Biomedical subjects

Volker Schumpelick

Publications and source records attributed to Volker Schumpelick.

At least 19 recordsLinked to original sources

PubMed2006

Incisional hernia: challenge of re-operations after mesh repair.

BACKGROUND AND AIMS: The widespread use of meshes for the repair of incisional hernia is currently followed by an increasing number of re-operations. The incidence of incisional hernia recurrence after mesh repair varies between 3 and 32%. The problem of mesh failure and options for another surgical intervention seem rather unattended. METHODS: We present our experience of 77 re-operations after previous mesh repair that were performed between 1995 and 2004 out of a total of 1,070 operations for incisional hernia. The retrospective analysis focused on recurrence in relation to location, material of the previous mesh repair and the surgical procedure to resolve the problem. RESULTS: The locations of the preceding meshes were epifascial as onlays (n=23), retromuscular as sublays (n=46), within the defect as inlays (n=6) or intraperitoneally (n=2). The direction of the incision was vertical medial (n=41) or horizontal crossing the linea semilunaris (n=36). Recurrences after median incisional hernia mesh repair mainly occurred at the cranial border of the mesh subxiphoidal. Except for two patients, all recurrences manifested at the margin of the enclosed mesh. CONCLUSIONS: Re-operation after previous mesh repair is a surgical challenge. The type of revision procedure has to consider the position and material of the previous mesh. In our clinic recurrences, heavyweight polypropylene meshes were mostly treated with mesh exchange and lightweight polypropylene meshes could be treated by extension with a second mesh. In contrast to suture techniques, deficient mesh repairs are more evidently related to technical problems.

Aged↗

PubMed2006

Comparative genomic hybridization analysis on male breast cancer.

The spectrum of genetic alterations in primary male breast cancer is not well established. We analyzed chromosomal imbalances in 39 tumor samples from primary male breast cancer by comparative genomic hybridization (CGH) and correlated CGH findings with clinicopathological factors. Chromosomal gains were most frequent at 1q (46%), 8q (46%), 16p (36%), 17q (36%), Xq (28%), 20q (26%) and Xp (18%). Losses were most commonly observed at 8p (36%), 16q (28%), 13q (28%), 6q (18%), 11q (18%) and 22q (18%). Gains at 16p, 20q and Xq and losses at 13q correlated significantly with higher degree of cytogenetic complexity. Significant associations with clinicopathological factors were observed for +8q and -16q with larger tumor size and -16q with lower proliferative activity and lower grade of malignancy. A comparison with reported CGH data from female breast cancer showed a similar pattern of chromosomal imbalances, including +1q, -8p, +8q, -13q, +16p, -16q, +17q and +20q. Our results indicate that male breast cancer shares a common pattern of imbalances with female breast cancer, suggesting that similar genetic events may underlie the development and progression of male and female breast cancer.

Adult↗

PubMed2006

Collagen in colon disease.

The pathophysiology of wound healing in the bowel wall suggests that collagen and matrix metalloproteinases (MMPs) have an important role in the changes of the bowel wall seen in several colonic diseases. Several recent studies suggest that disturbances of the collagen texture and the extracellular matrix (ECM) metabolism are major factors leading to the onset of diverticular disease. Changes of the ECM also play a role in the development of inflammatory bowel diseases. Regarding the permanent remodeling of the bowel wall, any imbalance of the ECM could support the onset of chronic inflammation and the development of fistula formation, such as that seen in patients with Crohn's disease. Disturbances of the ECM play a role in the pathogenesis of anastomotic leakage after large bowel surgery and suggest the presence of a genetically defined risk population with disturbed wound healing mechanisms. This concept could explain the well known situation where an anastomotic breakdown is observed, despite the absence of other known risk factors and after a technically correct anastomosis.

Collagen↗

PubMed2006

Evaluation of a modified piezoresistive technique and a water-capsule technique for direct and continuous measurement of intra-abdominal pressure in a porcine model.

