Differences in biomechanical stability using various fibrin glue compositions for mesh fixation in endoscopic inguinal hernia repair.

BACKGROUND: In hernia surgery, mesh fixation with fibrin glue instead of tacks and sutures can demonstrably reduce postoperative morbidity without increasing recurrence rates. In some cases there are significant differences in the biomechanical properties, depending on the functional structure of the meshes. Furthermore, there are various fibrin glue products on the market and these are used for mesh fixation. This study compared the fixation strength of fibrin glues in combination with various meshes. METHODS: Three different lightweight polypropylene meshes (TiMESH™ light, ULTRAPRO™, Optilene(®) LP) were tested. All meshes were fixed using 2 ml of each of the three different fibrin glues (TISSUCOL(®), QUIXIL(®), EVICEL(®)) and tested for their biomechanical stability. The defect in the muscle tissue used was 45 mm for a mesh size of 10 × 15 cm. Measurements were conducted using a standardized stamp penetration test, while aiming not to use a fixation strength of less than 32 N. RESULTS: With TISSUCOL, the fixation of Optilene LP proved to be significantly better than that of TiMESH or ULTRAPRO (97.3 vs. 47.9 vs. 34.9 N, p < 0.001). With EVICEL, it was possible to also achieve good tissue fixation for the ULTRAPRO mesh, while the results obtained for Optilene and TiMESH were relatively poorer [114.7 vs. 92.4 N (p = 0.056), vs. 64.3 N (p < 0.001)]. With QUIXIL, satisfactory results were obtained only for Optilene LP (43.6 N). CONCLUSION: This study showed that there were significant differences in the fixation strength of different polypropylene meshes in combination with various fibrin glues. Experiments demonstrated that for each mesh there is an optimum combination with a particular fibrin glue with respect to the fixation strength. It must now be verified whether these results can be extrapolated to clinical practice.

Comparison of a lightweight polypropylene mesh (Optilene® LP) and a large-pore knitted PTFE mesh (GORE® INFINIT® mesh)--Biocompatibility in a standardized endoscopic extraperitoneal hernia model.

PURPOSE: The use of a mesh with good biocompatibility properties is of decisive importance for the avoidance of recurrences and chronic pain in endoscopic hernia repair surgery. As we know from numerous experiments and clinical experience, large-pore, lightweight polypropylene meshes possess the best biocompatibility. However, large-pore meshes of different polymers may be used as well and might be an alternative solution. METHODS: Utilizing a totally extraperitoneal technique in an established animal model, 20 domestic pigs were implanted with either a lightweight large-pore polypropylene (PP) mesh (Optilene® LP) or a medium-weight large-pore knitted polytetrafluorethylene (PTFE) mesh (GORE® INFINIT® mesh). After 94 days, the pigs were sacrificed and postmortem diagnostic laparoscopy was performed, followed by explantation of the specimens for macroscopic, histological and immunohistochemical evaluation. RESULTS: The mean mesh shrinkage rate was 14.2% for Optilene® LP vs. 24.7% for INFINIT® mesh (p = 0.017). The partial volume of the inflammatory cells was 11.2% for Optilene® LP vs. 13.9% for INFINIT (n.s.). CD68 was significantly higher for INFINIT (11.8% vs. 5.6%, p = 0.007). The markers of cell turnover, namely Ki67 and the apoptotic index, were comparable at 6.4% vs. 12.4% (n.s.) and 1.6% vs. 2.0% (n.s.). In the extracellular matrix, TGF-ß was 35.4% for Optilene® LP and 31.0% for INFINIT® (n.s.). Collagen I (pos/300 µm) deposits were 117.8 and 114.9, respectively. CONCLUSION: In our experimental examinations, Optilene® LP and INFINIT® showed a comparable biocompatibility in terms of chronic inflammatory reaction; however, the shrinkage rate was significantly higher for INFINIT® after 3 months. The higher shrinkage rate of INFINIT® should be taken into account when choosing the mesh size for an adequate hernia overlap.

Single-Incision Cholecystectomy in about 200 Patients.

