Increased Elasticity Modulus of Polymeric Materials Is a Source of Surface Alterations in the Human Body.

The introduction of alloplastic materials (meshes) in hernia surgery has improved patient outcome by a radical reduction of hernia recurrence rate, but discussion about the biocompatibility of these implanted materials continues since observations of surface alterations of polypropylene and other alloplastic materials were published. This study intends to investigate if additives supplemented to alloplastic mesh materials merge into the solution and become analyzable. Four polypropylene and one polyester alloplastic material were incubated in different media for three weeks: distilled water, saline solution, urea solution, formalin, and hydrogen peroxide. No swelling or other changes were observed. Infrared spectroscopy scanning of incubated alloplastic materials and NMR studies of extracted solutions were performed to investigate loss of plasticizers. The surface of the mesh materials did not show any alterations independent of the incubation medium. FT-IR spectra before and after incubation did not show any differences. NMR spectra showed leaching of different plasticizers (PEG, sterically hindered phenols, thioester), of which there was more for polypropylene less for polyester. This could be the reason for the loss of elasticity of the alloplastic materials with consecutive physically induced surface alterations. A mixture of chemical reactions (oxidative stress with additive leaching from polymer fiber) in connection with physical alterations (increased elasticity modulus by loss of plasticizers) seem to be a source of these PP and PE alterations.

Sutureless open vascular anastomosis connector: An experimental study.

The objective of this study was to assess the safety of a new developed sutureless vascular adapter system in a porcine model. In five pigs, 4-cm-long polyester prosthesis (6 mm diameter) were implanted and anastomosed with the newly developed adapter proximally and suture anastomosis distally. The integration of the adapter was investigated in comparison to the suture anastomosis. These investigations were performed by light microscopy and scanning electron microscopy. Median operative time for performing the adapter anastomosis was significantly shorter compared to suture anastomosis (66 s vs. 246 s, p < 0.05). Median estimated blood loss during adapter anastomosis implementation was 22.5 mL (range 19.0-25.0 mL) compared to 48.2 mL (range 45.4-63.5 mL, p < 0.05). In five hand-sewn anastomoses, overall eight additional stitches were necessary whereas all adapter anastomoses showed primary leak tightness. This in vivo study shows the technical feasibility of the newly developed adapter.

Delayed Graft Function 5 Months After Living Donor Kidney Transplantation.

BACKGROUND: Delayed graft function is a clinical term to describe the failure of the transplanted kidney to function immediately after transplantation. CASE REPORT: A 59-year-old woman suffered from a rare case of delayed graft function lasting 148 days after unrelated living donor kidney transplantation. Until now, 15 years after transplantation, organ function is still good, with serum creatinine levels about 1.4 to 2.0 mg/dl. CONCLUSIONS: Even after prolonged graft dysfunction, good graft function can be achieved.

Long-term survival after simultaneous pancreas-kidney transplantation with primary function of at least one year--a single-center experience.

BACKGROUND: Simultaneous pancreas-kidney transplantation has been established as the treatment of choice for type 1 diabetes patients with renal dysfunction. Patient 1-year survival better than 95% has been achieved using this kind of transplantation. According to the postoperative complication rate (5% mortality), recipients appear to have a survival benefit not earlier than 2 years after transplantation. This study evaluates the long-term benefit of simultaneous pancreas-kidney recipients with functioning grafts after 1 year. MATERIAL/METHODS: A retrospective analysis of 176 patients after first transplantation with functioning grafts 1 year after simultaneous pancreas-kidney transplantation was performed. RESULTS: During the follow-up period starting 1 year after successful transplantation, 7 patients died due to various causes, 13 pancreas grafts (7.4%) and 13 kidney transplants (7.4%) lost their function during the 10-year follow-up period. Chronic graft failure was the most common reason for transplant loss. CONCLUSIONS: Our data support the excellent long-term prognosis of simultaneous pancreas-kidney transplantation recipients with functioning graft 1 year after transplantation.

Theodor Billroth's vision and Karl Ziegler's action: commemoration of the 40th day of death and the 50th anniversary of conferment of Nobel Prize for Chemistry of Karl Ziegler.