OBJECTIVE: Intravesical pressure measurement is considered to be the gold standard for the assessment of intra-abdominal pressure. However, this method is indirect and depends on a physiologic bladder function. We evaluated a modified piezoresistive technique and a water-capsule technique for direct and continuous intra-abdominal pressure measurement. DESIGN: Experimental study. SETTING: Animal research laboratory. SUBJECTS: Eleven male domestic pigs. INTERVENTIONS: In anesthetized and mechanically ventilated animals, CO2 was insufflated to stepwise increase the intra-abdominal pressure to 30 mm Hg. Pressure was then held constant for 9 hrs followed by decompression. Piezoresistive measurement and water-capsule measurement probes were placed intra-abdominally. MEASUREMENTS AND MAIN RESULTS: Readings of intravesical pressure measurement, piezoresistive measurement, and water-capsule measurement were taken hourly. Mean difference to insufflator readings, confidence intervals, and limits of agreement were calculated. Differences between applied pressure and intra-abdominal pressure readings were assessed using a two-factor analysis of variance. No significant differences between methods could be observed. During stepwise pressure increase, limits of agreements were -3.6 to 3.6 mm Hg. Confidence intervals were -3.4 to 3.5 (intravesical pressure measurement), -1.6 to 1.5 (piezoresistive measurement), and 0.5 to 2.9 mm Hg (water-capsule measurement). In the presence of constantly elevated intra-abdominal pressure, limits of agreement ranged from -8.2 to +8.2 mm Hg. Confidence intervals were -0.4 to 6.2 (intravesical pressure measurement), -0.2 to 2.7 (piezoresistive measurement), and 1.1 to 5.1 mm Hg (water-capsule measurement). CONCLUSIONS: Both piezoresistive measurement and water-capsule measurement had smaller confidence intervals than intravesical pressure measurement, indicating higher precision, whereas water-capsule measurement had a significant offset. Piezoresistive measurement could be the most suitable device for continuous direct intra-abdominal pressure monitoring in specific patients.

Abdomen↗

PubMed2005

Is there a risk of infertility after inguinal mesh repair? Experimental studies in the pig and the rabbit.

The implantation of a non-absorbable polypropylene mesh during hernia repair causes chronic foreign body reaction involving the surrounding tissue. In case of inguinal hernia repair using mesh techniques, the spermatic cord is potentially affected by this chronic inflammatory tissue remodeling. This effect has been investigated using standardized animal models (pig and rabbit). Fifteen adult male pigs underwent transinguinal preperitoneal implantation of a polypropylene mesh. The contralateral side with a Shouldice repair served as control. After 7, 14, 21, 28, and 35 days, three animals were sacrificed. The spermatic cords were resected and analyzed histologically. In a second experiment Lichtenstein repair using the same polypropylene mesh and Shouldice repair on the contralateral side was done in eight chinchilla rabbits. Three animals served as controls. Three months after operation, the analysis included testicular size, testicular temperature, and testicular and spermatic cord perfusion. We added histological evaluation of the foreign body reaction and the spermatogenesis using the Johnsen score. In the pig, we observed a certain foreign body reaction with diffuse infiltrating inflammatory cells after mesh implantation. Venous thrombosis of the spermatic veins occurred in five of 15 cases. One animal presented focal fibrinoid necrosis of the deferent duct wall. The side of Shouldice repair showed only minor postoperative changes. In the rabbit, we also observed a typical foreign body reaction at the interface between mesh and surrounding tissue, which was not detectable after Shouldice repair. The mesh repair led to a decrease of arterial perfusion, testicular temperature, and the rate of seminiferus tubules with regular spermatogenesis classified as Johnsen 10 (Lichtenstein: 48.1%, Shouldice: 63.8%, controls: 65.8%). Testicular volume increased about 10% after each operation. The implantation of a polypropylene mesh in the inguinal region induces major response of the structures of the spermatic cord. This may have an influence also on spermatogenesis. Due to this a strict indication for implantation of a prosthetic mesh during inguinal hernia repair is recommended.

Animals↗

PubMed2005

Missing effects of zinc in a porcine model of recurrent endotoxemia.

