Intestinal mucosal MMP-1 - a prognostic factor in colon cancer.

OBJECTIVE: There is evidence that transforming growth factor-ß1 (TGF-ß1) and matrix metalloproteinases (MMPs) play an important role in tumor invasion and progression in colorectal cancer. The aim of this study was to assess their utility in prediction of cancer-specific survival (CSS). MATERIALS AND METHODS: 136 patients undergoing curative surgery for colorectal carcinoma were prospectively included. Samples were taken from tumor and tumor-free intestinal mucosa and ELISA was used to assess protein levels in the tissues. Patients were followed for CSS. The median follow-up time for all included patients was 65 months (range: 45-92). The main outcome measure was CSS. RESULTS: T stage, lymph node involvement and high levels of MMP-1 as well as MMP-9 in tumor-free mucosa tissue were significantly associated with CSS in colon cancer in univariate analysis. This prognostic strength was maintained for MMP-1 and N-status in multivariate analysis. CONCLUSIONS: The results indicate that MMP-1 is independently associated with CSS in patients with colon cancer. Furthermore, a possible clinical implication is that MMP-1 protein expression in tumor-free mucosa could identify colon cancer patients with poor CSS in need of more intensified adjuvant treatment.

Seprafilm® adhesion barrier: (1) a review of preclinical, animal, and human investigational studies.

The aim of this study was to provide a single site resource for investigators, clinicians, and others seeking preclinical, animal, and human investigational studies concerning the postsurgical, anti-adhesion barrier Seprafilm™ (Genzyme Corporation, Cambridge, MA). All published preclinical, animal, human extra-abdominal research as of July 2011 have been summarized and included in this document. Searches of Medline and EMBASE Drugs and Pharmaceuticals databases were conducted for original preclinical, animal, and human extra-abdominal studies involving Seprafilm. Preclinical, animal, and extra-abdominal human investigational studies are the study selection for this manuscript. Intraabdominal use is discussed in the accompanying manuscript. Data extraction includes systematic manuscript review. Summary of preclinical, animal, and extra-abdominal human investigational use of Seprafilm by surgical discipline were gathered for data synthesis. The clinical use of Seprafilm, which was approved by the FDA for intra-abdominal procedures, is supported by preclinical and animal studies relating to general surgical and obstetrical/gynecological applications. Findings from preclinical, animal, and human investigational studies at other sites throughout the body raises the potential for additional human clinical trials to assess efficacy and safety following surgical procedures at non-abdominal locations.

Seprafilm(®) adhesion barrier: (2) a review of the clinical literature on intraabdominal use.

This study seeks to provide a review of the clinical data published as of July 2011 concerning the postsurgical adhesion barrier, Seprafilm (chemically modified hyaluronic acid and carboxymethylcelulose; Genzyme Corporation, Cambridge, MA). Included articles detail the application of Seprafilm for intraabdominal uses that have been approved (on-label) and those considered investigational (off-label) by the FDA. Medline and EMBASE Drugs and Pharmaceuticals databases were searched for all original clinical Seprafilm research published as of July 2011. All human Seprafilm intraabdominal clinical reports and studies, excluding those related to prosthetic mesh were included. Data extraction involved the systematic review of each article. The data synthesis is the summary of Seprafilm human intraabdominal clinical reports and studies describing safety and/or efficacy. The safety and efficacy of Seprafilm in reducing postoperative adhesions has been clearly demonstrated in abdominal and pelvic laparotomy. While reports have described the safe and successful use of Seprafilm following laparoscopy, pediatric laparotomy, and in patients with malignancy and/or infection, the safety and efficacy of Seprafilm use in these procedures has not been definitively established in randomized controlled trials.

Adhesion formation to hemostatic agents and its reduction with a sodium hyaluronate/carboxymethylcellulose adhesion barrier.