Background and Aims. We describe our experience of performing transumbilical single-incision laparoendoscopic cholecystectomy as standard procedure for acute and chronic gallbladder diseases. Methods. Between September 2008 and March 2010, 220 patients underwent laparoscopic single-incision surgery. A single port was used for 196 patients and two conventional 5 mm and one 10 mm port in 24 cases. All operations were performed with straight instruments. Results. Single-incision surgery was successfully performed in 215 patients (98%). Three patients (1.4%) required conversion to a three-port technique and two patients (0.9%) to an open procedure. Average age of 142 women (65%) and 78 men (35%) was 47 years (range: 15-89), average ASA status 2 (range: 1-3) and BMI 28 (range: 15-49). Mean operative time was 62 minutes (range: 26-174) and 57 patients (26%) had histopathological signs of acute cholecystitis. Eleven patients (5%) developed to surgery-related complications and nine (4%) of these required a reoperation. The mean followup was 331.5 (range: 11-590) days. Conclusion. Transumbilical single-incision cholecystectomy is a feasible and safe new approach for routine cholecystectomy. After a short learning curve, operation time and complication rate are comparable with standard multiport operation. In addition, most cases of acute cholecystitis can be performed with this technique.

Initial experience in laparoscopic single-port appendectomy: a pilot study.

BACKGROUND: We describe our initial experience performing a single-port (SP) advanced laparoscopic appendectomy in comparison to the conventional port (CP) technique, which uses three ports. METHODS: Between June and September 2009, 40 consecutive patients with acute appendicitis underwent laparoscopic appendectomy at Vivantes Klinikum Am Urban, Berlin, Germany. Twenty patients were operated on using the SP technique (SP group), and the data were compared to a control group of 20 patients operated on using the CP technique (CP group) during the same time period. RESULTS: SP surgery was successfully performed on all patients without conversion to CP laparoscopic appendectomy or an open procedure. The mean age was 27.7 ± 8.3 years in the SP group and 31.7 ± 9.3 in the CP group (p = 0.32). Gender (p = 0.352), status of the American Society of Anesthesiologists (p = 0.765) and body mass index (p = 0.971) did not differ significantly between the two groups. The mean operating time was 48.0 ± 13.2 min in the SP group versus 49.0 ± 19.9 min in the CP group (p = 0.694). No patient in the SP group developed surgical complications. No patient in either group developed an incisional hernia or wound infection during the mean follow-up of 98.17 ± 38.56 days. CONCLUSION: Transumbilical SP appendectomy via a tri-port system with a single incision is a feasible and safe new approach for routine appendectomy. It is easy to perform and good training for more advanced SP surgery.

Donor influence on outcome in patients undergoing liver transplant for primary biliary cirrhosis.

OBJECTIVES: Risk factors for survival after liver transplant owing to primary biliary cirrhosis have been extensively investigated, whereas the donor-specific influence and particularly, the histologic data, have not been sufficiently analyzed. PATIENTS AND METHODS: Donor data of 121 patients who underwent liver transplant for primary biliary cirrhosis and histologic findings of 69 donor liver grafts were assessed according to preoperative status and histologic criteria. Findings were correlated with the histologic and clinical course up to 20 years after orthotopic liver transplant. RESULTS: Risk factors for death were a longer stay in intensive care units (> 7 days) (P < .02), a hypotensive period > 60 minutes (P < .03), and the administration of red blood cells (P < .04). Grafts from donors with liver fibrosis (P < .03), fatty degeneration (P < .04), and liver cell hydrops (P < .04) resulted in a significantly higher risk of primary biliary cirrhosis recurrence. Log rank analysis revealed a significant decreased survival for patients if donors had a prolonged hypotensive period (P < .02) and administration of epinephrine (P < .03) and red blood cells (P < .05). CONCLUSIONS: Our results show that donor histology can affect disease recurrence, especially the grade of inflammation, fibrosis, and fatty degeneration. In addition, prolonged intensive care hospitalization for donors should be avoided.

Mayo risk score for primary biliary cirrhosis: a useful tool for the prediction of course after liver transplantation?