BACKGROUND: Chronic human sepsis often is characterised by the compensatory anti-inflammatory response syndrome (CARS). During CARS, anti-inflammatory cytokines depress the inflammatory response leading to secondary and opportunistic infections. Proved in vitro as well as in vivo, zinc's pro-inflammatory effect might overcome this depression. METHODS: We used the model of porcine LPS-induced endotoxemia established by Klosterhalfen et al. 10 pigs were divided into two groups (n = 5). Endotoxemia was induced by recurrent intravenous LPS-application (1.0 microg/kg E. coli WO 111:B4) at hours 0, 5, and 12. At hour 10, each group received an intravenous treatment (group I = saline, group II = 5.0 mg/kg elementary zinc). Monitoring included hemodynamics, blood gas analysis, and the thermal dilution technique for the measurement of extravascular lung water and intrapulmonary shunt. Plasma concentrations of IL-6 and TNF-alpha were measured by ELISA. Morphology included weight of the lungs, width of the alveolar septae, and rate of paracentral liver necrosis. RESULTS: Zinc's application only trended to partly improve the pulmonary function. Compared to saline, significant differences were very rare. IL-6 and TNF-alpha were predominately measured higher in the zinc group. Again, significance was only reached sporadically. Hemodynamics and morphology revealed no significant differences at all. CONCLUSION: The application of zinc in this model of recurrent endotoxemia is feasible and without harmful effects. However, a protection or restoration of clinical relevance is not evident in our setting. The pulmonary function just trends to improve, cytokine liberation is only partly activated, hemodynamics and morphology were not influenced. Further pre-clinical studies have to define zinc's role as a therapeutic tool during CARS.

Animals↗

PubMed2005

Adhesion prevention comparing liquid and solid barriers in the rabbit uterine horn model.

OBJECTIVE: The purpose of this study was to assess the ability of four different either solid or fluid barriers to reduce adhesions in an established model of gynecological surgery. STUDY DESIGN: 50 Chinchilla rabbits underwent bilateral deperitonealization and devascularization of the uterine horns (DUH). Afterwards solid membranes of either hyaluronic acid-carboxymethylcellulose (HA-CMC) or lactide-caprolactone-copolymer (LCC) were placed around the injured uterine horns or fluids (icodextrin (ID) or phospholipids (PL)) were intraperitonealy administered. The control group went without protection. After 10 days, adhesions were measured by planimetry. RESULTS: Phospholipids (median 49.8 mm2) significantly reduced adhesion areas in comparison to all other groups: surgical controls (median 230.6 mm2), HA-CMC (median 194.9 mm2), LCC (median 327.1 mm2), and icodextrin (median 242.1 mm2). CONCLUSIONS: These results prove the efficacy of phospholipids to reduce primary adhesion formation in the Chinchilla double uterine horn model compared to HA-CMC, LCC and icodextrin. Future clinical studies are recommended.

Animals↗

PubMed2005

Inhibition of gastric cancer cell adhesion in nude mice by inraperitoneal phospholipids.

Adhesion of tumor cells to mesothelial cells or extracellular matrix components is a pivotal step in developing peritoneal dissemination after gastric cancer. As phospholipids were found to reduce adhesion formation, especially at sites of peritoneal lesions, we assessed the inhibition of attachment of NUGC-4 gastric cancer cells by local treatment with phospholipids to the peritoneum in nude mice. Gastric cancer cells (1xl0(6)) suspended in either normal saline (controls) or phospholipid suspension 75 mg/kg body weight (PL75) or 150 mg/kg (PL150) were injected intraperitoneally into 90 female BALB/c nu/nu mice. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days the extent of peritoneal carcinosis and the Peritoneal Cancer Index were evaluated. Statistical analysis was performed with two factorial ANOVAs. The level of significance was adjusted according to Bonferrorni (alpha = 0.00278). During a 90-day observation period the survival rate was determined using the log rank test. After 30 days the intraperitoneal tumor volume was reduced by PL150 up to 0.6 ml (SEM 0.16) and 0.48 ml (SEM 0.09) in mice with peritoneal lesions compared to 0.9 ml (SEM 0.2) and 0.9 ml (SEM 0.1) in the control group (P = 0.04). The mean area of tumor adhesion amounted to 145 mm(2) (SEM 17) (P = 0.08) and 164 mm(2) (SEM 32.8) (P = 0.049) with peritoneal lesions after treatment with PL150 [controls: 216 mm(2) (SEM 28.5) and 245 mm(2) (SEM 29.3)]. The peritoneal cancer index was 16.4 (SEM 1.7) in the control group and 9 (SEM 1.68) with PL150 (P = 0.0002). In the subgroup with peritoneal lesions, the respective values were as follows: controls: 20.8 (SEM 0.85); PL 150:14.3 (SEM 1.07) (P = 0.0001). We found a prolonged survival rate after treatment with PL150. However, this effect was not significantly different to that seen in the control group. Treatment with PL75 had no significant influence. Phospholipids may be an efficacious and economic tool for reducing peritoneal tumor cell adhesion and consequently the development of peritoneal carcinosis after resection of gastric cancer.

