Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience.

AIM: Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. METHODS: All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. RESULTS: Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. CONCLUSION: In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

Fecal Calprotectin and Quality of Life Questionnaires Are Responsive to Change in Pouch Disease Activity After Antibiotic Therapy: Results From a Prospective Clinical Trial.

INTRODUCTION: Whether fecal calprotectin (FC) and quality of life (QoL) questionnaires reflect change in disease activity in patients with a J-pouch is unknown. METHODS: Patients with acute pouchitis were prospectively treated with a 2-week course of antibiotics. The full Pouchitis Disease Activity Index, FC, and QoL questionnaires were measured at baseline and after antibiotic therapy. RESULTS: Twenty patients were prospectively enrolled. After 2 weeks of antibiotic treatment, the Pouchitis Disease Activity Index decreased from a median of 9 to 5 ( P = 0.007). FC decreased from a median of 661 ug/g to 294 ug/g ( P = 0.02), and QoL questionnaires improved significantly. DISCUSSION: FC and QoL questionnaires reflect real-time changes in inflammatory pouch activity.

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. METHODS: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term "early metachronous metastases" applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with "late metachronous metastases" applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSIONS: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Implantation of an Impedance Sensor for Early Detection of Gastrointestinal Anastomotic Leaks.

INTRODUCTION: Accurate early diagnosis of a gastrointestinal anastomotic leak remains a challenge. When an anastomotic leak develops, the electrical properties of the tissue undergoing inflammatory processes change, resulting from the extravasation of inflammatory fluid and cellular infiltration. The method described here intends to provide a novel early anastomotic leak warning system based upon measurable changes in tissue impedance nearby an acute inflammatory process. METHODS: A biodegradable Mg-alloy was compared with a nonabsorbable stainless steel (STS) electrode connected to a wireless recording system for impedance measurement. In vitro measurements were made in physiological solutions and small animal (eight mice) and large animal (eight pigs) models with an anastomotic leak simulated by an open colotomy. Measurements were made at 10 mm intervals from the open colon at baseline and up to 120 min comparing these with a sutured colonic wound and normal tissue. RESULTS: In-vitro biodegradable magnesium electrode impedance evaluation showed good sensitivity to different media due to its environmental corrosion properties. The impedance of an acidic environment (1.06 ± 0.02 kΩ for citric acid) was twice that of phosphate-buffered saline (PBS) (0.64 ± 0.008 kΩ) with a distinction between Normal Saline (0.42 ± 0.013 kΩ) and PBS (0.64 ± 0.008 kΩ). This was in contrast to the performance characteristics of the control STS electrodes, where impedance in an acidic environment was lower than saline or PBS (citric acid:0.76 ± 0.01 kΩ versus PBS: 1.32 ± 0.014 kΩ). In a mouse model simulating an anastomotic leak, there was a significant increase in impedance after 120 min when compared with controls (99.7% increase versus 9.6% increase, respectively; P < 0.02). This effect was confirmed in a pig model when relative impedance measurements of the leak and control groups were compared (1.86 ± 0.46 versus 1.07 ± 0.02, respectively; P < 0.027). CONCLUSIONS: Electrophysiological measurement shows diagnostic sensitivity for a gastrointestinal leak with potential clinical utility in the postoperative detection of early intra-abdominal sepsis. Further investigation of biodegradable tissue sensors capable of monitoring an early anastomotic leak is required.

Comparison between laparoscopic and open Hartmann's reversal: results of a decade-long multicenter retrospective study.

