Background: For any anti-adhesive barrier developed for abdominal surgery, the use under conditions in which anastomotic healing is compromised needs to be investigated. The current study evaluates the effect of a new ultrapure alginate gel on early healing of high-risk anastomoses in the ileum and compares this with the gold standard used in clinical practice. Materials andMethods: In 75 adult male Wistar rats, a 5 mm ileal segment was resected and continuity was restored by construction of an inverted anastomosis. Rats were divided randomly into a control group and groups receiving either alginate gel or a sodium hyaluronate carboxymethylcellulose (HA/CMC) film around the anastomosis (n = 25 each). Carprofen, given in a daily dose of 1.25 mg/kg, was used to compromise anastomotic healing. At day three, animals were killed and scored for signs of anastomotic leakage and the presence of adhesions.Results: The incidence of adhesion formation was 95% in the HA/CMC film group, which was significantly higher than in the controls (64%, p = 0.010) and the alginate gel group (52%, p = 0.004). The adhesion score was nearly 40% lower in the alginate gel group compared with the HA/CMC film group. The incidence of ileal leakage in the HA/CMC film group (92%) was significantly higher than in the controls (68%, p = 0.016). Leakage rate did not differ between the alginate gel and control groups. There was no significant difference between groups in either incision bursting pressure or incision breaking strength.Conclusion: Ultrapure alginate gel does not interfere with repair of ileal anastomoses constructed under conditions in which chances of anastomotic dehiscence are high. The alginate gel performs better than the HA/CMC film.

BACKGROUND:Immunosuppressant agents are inevitable for solid organ recipients, but may have a negative effect on wound healing that is difficult to measure because of clinical use of a polydrug regime. The evidence on mycophenolate mofetil (MMF) is scarce and contradictory. This study aims to investigate the effect of MMF administration on wound healing.METHODS:Ninety-six male Wistar rats divided into 4 groups underwent anastomotic construction in ileum and colon at day 0. Three groups received daily oral doses of 20 or 40 mg/kg MMF or saline (control group) from day 0 until the end of the experiment. Half of each group was analyzed after 3 days and half after 7 days. Another group started the medication 3 days after the laparotomy and was analyzed after 7 days, half of this group received 20 mg/kg and half 40 mg/kg MMF. Wound strength in anastomoses and in the abdominal wall was measured using bursting pressure, breaking strength, and histology. Trough levels were measured.RESULTS:Significant differences in wound strength were seen in ileum tissue after 3 days, which surprisingly showed a stronger anastomosis in the experimental groups. Bursting pressure as well as breaking strength was higher in the low-dose and high-dose MMF group compared with the control group. A negative effect was measured in abdominal wall tissue for the highest-dose group, which disappeared when the medication was delayed for 3 days. Histology showed poorer bridging of the submucosal layer and more polymorphonuclear cell infiltration in the ileum specimens of the control group compared with the treatment groups.CONCLUSIONS:As a single agent in a preclinical wound healing model in the rat, MMF has no negative effect on healing of bowel anastomoses but might have a negative effect on the healing of abdominal wall.

In cancer, various MMPs play a role in progression and metastasis and their overexpression generally indicates a poor prognosis. MMP-14 is the main activator of MMP-2 and both molecules play a role in normal ovarian follicular development. Earlier reports indicated a prognostic value for both MMP-14 and MMP-2 in ovarian cancer. This study was designed to determine the prognostic value of MMP-14 and MMP-2 expression in ovarian cancer with data on long-term follow-up.

BACKGROUNDIntra-abdominal infection may lead to adhesion and abscess formation. An adhesion barrier can reduce these complications but also aggravate intra-peritoneal infection, causing the opposite effects. The fear of infection propagation has limited clinical adhesion barrier use in a contaminated or infected abdomen. This study evaluated both adhesion and abscess reduction and infection propagation of a new ultrapure alginate-based anti-adhesive barrier gel in a rat peritonitis model.METHODSIn 64 male Wistar rats, bacterial peritonitis was induced via intra-abdominal injection of a mixture of sterile feces, 10(5) colony-forming units (CFU) of Escherichia coli, and 10(4) CFU of Bacteroides fragilis. Surgical debridement and peritoneal lavage were performed 1 h after inoculation. Animals were randomly allocated in equal numbers to a control group or an alginate gel group. Animals were sacrificed on day five post-operatively. Death and the presence and size of intra-abdominal abscesses were noted, and adhesions were scored. All outcomes were compared in the two groups.RESULTSSeventeen rats (27%) died prematurely without any difference between the groups. Of the surviving rats in the alginate gel group, 88% developed abscesses vs. 100% of the control group. There was no significant difference in the abscess scores or incidence rates of adhesion formation between the groups. The adhesion scores were lower for the alginate gel group compared with control animals (p=0.04).CONCLUSIONUltrapure alginate gel reduces adhesion severity but not abscesses. The gel seemed to be safe, not aggravating intra-peritoneal infection in this abdominal infection model.