Animals↗

PubMed2005

Incisional hernia: open techniques.

Even with the routine use of mesh, repairing an incisional hernia is a challenge. Increasing evidence of impaired wound healing in these patients supports routine use of an open prefascial, retromuscular mesh repair. Basic pathophysiologic principles dictate that for a successful long-term outcome and prevention of recurrence a wide overlap underneath healthy tissue is required. The extent of this overlap should be 5 cm in all directions: surrounding the wound closure, subxiphoidal underneath the ribs, below the arcuate line, and retropubic.

Hernia, Ventral↗

PubMed2005

Gentamicin supplementation of polyvinylidenfluoride mesh materials for infection prophylaxis.

Hernia repair evolved from pure tissue repair to mesh repair due to decreased recurrence rates. However, concern exists about mesh-related infections occurring even several years after initial operation. Therefore, a polyvinylidenfluoride (PVDF) mesh material was constructed and surface modified by plasma-induced graft polymerization of acrylic acid (PVDF+PAAc). Antimicrobial treatment was sought by binding of gentamicin (PVDF+PAAc+Gentamicin). In vitro efficacy and cytotoxicity was measured by agar diffusion test, L929 cytotoxicity testing and by analyzing the amount of gentamicin release from the mesh surface. In vivo biocompatibility was evaluated in 45 Sprague-Dawley rats. 7, 21 and 90 days after mesh implantation the amount of inflammatory and connective tissue as well as the percentage of proliferating (Ki67) and apoptotic cells (TUNEL) were analyzed at the perifilamentary region. Agar diffusion tests showed sufficient local antimicrobiotic effects against the bacteria tested after 24h of incubation. No signs of cytotoxicity could be identified by L929 testing. Furthermore, surface modification did not affect the in vivo biocompatibility. At the end of the observation period, no significant differences were found for the perifilamentary amount of inflammatory cells and connective tissue and the percentage of Ki67 and TUNEL positive stained cells. The presented data confirm that an antibiotic surface modification of PVDF mesh samples is feasible. By analyzing cytotoxicity in vitro as well as biocompatibility in vivo no side effects were observed.

Animals↗

PubMed2005

Effect of zinc pretreatment on pulmonary endothelial cells in vitro and pulmonary function in a porcine model of endotoxemia.

BACKGROUND: During endotoxemia, the systemic inflammatory response often leads to severe pulmonary damages. Destruction of endothelial cells, interstitial edema, and interstitial alveolitis depress pulmonary circulation and raise extravascular lung water and intrapulmonary shunt. As protective effects of zinc are described in vitro as well as in vivo, this study investigates its impact on septic porcine pulmonary endothelial monolayers as well as on the pulmonary function of endotoxemic pigs. MATERIALS AND METHODS: Cell culture: Endothelial cells were incubated with ascending doses of zinc and pooled with septic plasma. Cellular damage, metabolism, and proliferation were measured by vital stain, XTT-assay, and BrDU-ELISA. HSP70 was visualized by immunohistochemistry. Animal study: We used an established porcine model. Twenty-four hours before endotoxemia (intravenous infusion of 1.0 microg/kg Escherichia coli endotoxin WO111:B4), each animal received an intravenous pretreatment. Group I (n = 3): saline pretreatment, group II (n = 5): zinc pretreatment (5 mg/kg elementary zinc). Monitoring included blood gas analysis and the thermal dye dilution technique. RESULTS: In vitro, zinc leads to significantly altered rates of viable cells, metabolism, and proliferation with the strongest cell-protective effect at moderate concentrations of 1 microg/ml Zn2+. This correlates with a qualitatively increased expression of HSP70. In vivo, the zinc pretreatment before LPS-induced endotoxemia grossly improves all measured hemodynamic and pulmonary parameters. CONCLUSION: Zinc pretreatment of endotoxemia decreases cellular damages in vitro and improved pulmonary function in vivo. This could be mediated by the heat shock response. Further studies, particularly concerning the dose-effect relationship and the underlying mode of action, are mandatory.

