Michele Carvello

Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer.

Background Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients. Methods Circulating levels of the inflammatory cytokines IL-1, IL-6, IL-10, TNFalpha, CCL2, CXCL8, VEGF and the acute phase protein Pentraxin-3 were measured by ELISA in preoperative serum samples prospectively collected from a cohort of sixty-nine patients undergoing surgical resection for stage 0–IV CRC and associated with post-operative disease recurrence. Results Cox multivariate analysis showed that combined high levels (≥ROC cut off-value) of CXCL8, VEGF and Pentraxin3 were associated with increased risk of disease recurrence [HR: 14.28; 95%CI: (3.13–65.1)] independently of TNM staging. Kaplan-Meier analysis showed that CXCL8, VEGF and Pentraxin3 levels were significantly associated with worse survival (P<0.001). Conclusions Circulating inflammatory mediators efficiently predicted postoperative recurrence after CRC surgery. Therefore, this study suggest that their validation in large-scale clinical trials may help in tailoring CRC post-surgical management.

MFSD2A Promotes Endothelial Generation of Inflammation-resolving Lipid Mediators and Reduces Colitis in Mice

BACKGROUND & AIMSnAlterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation.nnnMETHODSnWe performed lipidomic and functional analyses of MFSD2A in mucosal biopsies and primary human intestinal microvascular endothelial cells (HIMECs) isolated from surgical specimens from patients with active, resolving UC and healthy individuals without UC (controls). MFSD2A was knocked down in HIMECs with small hairpin RNAs or overexpressed from a lentiviral vector. Human circulating endothelial progenitor cells that overexpress MFSD2A were transferred to CD1 nude mice with dextran sodium sulfate-induced colitis, with or without oral administration of DHA.nnnRESULTSnColonic biopsies from patients with UC had reduced levels of inflammation-resolving DHA-derived epoxy metabolites compared to healthy colon tissues or tissues with resolution of inflammation. Production of these metabolites by HIMECs required MFSD2A, which is required for DHA retention and metabolism in the gut vasculature. In mice with colitis, transplanted endothelial progenitor cells that overexpressed MFSD2A not only localized to the inflamed mucosa but also restored the ability of the endothelium to resolve intestinal inflammation, compared with mice with colitis that did not receive MFSD2A-overexpressing endothelial progenitors.nnnCONCLUSIONSnLevels of DHA-derived epoxides are lower in colon tissues from patients with UC than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that overexpress MFSD2A reduce colitis in mice. This pathway might be induced to resolve intestinal inflammation in patients with colitis.

First experience in colorectal surgery with a new robotic platform with haptic feedback

The use of robotic techniques in colorectal surgery is increasing. Recently, the Senhance™ surgical robotic system was introduced as a novel robotic platform designed to overcome some of the limits of standard laparoscopy. This study describes the initial, single‐center experience, evaluating feasibility and safety of the new robotic system in performing colorectal surgical procedures.

Psychological Perspectives of Inflammatory Bowel Disease Patients Undergoing Surgery: Rightful Concerns and Preconceptions

Surgery has been associated with variable effect on the quality of life of inflammatory bowel disease (IBD) patients, depending on clinical patterns and baseline disease characteristics. However, surgical treatment is often conceived by these patients with distress and considered as the failure of their therapies. Lack of control, risk of complications, defacement of the body image, need of ostomy and hospitalization may be triggering concerns leading to anguish and anxiety. Even though the quality of life in most cases generally improves after surgery, some particular aspects such as sexual activity, bowel movements and the ability to deal with a possible stoma may present a slower amelioration trend. These problems represent common causes of distress and may lead to an heightened risk of depression and anxiety with respect to background population. The psychological impact and apprehension surrounding surgery will be discussed in this review. Pros and cons of the surgical treatment in various IBD populations and its long-term sequelae in terms of quality of life and psychological well-being will be highlighted. Furthermore the tools to encompass these issues such as complete patient information, gastroenterologist/surgeon synergy and psychological counseling will be explored analyzing their respective roles.

Single port laparoscopic ileocaecal resection for Crohn's disease: a multicentre comparison with multi-port laparoscopy

Single port (SP) ileocaecal resection (ICR) is an established technique but there are no large studies comparing SP and multi‐port (MP) laparoscopic surgery in Crohns disease (CD). The aim of this study was to compare postoperative pain scores and analgesia requirements after SP and MP laparoscopic ICR for CD.

Suprapubic single port ileocaecal resection for complicated Crohn's disease: a video vignette

Laparoscopic surgery in patients with complex Crohns disease (CD) can be technically challenging and often necessitates the use of multiple ports or conversion. 1, 2, 3 n nIn this video, we demonstrate our suprapubic single port (SPSP) technique for ileocecal resection (ICR) in a patient with a complex pelvic mass. n nThis article is protected by copyright. All rights reserved.

Fluorescence angiography during transanal trans-stomal proctectomy and ileal pouch anal anastomosis - a video vignette

Indocanine green (ICG) fluorescence is able to assess in vivo tissue perfusion. This technique has been validated in colorectal surgery and provides, by real time angiography, the evaluation of bowel perfusion before anastomosis[1]. This video shows the usefulness of ICG fluorescence application in ileal pouch anal surgery. This article is protected by copyright. All rights reserved.

Correction: Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer

[This corrects the article DOI: 10.1371/journal.pone.0148186.].

Refractory distal ulcerative colitis: is proctocolectomy always necessary?

Refractory distal ulcerative colitis (RDUC) is defined as persistence of symptoms caused by endoscopically proven colonic inflammation located at the rectum or left colon despite oral/topical steroids and 5-ASA. RDUC affects a small subset of patients and is associated with chronic disabling symptoms and increased social/medical costs. Moreover, patients with long-standing ulcerative colitis (UC) carry an elevated risk of developing colorectal cancer and colonic mucosa high-grade dysplasia. Alternative medical strategies in steroid refractory disease are unlikely to provide durable remission in all patients, carry potential severe side effects and, as immunosuppressants, the risk of other neoplasms, and may increase the short-term complication rate when surgery is finally required. Restorative proctocolectomy with ileal pouch-anal anastomosis (RP-IPAA) allows the complete removal of the diseased rectum and colon, virtually eliminating the risk of malignant transformation and reestablishing intestinal continuity with continence preservation. Since the introduction of this surgical procedure, morbidity and mortality rates have been drastically reduced. Despite the still notable rate of surgical complications, long-term quality of life assessment has shown excellent results in nearly all patients who have undergone RP-IPAA, comparing well with the general population. Furthermore, when performed for distal UC, RP-IPAA produces similar surgical outcomes with respect to pancolitis. In conclusion, RP-IPAA should always be considered in patients with RDUC, and multidisciplinary counseling should provide patients clear information about the advantages of surgery and possible complications as well as the chance to achieve disease remission with medical therapy.