The impact of hemostatic agents on postoperative adhesion formation has not been well studied. We hypothesized that hemostatic agents would be a significant nidus for adhesion formation and that a resorbable barrier would effectively reduce adhesions to hemostatic agents. Four commercial hemostatic agents, each composed of a different biomaterial matrix, were implanted in female Sprague-Dawley rats, and adhesion formation was examined 7 days after surgery. In separate studies, the effects of serosal trauma (via cecal abrasion), added blood, and the presence of chemically modified sodium hyaluronate/carboxymethylcellulose (HA/CMC) barrier on adhesion formation to hemostatic agents were studied. Significant adhesions formed to hemostatic agents even in the absence of traumatized tissue. When applied after cecal abrasion, the incidence of adhesions to the hemostatic agents increased. Addition of blood to this model increased adhesion formation even further, causing adhesions in every animal in the study. An HA/CMC adhesion barrier reduced adhesions to hemostatic agents in the presence of serosal trauma and maintained effectiveness even in the presence of blood. In conclusion, hemostatic agents potentiated adhesion formation at the site of application in a model without trauma. In more challenging models, their adhesiogenic contribution was overwhelmed by trauma and blood. HA/CMC adhesion barrier applied over hemostatic agents at the time of surgery provided significant protection against postoperative adhesions in these preclinical models.

Gynecologic use of Sepraspray Adhesion Barrier for reduction of adhesion development after laparoscopic myomectomy: a pilot study.

OBJECTIVE: To assess the safety and efficacy of Sepraspray Adhesion Barrier (a modified hyaluronic acid and carboxymethylcellulose powder) after laparoscopic surgery, in view of both the high efficacy of Seprafilm Adhesion Barrier in reducing postoperative adhesions after open surgical procedures and the difficulty with laparoscopic delivery. DESIGN: Multicenter, randomized, reviewer-blinded trial. SETTING: Reproductive endocrinology and infertility clinics. PATIENT(S): Women undergoing laparoscopic myomectomy for indications including infertility. INTERVENTION(S): Randomization to treatment with (n = 21) or without (n = 20) Sepraspray Adhesion Barrier. MAIN OUTCOME MEASURE(S): Postoperative adhesions development was assessed at early second-look laparoscopy. Adhesions were scored using the modified American Fertility Society scoring system. RESULT(S): Surgical procedure duration length was 99 versus 102 minutes in the control versus Sepraspray Adhesion Barrier groups, respectively, with the median number of fibroids removed being two in each group and corresponding fibroid weights of 134 ± 103 versus 113 ± 161 g, respectively. Adhesions scores increased in both the control and Sepraspray Adhesion Barrier groups, with larger although nonstatistically significant increases noted in control subjects when evaluating for the anterior uterus, the posterior uterus, and the entire uterus. CONCLUSION(S): Laparoscopic application of Sepraspray Adhesion Barrier after myomectomy in this pilot study was associated with a trend toward a reduction in postoperative adhesion development, as well as an encouraging safety profile. Further evaluation is warranted. CLINICAL TRIAL NUMBER: Sepraspray Adhesion Barrier #NCT00624930.

Tissue proteolysis in appendicitis with perforation.

BACKGROUND: Matrix metalloproteinases (MMPs) and serine proteases are able to degrade the extracellular matrix (ECM) and modulate immune responses in the gastrointestinal tract. The purpose of this study was to investigate local proteolysis in perforated appendicitis and its association with the appendix perforation. MATERIALS AND METHODS: Biopsies were taken at the sites of perforation (n = 15) and with a gradually increased distance from it. The expression and distribution of MMP-1, -2, and -9, the tissue inhibitor of metalloproteinases type (TIMP-1), plasminogen activator inhibitor type1 (PAI-1), and urokinase plasminogen activator (uPA) were measured by ELISA. The distribution of MMP-9, TIMP-1, uPA, and PAI-1 in perforated, nonperforated, and uninflamed appendix was investigated by immunohistochemistry with monoclonal antibody technique. RESULTS: MMP-1 expression was highest close to the perforation and was gradually decreased in biopsies in more distal locations (P < 0.01). MMP-9 showed a similar pattern being highest at the sites of perforation (P < 0.05), while MMP-2 expression showed a trend in the opposite direction without statistically significance. The expression of TIMP-1 trended lower at the sites of perforation. PAI-1 was highest at the sites of perforation (P < 0.01) and the uPA expression was similarly elevated close to and at the perforation. CONCLUSIONS: These data indicate a key role of MMP in the pathogenesis of appendix perforation. A local imbalance between MMP-9 and the inhibitor TIMP-1 could potentially contribute to the tissue injury leading to an appendix perforation. The overexpression of PAI-1 at the sites of perforation may also contribute to tissue damage.