Animals↗

PubMed2005

Changes of the extracellular matrix as a risk factor for anastomotic leakage after large bowel surgery.

BACKGROUND: Despite improved surgical techniques, anastomotic leakage remains as a serious complication in colorectal surgery, producing increased morbidity and mortality. This prospective study was initiated to test the hypothesis that preexisting disorders in the extracellular matrix (ECM) may be a factor influencing the onset of anastomotic wound healing complications. METHODS: In this prospective study of 119 patients with colorectal anastomoses, 30 clinical parameters with possible influence on anastomotic complications were evaluated. From all patients, samples of macroscopically intact colonic tissue were obtained at the index operation. Crosspolarization microscopy was performed to analyze the collagen type I/III ratio, and immunohistochemical studies were done to determine the expression of matrix metalloproteinase (MMP) 1, 2, 9, and 13. The patients with uncomplicated postoperative healing were compared with those developing anastomotic leakage. RESULTS: Patients with impaired anastomotic healing exhibited a significantly lower collagen type I/III ratio compared with the controls. Significantly higher expression of MMP-1 and MMP-2 in the mucosal layers and of MMP-2 and MMP-9 in the submucosal layers was found in the normal bowel wall of the leakage group. These findings were statistically independent from the clinical parameters. CONCLUSION: The present study confirms the hypothesis that disturbances of the ECM play a role in the pathogenesis of anastomotic leakage after large bowel surgery.

Anastomosis, Surgical↗

PubMed2005

Fluid resuscitation preserves cardiac output but cannot prevent organ damage in a porcine model during 24 h of intraabdominal hypertension.

According to a previous study, a pathologically increased intraabdominal pressure (IAP) reduces cardiac output (CO) and results in medium- to high-grade organ damage in a porcine model of the abdominal compartment syndrome (ACS). The purpose of this study was to evaluate whether fluid resuscitation can preserve organ integrity together with CO. We examined 12 domestic pigs with a mean body weight of 48 kg. We used a CO2 pneumoperitoneum to increase the IAP to 30 mmHg in 6 animals, and the others served as control group. The investigation period was 24 h. In addition to a standard infusion regimen, Ringer's solution was infused to maintain CO at the level of control animals. Hemodynamic parameters (ITBV, EVLW, MAP, CVP), urine output, inspiratory pressure, as well as serum parameters (e.g., ALT, lipase, AP, lactate, creatinine) were recorded. In the end histological examination of liver, bowel, kidney, and lung was performed. CO, ITBV, EVLW, and urine output did not change when compared with control. Fluid intake was increased (P < 0.01) when compared with control (10,570 +/- 1,928 vs. 3,918 +/- 1,042 mL). CVP, MAP, and inspiratory pressure were increased. Serum parameters did not change. Acidosis occurred in the study group. Liver, bowel, kidney, and lung displayed mean- to high-grade damage (P < 0.01). Although extensive fluid resuscitation preserved CO, diuresis, and serum parameters in this previously described model of the ACS, organ damage occurred. In the clinical regard, these results support decompressive treatment in the presence of pathologically high IAP despite "normalized" parameters.

Acidosis↗

PubMed2004

Phospholipids reduce gastric cancer cell adhesion to extracellular matrix in vitro.

