Risk Stratification of Ruptured Abdominal Aortic Aneurysms in Patients Treated by Open Surgical Repair.

OBJECTIVE: The present study tested scoring models for ruptured abdominal aortic aneurysms (rAAAs) in patients treated by open surgical repair (OSR). Scores were tested in a European population to validate their applicability for predicting outcome. METHODS: Between 2002 and 2013, 92 patients with rAAAs underwent OSR and medical records were reviewed retrospectively. The Edinburgh Rupture Aneurysm Score (ERAS), Vascular Study Group of New England (VSGNE) rAAA risk score, Hardman Index, and Glasgow Aneurysm Score (GAS) were calculated and analyzed according to in hospital mortality. The discriminatory power and calibration of all models were assessed by applying the receiver operating characteristic and the Hosmer-Lemeshow test χ(2). RESULTS: An ERAS ≤ 1 (n = 55), 2 (n = 15) and 3 (n = 16) was associated with a mortality of 27%, 47%, and 69%, respectively. The calibration was the best of all tested scores (χ(2) = 0.44; p = .81) and the area under the curve (AUC) was 0.71 (95% CI 0.6-0.82; p = .001). A VSGNE rAAA risk score = 0 (n = 19), 1 (n = 15), 2 (n = 19), 3 (n = 25), and ≥ 4 (n = 9) was associated with a mortality of 11%, 20%, 32%, 72%, and 56%, and an AUC of 0.76 (95% CI 0.66-0.87; p = .001). The calibration was reduced (χ(2) = 6.9; p = .08). The GAS and Hardman Index increased stepwise with increasing in hospital mortality, but were inferior to ERAS and the VSGNE rAAA risk score. The Hardman Index showed the smallest AUC (0.68; 95% CI 0.56-0.80; p = .011) and demonstrated a lack of fit (χ(2) = 8.2; p = .04). The GAS showed good discrimination (AUC = 0.75; 95% CI 0.64-0.85; p < .001) and calibration (χ(2) = 0.85; p = .66); however, the parametric scale of GAS limits its use to classifying patients according to their risk. CONCLUSION: The present study revealed remarkable differences in survival between subgroups (10-70%) and underscores the need for risk stratification. The ERAS was favorable with striking ease of use and high accuracy in predicting outcome.

Mid- and long-term results after replacement of infected peripheral vascular prosthetic grafts with biosynthetic collagen prosthesis.

AIM: We assess mid- and long-term outcome after prosthetic graft replacement with biosynthetic collagen prosthesis (Omniflow II®) in the presence of graft infection. METHODS: Between December 2010 and January 2012, an analysis of 9 consecutive patients was performed, who underwent replacement of an infected peripheral graft with a biosynthetic prosthesis. Morbidity, in-hospital mortality, primary and secondary patency were analyzed. FDG-PET was performed to diagnose graft infection, and exclude reinfection at long-term follow-up. RESULTS: Graft infection occurred after a median of 12 (range 3-97) months after the initial procedure. Replacement surgery was performed successfully in all 9 patients without intraoperative complications. Microbiological cultures revealed pathogenic infection in 7 cases. In 2 patients, no pathogen was isolated. The morbidity rate was 55.5% with no in-hospital deaths. Early and late bypass occlusion occurred in 2 patients. One high above-knee amputation was performed due to patient deterioration. The median length of stay was 23 (range 12-122) days and after graft replacement 13 (range 10-62) days. The median time of follow up was 23 (range 8-25) months. Primary and secondary patency rates were 66.6% and 78% at 19 months, respectively. FDG-PET was performed in 6 (85.5%) patients after a median follow up period of 19 (range 3-23) months, and excluded graft reinfection in all patients. CONCLUSION: Replacement of infected peripheral prosthetic grafts with the prosthesis (Omniflow II®) has encouraging results. The collagen prosthesis appears to be a promising alternative with a low reocclusion rate and no reinfection.

[Early results after peripheral vascular replacement with biosynthetic collagen prosthesis in cases of graft infection]. / Frühergebnisse nach peripherem Gefäßersatz mit einer biosynthetischen Kollagenprothese bei Protheseninfektionen.