A membrane slurry reduces postoperative adhesions in rat models of abdominal surgery.

BACKGROUND: Sodium hyaluronate and carboxymethylcellulose (HA-CMC) membrane is an effective barrier material for limiting postoperative adhesions, but can be difficult to apply in certain situations due to its physical properties. We tested whether HA-CMC membrane hydrated in saline (slurry) is an effective alternative to HA-CMC membrane for preventing surgical adhesions in rat models of abdominal surgery. MATERIALS AND METHODS: All studies were performed in rat cecal abrasion or sidewall defect models of adhesion formation. Adhesions were examined 7 d after surgery. In separate studies, the effects of variations in slurry composition, volume, and site of application on anti-adhesive properties were studied and compared with untreated controls. Finally, the effectiveness of HA-CMC membrane slurry for preventing adhesions was compared with that of conventional HA-CMC membrane. RESULTS: Application of HA-CMC membrane slurry to traumatized tissue resulted in a significant reduction in the incidence of adhesions compared with untreated controls in both rat surgery models. Slurry was equally effective when applied in low and high film-to-volume formulations, but had minimal effect when applied in a small volume or at a location distal to the injury. Comparison of HA-CMC membrane slurry and conventional HA-CMC membrane indicated similar efficacy for reducing postoperative adhesions. CONCLUSIONS: In rat models of abdominal surgery, HA-CMC membrane slurry reduced postoperative adhesion formation and may be an effective alternative for HA-CMC membrane in situations where its use is limited by its physical properties.

Reduced pain with use of proprietary hyaluronic acid with lidocaine for correction of nasolabial folds: a patient-blinded, prospective, randomized controlled trial.

BACKGROUND: Pain during and after implantation of dermal gel fillers is a consistent complaint of patients undergoing soft tissue augmentation. Reduction of pain during injection would increase patient comfort and improve the overall patient experience. OBJECTIVE: To evaluate pain at the injection site during and after the injection of Prevelle SILK or Captique and to evaluate outcomes after 2 weeks. METHODS & MATERIALS: In a patient-blinded, prospective, randomized, split-face design trial, a non-animal-derived hyaluronic acid based filler formulated with lidocaine (Prevelle SILK) was injected in one nasolabial fold (NLF), and the same filler without lidocaine (Captique) was injected in the contralateral NLF of 45 enrolled patients. Injection site pain was measured using a visual analogue scale at injection (time 0) and 15, 30, 45, and 60 minutes after injection. Patients were asked to return for an evaluation after 2 weeks and to complete a self-assessment questionnaire during the follow-up visit. RESULTS: There was more than 50% less pain associated with the dermal gel with lidocaine than with the same filler without lidocaine at all time points (p<.05). The greatest difference in pain was recorded at the time of injection, and then the effect gradually declined over the 60-minute period. Both fillers were well tolerated, and there was no difference in outcome after 2 weeks. CONCLUSION: Addition of lidocaine to a filler resulted in significantly less pain associated with the procedure without compromising outcomes.

Differential prognostic impact of uPA and PAI-1 in colon and rectal cancer.