BACKGROUND: Hartmann's reversal is a challenging surgical procedure with significant postoperative morbidity rates. Various surgical methods have been suggested to lower the risk of postoperative complications. In this study, we aimed to compare the postoperative results between open and laparoscopic techniques for Hartmann's reversal. METHODS: A retrospective study of all patients who underwent Hartmann's reversal in five centers in central Israel between January 2004 and June 2015 was conducted. Medical charts were reviewed, analyzing preoperative and operative parameters and short-term postoperative outcomes. RESULTS: 260 patients were included in the study. 76 patients were operated laparoscopically with a conversion rate of 26.3% (20 patients). No differences were found between patients operated laparoscopically and those operated in an open technique regarding gender (p = 0.785), age (61.34 vs. 62.64, p = 0.521), body mass index (26.6 vs. 26.2, p = 0.948), Charlson index score (1.79 vs. 1.95, p = 0.667), and cause for Hartmann's procedure (neoplastic vs. non-neoplastic, p = 0.644). No differences were seen in average time from the Hartmann's procedure to reversal (204.89 vs. 213.60 days, p = 0.688) and in overall complication rate (46.4 vs. 46.5%, p = 1). The Clavien-Dindo score for distinguishing between minor (0-2 score, p = 1) and major complications (3-5 score, p = 0.675) failed to demonstrate an advantage to laparoscopy, as well as to average length of stay (10.91 days in the laparoscopic group vs. 11.72 days in the open group, p = 0.529). An analysis based on the intention-to-treat with laparoscopy, including converted cases in the laparoscopic group, showed similar results, including overall complication rate (48.6 vs. 45.6%, p = 0.68) and Clavien-Dindo score in both minor (p = 0.24) and major complications (p = 0.44). Length of stay (10.92 vs. 11.81 days, p = 0.45) was also similar between the two groups. CONCLUSION: In this series, a laparoscopic approach to Hartmann's reversal did not offer any short-term advantage when compared to an open surgical approach.

Considerations for Hartmann's reversal and Hartmann's reversal outcomes-a multicenter study.

PURPOSE: Hartmann's procedure is commonly practiced in emergent cases with the restoration of bowel continuity planned at a second stage. This study assessed the rate of restorations following Hartmann's procedure and evaluated factors affecting decision-making. METHODS: Data on patient demographics, comorbidities, causes for Hartmann's procedure, reversal rate, and complications were collected in a multicenter retrospective cohort study of patients who underwent Hartmann's procedure in five medical centers. RESULTS: Six hundred forty patients underwent Hartmann's procedure for diverticular disease (36.1%), obstructing malignancy (31.8%), benign obstruction (5%), and other reasons (23.1%). Overall, 260 (40.6%) patients underwent subsequent restoration of bowel continuity. One hundred twenty-one (46.5%) patients had post-reversal complications, with an average Clavien-Dindo score of 1.4 and a mortality rate of 0.77%. Decision to avoid reversal was mostly related to comorbidities (49.7%) and metastatic disease (21.6%). Factors associated with the decision to restore bowel continuity included male gender (P = 0.02), patient age (62.3 years in Hartmann's reversal patients vs 73.5 years in non-reversal patients; P < 0.0001), number of comorbidities (1.1 vs 1.58; P < 0.001), average Charlson score (1.93 vs 3.44; P < 0.001), and a neoplastic etiology (P < 0.0001). A sub-analysis excluding all patients who died in the 30 days following Hartmann's procedure showed similar factors associated with ostomy closure. CONCLUSION: Many patients do not have restoration of bowel continuity after undergoing Hartmann's procedure. Hartmann's reversal is associated with a significant postoperative morbidity. Surgeons and patients should be aware of the possibility that the colostomy might become permanent.

Feasibility of an Intraluminal Bypass Device in Low Colorectal Anastomosis: Preliminary Results in a Porcine Model.