BACKGROUND:Nonsteroidal anti-inflammatory drugs have been associated with anastomotic leakage. It was studied if diclofenac affects anastomoses differently depending on the location in the gut. METHODS:Ninety-five rats were randomized to 6 groups with an anastomosis in either ileum (IL), proximal colon (PC), or distal colon (DC). Groups IL+ (n = 10), PC+ (n = 30), and DC+ (n = 10) received diclofenac (3 mg/kg/day) from day 0 until sacrifice on day 3. Group PC- (n = 15) did not receive diclofenac. Groups PC1+ and PC2+ (n = 15 each) were given diclofenac from day 1 to 4 and from day 2 to 5. RESULTS:Leak rates were 10/10 in group IL+, 22/30 in PC+, 1/10 in DC+, and 1/15 in PC-. Delayed administration of diclofenac by 1 or 2 days (6/15, P = .05) resulted in reduced leakage rates. Mechanical strength results corresponded with leak rates. CONCLUSIONS:Diclofenac causes leakage of anastomoses in rat IL and PC, but not in the DC. This suggests a role for the ileal and proximal colonic content in diclofenac-induced leakage.

Adhesiolysis at repeat surgery induces adhesion reformation which seems more virulent than development of de novo adhesions. We studied the effect of a new ultrapure alginate gel on adhesion reformation.

Background: Ultrapure alginate gel is promising in terms of adhesion prevention. Because anti-adhesive barriers have been shown to disturb healing of bowel anastomoses, the effect of ultrapure alginate gel on the repair of colon anastomoses was studied.Materials and methods: In 102 male Wistar rats, a 0.5-cm segment was resected from the descending colon and continuity was restored by an inverted single-layer end-to-end anastomosis. Animals were randomized into a control, an alginate gel, and a sodium hyaluronate carboxymethyl cellulose film group, each n = 34. Half of each group was sacrificed at day 3 and 7 postoperatively. Anastomotic strength was assessed by measuring both bursting pressure and breaking strength. Hydroxyproline content was measured and histologic analysis was performed. The incidence of adhesion and abscess formation was scored at sacrifice.Results: No difference in either anastomotic-bursting pressure or breaking strength was found between experimental groups and the controls at any time point. Both the incidence of adhesion formation (35% versus 71%, P = 0.007) and the adhesion score (0.38 versus 0.79, P = 0.009) were significantly lower in the alginate gel group than in the controls. The abscess rate was higher (46% versus 18%, P = 0.030) in the hyaluronate carboxymethyl cellulose group than in the controls and unchanged in the alginate gel group.Conclusions: While reducing adhesion formation, ultrapure alginate gel does not interfere with the development of colonic anastomotic strength during the crucial early healing period. (C) 2014 Elsevier Inc. All rights reserved.

BACKGROUND: Biologic grafts hold promise of a durable repair for ventral hernias with the potential for fewer complications than synthetic mesh. This systematic review was performed to evaluate the effectiveness and safety of biologic grafts for ventral hernia repair.METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for studies on biologic grafts for the repair of ventral hernias. Outcomes are presented as weighted pooled proportions.RESULTS: Twenty-five retrospective studies were included. Recurrence depended on wound class, with an overall rate of 13.8% (95% confidence interval [CI], 7.6-21.3). The recurrence rate in contaminated/dirty repairs was 23.1% (95% CI, 11.3-37.6). Abdominal wall laxity occurred in 10.5% (95% CI, 3.7-20.3) of patients. The surgical morbidity rate was 46.3% (95% CI, 33.3-59.6). Infection occurred in 15.9% (95% CI, 9.8-23.2) of patients but only led to graft removal in 4.9% of cases.CONCLUSIONS: No randomized trials are available to properly evaluate biologic grafts for ventral hernia repair. The current evidence suggests that biologic grafts perform similarly to other surgical options. Biologic grafts are associated with a high salvage rate when faced with infection. (C) 2013 Elsevier Inc. All rights reserved.