BACKGROUND AND OBJECTIVES: Degradation of extracellular matrix is important for tumour growth and invasion, which in part is regulated by the plasminogen activation system. The aim of the study was to evaluate the protein expression of urokinase plasminogen activator (uPA) and plasminogen-activating inhibitor-1 (PAI-1) in plasma, tumour-free mucosa and tumour tissue regarding their prognostic value in colon and rectal cancer. METHODS: Patients (n = 221) undergoing surgery for colorectal cancer were prospectively included. Samples were assayed by ELISA technique. RESULTS: PAI-1 in tumour tissue (p = 0.006), plasma (<0.0001) and uPA in tumour-free mucosa (p = 0.006) were associated with survival in rectal cancer in univariate analysis. An uPA expression level below 1.1 ng/mg (log rank test, p < 0.0001) in tumour-free mucosa was associated with poor survival in rectal cancer. This was true also for patients without disseminated disease (M(0), p = 0.02). PAI-1 in plasma correlated with metastatic disease (p < 0.0001). uPA and PAI-1 were not associated with survival in either tumour tissue, mucosa or plasma in patients with colon cancer. CONCLUSIONS: uPA and PAI-1 have a differential prognostic impact in colon and rectal cancer. Preoperative mucosal uPA and plasma PAI-1 protein expression could possibly be used as prognostic factors in rectal cancer.

The peritoneal fibrinolytic response to conventional and laparoscopic colonic surgery.

BACKGROUND: Laparoscopic surgery is considered to induce less peritoneal trauma than conventional surgery. The peritoneal plasmin system is important in the processes of peritoneal healing and adhesion formation. The present study assessed the peritoneal fibrinolytic response to laparoscopic and conventional colonic surgery. METHODS: Twenty-four patients scheduled for a right colonic resection were enrolled in the trial. Twelve underwent conventional surgery and 12 were operated laparoscopically. Biopsies of the parietal peritoneum were taken at standardized moments during the procedure. Tissue concentrations of tissue-type plasminogen activator (tPA) and its specific activity (tPA-activity), urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1) were measured, using commercial assays. RESULTS: After mobilization of the colon, peritoneal levels of tPA antigen and activity were significantly higher in the laparoscopic group (p < 0.005) due to a decrease in the conventional group (p < 0.05). At the end of the procedure, the concentrations of tPA antigen and activity significantly (p < 0.05) decreased in the laparoscopic group to levels comparable with the conventional group. Neither uPA antigen nor PAI-1 antigen changed throughout the procedures. CONCLUSIONS: Both conventional and laparoscopic surgery inflict a decrease in tPA antigen and its specific activity. Peritoneal hypofibrinolysis initiates more rapidly during conventional, compared to laparoscopic, surgery, but at the conclusion of the surgery, the effect was the same.

Progress of tissue injury in appendicitis involves the serine proteases uPA and PAI-1.

OBJECTIVE: Serine proteases and the matrix metalloproteinases (MMPs) are key factors in the proteolytic cascade and participate in extracellular matrix (ECM) degradation. Fibrinolytic activators and inhibitors may have an effect on inflammatory cells, thereby modulating the inflammatory response. It is reasonable to assume that they may be implicated in the tissue injury in acute appendicitis that subsequently leads to appendix perforation. The purpose of this study was to investigate the expression and distribution of urokinase-type plasminogen activator (uPA) and plasminogen-activator inhibitor type 1 (PAI-1) in appendicitis. MATERIAL AND METHODS: Expression of uPA and expression of PAI-1 were measured in tissue specimens from patients with appendicitis (n=30) and in control specimens (n=9), using the quantitative ELISA technique. Distribution of enzymes was studied with immunohistochemistry. The uPA and PAI-1 levels in the subgroups of appendicitis and controls were compared. RESULTS: The overall expressions of uPA and PAI-1 were greater in appendicitis than in control specimens (p <0.001 and p<0.0001, respectively). Expressions of uPA and PAI-1 in phlegmonous (n=15), gangrenous (n=6) and perforated appendicitis (n=9) were all higher than those in controls (n=9), (p<0.01). Moreover, the PAI-1 level was elevated in perforated appendicitis compared with phlegmonous appendicitis (p<0.01). uPA staining was observed in connection with vascular endothelial cells and the serosa stained intensely in specimens from perforated appendicitis. CONCLUSIONS: The expression of uPA and especially the over-expression of PAI-1 seem to correlate to the progression of local inflammatory response in acute appendicitis.