BACKGROUND: The Cologuard CG-100 is a novel intraluminal bypass device designed to reduce the clinical outcomes associated with low colorectal anastomotic leak. The device is inserted transanally, anchored to the colon above the anastomosis, and deployed intraluminally to cover the anastomosis from within. The purpose of this study was to evaluate the safety and performance of the device in a porcine model. METHOD: Twelve pigs underwent low colorectal anastomosis with insertion of the Cologuard CG-100 device. Contrast material injection, abdominal X-ray, and histologic studies were used to evaluate sealing quality, device positioning, and tissue damage, respectively. The surgeons completed a usability and satisfaction questionnaire after completion of the procedure. RESULTS: Absolute sealing was observed in all 4 animals euthanized immediately after surgery. In the other 8 animals, the device was kept in situ for 10 days and then extracted. X-ray films with injection of contrast material through a designated injection tube before device removal showed that the sheath and ring were correctly placed. No leak was demonstrated. There were no device-related adverse events, and no critical histological abnormalities were noted in the bowel area that was compressed by the device. The device was found to be easy to insert, position, and extract. CONCLUSION: The Cologuard CG-100 device efficiently reduced contact between fecal content and low colorectal anastomosis in a porcine model and is easily deployed and extracted. It holds promise for possible clinical use pending further studies.

Early detection of breast cancer using total biochemical analysis of peripheral blood components: a preliminary study.

BACKGROUND: Most of the blood tests aiming for breast cancer screening rely on quantification of a single or few biomarkers. The aim of this study was to evaluate the feasibility of detecting breast cancer by analyzing the total biochemical composition of plasma as well as peripheral blood mononuclear cells (PBMCs) using infrared spectroscopy. METHODS: Blood was collected from 29 patients with confirmed breast cancer and 30 controls with benign or no breast tumors, undergoing screening for breast cancer. PBMCs and plasma were isolated and dried on a zinc selenide slide and measured under a Fourier transform infrared (FTIR) microscope to obtain their infrared absorption spectra. Differences in the spectra of PBMCs and plasma between the groups were analyzed as well as the specific influence of the relevant pathological characteristics of the cancer patients. RESULTS: Several bands in the FTIR spectra of both blood components significantly distinguished patients with and without cancer. Employing feature extraction with quadratic discriminant analysis, a sensitivity of ~90 % and a specificity of ~80 % for breast cancer detection was achieved. These results were confirmed by Monte Carlo cross-validation. Further analysis of the cancer group revealed an influence of several clinical parameters, such as the involvement of lymph nodes, on the infrared spectra, with each blood component affected by different parameters. CONCLUSION: The present preliminary study suggests that FTIR spectroscopy of PBMCs and plasma is a potentially feasible and efficient tool for the early detection of breast neoplasms. An important application of our study is the distinction between benign lesions (considered as part of the non-cancer group) and malignant tumors thus reducing false positive results at screening. Furthermore, the correlation of specific spectral changes with clinical parameters of cancer patients indicates for possible contribution to diagnosis and prognosis.

Home electrical stimulation for women with fecal incontinence: a preliminary randomized controlled trial.

PURPOSE: The purpose of this study is to compare the effectiveness and cost of home electrical stimulation and standardized biofeedback training in females with fecal incontinence METHODS: Thirty-six females suffering from fecal incontinence were randomized into two groups, matched for mean age (67.45 ± 7.2 years), mean body mass index (kg/m2) (26.2 ± 3.9), mean disease duration (4.1 ± 0.8 years), mean number of births (2.7 ± 1.3), and reports of obstetric trauma (25%). Questionnaires were used to evaluate their demographics, medical, and childbearing history. Subjects were randomized to home electrical stimulation or standardized biofeedback training for a period of 6 weeks. Subjective outcome measures included the frequency of fecal, urine, and gas incontinence by visual analog scale, Vaizey incontinence score, and subjects' levels of fecal incontinence related anxiety. Objective outcome measures included pelvic floor muscle strength assessed by surface electromyography. We also compared the cost of each treatment modality. RESULTS: Only females who received home electrical stimulation (HES) reported a significant improvement in Vaizey incontinence score (p = 0.001), anxiety (p = 0.046), and in frequency of leaked solid stool (p = 0.013). A significant improvement in pelvic floor muscle strength was achieved by both groups. HES was much cheaper compared to the cost of standardized biofeedback training (SBT) (US $100 vs. US $220, respectively). Our study comprised a small female population, and the study endpoints did not include objective measures of anorectal function test, such as anorectal manometry, before and after treatment. CONCLUSIONS: Home electrical stimulation may offer an alternative to standardized biofeedback training as it is effective and generally well-tolerated therapy for females with fecal incontinence.

