Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study.

BACKGROUND AND AIMS: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle-derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy. METHODS: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months. RESULTS: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. CONCLUSIONS: Injection of a high dose of autologous skeletal muscle-derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32).

Neoadjuvant chemoradiotherapy of rectal carcinoma : Baseline hematologic parameters influencing outcomes.

BACKGROUND: The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: From 2009-2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival). RESULTS: Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95 % CI 1.00-1.07); T downstaging (p = 0.006; OR 1.03, 95 % CI 1.01-1.05); N downstaging (p = 0.09; OR 1.02, 95 % CI 1.00-1.04); T or N downstaging (p = 0.007; OR 1.04, 95 % CI 1.01-1.07); T and N downstaging (p = 0.02; OR 1.02, 95 % CI 1.00-1.04); Hb and RBC were the most significant parameters influencing OS; PLT was a negative prognostic factor for OS and DFS (p = 0.008 for OS); an NLR value of 2.8 was associated with the greatest significance for OS (p = 0.03) and primary tumor downstaging (p = 0.02). CONCLUSION: Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma.

CT/MRI pelvimetry as a useful tool when selecting patients with rectal cancer for transanal total mesorectal excision.

BACKGROUND: The quality of a total mesorectal excision (TME) is one of the most important prognostic factors for local recurrence of rectal carcinoma. The aim of this study was to clarify the manner in which lesser pelvis dimensions affect the quality of TME via the transabdominal approach, while simultaneously defining the criteria for selecting patients most likely to have Grade 3 TME outcomes for a transanal approach using the TaTME technique. METHODS: An analysis from the registry was conducted using 93 of total 198 patients with rectal cancer of the mid- and lower third of the rectum who underwent: (1) a low anterior resection, (2) an ultra-low resection with coloanal anastomosis, or (3) an intersphincteric rectal resection, all with total mesorectal excision. The procedures were carried out at the Department of Surgery at the University Hospital Hradec Králové between 2011 and 2014. Rectal specimens were histopathologically examined according to a standardized protocol. Pelvimetry data were obtained using anteroposterior, transverse, and sagittal CT or MRI scans. RESULTS: A correlation was found between the quality of the TME and pelvimetry parameter A5, i.e., the angle between the longitudinal axis of the symphysis, and the lines between the symphysis and the promontory (R(2) = -0.327, p < 0.001). The ordinal regression method was used to identify parameters of the model describing levels of probability for TME quality. These relationships were described by equations that provide probability of the achievement of each grade of TME. CONCLUSION: The correlation described by obtained equations between pelvimetry parameters and the quality of TME represents a new tool for use in preoperative decision-making with regard to resection via the transanal approach (TaTME).

Analysis of Cumulative Fluid Balance Impact on the Stability of Gastrointestinal Tract Anastomosis.

Anastomotic leakage is a serious postoperative complication following a low anterior resection of rectum. Current research in colorectal surgery focuses on searching for techniques which could minimize the risk of leakage. The main objective of this study was to evaluate the impact of cumulative fluid balance on microcirculatory changes at the anastomotic site.This experimental study used 15 domestic pigs; all of the animals underwent rectal resection. Then the animals were divided into three groups and received IV crystalloids at various rates, i.e. 5 ml/kg/h; 10 ml/kg/h; and 20 ml/kg/h. Large bowel micro-perfusion was measured using laser Doppler flowmetry during and following the surgical procedure.The experiments were successfully performed in all 15 cases. No animal died during the procedure or during the follow-up. We found no differences in micro-perfusion of the bowel between the experimental groups during the surgical procedure and during the follow-up period after the surgery. A significant decrease in micro-perfusion was observed after the transection of the inferior mesenteric artery in all the groups; again, no differences between the groups were observed.We did not confirm the original hypothesis that excessive load of IV crystalloids during the surgery would have a negative effect on bowel micro-perfusion and thus a negative effect on the healing of the anastomosis. However, laser Doppler flowmetry was found to have high accuracy in measuring tissue microcirculation and has the potential to be used in clinical practice.