BACKGROUND: Nidation of floating tumour cells initiates peritoneal carcinosis and limits prognosis of gastro-intestinal tumours. Adhesion of tumour cells to extracellular matrix components is a pivotal step in developing peritoneal dissemination of intraabdominal malignancies. Since phospholipids efficaciously prevented peritoneal adhesion formation in numerous animal studies we investigated their capacity to reduce adhesions of gastric cancer cells to extracellular matrix components (ECM). METHODS: Human gastric cancer cells (NUGC-4, Japanese Cancer Research Resources Bank, Tokyo, Japan) were used in this study. Microtiter plates were coated with collagen IV (coll), laminin (ln) and fibronectin (fn). Non-specific protein binding of the coated wells was blocked by adding 1% (w/v) BSA (4 degrees C, 12 h) and rinsing the wells with Hepes buffer. 50.000 tumour cells in 100 microl medium were seeded into each well. Beside the controls, phospholipids were added in concentrations of 0.05, 0.1, 0.5, 0.75 and 1.0/100 microl medium. After an incubation interval of 30 min, attached cells were fixed and stained with 0.1% (w/v) crystal violet. The dye was resuspended with 50 microl of 0.2% (v/v) Triton X-100 per well and colour yields were then measured by an ELISA reader at 590 nm. Optical density (OD) showed a linear relationship to the amount of cells and was corrected for dying of BSA/polystyrene without cells. RESULTS: The attachment of gastric cancer cells to collagen IV, laminin, and fibronectin could be significantly reduced up to 53% by phospholipid concentrations of 0.5 mg/100 microl and higher. CONCLUSION: These results, within the scope of additional experimental studies on mice and rats which showed a significant reduction of peritoneal carcinosis, demonstrated the capacity of phospholipids in controlling abdominal nidation of tumour cells to ECM components. Lipid emulsions may be a beneficial adjunct in surgery of gastrointestinal malignancies.

Cell Adhesion↗

PubMed2004

Phospholipids reduce the intraperitoneal adhesion of colonic tumor cells in rats and adhesion on extracellular matrix in vitro.

OBJECTIVE: To evaluate the influence of intraperitoneal treatment with phospholipids on the formation of peritoneal carcinosis after inoculation of colonic tumor cells in rats. The presence of tumor cells in the peritoneal cavity serves as a prognostic marker for postoperative survival after resection of gastrointestinal cancer. Intraperitoneal tumor cell attachment is a pivotal step in developing peritoneal carcinosis. Intraabdominal application of phospholipids resulted in a significant decrease of adhesion formation, especially at sites of peritoneal lesions. METHODS: 2x10(6) colonic tumor cells (DHD/K12/TRb) were injected intraperitonely in female BD-IX rats. A total of 90 rats were divided into three groups with treatments of phospholipids at 75 mg/kg or 150 mg/kg bodyweight or sodium chloride at 0.9% in the control group. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days, the extent of peritoneal carcinosis was determined by measuring the tumor volume, the area of tumor attachment and the Peritoneal Cancer Index. Over a 90-day observation period, the survival rate was analyzed. In vitro, we examined the reduction of tumor cell adhesion on extracellular matrix components after treatment with phospholipids. Microtiter plates were coated with laminin, fibronectin or collagen IV for adhesion experiments. RESULTS: In our study, we found a significant reduction of peritoneal dissemination with respect to all evaluation methods after treatment with phospholipids at 150 mg/kg in animals without peritoneal lesions. This could not be achieved using the lower concentration of phospholipids (75 mg/kg). In vitro, the maximum reductions of tumor cell adhesion by phospholipids compared with the control values for laminin and fibronectin were 46% and 37%, respectively, whereas for collagen IV the reduction was only 24% ( p<0.0001). CONCLUSIONS: A new method of prevention of intraperitoneal tumor cell adhesion, possibly leading to a reduced incidence of peritoneal carcinosis after surgery of gastrointestinal tumors, is introduced.

Adenocarcinoma↗

PubMed2004

Simultaneous determination of matrix metalloproteinase (MMP)-7, MMP-1, -3, and -13 gene expression by multiplex PCR in colorectal carcinomas.

BACKGROUND AND AIMS: MMP-7, a member of the matrix metalloproteinase family, is believed to play a significant role in the growth and proliferation of colon cancer cells. The aim of this study was to evaluate MMP-7 gene expression in comparison with MMP-1, MMP-3, and MMP-13 in patients with resectable rectal and colon cancer by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: Biopsy samples of tumor ( n=30) and distant normal mucosa ( n=30) from 30 patients were obtained intraoperation. Messenger (m)RNA was extracted from all of the tissue samples and reverse transcribed to double-stranded cDNA. Semi-quantitative RT-PCR was performed to study the MMP gene expression in both the tumor and normal mucosal specimens. MMP mRNA values were expressed relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample. RESULTS: In all 30 cases an increase in MMP-7 mRNA expression was detected in the cancerous tissue ( p=0.00004). In 21 out of 30 cases an increase in MMP-13 mRNA ( p=0.023) and in 22 out of 30 cases an increase in MMP-3 mRNA ( p=0.075) was detected in the cancerous tissue. In contrast, there was no significant change in the MMP-1 expression of normal and cancerous mucosal specimens in either colon or rectal carcinomas. There were no significant differences between rectum and colon carcinomas. CONCLUSION: Taking into account our earlier studies, we conclude that most cases of colorectal carcinogenesis are characterized by enhanced expression of MMP-7, -13, -3 and the gelatinases, whereas MMP-1-expression is very inconsistent and not overexpressed in many cases. MMP-7 inhibition as well as inhibition of MMP-13 and MMP-3 may be a useful preventive or therapeutic adjunct in colorectal cancer.