Comparison of Post-Operative Outcomes of Right Colectomy between Crohn's Disease and Adenocarcinoma of the Right Colon: A Retrospective Cohort Study.

(1) Background: Crohn's disease (CD) and right-sided colorectal-carcinoma (CRC) are two common indications for right colectomies. Many studies have tried to identify risk factors associated with post-operative complications for both CD and CRC. However, data directly comparing the outcomes of the two are sparse. This study aims to compare the 30-day post-operative outcome after a right colectomy for CD versus CRC. Its secondary aim is to identify the factors associated with these outcomes for each group. (2) Methods: A retrospective cohort study of 123 patients who underwent a right colectomy for CD or CRC in a single institution between March 2011 and March 2016. (3) Results: There were no significant differences between the groups when comparing the overall complication rate, the median Clavien-Dindo score, reoperation rates and the length of hospitalization. The leak rate was higher in the Crohn's group (13.95% (6/43) vs. 3.75% (3/80)), p = 0.049), although the stoma rate was the same (4/43 9.5%; 7/80 9.9%). (4) Conclusions: This study has shown that post-operative complication rate is similar for right colectomy in CD and CRC. However, Crohn's disease patients did have a higher leak rate.

Risk Factors for Rectal Cancer Recurrence after Local Excision of T1 Lesions from a Decade-Long Multicenter Retrospective Study.

Background: Local surgical excision of T1 rectal adenocarcinoma is a well-established approach. Yet, there are still open questions regarding the recurrence rates and its risk factors. Methods: A retrospective multicenter study including all patients who underwent local excision of early rectal cancer with an open or MIS approach and had a T1 lesion from 2010 to 2020 in six academic centers. Data included demographics, preoperative studies, surgical findings, postoperative outcomes, and local and systemic recurrence. A univariable and multivariable logistic regression analysis was performed to identify risk factors for recurrence. Results: Overall, 274 patients underwent local excision of rectal lesions. Of them, 97 (35.4%) patients with a T1 lesion were included in the cohort. The mean age was 69 ± 10.5 years, and 42 (43.3%) were female. The mean distance of the lesions from the anal verge was 7.8 ± 3.2 cm, and the average tumor size was 2.7 ± 1.6 cm. Eighty-two patients (85%) had a full-thickness resection. Eight patients (8%) had postoperative complications. Kikuchi classification of submucosal (SM) involvement was reported in 29 (30%) patients. Twelve patients had SM1, two SM2, and fifteen SM3. Following pathology, 24 patients (24.7%) returned for additional surgery or treatment. The overall recurrence rate was 14.4% (14 patients), with 11 patients having a local recurrence and 6 having a systemic metastatic recurrence, 3 of which had both. The mean time for recurrence was 2.78 ± 2.8 years and the overall mortality rate was 11%. On univariable and multivariable logistic regression analysis of recurrence vs. non-recurrence groups, the strongest and most significant association and possible risk factors for recurrence were larger lesions (4.3 vs. 2.5 cm, p < 0.001) with an OR of 6.67 (CI-1.82-24.36), especially for tumors larger than 3.5 cm, mucinous histology (14.3% vs. 1.2%, p = 0.004, OR of 14.02, CI-1.13-173.85), and involved margins (41.7% vs. 16.2%, p = 0.003, OR of 9.59, CI-2.14-43.07). The open transanal excision (TAE) approach was also identified as a possible significant risk factor in univariant analysis, while SM3 level penetration showed only a trend. Conclusion: Surgical local excision of T1 rectal malignancy is a safe and viable option. Still, one in four patients received additional treatment. There is an almost 15% chance for recurrence, especially in large tumors, mucinous histology, or involved margin cases. These high-risk patients might warrant additional intervention and stricter surveillance protocols.