BACKGROUND: Use of immunosuppressant drugs has been associated with complications in wound healing. The calcineurin inhibitor tacrolimus is thought to have a relatively low complication rate, but preclinical research has yielded contradictory data, prompting the current comprehensive study. METHODS: Three groups of 33 male Wistar rats received a daily subcutaneous dose of 0,5, 2 or 5 mg/kg tacrolimus. A control group received saline. On day 0 a resection of 1 cm ileum and 1 cm colon was performed, and end-to-end anastomoses were constructed. Ten rats of each group were killed on day 3 and day 5 and the remaining animals on day 7. Both anastomoses and the wound in the abdominal wall were analyzed. Wound strength was the primary outcome parameter. RESULTS: Mean strength of the abdominal wall increased significantly over time in all groups (p<0.0001). Both the breaking strength and the bursting pressure of the ileum and colon anastomoses followed the same pattern. No differences were observed between control and experimental groups. In addition, no consistent differences were found between groups regarding wound hydroxyproline content and the activities of matrix metalloproteinase-2 and -9. CONCLUSION: Tacrolimus does not affect early wound healing.

During the treatment of colorectal liver metastases, evaluation of treatment efficacy is of the utmost importance for decision making. The aim of the present study was to explore the ability of preclinical imaging modalities to detect experimental liver metastases. Nine male Wag/Rij rats underwent a laparotomy with intraportal injection of CC531 tumor cells. On days 7, 10, and 14 after tumor induction, sequential positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) scans were acquired of each rat. At each time point, three rats were euthanized and the metastases in the liver were documented histologically. Topographically, the liver was divided into eight segments and the image findings were compared on a segment-by-segment basis with the histopathologic findings. Sixty-four liver segments were analyzed, 20 of which contained tumor deposits. The overall sensitivity of PET, CT, and MRI was 30%, 25%, and 20%, respectively. For the detection of tumors with a histologic diameter exceeding 1 mm (n = 8), the sensitivity of PET, CT, and MRI was 63%, 38%, and 38%, respectively. The overall specificity of PET, CT, and MRI was 98%, 100%, and 93%, respectively. This study showed encouraging detectability and sensitivity for preclinical imaging of small liver tumors and provides valuable information on the imaging techniques for designing future protocols.

Purpose Protecting the anastomotic integrity using suture or staple line reinforcement remains an important goal for ongoing research. The present comprehensive study aims to establish the effects of fibrin glue on the early phase of anastomotic healing in the rat intestine. Methods One hundred and eight young adult male Wistar rats underwent resection and anastomosis of both the ileum and colon. In half, fibrin glue was applied around the anastomoses. Parameters for repair included wound strength, both bursting pressure and breaking strength at days 1, 3, and 5 after operation; hydroxyproline content; and histology, the latter also after 7 days. Results A transient colonic ileus was observed in the experimental group. Anastomotic breaking strength was always similar in both the control and fibrin glue groups. Anastomotic bursting pressures remained low at days 1 and 3, without any differences between the groups. In both groups, the bursting pressure increased sharply ( p < 0.001) between days 3 and 5. At day 5, the bursting pressure in the fibrin glue group remained below than that in the controls, although only significantly ( p = 0.0138) so in the ileum. At day 5, but not at day 7, the wounds in the fibrin glue group contained less collagen. Other aspects of microscopic wound architecture appeared to be the same. Conclusions There is no justification for using fibrin glue on patent anastomoses constructed under low-risk conditions. Its potential benefit under conditions where chances for anastomotic leakage are enhanced needs further investigation.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a known method to diagnose inflammatory processes and thus may be a promising imaging technique to detect anastomotic bowel leak. The aim of this study was to assess postoperative FDG uptake in colorectal anastomosis in patients without suspicion of active infection or anastomotic leakage. Patients, methods: Design of a prospective observational pilot study in order to assess normal FDG uptake in the patient anastomosis after colorectal surgery. Patients that underwent colorectal surgery with primary anastomosis received FDG-PET of the abdomen, 2–6 days postoperatively. Results: 35 patients met the inclusion criteria. Three patients were not scanned for various reasons. Of the remaining 32 patients, one demonstrated an increased uptake of FDG at the site of the anastomosis. In the other 31 patients FDG uptake was negligible (n = 17) or scored as physiological (n = 14). None of the scanned patients developed a clinical relevant anastomotic leakage within the first 30 days after surgery. Conclusion: The present study shows that FDG uptake in colorectal anastomosis remains low within the first six days after surgery in patients without anastomotic leakage. Therefore, FDG-PET might be useful to investigate further as a tool to detect anastomotic leakage in an the early postoperative phase.

