Comparability of histological outcomes in rats and humans in a hernia model.

BACKGROUND: Hernia repair is one of the most frequently performed operations. In search of the ideal mesh for hernia repair, animal research is required. Although rats are most often used in experimental mesh experiments, no correlation with clinical findings in humans has ever been shown. Therefore, the aim of our study was to investigate whether adhesion formation and foreign body reactions to meshes in rats are comparable with the reactions in humans. MATERIALS AND METHODS: A fixed type of mesh was implanted intraperitoneally in a group of 10 rats and 10 patients undergoing elective, temporary stoma formation. In case of the latter, meshes were placed around the stoma. After a follow-up period of 12 wk in rats and after a median follow-up of 6 mo in humans, samples of the mesh were collected. Adhesion assessments were performed, and (immuno-) histochemical evaluation was performed by a specialized experimental pathologist and an experienced clinical pathologist. RESULTS: After the follow-up period, adhesion formation did not differ significantly between rats and humans. Moreover, general inflammation scores were comparable, although granulocytes and giant cells were more present in rats, compared with humans. On the other hand, the presence of fibrosis was more evident in humans compared with rats. CONCLUSIONS: To our knowledge, this is the first study, which showed that a specific animal model, namely a rat model, correlates with adhesion formation and the foreign body reaction to meshes in humans. It can be recommended to use rats in future experimental mesh for incisional hernia research.

Impact of tissue adhesives on the prevention of anastomotic leakage of colonic anastomoses: an in vivo study.

BACKGROUND: Tissue adhesives (TA) may be useful to strengthen colorectal anastomoses, thereby preventing anastomotic leakage (AL). Previous studies have identified cyanoacrylate (CA) TAs as the most promising colonic anastomotic sealants. This study investigates the protective effects of sealing colonic anastomoses with various CAs. MATERIALS AND METHODS: Fifty-five Wistar rats underwent laparotomy and transection of the proximal colon. An anastomosis was created with 4 interrupted sutures followed by either application of Histoacryl Flexible, Omnex, Glubran 2, or no TA seal. An additional control group was included with a 12-suture anastomosis and no TA seal. After 7 days, the rats were sacrificed and scored for the presence of AL as the main outcome. Secondary outcomes were the occurrence of bowel obstruction, adhesions, and anastomotic bursting pressure. Histological evaluation was performed. RESULTS: The highest AL rate was found in the Glubran 2 group (7/11), followed by the 4-sutures group without TA (5/11), and the Omnex group (5/11). Histoacryl Flexible showed the lowest AL rate (2/11). In the control group, only one rat showed signs of AL. Histologically, the highest influx of inflammatory cells was found in the 4-suture group without TA and for Omnex and Glubran 2. Histoacryl Flexible caused more mature collagen deposition when compared to the other TA groups. CONCLUSIONS: Histoacryl Flexible showed the lowest leakage rate compared to the other TA groups and to the 4-suture control group. Glubran 2 showed the highest AL rate and a high inflammatory response. Histoacryl Flexible was associated with the presence of more mature collagen and seems to promote anastomotic healing.

Beneficial Effects of Early Enteral Nutrition After Major Rectal Surgery: A Possible Role for Conditionally Essential Amino Acids? Results of a Randomized Clinical Trial.

OBJECTIVES: To investigate direct postoperative outcome and plasma amino acid concentrations in a study comparing early enteral nutrition versus early parenteral nutrition after major rectal surgery. Previously, it was shown that a low plasma glutamine concentration represents poor prognosis in ICU patients. DESIGN: A preplanned substudy of a previous prospective, randomized, open-label, single-centre study, comparing early enteral nutrition versus early parenteral nutrition in patients at high risk of postoperative ileus after surgery for locally advanced or locally recurrent rectal cancer. Early enteral nutrition reduced postoperative ileus, anastomotic leakage, and hospital stay. SETTING: Tertiary referral centre for locally advanced and recurrent rectal cancer. PATIENTS: A total of 123 patients with locally advanced or recurrent rectal carcinoma requiring major rectal surgery. INTERVENTIONS: Patients were randomized (ALEA web-based external randomization) preoperatively into two groups: early enteral nutrition (early enteral nutrition, intervention) by nasojejunal tube (n = 61) or early parenteral nutrition (early parenteral nutrition, control) by jugular vein catheter (n = 62). Eight hours after the surgical procedure artificial nutrition was started in hemodynamically stable patients, stimulating oral intake in both groups. Blood samples were collected to measure plasma glutamine, citrulline, and arginine concentrations using a validated ultra performance liquid chromatography-tandem mass spectrometric method. MEASUREMENTS AND MAIN RESULTS: Baseline concentrations were comparable for both groups. Directly after rectal surgery, a decrease in plasma amino acids was observed. Plasma glutamine concentrations were higher in the parenteral group than in the enteral group on postoperative day 1 (p = 0.027) and day 5 (p = 0.008). Arginine concentrations were also significantly increased in the parenteral group at day 1 (p < 0.001) and day 5 (p = 0.001). CONCLUSIONS: Lower plasma glutamine and arginine concentrations were measured in the enteral group, whereas a better clinical outcome was observed. We conclude that plasma amino acids do not provide a causal explanation for the observed beneficial effects of early enteral feeding after major rectal surgery.