Discordant effects of Janus kinases inhibition ex-vivo on inflammatory responses in colonic compared to ileal mucosa.

BACKGROUND & AIMS: Janus kinase (JAK) inhibitors are used for treating inflammatory bowel diseases (IBD). We aimed to identify molecular effects of JAK inhibition in human intestinal mucosa, considering IBD location and phenotype. METHODS: Colonic and ileal explants from patients with ulcerative colitis (UC), Crohn's disease (CD), and non-IBD controls (NC) were assessed for phosphorylated signal transducers and activators of transcription (p-STAT) levels and Inflammatory genes expression panel in response to ex-vivo JAK inhibitor (tofacitinib). Cytokine production by lamina propria lymphocytes in response to tofacitinib was assessed. Human intestinal organoids were used to investigate JAK inhibitors' effects on iNOS expression. RESULTS: Explants were collected from 68 patients (UC=20; CD=20; NC=28). p-STAT1\3\5 inhibition rates varied, being higher in colonic compared to ileal explants. p-STAT1\3 inhibition rates negatively correlated with CRP levels. While significant alterations in 120 of 255 inflammatory genes were observed in colonic explants, only 30 were observed in ileal NC explants. In colonic explants from UC, significant alterations were observed in 5 genes, including NOS2. JAK inhibition significantly decreased Th1\Th2\Th17-related cytokine production from lamina propria lymphocytes. Various JAK inhibitors reduced IFN-γ-induced increase in iNOS expression in organoids. CONCLUSIONS: Site-specific anti-inflammatory effect of JAK inhibition by tofacitinib was noticed, whereby the colon was more robustly affected than the ileum. Ex-vivo response to tofacitinib is individual. JAK inhibition may attenuate inflammation by decreasing iNOS expression. Ex-vivo mucosal platforms may be a valuable resource for studying personalized drug effects in patients with IBD.

Grading of complications and risk factor evaluation in laparoscopic colorectal surgery.

BACKGROUND: A grading system for postoperative complications is important for quality control and comparison among investigations. The objective of the current study was to evaluate complications associated with laparoscopic colorectal surgery according to a standardized grading system, and to examine risk factors associated with different complication grades. METHODS: Data of all patients who underwent elective laparoscopic colorectal surgery at two medical centers between September 2003 and January 2011 were collected prospectively. Complications were graded retrospectively into five categories based on a previously proposed grading system for colorectal operations. Age, gender, BMI, Charlson comorbidity score, indication for surgery, pathology site, conversion rate, learning curve, operative times, previous abdominal surgery, concurrent surgical procedures performed, and length of hospital stay were evaluated as risk factors and outcome measures for complications. RESULTS: A total of 501 patients were included in the study. Of them, 30.5 % suffered at least one complication and 6.5 % more than one. Complications that were mainly medical or surgical site infections requiring minor intervention (grades 1 and 2) occurred in 22.9 % of patients. Surgical complications requiring invasive interference (grades 3 and 4) occurred in 7.4 % of patients and mortality (grade 5) occurred in 0.2 % (1 patient). Length of hospital stay was directly related to complication grade. Average hospital stay was 6.8 ± 3.5, 10.5 ± 5.1, and 20.2 ± 12.3 days for patients with no complications, grade 1-2 complications, and grade 3-4 complications, respectively (p < 0.01). Minor complications (grades 1-2) were associated with conversion (p < 0.01), high Charlson score (p = 0.004), and additional surgical procedures (p = 0.04). Major complications (grades 3-4) were associated solely with conversion (p < 0.01) and rectal pathology (p < 0.01). CONCLUSION: This study demonstrates the use of a uniform grading system for complications in laparoscopic colorectal surgery. Conversion was found to be associated with all grades of complications.