Studies of TGF-beta(1-3) in serosal fluid during abdominal surgery and their effect on in vitro human mesothelial cell proliferation.

BACKGROUND: Increased transforming growth factor-beta (TGF-beta) levels are associated with fibrosis, affected cell proliferation, and postsurgical adhesion development, but the knowledge regarding TGF-beta response to the surgical trauma is limited. This study investigated TGF-beta(1-3) isoforms and fibrinolytical factors in peritoneal serosal fluid during abdominal surgery, together with the in vitro effect of TGF-beta(1-3) on human mesothelial cell proliferation. MATERIALS AND METHODS: Total as well as biologically active TGF-beta(1-3) and fibrinolytic factors: t-PA, uPA, and PAI-1 were measured in serosal fluid and plasma from 23 patients undergoing colorectal cancer surgery. In vitro proliferation of human primary mesothelial cell cultures upon TGF-beta(1-3) stimulation was also investigated. RESULTS: Total TGF-beta1 and TGF-beta2 levels were similar in serosal fluid and plasma while active fractions were increased in serosal fluid. In contrast, total fraction of TGF-beta3 was higher in serosal fluid compared with plasma, while levels of active fractions did not differ. Plasminogen activators (t-PA, uPA) were elevated while the inhibitor (PAI-1) was decreased in serosal fluid compared with plasma. The in vitro mesothelial cell proliferation studies revealed that high TGF-beta(1-3) concentrations decreased cell proliferation, while lower concentrations of TGF-beta1 increased mesothelial cell proliferation. CONCLUSIONS: This human study shows increased active TGF-beta levels in peritoneal serosal fluid, compared with plasma, during abdominal surgery and that TGF-beta1 at physiological concentrations increased human mesothelial cell proliferation in vitro. TGF-beta cytokines may be involved in postsurgical adhesion formation.

Decreased peritoneal tissue plasminogen activator during prolonged laparoscopic surgery.

BACKGROUND: Peritoneal fibrinolysis is crucial in the peritoneal healing processes and subsequent adhesion formation. During conventional surgery, the peritoneal fibrinolytic system is rapidly disturbed. Short-term laparoscopy does not seem to affect peritoneal fibrinolysis. The aim of the present study was to assess the effect of prolonged laparoscopic surgery on peritoneal fibrinolysis. METHODS: Twelve consecutive patients undergoing laparoscopic gastric bypass surgery for morbid obesity were included in the study. During the procedure, biopsies of the parietal peritoneum were taken at the start of the procedure and each 45 min afterward. Tissue samples were homogenized and tissue-type plasminogen activator (tPA) antigen, tPA activity, urokinase-type PA antigen, and plasminogen activating inhibitors type 1 antigen were measured using commercial assay techniques. RESULTS: Both tPA antigen and its activity progressively decreased during the procedure, reaching significant levels after 90 min of surgery. The levels of uPA antigen and plasminogen activating inhibitors antigen did not significantly change throughout the procedure. CONCLUSIONS: As for conventional surgery, prolonged laparoscopic surgery causes a decreased fibrinolytic activity in the peritoneum due to decreased tPA levels.

A local imbalance between MMP and TIMP may have an implication on the severity and course of appendicitis.

BACKGROUND: Matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) have been demonstrated to be involved in inflammatory conditions in the intestine. The purpose of this study was to investigate whether the alterations of the MMP/TIMP balance might reflect the course of the inflammatory process in acute appendicitis and if the expression and localisation of MMPs and TIMP is variable in the various clinical manifestations of appendicitis. MATERIALS AND METHODS: The study comprises 40 patients (26 men and 14 women) having emergency appendectomy and a control group constituting of 10 patients (5 men and 5 women) having a hemicolectomy for other reasons. MMP and TIMP expressions were assessed and compared in tissue specimens from phlegmonous (n = 15), gangrenous (n = 7), perforated appendicitis (n = 11) and controls with noninflamed appendices (n = 10) by means of enzyme-linked immunosorbent assay technique. Localisation of the enzymes was performed by immunohistochemistry. RESULTS: MMP-1 was significantly higher in gangrenous and perforated appendicitis compared with phlegmonous appendicitis and controls (p < 0.05) while MMP-2 was significantly lower in gangrenous appendicitis compared with phlegmonous appendicitis and controls. MMP-2 was also lower in perforated appendicitis when compared with controls (p < 0.01). Elevated expression of MMP-9 was demonstrated in all groups of appendicitis compared with the controls (p < 0.001). CONCLUSIONS: MMP-9 is the most abundantly expressed MMP of those investigated in inflamed appendix. We postulate that a local imbalance between MMP-9 and TIMP-1 may trigger a perforation. These results suggest that MMPs might be useful as biomarkers of appendices prone to perforation.