Guideline for the diagnosis and treatment of Faecal Incontinence-A UEG/ESCP/ESNM/ESPCG collaboration.

INTRODUCTION: The goal of this project was to create an up-to-date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g., general practitioners, surgeons, gastroenterologists, other healthcare workers) and any patients who are interested in information regarding the diagnosis and management of FI. METHODS: These guidelines have been created in cooperation with members from the United European Gastroenterology (UEG), European Society of Coloproctology (ESCP), European Society of Neurogastroenterology and Motility (ESNM) and the European Society for Primary Care Gastroenterology (ESPCG). These members made up the guideline development group (GDG). Additionally, a patient advisory board (PAB) was created to reflect and comment on the draft guidelines from a patient perspective. Relevant review questions were established by the GDG along with a set of outcomes most important for decision making. A systematic literature search was performed using these review questions and outcomes as a framework. For each predefined review question, the study or studies with the highest level of study design were included. If evidence of a higher-level study design was available, no lower level of evidence was sought or included. Data from the studies were extracted by two reviewers for each predefined important outcome within each review question. Where possible, forest plots were created. After summarising the results for each review question, a systematic quality assessment using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was performed. For each review question, we assessed the quality of evidence for every predetermined important outcome. After evidence review and quality assessment were completed, recommendations could be formulated. The wording used for each recommendation was dependent on the level of quality of evidence. Lower levels of evidence resulted in weaker recommendations and higher levels of evidence resulted in stronger recommendations. Recommendations were discussed within the GDG to reach consensus. RESULTS: These guidelines contain 45 recommendations on the classification, diagnosis and management of FI in adult patients. CONCLUSION: These multidisciplinary European guidelines provide an up-to-date comprehensive evidence-based framework with recommendations on the diagnosis and management of adult patients who suffer from FI.

High-frequency ultrasound probe sonography staging for colorectal neoplasia with superficial morphology: its utility and impact on patient management.

BACKGROUND: This prospective study aimed to evaluate the impact of high-frequency ultrasound probe sonography (HFUPS) staging on the management of patients with superficial colorectal neoplasia (SCN) as determined by the endoscopic characteristics of lesions. METHODS: Consecutive patients referred for endoscopic treatment of nonpedunculated SCN were enrolled in this study. A lesion was considered high risk if a depressed area or invasive pit pattern was present. The gold standard for final staging included histology from endoscopic or surgical resection. The impact on treatment was defined as any modification of the therapeutic algorithm based on the result of the HFUPS examination compared with that based on endoscopy alone. RESULTS: In this study, 48 lesions in 48 patients were evaluated. Of these, 28 (58%) were considered high risk, and the remaining 20 (42%) were regarded as low risk. A total of seven lesions (15%) that could not be examined with HFUPS and another non-neoplastic lesion were excluded from final analysis. For the remaining 40 lesions, the overall accuracy of the HFUPS examination to predict the correct T-stage was 90% (95% confidence interval [CI], 77-96%). The HFUPS examination had a positive impact on the treatment of 0 low-risk and 11 high-risk (42%) lesions. CONCLUSION: The impact of HFUPS on the treatment of SCN depends on their endoscopic characteristics. It is negligible for low-risk SCNs, and these lesions can be treated on the basis of their endoscopic appearance alone. Nevertheless, compared with endoscopy alone, HFUPS changed the subsequent therapeutic approach in a positive way for up to 42% of high-risk lesions, including those with a depressed component and an invasive pit pattern. These endoscopic features can therefore be recommended as the entry criteria for an HFUPS examination.

Gene Expression of Antioxidant Enzymes in the Resected Intestine in Crohn's Disease.