BACKGROUND: Paracetamol is a cornerstone for perioperative pain relief. Its mechanism of action may include a local antiinflammatory effect with inhibition of cyclooxygenase isoenzymes. The scarce literature available on its effects on wound healing consists of preclinical studies into the effect of paracetamol on healing of the musculoskeletal system. Although the drug is used abundantly for pain relief after surgery of the gastrointestinal tract, there are no published data on the influence of paracetamol on anastomotic and abdominal healing. This also holds for the crucial, early inflammatory phase of repair. The recovery of wound strength could therefore conceivably be affected by paracetamol.METHODS: In 78 male Wistar rats, we constructed an anastomosis in colon and ileum. The rats received either low- or high-dose (50 or 200 mg/kg/d, divided over 2 doses) paracetamol or vehicle (controls) until they were killed on day 3 or 7 after surgery (n = 13 each). In anastomoses, the main outcome variables were 2 independent measures for wound strength, bursting pressure, and breaking strength, the latter being the primary outcome variable. In addition, collagen levels were measured and histology was performed. In fascia, breaking strength was analyzed.RESULTS: No significant differences were found between control and paracetamol-treated groups at any time point for any of the variables. Wound strength increased significantly from day 3 to day 7 in all groups. In the colon anastomosis, the breaking strength increased from 130 +/- 9 g (mean +/- SEM) at day 3 to 232 +/- 17 g at day 7 in the control group, from 144 +/- 10 to 224 +/- 9 g in the low-dose group, and from 130 +/- 12 to 263 +/- 28 g in the high-dose group. The lower limit for the 95% confidence interval was -11 for the difference between control and low-dose groups at day 3 and -25 for the difference between control and high-dose groups. No differences in collagen levels were found between the high-dose and control groups. Histology did not indicate the presence of gross differences between groups.CONCLUSIONS: Perioperative use of paracetamol in a rat model of intestinal surgery does not significantly impede wound repair in the early postoperative period. (Anesth Analg 2012;115:1451-6)

BACKGROUND:There is increasing evidence that perioperative use of NSAIDs may compromise the integrity of intestinal anastomoses. This study aims to characterize the negative effects of carprofen on early anastomotic healing in the rat ileum.RESULTS:In 159 male Wistar rats an anastomosis was constructed in the ileum. In experiment 1 eighty-four rats were divided over control and experimental groups, which received daily buprenorphine or carprofen, respectively, as an analgesic and were killed on day 1, 2 or 3 after surgery. In experiment 2 three groups of 15 rats received carprofen either immediately after surgery or with a delay of 1 or 2 days. Animals were killed after 3 days of carprofen administration. In experiment 3 three groups of 10 rats received different doses (full, half or quarter) of carprofen from surgery. In significant contrast to buprenorphine, which never did so, carprofen induced frequent signs of anastomotic leakage, which were already present at day 1. If first administration was delayed for 48 hours, the leakage rate was significantly reduced (from 80 to 20%; p = 0.0028). Throughout the study, the anastomotic bursting pressure was lowest in animals who displayed signs of anastomotic leakage. Loss of anastomotic integrity did not coincide with reduced levels of hydroxyproline or increased activity of matrix metalloproteinases.CONCLUSIONS:Carprofen interferes with wound healing in the rat ileum at a very early stage. Although the mechanisms responsible remain to be fully elucidated, one should be aware of the potential of NSAIDs to interfere with the early phase of wound repair.

Perioperative intraperitoneal chemotherapy is used as an adjunct to cytoreductive surgery (CS) for peritoneal carcinomatosis (PC) in order to prolong survival. Worldwide, hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and combinations of the two are used. It remains unclear which regimen is most beneficial.

The use of mammalian target of rapamycin inhibitors coincides with an increased incidence of surgical complications. In previous experiments, serious negative effects of postoperative everolimus on anastomotic strength were found. This study aims to investigate if delayed drug administration can prevent loss of wound strength. Ten groups of Wistar rats each received daily oral doses of 1.0 or 2.0 mg/kg everolimus, starting the day of anastomotic construction in both ileum and colon, or 1, 2, 3, or 4 days later. The 11th group received saline. Seven days later, wound strength in anastomoses and in the abdominal wall and wound hydroxyproline levels were measured. Mean wound strength was significantly and dose-dependently reduced if everolimus was started on the day of operation. In ileum and colon, strength was not affected if drug administration was delayed until the third or second day, respectively. In abdominal fascia, this was the case only if everolimus was withheld until day 4. In general, changes in wound hydroxyproline content showed similarities to changes in wound strength. Thus, delaying administration of everolimus for 2-4 days after operation can prevent a serious loss of wound strength, both in the intestine and in the abdominal fascia.