Postoperative abdominal adhesions and bowel obstruction. A survey among Dutch general practitioners.

BACKGROUND: There is increasing interest among specialists in the complications after abdominal surgery due to adhesions. OBJECTIVE: Exploration of experiences, attitudes and expectations of general practitioners concerning bowel obstruction and postoperative abdominal adhesions. METHODS: In October 2012 a postal questionnaire was sent to a random sample of 800 Dutch GPs. RESULTS: The response rate was 45%, 24% (n = 190) filled out the questionnaire completely, 12% (n = 99) had no experience with the subject and 7% (n = 57) had no time to respond. A history of abdominal surgery does play a part in more than 80% of GP's differential diagnosis of abdominal complaints. Seventy-five per cent consider some types of surgery to induce more adhesions. Eighty-five per cent ponder the differentiation between adhesion related complaints and IBS as clear, however difficult (78%) in specific patients. Intestinal transit problems likely due to adhesions are treated with extra fluid (n = 64), more fibres (n = 85) and laxatives (n = 153). Referral to a specialist for adhesiolysis is rarely considered (11%). Forty per cent of the GPs would refer a patient with abdominal pain and suspected adhesions. Seventy-six per cent denote knowledge gaps and low experience in the treatment of intestinal transit problems. Some (n = 23) indicate the need for information about adhesions and obstruction through CME papers. CONCLUSION: Respondents are well equipped to deal with abdominal complaints and intestinal transit problems due to postoperative adhesions. Some indicate the need for information about adhesions and prevention of obstruction through CME papers.

A new poly(1,3-trimethylene carbonate) film provides effective adhesion reduction after major abdominal surgery in a rat model.

BACKGROUND: Postoperative adhesions remain a major clinical problem after abdominal surgery. We evaluated the efficacy of a new poly(trimethylene carbonate) (PTMC) film as an antiadhesive material. In many abdominal operations, there is an increased risk of fecal contamination; the risk of (increased) infection in presence of PTMC film was studied in 2 additional animal models. METHODS: A validated rat adhesion model with peritoneal ischemic buttons was used to compare the new PTMC film with a hyaluronate carboxymethylcellulose (HA-CMC) sheet, icodextrin solution, and a control group. Primary endpoint was occurrence of adhesions at the ischemic buttons after 14 days in 44 rats (n = 11 per group). To evaluate potential risks associated with the film, both an anastomotic leakage model and a cecal ligation and puncture model were used. Kruskal-Wallis tests with subsequent Mann-Whitney tests were used to detect differences between groups. RESULTS: PTMC film showed a significant reduction in the amount of adhesions (median, 0.5 buttons) compared with control group (median, 4 buttons; P < .001) and icodextrin group (median, 4.5; P < .001). The amount of adhesions was similar to the HA-CMC group (median, 2; P = .04). The presence of the film did not increase the risk of anastomotic leakage or bacterial growth in a contaminated environment. CONCLUSION: The presence of a PTMC film leads to a significant reduction in the amount of adhesions after 14 days in an ischemic button rat model. Furthermore, this film was found to be safe in an animal model, even in complex abdominal operations with an increased risk of fecal contamination.

Prophylactic intraperitoneal mesh placement to prevent incisional hernia after stoma reversal: a feasibility study.

BACKGROUND: Incisional hernias in old stoma wounds occur in one-third of former stoma patients and pose a significant clinical problem. Parastomal hernias can be prevented by prophylactic mesh placement; however, no trial results are available for incisional hernia prevention after stoma reversal. In this feasibility study, we explore the safety of placing an intraperitoneal mesh to prevent incisional herniation after temporary stoma reversal. METHODS: Ten patients who underwent a low anterior resection with a deviating double-loop stoma for rectal cancer received an intraperitoneal parastomal mesh at the time of stoma formation. At stoma reversal, laparoscopy was performed and adhesions were scored. After reversal, the mesh defect was closed. Mesh and stoma complications were closely monitored. Incisional herniation was assessed at the 2-year follow-up after stoma reversal using ultrasonography. RESULTS: No infections occurred after mesh placement. After a median of 6 months, stomas were reversed. Laparoscopy could be performed in seven patients; all patients had adhesions (median of 25 % of mesh surface). In three patients, the bowel was involved; one required a laparotomy for bowel mobilization during stoma reversal. No adhesion-related morbidity was noted at any time. Except for one superficial wound infection after stoma reversal, no infectious complications were observed. After a median follow-up of 26 months, no incisional herniations were demonstrated. CONCLUSIONS: Prophylactic mesh placement in temporary stoma formations seems safe and feasible and prevents incisional herniation 2 years after stoma reversal.

Reduction of postoperative ileus by early enteral nutrition in patients undergoing major rectal surgery: prospective, randomized, controlled trial.