Alloplastic materials are broadly used in modern surgery. Until the middle of the 20th century, metal materials and especially silver were used because of their antimicrobial properties. With the development of a new catalytic process for the production of high-density polyethylene and polypropylene materials, a new era of prosthesis was introduced. These polymers are integral part of our everyday operations surgery, especially in hernia repair. The famous surgeon Billroth mentioned to his pupil Czerny in 1878: "If we could artificially produce tissues of the density and toughness of fascia and tendon, the secret of the radical cure of hernia would be discovered". The polypropylene developed by Karl Ziegler gave the surgeon a material for daily practice, which in its properties (nearly) achieved Billroth's initial vision. In 1963 the Nobel Prize for Chemistry was awarded to Karl Ziegler and Giulio Natta in Stockholm. Furthermore, August 11, 2013 will be the 40th anniversary of Karl Ziegler's death. This manuscript honors both days.

Short term and long term results after open vs. laparoscopic appendectomy in childhood and adolescence: a subgroup analysis.

BACKGROUND: A comparative study was performed to compare quality of life after laparoscopic and open appendectomy in children and adolescents in a German General Hospital. The same study population was re-evaluated regarding their quality of life several years after operation. METHODS: Children and adolescents (n = 158) who underwent appendectomy for acute appendicitis between 1999 and 2001 were retrospectively analysed. Seven years after surgery those patients were interviewed applying a SF-36 questionnaire regarding their quality of life. RESULTS: For short term outcomes there was a trend towards reduced specific postoperative complications in the laparoscopically operated group (9.3 vs. 10.7%). Significantly more patients in the laparoscopic group would recommend the operation procedure to family members or friends than in the open group. Among the evaluated patients there was a significantly higher satisfaction concerning size and appearance of their scars in the laparoscopic group. The results of the evaluation in the eight categories of the SF-36 showed similar results in both groups. CONCLUSIONS: More patients with laparoscopic appendectomy appeared to be satisfied with their operation method as becomes evident by a higher recommendation rate and a higher satisfaction concerning their scars.

Laparoscopic versus open appendectomy--quality of life 7 years after surgery.

BACKGROUND: In spite of the widespread use of laparoscopic appendectomy, there is an ongoing debate on the advantages of this method when compared to open appendectomy. In the evaluation of a postoperative procedure, long-term quality of life is essential. PATIENTS AND METHODS: From 1999 to 2001, 493 patients diagnosed with acute appendicitis were operated in a German general district hospital and included in an observational study. In a median postoperative interval of 7 years, these patients were re-evaluated regarding their quality of life after surgery. A Short-Form 36 Health Survey (SF-36) questionnaire was applied to evaluate the general parameters of quality of life after surgery. This questionnaire was supplemented by an additional self-developed module referring to the appendectomy. The primary outcome was the recommendation of the experienced operating procedure to relatives and friends. RESULTS: A total of 243 patients underwent a laparoscopic procedure: 132 patients were re-evaluated (recovery rate 54%). In the open group, 250 patients were operated: 121 patients were re-evaluated (recovery rate 48%). The median interval from operation to evaluation was 7 years in the laparoscopic group and 7.7 years in the open group. For the primary outcome, patients with laparoscopic appendectomy would significantly more often recommend the procedure than patients with the open operation method. For secondary outcomes, the cosmetic results were judged significantly more favourably in the laparoscopic group. The eight scaled scores of the SF-36 questionnaire did not differ significantly between the two groups. Four patients of the open group and nine patients of the laparoscopic group (including one converted procedure) needed a reoperation because of incisional hernia, adhesions and late infections. CONCLUSION: Patients after laparoscopic appendectomy show a higher degree of satisfaction with their body and their scar than patients after open appendectomy.

Self-fixating mesh for the Lichtenstein procedure--a prestudy.

