Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism.

Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.

Single center experience with salvage surgery for chronic pelvic sepsis.

Chronic pelvic sepsis eventually requires salvage surgery in half of all patients. The goal of surgery is to resolve pelvic inflammation while restoring intestinal continuity. Our salvage procedure achieves this by bringing a healthy conduit into the pelvis and creating an anastomosis beyond the source of sepsis. We aimed to review our single center experience with this procedure for the treatment of chronic pelvic sepsis. All patients requiring the procedure from 2010 to 2018 were retrospectively reviewed using a prospective database. Morbidity and mortality were evaluated, and restoration of bowel continuity at 1-year rate was the endpoint. Twenty patients were included. The main indication was pelvic sepsis after anastomotic leak (AL). The median age was 60 (42-86) years and the median BMI was 26 (18-37) kg/m2. The median time carrying a stoma before the intervention was 15 months, and median time to intervention was 32 months. All patients had a diverting stoma. There were no death and overall morbidity reached 60%, and AL rate was 10%. At 1 year, 70% of the patients had their intestinal continuity restored. In expert hands, salvage surgery for chronic pelvic sepsis has acceptable morbidity rates, an acceptable rate of AL, and a bowel restoration success rate 70% at 1 year, and is a valuable option for patients failing conservative treatment.

Para-anal lipoma as a rare consequence to perineal trauma. Case-report and review of the literature.

Introduction: Lipomas are the most common benign mesenchymal tumors which can be found in any part of the body. Nevertheless, their etiology and pathogenesis remain unknown. It is hypothesized that some of these lesions could result from an acute or chronic trauma. Patients and methods: We report a case of a 54-year-old man presenting a perineal lipoma which volume grew rapidly after he fell on his buttock, in the context of inaugural epileptic seizure. Pelvic MRI showed a voluminous fatty mass, measuring 6.6 × 5 × 9 cm without any signs of local invasion. Furthermore, we review the latest research on lipomas originating from traumatic lesion. Results: The mass was completely excised in one block under general anesthaesia, using an elliptical incision and a deep dissection. We did not close the skin incision in view of the cutaneous defect. Post-operative recovery was uneventful and the patient was discharged from hospital two days after the operation. Histopathology indicated a reorganised lipoma with no evidence of malignancy. Conclusion: Perineal lipomas are extremely rare, pathological examination of imaging guided biopsies are needed to exclude malignancy especially a well-differentiated liposarcoma. MRI remains the first option and radical surgical excision is the gold standard treatment.

Day Surgery for Acute Appendicitis in Adults: A Prospective Series of 102 Patients.

AIM: To report the results of a consecutive series of day surgery appendectomy (DSA) for acute appendicitis. METHODS: Selection criteria for DSA were as follows: body mass index<28 kg/m, white cell count <15,000/mL, C-reactive protein<30 mg/L, no radiological signs of perforation, and appendix diameter ≤10 mm. All patients with radiologically proven appendicitis and 4 or 5 criteria were proposed for DSA and prospectively included. RESULTS: A total of 102 patients (female=39.2%) were operated between January 1, 2013 and January 5, 2015 with a median age of 29.5 years [interquartile range (IQR), 23 to 37 y]. Diagnosis was mainly supported by computed tomographic scan (75.5%). About 60 patients (59%) were reconvened on the next morning for surgery with oral antibiotics. The median operative time was 40 minutes (IQR, 30 to 52 min), and 92 (90%) patients were discharged on day 0 after a postoperative period of 5h:12min (IQR, 4h:14min to 6h:33min). The overall median hospital length of stay was 8h:04min (IQR, 6h:46min to 10h:23min). Surgical morbidity was 6.9% (n=7), with 1.9% (n=2) major complications. CONCLUSIONS: DSA is a safe procedure for selected patients; it reduces the hospital length of stay without increasing morbidity.

Novel insight into the role of microbiota in colorectal surgery.

Recent literature undeniably supports the idea that the microbiota has a strong influence on the healing process of an intestinal anastomosis. Understanding the mechanisms by which the bacterial community of the gut influences intestinal healing could open the door for new preventive and therapeutic approaches. Among the different mechanisms, data have shown that the production of specific reactive oxygen species (ROS) and the activation of specific formyl peptide receptors (FPRs) regulate intestinal wound healing. Evidence suggests that specific gut microbes such as Lactobacillus spp and Akkermansia muciniphila help to regulate healing processes through both ROS-dependent and FPR-dependent mechanisms. In this review, we will discuss the current knowledge and future perspectives concerning the impact of microbiota on wound healing. We will further review available evidence on whether mechanical bowel preparation and the use of specific antibiotics are beneficial or harmful procedures, an ongoing matter of debate. These practices have a profound effect on the gut microbiota composition at the level of both the mucosal and the luminal compartments. Therefore, a key question remains unanswered: should we continue to prepare the gut before surgical intervention? Current knowledge and data do not clearly support the use of one technique or another to avoid complications such as anastomotic leak. There is an urgent need for appropriate interventions with a deep microbiota analysis to investigate both the surgical technical benefits of a proper anastomosis compared with the potential effect of the gut microbes (beneficial vs harmful) on the processes of wound healing and anastomotic leakage reduction.