BACKGROUND: The current trend in postoperative nutrition is to promote a normal oral diet as early as possible. However, postoperative ileus is a frequent and common problem after major abdominal surgery. This study was designed to investigate whether early enteral nutrition (EEN), as a bridge to a normal diet, can reduce postoperative ileus. METHODS: Patients undergoing major rectal surgery for locally advanced primary or recurrent rectal carcinoma (after neoadjuvant (chemo)-radiation, with or without intraoperative radiotherapy) were randomly assigned to EEN (n = 61) or early parenteral nutrition (EPN, n = 62) in addition to an oral diet. Early nutrition was started 8 hours after surgery. Early parenteral nutrition was given as control nutrition to obtain caloric equivalence and minimize confounding. The primary endpoint was time to first defecation; secondary outcomes were morbidity, other ileus symptoms, and length of hospital stay. RESULTS: Baseline characteristics were similar for both groups. In intention-to-treat analysis, the time to first defecation was significantly shorter in the enteral nutrition arm than in the control arm (P = 0.04). Moreover, anastomotic leakage occurred significantly less frequently in the enteral group (1 patient) compared with parenteral supplementation (9 patients, P = 0.009). Mean length of stay in the enteral group was 13.4 ± 2.2 days versus 16.7 ± 2.3 days in the parenteral group (P = 0.007). CONCLUSIONS: Early enteral nutrition is safe and associated with significantly less ileus. Early enteral nutrition is associated with less anastomotic leakage in patients undergoing extensive rectal surgery.

Coated meshes for hernia repair provide comparable intraperitoneal adhesion prevention.

BACKGROUND: Laparoscopic incisional hernia repair with intraperitoneal mesh is associated with a certain degree of adhesion formation to the mesh. This experimental study examined the efficacy of several coated meshes for adhesion reduction. METHODS: Five commercially available meshes with a layered coating were placed intraperitoneally in rats and followed up for 90 days: polypropylene and polyester meshes, both coated with absorbable collagen (Parietene Composite and Parietex Composite, respectively), and three polypropylene meshes respectively coated with absorbable omega-3 fatty acids (C-Qur Edge), absorbable cellulose (Sepramesh IP), and nonabsorbable expanded polytetrafluoroethylene (Intramesh T1). Uncoated polypropylene and collagen meshs (Parietene and Permacol, respectively) served as the control condition. Adhesions, incorporation, and tissue reaction were evaluated macro- and microscopically. Additionally, the development of the neoperitoneum was examined. RESULTS: All the coated meshes performed equally well in terms of adhesion reduction. The collagen mesh performed comparably, but the uncoated polypropylene mesh performed significantly worse. The different coatings led to very differing degrees of inflammation. Ingrowth was observed only at the place of suture but was comparable for all the meshes except C-Qur Edge, which showed the weakest incorporation. Development of a neoperitoneum on the mesh surface occurred independently of whether an absorbable or nonabsorbable coating or no coating at all was present. CONCLUSIONS: Commercially available meshes with a layered coating deliver comparable adhesion reduction. The physical presence of a layered coating between the intraperitoneal content and the abdominal wall seems to be more important than the chemical properties of the coating in adhesion formation.

One-year outcome of biological and synthetic bioabsorbable meshes for augmentation of large abdominal wall defects in a rabbit model.

BACKGROUND: Long-term efficacy of biological and synthetic bioabsorbable meshes for large hernia repair is currently unclear. This rabbit study is aimed at investigating 1-y outcome of biological and synthetic bioabsorbable meshes for augmentation of large abdominal wall defects. MATERIALS AND METHODS: In 46 rabbits, an 11 × 4 cm, full-thickness abdominal wall defect was repaired primarily, or with cross-linked (Permacol, Collamend) or non-cross-linked (Surgisis 4-ply, Surgisis Biodesign) biological, synthetic bioabsorbable (GORE BIO-A Tissue Reinforcement [TR], TIGR Matrix Surgical Mesh [MSM]), or polypropylene (Bard Mesh) meshes, using the underlay augmentation technique. One year after surgery, primary outcome was recurrence; secondary outcomes were tensile strength, histologic degree of tissue remodeling, and intraabdominal adhesion formation. RESULTS: Only two Surgisis 4-ply animals (50%) presented with a recurrent hernia. All GORE BIO-A TR meshes were completely resorbed and, as after primary repair, well-organized connective tissue without inflammation was present, with moderate adhesion formation and sufficient tensile strength. Cross-linked biological and TIGR MSM meshes demonstrated highest tensile strength but were only partially incorporated, with similar foreign body reaction and adhesion formation as polypropylene meshes in the TIGR MSM group, and minimal degradation and moderate adhesion formation in the cross-linked biological group. In the non-cross-linked biological group sufficient tensile strength and moderate adhesion formation were found, with pronounced inflammation if mesh remnants were present. CONCLUSIONS: Synthetic bioabsorbable GORE BIO-A TR meshes were associated with optimal tissue remodeling, with complete resorption, presence of well-organized tissue, and no inflammation. However, mesh augmentation had no advantages regarding recurrence rate versus primary repair of large abdominal wall defects.