INTRODUCTION: Secure fixation of the mesh in groin hernia repair is essential to avoid mesh dislocation. The fixation, however, is also thought to be a source of chronic postoperative pain. We tested the new self-fixating mesh Parietene progrip vs. traditional suture fixating Lichtenstein repair in a double-blinded randomized study evaluating postoperative pain and the use of analgesics. METHODS: Fifty patients were randomized into two groups: Patients of group A (24 patients) were operated with the new self-fixating Parietene progrip mesh without fixation sutures and patients of group B (26 patients) were operated with the traditional Lichtenstein repair. Postoperative course including pain and the use of analgesics were monitored. Patients were reinvestigated after 6 months regarding pain score and the amount of analgesics used during this interval. Primary end point was pain on the first operative day. RESULTS: The visual analog scale pain score showed at the first postoperative day a significantly lower level in group A than in group B (mean 17.9 vs. 32.3 mm, p = 0.03). Additionally, the cumulative dose of postoperatively required analgesics was lower in group A than in group B. The operative time in group A was significantly shorter than in group B. Six months after the operation, a trend toward a lower pain score was observed in group A, but this did not reach statistical significance. CONCLUSIONS: This is the first randomized study to show a beneficial effect of the new self-fixating mesh on pain score. According to our investigations, operative time is reduced, which is a considerable fact with regard to economic aspects as well as the beneficial aspects for the patients. A study with a larger cohort of patients should be conducted to confirm the promising results of this exploratory study.

Open versus laparoscopic incisional hernia repair: something different from a meta-analysis.

BACKGROUND: Incisional hernias after laparotomy are a large financial burden for society as well as for the patients suffering from pain and limitations of activity over time. The introduction of alloplastic materials such as polypropylene seems to improve the results. The question of whether to apply open or laparoscopic implantation of the mesh is of ongoing interest. We compare the available alloplastic materials and try to clarify the question of whether the laparoscopic procedure is superior to the conventional (open) technique based on the available randomized studies. METHODS: All available meshes for intraperitoneal and extraperitoneal implantation were described regarding their handling and their pros and cons. A database search (PubMed, Medline, Ovid, and in the secondary literature) was carried out to retrieve all randomized studies comparing laparoscopic and open hernia repair. Data were reviewed by two independent scientists for surgical and statistical design. RESULTS: The ideal mesh for a laparoscopic maintenance of abdominal wall hernias as well as the optimal fixation of the mesh has not been found yet. Recent available literature shows no evidence demonstrating the superiority of one of these meshes. The available studies found a lower infection rate, but higher occurrence of seroma for the laparoscopic procedure. The value of the different studies is reduced due to deficiency in study design and power. Guidelines for further studies are discussed to avoid surgical and statistical pitfalls. CONCLUSIONS: Laparoscopic incisional hernia repair shows, in some (randomized) studies as well as a large number of retrospective analyses and in case control studies, superiority compared to conventional hernia repair. Long-term results with a high level of evidence are not available. Additional well-designed randomized trials including long-term observation of patients are required in order to clarify a number of interesting questions.

Characterisation of a novel matrix metalloproteinase inhibitor on pancreatic adenocarcinoma cells in vitro and in an orthotopic pancreatic cancer model in vivo.

Matrix metalloproteinases (MMPs) play a central role in tissue maintenance, inflammation and during tumour invasion and metastasis. The impact of MMPs in cancer has encouraged the development of novel MMP-inhibitors without adverse effects on the cell viability. We describe here the synthesis and characterisation of a triazine-derivative as a highly potent MMP-inhibitor. The new compound Triazin 17-2 was developed on the basis of a triazine backbone as a well known and well tolerated chemical scaffold. It was de novo synthesized and tested for MMP inhibition in a cell free assay. In vitro characterisation included tests for cell viability, protein expression and MMP activity in PancTu-1 cells. Effectivity of MMP inhibition was analysed in vitro by invasion assay. Triazin 17-2 was investigated in vivo using an orthotopic pancreatic ductal adenocarcinoma (PDAC) xenograft model in SCID/bg mice. Triazin 17-2 proved to have no adverse effects on cell viability in vitro at concentrations effectively inhibiting MMPs in an invasion assay. Application of Triazin 17-2 in vivo in the orthotopic PDAC model in SCID/bg mice showed a significant reduction of primary tumour weight using conservative therapy and inhibition of metastasis in adjuvant therapy. The MMP-inhibitor Triazin 17-2 was developed and characterised in vitro and in vivo. The new compound has no intrinsic activity to kill cells but is very effective in inhibition of MMPs. In vivo testing revealed that MMP-inhibitors are useful tools in anticancer therapy reducing tumour size and invasion even without direct effects on cell survival.

Animal models of pancreatic cancer for drug research.

BACKGROUND: The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. OBJECTIVE: Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. METHODS: The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. CONCLUSION: The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

A modified random oligonucleotide-based combination therapy for adjuvant treatment of pancreatic ductal adenocarcinoma.