INTRODUCTION: Vascular graft infection in peripheral bypass surgery represents a highly significant risk with regard to limb loss and morbidity. In the absence of autologous superficial veins, finding a suitable replacement material can be difficult. Silver-coated polyester grafts, homografts, or use of deep veins can pose additional risks. Use of a biosynthetic collagen prosthesis on a Dacron matrix ("Omniflow-II®") was investigated as an alternative method, and the cost-effectiveness was evaluated. MATERIALS AND METHODS: From December 2010 to December 2011, eight patients with clinical symptoms of vascular graft infection, confirmed by imaging, were treated. Graft function or acute graft failure due to the infection was necessary for enrollment in the study. Infected material was removed, microbiological specimens taken and, in the absence of superficial veins, an "Omniflow-II®" prosthesis was implanted in an orthotopic position. Patients were followed up to evaluate their outcome, and the cost-effectiveness of the procedure was also analysed. RESULTS: The technical feasibility of the procedure was assessed in all cases. Pathogens were detected in five of eight cases. After a mean follow-up of 8 months, seven of eight patients showed that they were clinically cured of infection. Primary patency was 63%, secondary patency was 75%, and prevalence of limb salvage was 88%. One patient had to undergo limb amputation to avoid sepsis, and another unsuccessfully underwent thrombectomy after 12 months. Four PET-CT follow-up studies showed a reduction of uptake in the affected area. To generate adequate revenue by using this technique, specialised knowledge of the diagnosis-related group system is necessary. DISCUSSION: Treatment of vascular graft infections in peripheral bypass surgery in the absence of endogenous material necessitates the use of infection-resistant materials. The present study showed promising results using a collagen-biosynthetic prosthesis. Due to a lack of long-term results, the graft should be used only after detailed informed consent is obtained from the patient. The expenses incurred by using the biosynthetic graft should be covered adequately by revenues from these patients.

[Injury to the spinal accessory nerve during lymph node biopsy: expert witnesses and evidence-based procedures]. / Verletzung des Nervus accessorius im Rahmen von Lymphknotenexstirpationen - Begutachtung und evidenzbasierte operative Techniken.

INTRODUCTION: Injury to the spinal accessory nerve during lymph node biopsy in the lateral cervical triangle is a dreaded complication. It is disproportionately frequently the basis for medico-legal debates even though an evidence base is lacking. The scientific clarification of meaningful and mandatory measures during the procedure is essential. MATERIALS AND METHODS: A legal database query from 1970 to 2011 was carried out using related keywords. Judgements were examined for expert witnesses, and a literature search regarding expert witnesses was done. The arguments found were verified with respect to evidence. RESULTS: From 1970 to 2011, 18 verdicts were found with 11 claims upheld and seven rejected. Expert witnesses regularly asked for clear preparation of the nerve as well as the requirement of specialist standards, and often used the prima facie argument to show surgeon errors. In contrast, analyses of the literature showed a significant risk of injury during nerve preparation. The need for specialist standards remains, however, with significantly lower demands upon the expertise of the surgeon as described by expert witnesses. DISCUSSION: There was a lack of scientific evidence for special manoeuvers during surgical procedures in the lateral cervical triangle. This prompted experts to ask for scientifically unproved manoeuvers during the procedure. "Eminence-based" expert witnesses with a teaching aptitude still have considerable influence on judicial decisions but are an unnecessary burden regarding the provision of medical treatment.

[Arterial allografts in vascular surgery--best choice in cases of aortic graft infection?!]. / Arterielle Homografts in der Gefäßchirurgie - idealer Gefäßersatz bei aortalen Gefäßprotheseninfektionen?!