Aged↗

PubMed2003

Decreased collagen type I/III ratio in patients with recurring hernia after implantation of alloplastic prostheses.

BACKGROUND: Abnormal collagen metabolism is suspected to play an important role in the pathogenesis of recurring inguinal and incisional hernias. Whereas alloplastic prostheses are nowadays routinely used, the quantity and quality of collagen formation after repair in humans has not been analysed in a large cohort. METHOD: Seventy-eight prostheses (Prolene, Atrium, Marlex, Vypro, Mersilene, Gore-Tex) implanted for inguinal and incisional hernia repair were explanted because of recurrence, chronic pain or infection. The mean implantation period was 17.9+/-11.2 (range 0.5-48) months. Collagen formation was investigated quantitatively (collagen-protein ratio) and qualitatively (collagen type I/III ratio). Results were related to clinical data that included gender, age, implantation period, indication for implantation/explantation, type and location of prosthesis. RESULTS: Mean collagen-protein ratio was 45.3+/-8.5 microg/mg, with significant differences between male (43.8+/-9.1 microg/mg) and female tissue samples (48.1+/-6.8 microg/mg, P=0.033). The mean collagen type I/III ratio of all samples investigated was 2.1+/-1.4. Samples explanted for recurring hernias exhibited a significantly decreased ratio (1.3+/-0.7, P<0.05) compared to samples explanted because of pain (3.4+/-1.2) or infection (2.9+/-1.6). Multivariate analysis excluded independent effects of age, gender, indication for implantation of prostheses, location and implantation period on collagen type I/III ratio. CONCLUSION: The present study confirms the importance of a biological approach, next to technical aspects, to the understanding of the pathogenesis of recurrent hernia formation and underscores the presence of a disturbed scarring process. The composition of scar tissue with a lowered collagen type I/III ratio and, therefore, reduced tensile strength may be a major contribution to hernia recurrence.

Cicatrix↗

PubMed2003

Evaluation of two novel methods for the direct and continuous measurement of the intra-abdominal pressure in a porcine model.

OBJECTIVE: Intravesical bladder pressure (IVP) measurement is considered to be the gold standard for the assessment of intra-abdominal pressure (IAP). However, this method is indirect, discontinuous, and potentially infectious and relies on a physiological bladder function. This study evaluated two novel methods for direct, continuous IAP measurement. DESIGN AND SETTING: Experimental study in an animal research laboratory. SUBJECTS: 18 male domestic pigs. INTERVENTIONS: CO(2) was insufflated to increase the IAP to 30 mmHg for 18 and 24 h in six animals each. Another six animals served as controls. A piezoresistive (PRM) and an air-capsule (ACM) pressure measurement probe were placed intra-abdominally and of IAP was measured every 1 h (PRM/ACM) or every 2 h (IVP). The mean difference between insufflator readings and IAP values and limits of agreement (mean difference +/-2 SD) were calculated. MEASUREMENTS AND RESULTS: In the presence of applied pressure IVP and PRM remained significantly below insufflator readings while ACM values showed no difference. Mean difference (and limits of agreement) were 4.5 (-2.1 to 11.1 mmHg), 1.6 (-8.0 to 11.2 mmHg), and 0.5 (-4.5 to 5.4 mmHg) for IVP, PRM, and ACM. The mean measurement-to-measurement drift of the ACM values was 9.0+/-10.2 mmHg. CONCLUSIONS: In this model agreement of PRM and ACM with insufflator readings was comparable to IVP. As both methods may be advantageous regarding continuous straightforward measurement of IAP, the employment in further experimental and clinical investigations is suggested.

Abdomen↗