INTRODUCTION: The inflammatory process in Crohn's disease (CD) is closely associated with the formation of reactive oxygen species. Antioxidant enzymes can play an important role in the outcome of CD and may influence postoperative recurrence in these patients. The aim of our study was to evaluate gene expression of intracellular antioxidant enzymes in surgically resected intestinal specimens of patients with CD, both in macroscopically normal and in inflamed tissue. METHODS: A total of 28 patients referred for elective bowel resection were enrolled in the study. Full-thickness small intestinal specimens were investigated. Gene expression of antioxidant enzymes - superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GSR) - was evaluated both in macroscopically normal and inflamed samples. RESULTS: There were significantly lower levels of SOD1 mRNA (p = 0.007) and GSR mRNA (p = 0.027) in inflamed tissue compared to macroscopically normal areas. No significant differences were found between affected and non-affected intestinal segments in mRNA for SOD2, SOD3 and GPX. CONCLUSIONS: Our pilot data clearly showed that the gene expression of major antioxidant enzymes is not a uniform mechanism in the pathogenesis of Crohn's disease. Topically decreased gene expression of SOD1 and GSR might facilitate the segmental tissue injury caused by reactive oxygen species.

Neopterin, kynurenine and tryptophan as new biomarkers for early detection of rectal anastomotic leakage.

INTRODUCTION: At present, there are no strong predictors, nor a useful scoring system, that clearly identifies patients at risk for anastomotic leakage. AIM: This study aimed to investigate a new method that assesses this risk by monitoring levels of neopterin, tryptophan, and kynurenine, in bodily fluids. MATERIAL AND METHODS: This prospective study included patients who underwent elective rectal resection for carcinoma. The basic condition for inclusion was rectal anastomosis using the double-stapling technique. Preoperative levels of neopterin, tryptophan, kynurenine, and their ratios, were assessed with blood and urine samples. These levels were then monitored for 6 postoperative days in venous blood, urine, and abdominal drainage fluid. RESULTS: A total of 42 patients were enrolled in the study. Thirty-six patients underwent a laparoscopic resection and 6 patients had an open procedure. No differences were found among neopterin, tryptophan, and kynurenine serum levels. However, the groups were observed to have significant differences in the urinary neopterin/creatinine ratio: the preoperative neopterin/creatinine ratio was 139.5 µmol/mol in the group with leakage, vs 114.8 µmol/mol in the group without complications, p = 0.037. The same results were observed during the postoperative period, p = 0.012. Additionally, the group with complications had a higher mean value of neopterin in drainage fluid, p = 0.048. CONCLUSIONS: Our study demonstrated that high preoperative levels of urinary neopterin could be interpreted as a risk for anastomotic leakage. Moreover, pathological levels of neopterin in urine and abdominal drainage fluid could be useful for early identification of anastomotic leakage during the postoperative period prior to its clinical development.

Enterocolic lymphocytic phlebitis as a newly recognized manifestation of IgG4-related disease.

Herein we present a case of a 65-year-old woman with enterocolic lymphocytic phlebitis (ELP) who presented with anemic syndrome and in whom severe stenosis of the right flexure of large bowel was detected. The microscopic examination revealed fibrosis of the submucosa and lymphoplasmacytic phlebitis of small veins and venules, whereas arteries were spared. There were 110 IgG4-positive and 160 IgG-positive plasma cells in 1 high-power field, respectively, with corresponding IgG4/IgG ratio of 0.69. The IgG4 serum level was 2.42 g/L. According to the currently proposed criteria, this ELP case is the first that may be diagnosed as definite IgG4-related disease (IgG4-RD). Although based on the sole case description, taken together with a recent review and a case report, we presume that a subset of ELPs is a manifestation of IgG4-RD.

Laparoscopic radical prostatectomy and resection of rectum performed together: first experience.

INTRODUCTION: Laparoscopy is an increasingly used approach in the surgical treatment of rectal cancer and prostate cancer. The anatomical proximity of the two organs is the main reason to consider performing both procedures simultaneously. AIM: To present our first experience of laparoscopic rectal resection and radical prostatectomy, performed simultaneously, in 3 patients. MATERIAL AND METHODS: The first patient was diagnosed with locally advanced rectal cancer and tumor infiltration of the prostate and seminal vesicles. The other 2 patients were diagnosed with tumor duplicity. The surgery of the first patient started with laparoscopic prostatectomy except division of the prostate from the rectal wall. The next step was resection of the rectum, extralevator amputation of the rectum and vesicourethral anastomosis. In the other patients, resection of the rectum, followed by radical prostatectomy, was performed. RESULTS: The median follow-up was 12 months. The median operation time was 4 h 40 min, with blood loss of 300 ml. The operations and postoperative course were without incident in the case of 2 patients. However, 1 patient had stercoral peritonitis and a vesicorectal fistula in the early postoperative stage. Sigmoidostomy and postponed ureteroileal conduit were carried out. All patients were in oncologic remission. CONCLUSIONS: Combined laparoscopic rectal resection and radical prostatectomy is a viable option for selected patients with locally advanced rectal cancer or tumor duplication. The procedures were completed without complications in 2 out of 3 patients.