Infection of vascular prostheses, particularly in the central aortic position, is a growing challenge in vascular surgery. Beside the use of extra-anatomic prosthetic bypasses the need for anatomic reconstruction with infection-resistant materials is growing. The use of arterial allografts is an established method in many centres for in situ reconstruction. Used historically as the only option for vessel replacement, allografts were seldom used once the development of synthetic prostheses started. Use as a vascular graft in infected regions began in the 1990s. Discussions about the use of "fresh" allografts without preservation were terminated by order of the European Union in 2003 (although the long-term benefits have been foreseen). Currently, because of the German Tissue Act, only "cryopreserved" allografts can be used. Larger, partially controlled studies about the outcome after cryopreserved allograft transplantation have shown similar results to the use of silver prostheses, with a significantly lower prevalence of re-infection. Questions remain about the use of immunosuppression after human allograft transplantation. Immunological interactions are mainly involved in allograft degeneration. Aneurysmal changes (most commonly late degeneration of allografts) can be treated with endovascular procedures and therefore have no direct impact on long-term results. The availability of allografts in Europe tends to be restricted, but companies based outside the EU permit a good supply. The use of allografts in non-university institutions shows the wide acceptance of the material and its suitability for routine use in vascular surgery, even if the treatment of infected vascular prostheses in the central position remains associated with high morbidity and mortality.

[Liability of surgeons with respect to injuries to the bile duct during laparoscopic cholecystectomy : Analyses of malpractice litigations in the years 1996-2009]. / Arzthaftung bei Gallengangsverletzungen nach laparoskopischer Cholezystektomie : Analyse der gerichtlichen Urteile der Jahre 1996 bis 2009.

BACKGROUND: Injuries to the bile duct during laparoscopic cholecystectomy are often a cause of malpractice litigations. METHODS: A total of 13 legal verdicts as a result of bile duct injury from 1996 to 2009 were reviewed. Comments on the verdicts and the opinions of expert witnesses were analyzed. RESULTS: Out of 13 claims, 7 were upheld and 6 were rejected. Most expert witnesses from 1996 to 2002 stated that not carrying out a cholangiography and insufficient preparation of the cystic duct constituted a performance below the standard of care expected. Expert witness testimonies from 2004 to 2009, however, regarded injury to the bile duct as predominantly inherent to treatment. CONCLUSION: With the expansion and acceptance of laparoscopic interventions, changes in the results of malpractice litigation have become evident. In contrast to the phase during establishment of the technology, an injury to the bile duct is nowadays judged predominantly as inherent to treatment.

Complication rate of pancreas retransplantation after simultaneous pancreas-kidney transplantation compared with pancreas after kidney transplantation.

Simultaneous pancreas kidney transplantation is currently the state of the art therapy for patients with type 1 diabetes mellitus and diabetic nephropathy. Up to 30% of patients loose the pancreas with a kidney graft that continues to function. Under those conditions, isolated pancreas retransplantation can be indicated. We compared the outcome of these patients with the outcome of patients undergoing primary pancreas after kidney transplantation. From 1998 to 2005, we performed 205 pancreas transplantations. Three patients were considered for isolated pancreas retransplantation; to date, two have received a new organ. One was retransplanted twice. In two cases, the reasons for the initial graft loss in the retransplantation group were pancreatitis with hemorrhagic bleeding and in the third case severe rejection. After retransplantation two of three patients lost their graft owing to bleeding and venous thrombosis. One of three organs was successfully transplanted and the patient does not require insulin. During the same time, three pancreas after kidney transplantations were performed; all are doing well und are free of insulin. The study despite the small number of cases shows a high complication rate after pancreas retransplantation. Nevertheless, pancreatic retransplantation should be considered in selected patients.

Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas.

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) is known to be related to development of lymphatic vessels. Papillary thyroid carcinoma characteristically metastasizes to regional lymph nodes, whereas follicular thyroid carcinoma commonly spreads hematogenously. The present study was designed to determine whether expression of the VEGF-C gene is related to the different metastatic features of these 2 types of thyroid carcinoma. METHODS: Thyroid carcinoma specimens were obtained from 15 patients with papillary carcinoma and 4 patients with follicular carcinoma of the thyroid. VEGF-C gene expression was examined by Northern blotting and in situ hybridization. Immunohistochemistry was performed to localize the deposition of VEGF-C protein. RESULTS: The ratios of VEGF-C gene expression determined by Northern blot analysis were significantly higher in papillary than in follicular carcinoma. Nonmalignant thyroid tissue from patients with papillary carcinoma also expressed higher levels of VEGF-C than tissue from patients with follicular carcinoma. Expression of the VEGF-C gene was observed by in situ hybridization in cells of papillary thyroid carcinoma but not in those of follicular carcinoma. Positive staining with antibody against VEGF-C was detected in papillary cancer cells. CONCLUSIONS: Concurrent overexpression of the VEGF-C gene by both tumor cells and the surrounding tissue may be related to the prevalence of intrathyroidal spread through lymphatics and regional lymph node metastasis in patients with papillary thyroid carcinoma.