Increased TGF-beta 1 protein expression in patients with advanced colorectal cancer.

INTRODUCTION: There is evidence that TGF-beta 1 plays a role as a tumor suppressor in early disease and has pro-oncogenic effects in advanced tumor stage. The aim of the study was to correlate TGF-beta 1 in plasma and tissue to clinical and pathological parameters in patients with various stages of disease progression. METHODS: One hundred sixty-nine patients who underwent surgery for a colorectal carcinoma were prospectively included. Blood samples, tumor free mucosa and tumor biopsies were assayed. RESULTS: TGF-beta 1 protein expression in tumors increased with increasing T-stage regardless of whether patients with metastatic disease were included or not (P = 0.0006). Patients with metastatic disease showed elevated TGF-beta 1 protein expression in both tumor tissue (P = 0.004) and plasma (P = 0.001) compared to those without metastatic disease. TGF-beta 1 protein expression was higher in the colon compared with the rectum in both tumor tissue and tumor-free bowel (P = 0.03), regardless of whether patients with metastatic disease were included or not. This difference was mainly attributable to a higher TGF-beta 1 protein expression in non-metastatic patients with lymph node positivity (P = 0.005). CONCLUSIONS: Higher TGF-beta 1 protein expression is associated with increasing T-stage and metastatic disease, indicating that TGF-beta 1 is of importance in tumor progression. The localization of the tumor seems to influence the TGF-beta 1 protein expression in patients with tumor cell-positive lymph nodes.

Peritoneal and systemic pH during pneumoperitoneum with CO2 and helium in a pig model.

BACKGROUND: Local peritoneal effects of laparoscopic gases might be important in peritoneal biology during and after laparoscopic surgery. The most commonly used gas, CO(2), is known to be well tolerated, but also causes changes in acid-base balance. Helium is an alternative gas for laparoscopy. Although safe, it is not widely used. In this study a method for monitoring peritoneal pH during laparoscopy was evaluated and peritoneal pH during CO(2) and helium pneumoperitoneum was studied as well as its systemic reflection in arterial pH. METHODS: For these experiments 20 pigs were used, with ten exposed to pneumoperitoneum with CO(2), and ten to helium. Peritoneal and sub-peritoneal pH were continuously measured before and during gas insufflation, during a 30-minute period with a pneumoperitoneum and during a 30-minute recovery period. Arterial blood-gases were collected immediately before gas insufflation, at its completion, at 30 minutes of pneumoperitoneum and after the recovery period. RESULTS: Peritoneal pH before gas insufflation was in all animals 7.4. An immediate local drop in pH (6.6) occurred in the peritoneum with CO(2) insufflation. During pneumoperitoneum pH declined further, stabilising at 6.4, but was restored after the recovery period (7.3). With helium, tissue pH increased slightly (7.5) during insufflation, followed by a continuous decrease during pneumoperitoneum and recovery, reaching 7.2. Systemic pH decreased significantly with CO(2) insufflation, and increased slightly during helium insufflation. Systemic pH showed co-variation with intra-peritoneal pH at the the end of insufflation and after 30 minutes of pneumoperitoneum. CONCLUSIONS: Insufflation of CO(2) into the peritoneal cavity seemed to result in an immediate decrease in peritoneal pH, a response that might influence biological events. This peritoneal effect also seems to influence systemic acid-base balance, probably due to trans-peritoneal absorption.