Higher risk of incomplete mesorectal excision and positive circumferential margin in low rectal cancer regardless of surgical technique.

INTRODUCTION: Currently, the predominant question is whether a laparoscopic approach is comparatively radical in comparison with an open access approach, especially in the circumferential resection margin and quality of the completeness of total mesorectal excision. These factors are important in determining the quality of surgical care as well as long-term results of the treatment. AIM: This article focuses on the evaluation of circumferential resection margins and on the quality of mesorectal excision of middle and lower rectum tumors. In addition, laparoscopic and open techniques are compared. MATERIAL AND METHODS: Data were collected prospectively and stored in a rectal cancer registry over a 3-year period. The parameters studied were age, sex, body mass index, localization and topography of the tumor, clinical stage, neoadjuvant chemotherapy and its response, the type of surgery, character of the circumferential and distal margins, quality of the mesorectal excision, pT and pN. RESULTS: One hundred and twenty-five patients were chosen for our study. Laparoscopy was performed in 53 operations and a conventional approach was performed in 72 operations. Complete mesorectal excision was achieved in 54.7% of laparoscopic operations versus 44.4% in the conventional technique; partially complete excision was performed in 20.8 and 12.5%, respectively. Incomplete excisions were described in 24.5 and 43.1% (p = 0.085). Positive circumferential margin occurred during laparoscopic surgery in 11 (20.8%) patients, and in the case of conventional resection in 27 (37.5%) patients (p = 0.044). CONCLUSIONS: Our study showed comparable results between laparoscopic and open access procedures during rectal resection. The results achieved, in particular in the quality of the mesorectal excision and negative circumferential resection margin, show that the laparoscopic approach is comparable to conventional surgical techniques, with an adequate surgical outcome, in the treatment of rectal cancer.

Guideline for the diagnosis and treatment of faecal incontinence: a UEG/ESCP/ESNM/ESPCG collaboration [Pré-print]

The goal of this project was to create an up-to-date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g., general practitioners, surgeons, gastroenterologists, other healthcare workers) and any patients who are interested in information regarding the diagnosis and management of FI. These guidelines have been created in cooperation with members from the United European Gastroenterology (UEG), European Society of Coloproctology (ESCP), European Society of Neurogastroenterology and Motility (ESNM) and the European Society for Primary Care Gastroenterology (ESPCG). These members made up the guideline development group (GDG). Additionally, a patient advisory board (PAB) was created to reflect and comment on the draft guidelines from a patient perspective. Relevant review questions were established by the GDG along with a set of outcomes most important for decision making. A systematic literature search was performed using these review questions and outcomes as a framework. For each predefined review question, the study or studies with the highest level of study design were included. If evidence of a higher-level study design was available, no lower level of evidence was sought or included. Data from the studies were extracted by two reviewers for each predefined important outcome within each review question. Where possible, forest plots were created. After summarising the results for each review question, a systematic quality assessment using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was performed. For each review question, we assessed the quality of evidence for every predetermined important outcome. After evidence review and quality assessment were completed, recommendations could be formulated. The wording used for each recommendation was dependent on the level of quality of evidence. Lower levels of evidence resulted in weaker recommendations and higher levels of evidence resulted in stronger recommendations. Recommendations were discussed within the GDG to reach consensus. These guidelines contain 45 recommendations on the classification, diagnosis and management of FI in adult patients. These multidisciplinary European guidelines provide an up-to-date comprehensive evidence-based framework with recommendations on the diagnosis and management of adult patients who suffer from FI.