Healing of ileocolic nitinol compression anastomosis: a novel porcine model of subtotal colectomy.

BACKGROUND: There are limited large animal models for the research of novel anastomotic technologies. Subtotal colectomy requires the anastomosis of relatively remote segments of the alimentary tract that are different anatomically, histologically, and pose significant physiological challenge. The quest for a foreign material-free anastomotic line reintroduced nitinol compression anastomosis into clinical use in the last decade. OBJECTIVE: To evaluate the safety, histological, and physiological parameters of side-to-side ileocolic nitinol compression anastomosis in a newly developed large animal model, mimicking the human subtotal colectomy. INTERVENTION: Resection of the entire spiral colon with an ileocolic side-to-side compression anastomosis in 12 animals, compared to resection of a short ileal segment in 6 animals. All anastomoses were constructed by using a novel nitinol-based compression device. The animals were followed up to 30 days postoperatively and were reoperated and sacrificed. RESULTS: All 12 animals underwent successful subtotal colectomy with side-to-side nitinol compression anastomosis. No signs of abdominal infection were found. The increase in the colectomized animals' bodyweight over the postoperative course was significantly lower and the animals presented with longer periods of diarrhea. The histopathology revealed minimal inflammation and foreign body reaction with good alignment of the bowel wall layers in both groups. The anastomotic line width was shown to be reduced during the healing course of the compression anastomoses. CONCLUSIONS: Side-to-side nitinol compression anastomosis is safe and demonstrates favorable functional and histopathological features. The porcine model of subtotal colectomy can be used for further research of novel anastomotic technologies.

Reduction in surgical site infections by localized administration with D-PLEX100 in patients with multiple risk factors undergoing colorectal surgery.

BACKGROUND: D-PLEX100 is a novel drug-eluting lipid polymer matrix that supplies a high, local concentration of doxycycline for approximately 30 days. The objective of this post-hoc analysis was to assess the efficacy of D-PLEX100 in preventing superficial and deep SSIs in patients with ≥2 risk factors. PATIENTS AND METHODS: A post-hoc analysis of a previously reported prospective randomized trial assessing D-PLEX100 plus Standard of Care (SOC) versus SOC alone in colorectal surgery was performed to assess SSI rate in patients with ≥2 risk factors. RESULTS: The overall incidence of SSI was significantly lower for the D-PLEX100 arm (9.9%) versus SOC (21%), p = 0.033. Patients with ≥2 risk factors, SSI incidence was 37.5% for SOC and 15.8% in D-PLEX100 treated patients. CONCLUSIONS: D-PLEX100 reduces the incidence of SSIs beyond benefits associated with SOC treatment alone and including patients with ≥2 risk factors. D-PLEX100 may be a promising addition to established SSI prophylaxis bundles.

Rectal Cancer following Local Excision of Rectal Adenomas with Low-Grade Dysplasia-A Multicenter Study.

Purpose: Rectal polyps with low-grade dysplasia (LGD) can be removed by local excision surgery (LE). It is unclear whether these lesions pose a higher risk for recurrence and cancer development and might warrant an early repeat rectal endoscopy. This study aims to assess the rectal cancer rate following local excision of LGD rectal lesions. Methods: A retrospective multicenter study including all patients that underwent LE for rectal polyps over a period of 11 years was conducted. Demographic, clinical, and surgical data of patients with LGD werecollected and analyzed. Results: Out of 274 patients that underwent LE of rectal lesions, 81 (30%) had a pathology of LGD. The mean patient age was 65 ± 11 years, and 52 (64%) were male. The mean distance from the anal verge was 7.2 ± 4.3 cm, and the average lesion was 3.2 ± 1.8 cm. Full thickness resection was achieved in 68 patients (84%), and four (5%) had involved margins for LGD. Nine patients (11%) had local recurrence and developed rectal cancer in an average time interval of 19.3 ± 14.5 months, with seven of them (78%) diagnosed less than two years after the initial LE. Seven of the nine patients were treated with another local excision, whilst one had a low anterior resection, and one was treated with radiation. The mean follow-up time was 25.3 ± 22.4 months. Conclusions: Locally resected rectal polyps with LGD may carry a significant risk of recurring and developing cancer within two years. This data suggests patients should have a closer surveillance protocol in place.