The complement-activating protease P100 is expressed by hepatocytes and is induced by IL-6 in vitro and during the acute phase reaction in vivo.

Ra reactive factor, a lectin present in the sera of a wide variety of vertebrates, is composed of mannan-binding proteins and a serine protease termed P100, which is known to activate complement. Using differential mRNA display technology to study the "activation"-dependent gene expression of hepatic stellate cells (HSC), we partially cloned a cDNA encoding the rat homolog of P100, which displayed 94% and 88% homology to mouse and human P100 cDNA, respectively. In the rat P100, specific transcripts 5.4, 4.0, and 3.3 kb in size were detected in major amounts in normal liver, but were absent or near the detection limit in other organs. Among the different liver cell populations studied during primary culture, P100-specific transcripts of 4.0 kb were prominent in HSC and present in hepatocytes and hepatoma cells, whereas Kupffer cells and sinusoidal endothelial cells were P100-negative. In addition to 4.0-kb mRNA, freshly isolated hepatocytes also contained transcripts of 5.4 and 3.3 kb, which were down-regulated during primary culture. In situ hybridization of normal liver tissue confirmed the in vitro data in that P100 was expressed by hepatocytes and nonparenchymal liver cells, which probably represent HSC. In vitro P100 steady-state mRNA levels of hepatocytes were stimulated by IL-6 and/or dexamethasone. During the acute phase reaction induced by turpentine injection, P100 steady-state mRNA levels were up-regulated in rat liver. The data demonstrate that: (a) the liver is the primary site for P100 expression in the rat; (b) HSC and hepatocytes appear to represent the cellular sources; and (c) P100 steady-state mRNA levels are up-regulated by the acute phase mediators IL-6 and dexamethasone in vitro and during the acute phase reaction in vivo, suggesting that P100 represents a novel, positive acute-phase gene in the rat.

Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and upregulated by transforming growth factor-beta 1.

Bone morphogenetic protein-6 (BMP-6) is a member of the TGF-beta superfamily, which controls growth and differentiation during embryogenesis and acts as an osteoinductive factor in the adult organism. In order to gain further insights into the role of BMP-6, the present study analyzed the expression pattern of BMP-6 in adult rat tissues with special emphasis to the liver, since TGF-beta 1, another member of the TGF-beta superfamily, has been shown to play a fundamental role in liver physiology. Rat BMP-6-coding cDNAs were generated by homology cloning using RT-PCR and displayed 89.6 and 83.4% homology to mouse and human BMP-6, respectively. By Northern blotting BMP-6-specific transcripts 3.7 kb in size were detected in major amounts in lung and in minor quantities in spleen, kidney, heart, brain, and liver. Among the different hepatic cell populations tested BMP-6 expression was confined to nonparenchymal liver cells, namely rat hepatic stellate cells (HSC) and Kupffer cells (KC). During primary culture BMP-6 expression was increased in HSC but declined in KC. Interestingly, TGF-beta 1 stimulated BMP-6 expression of HSC especially at an early time point of culture, while interferon-gamma downregulated BMP-6 expression. The detection of BMP-6 transcripts in the liver, the cell-type-restricted expression pattern, and its regulation propose that, in addition to its osteoinductive properties, BMP-6 might play a role in liver growth and differentiation, in particular after tissue damage.

Gene expression and regulation of plasminogen activator inhibitor type I in hepatic stellate cells of rat liver.