Increased concentration of tissue-degrading matrix metalloproteinases and their inhibitor in complicated diverticular disease.

OBJECTIVE: Complicated diverticular disease is associated with extensive structural changes of the colonic wall. Turnover of extracellular matrix (ECM) plays a pivotal role in this process. Proteolytic enzymes, including matrix metalloproteinases (MMPs), are capable of degrading most components of ECM. Their activity is regulated by inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Disturbances of the MMP-TIMP balance can cause tissue degradation or fibrosis. The aim of this study was to assess the concentration and distribution of MMPs and TIMPs in colonic biopsies. MATERIAL AND METHODS: Twenty-seven patients who had undergone sigmoid colectomy were included in the study. Full-thickness biopsies from affected and non-affected parts of each resected specimen were collected. Expressions of the proteins MMP-1, -2, -3, -9, TIMP-1 and TIMP-2 were quantified by ELISA and localized by immunohistochemistry. RESULTS: The concentrations of MMP-1, MMP-2 and TIMP-1 were significantly higher in affected tissue than concentrations in non-affected tissue (MMP-1 p=0.005, MMP-2 p=0.0003 and TIMP-1 p<0.0001). In affected segments in general, there was an increased expression in the entire bowel wall, predominantly for MMP-2, MMP-3 and TIMP-1. CONCLUSIONS: Concentrations of MMP-1, MMP-2 and TIMP-1 were increased in intestinal segments affected by complicated diverticular disease and distributed throughout the entire bowel wall, which may explain the structural changes.

Peritoneal transforming growth factor beta-1 expression during laparoscopic surgery: a clinical trial.

BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1) is a growth factor involved in various biologic processes, including peritoneal wound healing and dissemination of malignancies. Laparoscopic surgery is evolving rapidly, and indications are increasing. The peritoneal TGF-beta1 expression during laparoscopic surgery is unknown. METHODS: For this study, 50 patients scheduled for laparoscopic cholecystectomy were randomized into five groups, then surgically treated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and end of surgery. Tissue concentrations of total and active TGF-beta1 were measured using enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: There was no significant difference in either total or active TGF-beta1 concentration between peritoneal biopsies taken at the start of surgery and samples taken at the end of the procedure. Patients who underwent surgery with the ultrasonic scalpel had significant lower levels of both active (p < 0.005) and total (p < 0.01) TGF-beta1 at the end of surgery than patients treated with electrocautery. Patients who had surgery with a high light intensity had significantly lower levels of total TGF-beta1 levels (p < 0.005) with an unchanged active part than patients who had surgery with low light intensity. CONCLUSION: The choice of dissection device and the light intensity used in laparoscopic surgery affect peritoneal TGF-beta1 concentrations, indicating that peritoneal biology can be affected by laparoscopic surgery. Because TGF-beta1 is involved in various biologic processes in the peritoneal cavity, this observation may have important clinical consequences.

Peritoneal fibrinolytic response to various aspects of laparoscopic surgery: a randomized trial.

BACKGROUND: Peritoneal fibrinolysis is important in peritoneal wound healing processes and adhesion formation. The peritoneal fibrinolytic response to laparoscopy is merely unknown. In the present study we investigate the effect of short-term laparoscopy on the peritoneal fibrinolytic response and the influence of intra-abdominal pressure, light intensity and choice of dissection device on this response. METHODS: There were 50 patients scheduled for laparoscopic cholecystectomy randomized in five groups operated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and the end of the procedure. Tissue concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1), and the tPA-activity were measured using ELISA techniques. RESULTS: There were no differences in tPA antigen, tPA-activity, uPA antigen, or PAI-1 antigen concentrations in biopsies taken at the beginning compared to samples taken at the end of the operation. Different intra-abdominal pressures, light intensities and the choice dissection device did not affect any of the measured parameters. CONCLUSION: Short-term laparoscopy does not affect the peritoneal fibrinolytic activity. The used intra-abdominal pressure, light intensity and choice of dissection device do not affect peritoneal activity during short-term laparoscopy.