Anti-cancer therapy in pancreatic ductal adenocarcinoma (PDAC) is mostly based on surgical removal or palliative therapy using antimetabolites, like 5'-fluorouracil or gemcitabine. Adjuvant treatment using these chemotherapeutics has recently proven a beneficial concept, though general survival rates are still poor. Most recently, combination therapy of gemcitabine with other targeted drugs was evaluated in clinical trials. We present here a study performed in a mouse orthotopic xenotransplant model of PDAC, using an oligo-nucleotide-based approach. We have shown previously that antisense oligonucleotides against p53 reduce the weight of orthotopic pancreatic tumours in immune-deficient mice. We further characterised terminal modifications of phosphorothioate oligonucleotides in vitro and found a random, unrelated control sequence carrying a D,L-alpha-tocopherol modification at the 5' and 3' ends to be most efficient in induction of cell death in PancTu-1 cells. Modified random oligonucleotide (MRON) were thus further tested in vivo. MRON showed a reduction of tumour weight in established primary orthotopic tumours in SCID/bg mice. In a surgically adapted pre-clinical model, where primary tumours were resected and animals received adjuvant treatment, MRON was very efficient in suppression of relapse and metastasis, when combined with gemcitabine. While the exact molecular mechanism of MRON activity still needs to be elucidated, the compound showed a remarkable preference for uptake into tumour cells in vivo.

Adjuvant treatment of pancreatic carcinoma in a clinically adapted mouse resection model.

BACKGROUND: The high rate of local recurrence after radical resection of pancreatic adenocarcinoma fosters intensive efforts to develop new approaches for adjuvant treatment. The established animal models show significant limitations in simulating an adjuvant therapeutic setting. For optimal approximation to the clinical situation we therefore improved a murine orthotopic human xenotransplantation model. METHODS: Subtotal pancreatectomy in mice was performed after orthotopic inoculation of human pancreatic cancer cells and manifestation of solid tumours. The natural course of disease, tumour growth and metastases were analysed. Gemcitabine as a cytotoxic drug was tested in vitro on the cell line used in this model and the effect of adjuvant treatment with gemcitabine in vivo was investigated. RESULTS: All tumour-resected animals showed local recurrence. Organ metastases occurred in 67% in resected compared to 25% of non-resected animals. Gemcitabine in vitro was ineffective, but as adjuvant monotherapy resulted in a highly significant reduction of tumour weight and metastatic events. CONCLUSION: Subtotal pancreatectomy for xenotransplanted pancreatic cancer in SCID beige mice is feasible. Due to high rates of local recurrence and increased organ metastases, this model offers a relevant option for preclinical adjuvant testing, especially as in vitro and in vivo effects of cytotoxic drugs differ enormously.

Differential effect of tacrolimus on dermal and intestinal wound healing.

Tacrolimus, used in organ transplantation, inhibits cellular immune function. Little is known about the effect on dermal and colonic healing. Groups of 10 rats underwent dorsal skin incision, and polyvinyl alcohol sponges were implanted subcutaneously. Beginning at the day of wounding, rats were treated intraperitoneal with 1.0 or 2.0 mg tacrolimus/kg/day. Animals were sacrificed 10 d later to determine wound breaking strength and reparative collagen deposition. Expression of transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma was studied in wounds. Groups of 8 rats underwent laparotomy and left colonic anastomosis. These rats were treated by subcutaneous injections with 2.0 or 5.0 mg tacrolimus/kg. Animals were sacrificed 5 d later to test colonic bursting pressure and reparative collagen deposition. Expression of TGF-beta, TNF-alpha, IFN-gamma, and CD4 and CD8 in the anastomosis was investigated. Tacrolimus impaired dermal healing (p < .05). This was paralleled by decreased expression of TGF-beta (stimulates healing) and increased expression of IFN-gamma and TNF-alpha (both inhibit healing) (p < .05). In contrast, tacrolimus did not inhibit healing of colonic anastomoses. No effect was seen on the expression of TGF-beta, TNF-alpha, IFN-gamma, and CD4 and CD8 in colonic anastomoses. We concluded that tacrolimus differentially effects tissue healing and expression of cellular mediators in dermal and intestinal wounds.

Laparoscopic appendicectomy is associated with a lower complication rate even during the introductory phase.