Reconstruction of an abdominal wall defect with biologic mesh after resection of a desmoid tumor in a patient with a Gardner's syndrome.

INTRODUCTION: Desmoid tumors are rare proliferative and invasive benign lesions. They can be sporadic, but in most instances, desmoid tumors develop in the context of Gardner's syndrome with principal localization in the abdominal cavity and abdominal wall. CASE-REPORT: We report the case of a 24-year-old female presenting Gardner's syndrome with a symptomatic abdominal wall desmoid tumor. Lack of response to medical treatment led to surgical management consisting in a complete resection and parietal reconstruction with a biologic mesh. Postoperative course was uneventful and there was no evidence of recurrence at 12 months of follow-up. DISCUSSION: Conventional treatment of abdominal wall desmoid tumors consists in a wide and radical resection. However, complete resection is not always feasible because of difficulty to differentiate the desmoid tumor from adjacent tissues. The surgical approach may require different techniques to repair the parietal defect including prosthetic material such as synthetic or biologic meshes. Biological mesh is an ideal alternative to synthetic graft, mainly in case of infection. CONCLUSION: We have encountered a case of a symptomatic growing desmoid tumor of the abdominal wall in a young patient with Gardner's syndrome, successfully treated by complete resection and reconstruction with a biologic mesh to correct the parietal defect.

Surgical Treatment of Colorectal Cancer with Peritoneal and Liver Metastases Using Combined Liver and Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Report from a Single-Centre Experience.

BACKGROUND: Chemotherapeutic advances have enabled successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) expansion in treating metastatic colorectal cancer. OBJECTIVES: The aims of this study were to evaluate the safety of combining liver surgery (LS) with HIPEC and CRS (which remains controversial) and its impact on overall survival (OS) rates. METHODS: From 2007 to 2015, a total of 77 patients underwent CRS/HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. Twenty-five of these patients underwent concomitant LS for suspicion of liver metastases (LM; group 2), and were compared with patients who underwent CRS/HIPEC only (group 1). Demographic and clinical data were reviewed retrospectively. RESULTS: Among the group 2 patients, two underwent major hepatectomies, six underwent multiple wedge resections, 16 underwent single wedge resections (one with radiofrequency ablation), and one underwent radiofrequency ablation alone. For groups 1 and 2, median peritoneal cancer index was 6 and 10 (range 0-26; p = 0.08), complication rates were 15.4 and 32.0 % (Dindo-Clavien ≥3; p = 0.15), and median follow-up was 34.2 and 25.5 months (range 0-75 and 3-97), respectively. One group 2 patient died of septic shock after 66 days. Pathology confirmed LM in 21 patients in group 2 (four with benign hepatic lesions were excluded from long-term outcome analysis). Two-year OS rates were 89.5 and 70.2 % (p = 0.04), and 2-year recurrence-free survival rates were 38.3 and 13.4 % (p = 0.01) in groups 1 and 2, respectively. CONCLUSIONS: Simultaneous surgery for colorectal LM and PC is both feasible and safe, with low postoperative morbidity. Further longer-term studies would help determine its impact on patient survival.

Ovine cord blood accommodates multipotent mesenchymal progenitor cells.

BACKGROUND: Stem cells derived from umbilical cord blood display mesenchymal multipotency and can differentiate into osteoblasts, chondroblasts and adipoblasts in vitro under defined stimuli. Although sheep have been used as experimental models for investigations on xenoreactivity after transplantation of stem cells isolated from human umbilical cord blood, the potential of ovine cord blood stem cells to differentiate has been examined to date. MATERIALS AND METHODS: Mononuclear cells from the placentoms of 3 lambs were isolated via density gradient centrifugation and cultivated. After expansion up to 3 passages, the cells were stimulated to differentiate towards osteogenic (dexamethasone, ascorbic-acid-2-phosphate, beta-glycerolphosphate), chondrogenic (TGF-beta3, insulin, transferrin, selenium, dexamethasone, ascorbic-acid-2-phosphate) and adipogenic (indomethacine, insulin, 3-isobutyl-1-methylxanthine, dexamethasone) lines for 20 days. The cells were characterized morphologically by transmission and phase contrast light microscopy during lineage-specific stimulation. Immunocytochemistry and conventional stains were used to detect lineage-typical markers: fat vacuoles and peroxisome proliferation-acitivated receptor gamma2 (PPAR) served to detect adipoblasts, whereas osteopontin (OP) was used to characterize osteoblasts. A positive antibody reaction to collagen II and chondrogenic oligomeric protein (COMP) revealed the presence of chondroblasts. RESULTS: The osteogenic line formed bone nodules, adipogenic cells developed lipid droplets and the cells of the chondrogenic line showed typical chondroblast-like morphology. CONCLUSION: It was demonstrated that ovine mesenchymal stem cells, derived from umbilical cord blood (sheep unrestricted somatic stem cells, S-USSCs), can be isolated via gradient density centrifugation and expanded in vitro. Under lineage-specific stimulation, S-USSCs differentiated into osteo-, chondro- and adipoblasts with typical morphological characteristics. Significant quantitative differences between the stimulated and control groups in lineage-typical immunocytochemical markers verified these findings.