Human intestinal epithelial cells can internalize luminal fungi via LC3-associated phagocytosis.

Background: Intestinal epithelial cells (IECs) are the first to encounter luminal microorganisms and actively participate in intestinal immunity. We reported that IECs express the ß-glucan receptor Dectin-1, and respond to commensal fungi and ß-glucans. In phagocytes, Dectin-1 mediates LC3-associated phagocytosis (LAP) utilizing autophagy components to process extracellular cargo. Dectin-1 can mediate phagocytosis of ß-glucan-containing particles by non-phagocytic cells. We aimed to determine whether human IECs phagocytose ß-glucan-containing fungal particles via LAP. Methods: Colonic (n=18) and ileal (n=4) organoids from individuals undergoing bowel resection were grown as monolayers. Fluorescent-dye conjugated zymosan (ß-glucan particle), heat-killed- and UV inactivated C. albicans were applied to differentiated organoids and to human IEC lines. Confocal microscopy was used for live imaging and immuno-fluorescence. Quantification of phagocytosis was carried out with a fluorescence plate-reader. Results: zymosan and C. albicans particles were phagocytosed by monolayers of human colonic and ileal organoids and IEC lines. LAP was identified by LC3 and Rubicon recruitment to phagosomes and lysosomal processing of internalized particles was demonstrated by co-localization with lysosomal dyes and LAMP2. Phagocytosis was significantly diminished by blockade of Dectin-1, actin polymerization and NAPDH oxidases. Conclusions: Our results show that human IECs sense luminal fungal particles and internalize them via LAP. This novel mechanism of luminal sampling suggests that IECs may contribute to the maintenance of mucosal tolerance towards commensal fungi.

Escherichia coli Strains from Patients with Inflammatory Bowel Diseases have Disease-specific Genomic Adaptations.

BACKGROUND AND AIMS: Escherichia coli is over-abundant in the gut microbiome of patients with inflammatory bowel disease [IBD]. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages. METHODS: We investigated E. coli genomes from patients with ulcerative colitis [UC], Crohn's disease [CD] or a pouch, and healthy subjects. The majority of genomes were reconstructed from metagenomic samples, including newly sequenced faecal metagenomes. Clinical metadata were collected. Functional analysis at the gene and mutation level were performed and integrated with IBD phenotypes and biomarkers. RESULTS: Overall, 530 E. coli genomes were analysed. The E. coli B2 lineage was more prevalent in UC compared with other IBD phenotypes. Genomic metabolic capacities varied across E. coli lineages and IBD phenotypes. Host mucin utilisation enzymes were present in a single lineage and depleted in patients with a pouch, whereas those involved in inulin hydrolysis were enriched in patients with a pouch. E. coli strains from patients with UC were twice as likely to encode the genotoxic molecule colibactin than strains from patients with CD or a pouch. Strikingly, patients with a pouch showed the highest inferred E. coli growth rates, even in the presence of antibiotics. Faecal calprotectin did not correlate with the relative abundance of E. coli. Finally, we identified multiple IBD-specific non-synonymous mutations in E. coli genes encoding for bacterial cell envelope components. CONCLUSIONS: Comparative genomics indicates that E. coli is a commensal species adapted to the overactive mucosal immune milieu in IBD, rather than causing it. Our results reveal mutations that may lead to attenuated antigenicity in some E. coli strains.