BACKGROUND: The benefit of laparoscopic appendicectomy is under debate. To study the beneficial clinical effects of laparoscopic appendicectomy during the introductory phase we analysed, retrospectively, 493 patients from one district general hospital. PATIENTS AND METHODS: During a period of 3 years 250 patients were operated on prospectively by open appendicectomy, and 243 patients were operated on laparoscopically. Both groups were compared with regard to their demographic data, operation time, body mass index and complication rate. RESULTS: The conversion rate was 4.5%. The distribution of histological stages of inflammation was comparable in both groups. The median operating time was significantly longer for the open (40 min) than for the laparoscopic procedure (35 min, P=0.002). The body mass index in the laparoscopic group was significant higher (23.7 kg/m(2) vs 22.6 kg/m(2), P=0.009). Perioperative white blood cell count, C-reactive protein and body temperature were equal in both groups. There was no significant difference with regard to the analgesia required postoperatively between the open and the laparoscopic group. Nevertheless, the specific complication rate after open appendicectomy (18.4%) was significantly higher than that following laparoscopic appendicectomy (10.8%, P=0.03). CONCLUSION: Even during the introductory phase, laparoscopic appendicectomy is a safe and clinically beneficial operating procedure.

Terminally modified oligodeoxynucleotides directed against p53 in an orthotopic xenograft model: a novel adjuvant treatment strategy for pancreatic ductal carcinoma.

OBJECTIVES: Investigation of a terminally modified oligodeoxynucleotide (ODN) directed against p53 mRNA (p53-3' polyethylene glycol-5' tocopherol ODN as a novel drug for pancreatic ductal carcinoma therapy in vitro and in vivo. METHODS: The impact of lipophilic modifications at the 5' end of p53-directed ODNs on cellular uptake was analyzed in vitro using proliferation assays, fluorescence-activated cell sorting analysis, and confocal laser scanning microscopy. The in vivo effects of p53-PT-ODN on the growth of orthotopically xenografted human pancreatic ductal carcinoma cells (PancTuI) were studied in SCID beige mice. Distribution was examined in vitro and in vivo using Cy3-labeled ODNs. RESULTS: Terminally modified p53-PT-ODN showed excellent cellular uptake without using transfection reagents. Microscopically detectable levels of p53-PT-ODN were reached in vivo within 3 hours after intraperitoneal injection, even in extraperitoneal organs. At this time, Cy3-labeled p53-PT-ODN was found in solid tumor formations. We observed a significant inhibition of tumor growth (50%) in vivo at low doses of p53-PT-ODN, whereas at high doses, 2 of 9 animals had no detectable tumors at necropsy. When p53-PT-ODN was injected on the day of tumor cell inoculation, the growth inhibition of solid tumors was significantly stronger compared with that with delayed treatment. CONCLUSIONS: p53-Directed modified ODNs might be of therapeutic value in pancreatic ductal carcinoma, particularly as adjuvant therapy after pancreatic tumor resection.

Prospective evaluation of diagnostic modalities in suspected acute appendicitis.

BACKGROUND: The aim of this prospective study was to evaluate different diagnostic modalities routinely employed in a district hospital. METHOD: Four hundred subsequent patients presenting with acute abdominal pain were included over a period of 18 months. Patient characteristics, diagnostic work-up, intraoperative findings, histology and clinical outcome were documented. Rectal temperature, white cell count (WCC), C-reactive protein (CRP), ultrasonography (US) and Ohmann score were analysed with relation to diagnostic value. RESULTS: Negative appendicectomy rate and negative laparotomy rate on the day of admission were 22% and 21%, respectively. Sensitivity was highest for WCC and CRP (0.82 and 0.85) but US showed highest values for specificity (0.92), accuracy (0.85) and odds ratio (13.06). No patient with an Ohmann score below 6.5 suffered from acute appendicitis. With regard to different levels of training in US, experienced surgeons and radiologists had best values for specificity (1.00 and 0.98) and accuracy (0.90 and 0.94). Surprisingly, less-experienced sonographers also achieved good results with regard to specificity (up to 0.96) and positive predictive value (up to 0.89). CONCLUSION: Diagnostic accuracy of acute appendicitis remains insufficient, with an unacceptable high rate of unnecessary operations. Only the promotion of routine ultrasonography might contribute to an improvement in the near future.