients have undergone LARVH and RAH, respectively, for FIGO stage IA/IB carcinoma of the cervix. Both groups were similar with respect to age and Quetelet index. There were no differences in tumor size, histology, grade, depth of invasion, lymph node metastases, or surgical margins. All laparoscopic procedures were completed successfully with no conversions to laparotomy. Intra-operative morbidity characteristics analyzed (LARVH vs. RAH) were blood loss 300 ml vs. 500 ml (
P < 0.001), operative time 3.5 h vs. 2.5 h (
P < 0.001), and intra-operative complications 13% vs. 4% (
P < 0.03). Intra-operative complications in the LARVH group included: cystotomy (7), ureteric injury (1), and bowel injury (1). There was no difference in transfusion rates. There was no difference between post-operative infectious and non-infectious complications (LARVH vs. RAH), 9% vs. 5% and 5% vs. 2%, respectively. The median time to normal urine residual was 10 days vs. 5 days (
P < 0.001), and the median length of hospital stay was 1 day vs. 5 days (
P < 0.001). Twenty-two percent of patients received post-operative radiotherapy for high-risk features in both groups. After a median follow-up of 17 and 21 months, there have been 4 recurrences in the LARVH group and 13 in the RAH (
P = NS). The overall 2-year recurrence-free survival was 94% and 94% in the LARVH and RAH groups, respectively (
P = NS).
Conclusion. Our data demonstrate that early cervical cancer can be treated successfully with LARVH with similar efficacy and recurrence rates to RAH. The major benefits are less intra-operative blood loss and shorter hospital stay. It is a safe procedure with low overall morbidity and complication rates. However, at present, LARVH is associated with an increase in intra-operative complications, and patients may have an increased time to return to normal bladder function.
Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the ...United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product.
Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days.
Clinical response was 83·9% (95% CI 76·0%–90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%–89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups.
The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.
To determine the incidence of parametrial involvement in clinical stage IA and IB1 cervical cancer and whether pelvic lymph node status is a predictor of parametrial status.
Retrospective review of ...120 patients with FIGO stage IA/IB1 cervical carcinoma treated by class II radical abdominal hysterectomy between January 1997 and December 2001 was performed. The parametria were examined for microscopic involvement of parametrial lymph nodes and/or tissue. Continuous variables were compared using Wilcoxon rank sum test, and Fisher's exact test was used to categorical variables. Kaplan–Meier curves were constructed for overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards model was used to investigate prognostic factors.
One hundred ten patients were eligible. Five patients (5%) had positive parametria and 13 patients (12%) had positive pelvic lymph nodes. Four (80%) patients with positive parametria had positive pelvic lymph nodes. The groups did not differ significantly in terms of age (
P = 0.92), histology (
P = 0.15), or LVSI (
P = 0.20). Positive parametria was associated with larger tumor size (3.0 vs. 2.0 cm,
P < 0.05), greater depth of invasion (16 mm vs. 5 mm,
P = 0.03), and pelvic lymph node metastases (80% vs. 10%,
P = 0.001). The only variable that was significant in the proportional hazards model was lymph node status (
P = 0.02). After median follow-up of 48 months, there was a significant difference in recurrence (40% vs. 4%,
P = 0.03) and RFS (0.0003).
Acknowledging small sample size and retrospective study, positive parametrial involvement in stage IA and IB1 cervical cancer is infrequent. There is a significant association with lymph node status. Thus, there may be a role for less radical surgery combined with pelvic lymphadenectomy in this patient population.
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