BACKGROUND: Survival after orthotopic liver transplantation (OLT) for primary biliary cirrhosis (PBC) is excellent. In order to define the optimal time point for OLT, the Mayo risk score (MRS) was developed and a score of 7.8 was identified for transplantation. However, in reality most recipients are in a bad condition with a MRS above 7.8. So far it is still unknown if a higher score is associated with more complications after OLT perioperatively and in a long-term follow-up. Therefore, this study was designed to investigate the association of the MRS score with postoperative survival and complications. MATERIAL/METHODS: Between 1989 and 2006, 115 patients were transplanted for histologically proven PBC at the Charité Campus Virchow Clinic. In 98 of these patients, MRS data was available and retrospectively analyzed. Median age of 87 women and 11 men was 54 years (25 to 66 years). RESULTS: The median follow-up after liver transplantation was 109 months (0.5-205 months). Actuarial patient survival after 5, 10 and 15 years was 90%, 88%, and 83%. Calculated survival by MRS without transplantation after 1, 5 and 7 years was 20%, 2% and 1% for these patients. Twelve patients (12%) died and histological recurrence of PBC was detected in 14 patients (14%). Seven patients underwent retransplantation (7%) and 58 patients developed an acute rejection episode (59%). Mean MRS was in all patients 9.54+/-1.35 and did not differ between patients with lethal course, retransplantations, PBC recurrence, rejection episodes and duration of hospital stay. Classification of all patients into a low (<8.5), middle (8.5-10) and high MRS score (>10) did not show a significant difference in long-term survival. Univariate analysis for identifying the level of MRS as risk for death, PBC-recurrence, retransplantation, acute rejection episodes and hospital stay only showed a significant increased risk for acute rejection episodes (1 episode = 0.04; 2 episodes = 0.01) for patients with a MRS above 8.5. CONCLUSIONS: The Mayo risk score is an approved mathematical model predicting survival in non-transplanted patients suffering from PBC. However, the score did not predict the course of our liver transplanted patients in a long-term follow-up. We could not demonstrate a reduced patient survival at a median MRS of 9.4 and about 10.0. Therefore, it is, from our point of view, questionable if the optimal time point for OLT is still 7.8.

Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells.

BACKGROUND AND AIM: Poly (ADP-ribose) polymerase (PARP) inhibitors such as 3-aminobenzamide (3-ABA) enhance the in vitro cytotoxicity of DNA mono-functional alkylating agents such as radiation or chemotherapeutic agents. The aim of this study was to test an approach combining the PARP inhibitor 3-ABA with standard gemcitabine therapy in human pancreatic cancer cells. METHODS: Cell viability was determined by proliferation assay (XTT). Cell-cycle analysis (FACS), ELISA (M30 Apoptosense), Western blot for caspase 8 and PARP, and electron microscopy were used to identify apoptosis. Tumor growth and survival was assessed in nude mice by subcutaneously injected Capan-1 cells. In addition, Ki67 staining was performed on tumors for cell proliferation and in vivo apoptosis induction was measured by TUNEL assay and ELISA. RESULTS: Combination therapy of gemcitabine and 3-ABA suppressed tumor cell growth more than gemcitabine alone in XTT, FACS and ELISA analysis. CONCLUSION: This in vivo study demonstrated a significantly reduced tumor weight and increased survival up to 40 days after cell inoculation with combination therapy compared to animals treated with PBS, gemcitabine or 3-ABA alone. Furthermore, TUNEL assay revealed a significant apoptosis induction and reduced proliferation in the combination group.

Jejunal loop drainage versus direct pancreatic duct drainage after pancreatic head resection.

PURPOSE: Perioperative mortality after pancreatic head resection has fallen to below 5% in high-volume centers, but dehiscence of the pancreatojejunostomy remains a major concern. Despite various methods of protection, insufficiency rates still range from 6% to 19%. External drainage of pancreatic juice from the anastomotic site has shown promising results in the last decade. We compared the morbidity and mortality of two widely used drainage systems. METHODS: The subjects were 143 patients who underwent pancreatic head resection, followed by jejunal loop drainage with the top of the drain being placed between the pancreatojejunostomy and hepaticojejunostomy in 89, and by direct drainage of the pancreatic duct in 54. RESULTS: The median age was similar in both groups. Pancreatic fistula developed in 3 (5%) patients with a pancreatic drain and 6 (7%) with a loop drain. Breakdown of the pancreatojejunostomy occurred in 1 (2%) patient with a pancreatic drain and 2 (2%) with a loop drain. The overall perioperative mortality was 0.7%. The surgical and medical complications and postoperative course were similar in the two groups. CONCLUSION: The choice of drainage system did not impact on the number or severity of postoperative complications or survival, indicating that loop drainage is as safe and effective as direct pancreatic duct drainage.

Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients.

Orthotopic liver transplantation (OLT) is the only effective curative therapy for end-stage primary biliary cirrhosis (PBC). Survival after OLT is excellent, although recent data have shown a recurrence rate of PBC of up to 32% after transplantation. The aim of this study is to investigate the course after disease recurrence, particularly with regard to liver function and survival in a long-term follow-up. Between April 1989 and April 2003, 1,553 liver transplantations were performed in 1,415 patients at the Charité, Virchow Clinic. Protocol liver biopsies were taken after one, three, five, seven, 10 and 13 yr. One hundred (7%) patients suffered from histologically proven PBC. Primary immunosuppression consisted of cyclosporine (n = 54) or tacrolimus (Tac) (n = 46). Immediately after OLT, all patients received ursodeoxycholic acid. Corticosteroids were withdrawn three to six months after OLT. The median age of the 85 women and 15 men was 55 yr (range 25-66 yr). The median follow-up after liver transplantation was 118 months (range 16-187 months) and after recurrence 30 months (range 4-79 months). Actuarial patient survival after five, 10 and 15 yr was 87, 84 and 82% respectively. Ten patients (10%) died after a median survival time of 32 months. Two of these patients developed organ dysfunction owing to recurrence of PBC. Histological recurrence was found in 14 patients (14%) after a median time of 61 months (range 36-122 months). Patients with Tac immunosuppression developed PBC recurrence more often (p < 0.05) and also earlier (p < 0.05). Fifty-seven patients developed an acute rejection and two patients a chronic rejection episode. Liver function did not alter within the first five yr after histologically proven PBC recurrence. Multivariate analysis of the investigated patients showed that the recipient's age and Tac immunosuppression were significant risk factors for PBC recurrence. Long-term follow-up of up to 15 yr after liver transplantation, owing to PBC, in addition to maintenance of liver function, shows excellent organ and patient survival rates. Although protocol liver biopsies revealed histological recurrence in 14 (14%) patients, only two patients developed graft dysfunction. Tac-treated patients showed more frequently and also earlier histologically proven PBC recurrence; however, in our population we could not observe an impact on graft dysfunction and patient's survival.

Overcoming acquired resistance to TRAIL by chemotherapeutic agents and calpain inhibitor I through distinct mechanisms.

We recently found that repeated application of adenovectors expressing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or recombinant TRAIL proteins to TRAIL-susceptible cancer cells resulted in selection and expansion of TRAIL-resistant cells. Overcoming this acquired resistance to TRAIL is desirable for TRAIL-mediated cancer therapy. Here we demonstrate that several chemotherapeutic agents, including 5-fluorouracil (5-FU) and mitomycin, and calpain inhibitor I, an NFkappaB inhibitor, can overcome acquired resistance to TRAIL in DLD1 colon cancer cells. The combination of TRAIL (approved gene symbol TNFSF10) gene therapy and 5-FU enhanced tumor suppression in vivo in nude mice bearing subcutaneous tumors established from TRAIL-resistant colon cancer cells. Whereas treatment with the combination of TRAIL and 5-FU or mitomycin led to enhanced activation of caspase-3, the combination of TRAIL and calpain inhibitor I resulted in enhanced activation of both caspase-8 and caspase-3. Moreover, mitomycin, but not 5-FU or calpain inhibitor I, induced overexpression of the BAX gene, which was correlated with enhanced TRAIL-induced cell killing in TRAIL-resistant DLD1 cells. Together, these results suggest that acquired resistance to TRAIL can be overcome by different mechanisms and that combinations of TRAIL gene therapy and chemotherapy may be a useful approach for cancer treatment.

Induction of apoptosis and down-regulation of Bcl-XL in cancer cells by a novel small molecule, 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol.

In a search for new anticancer agents, we identified that 2[[3-(2,3-dichlorophenoxy) propyl]amino]ethanol (2,3-DCPE) induced apoptosis more effectively in various cancer cells than in normal human fibroblasts. We further evaluated the cell-killing effects of this compound in vitro in several human cancer cell lines and normal human fibroblasts. A cell viability assay showed that IC(50)s for human colon cancer cell lines LoVo and DLD-1, for human lung cancer cell lines H1299 and A549, and for normal human fibroblasts were 0.89, 1.95, 2.24, 2.69, and 12.6 micro M, respectively. Subsequent studies revealed that 2,3-DCPE could cause cleavage of caspase-8, caspase-3, caspase-9, and poly(ADP-ribose) polymerase and release of cytochrome c in cancer cells but not in normal human fibroblasts. Our data also showed that 2,3-DCPE attenuated the protein level of Bcl-XL and that apoptosis induction by 2,3-DCPE could be blocked by enforced overexpression of Bcl-XL. Our results suggest that 2,3-DCPE might be a potential new anticancer agent.