BACKGROUND & AIMS: Plasminogen activator inhibitor type 1 (PAI-1) plays a crucial role in the regulation of extracellular matrix-degrading enzymes and in the production of fibrogenic mediators such as transforming growth factor beta through inhibition of plasminogen activation. Because hepatic stellate cells (HSCs), the principal matrix-producing cell of the liver, might also affect extracellular matrix degradation and growth factor activation, the aim of this study was to analyze PAI-1 expression and its regulation in HSCs compared with other liver cells. METHODS: PAI-1 synthesis of liver cells at different time points of primary culture was studied by immunoprecipitation of endogenously labeled proteins followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by Northern blotting. RESULTS: Among the various types of liver cells, PAI-1 protein and specific transcripts were present in HSCs and endothelial cells, and no major PAI-1 synthesis was detected in Kupffer cells and hepatocytes. Transforming growth factor beta 1, tissue plasminogen activator, and dexamethasone increased PAI-1 production in HSCs. CONCLUSIONS: Apart from their role as the principal connective tissue-producing cell of the liver, HSCs might regulate extracellular matrix accumulation by modulating the activities of matrix-degrading enzymes and fibrogenic mediators through the production of PAI-1.

Transforming growth factor beta 1-regulated gene expression of Ito cells.

During liver fibrogenesis, Ito cells are regarded as the principal matrix synthesizing cells and transforming growth factor beta 1 (TGF-beta 1) appears to be the main fibrogenic mediator. This study analyzed the effects of TGF-beta 1 on Ito cell activation, proliferation, and on the expression of a set of matrix proteins, antiproteases, and TGF-beta receptors both in "early cultured" and "culture-activated" Ito cells. Rat liver Ito cells at day 2 of primary culture ("early cultured" cells) were mainly smooth muscle alpha actin (SMA)-negative, whereas cells at day 6 were judged as "activated" cells (SMA-positive). Following 24-hour exposure to 1 ng/mL TGF-beta 1, total protein synthesis, cell proliferation, and expression of the "activation" marker SMA were not significantly changed. In addition to previously described stimulatory effects on collagen types I and III, fibronectin, undulin, and proteoglycan-gene expression, TGF-beta also dose-dependently increased synthesis and secretion of tenascin, laminin, entactin, collagen type IV, and alpha 2-macroglobulin, but decreased C1-esterase inhibitor production by Ito cells, as revealed by immunoprecipitation of endogenously labeled proteins and by Northern blot analysis. The stimulatory effect of TGF-beta was evident both in "early cultured" as well as "culture-activated" Ito cells. By reverse-transcription polymerase chain reaction (RT-PCR) analysis, TGF-beta type II, III, and TGF-beta/activin type I receptors were present in Ito cells, and their expression pattern was not changed upon TGF-beta exposure. Northern blot analysis demonstrated that type I TGF-beta/activin receptor was induced during in vitro activation and that TGF-beta exposure resulted in a slight increase of type I and III receptor messenger RNAs. In summary, the data illustrate that TGF-beta is an important fibrogenic mediator acting both on "early cultured" as well as "culture-activated" Ito cells, rather than a mitogenic or morphogenic mediator. The differential regulation of TGF-beta/activin receptors during in vitro activation and their up-regulation by TGF-beta 1 might represent a mechanism by which the receptor complex regulates TGF-beta signalling in Ito cells.

Glial fibrillary acidic protein--a cell type specific marker for Ito cells in vivo and in vitro.

BACKGROUND/AIMS: Glial fibrillary acidic protein is an intermediate filament first identified in the brain in astrocytes. This study examines glial fibrillary acidic protein immunoreactivity in normal and damaged rat livers. Glial fibrillary acidic protein-gene-expression in Ito cells, endothelial cells, Kupffer cells, and hepatocytes is also analyzed. METHODS: Sequential cryostat sections from normal, as well as acutely or chronically CC14 damaged rat livers were analyzed by immunostaining for the presence of glial fibrillary acidic protein and desmin. Glial fibrillary acidic protein-expression in isolated liver cells was studied by immunocytology, Western blot, Northern blot analysis, and reverse-transcription polymerase chain reaction. The specificity of polymerase chain reaction products was tested by Southern blot hybridization and partial sequencing. RESULTS: In the normal liver, glial fibrillary acidic protein-positive cells were detected in the perisinusoidal area. These cells were also desmin-immunoreactive as determined by immunostaining. In contrast, cells of the vessel walls were desmin-positive, but glial fibrillary acidic protein-negative. In the acutely damaged livers glial fibrillary acidic protein-positivity was detectable along the non-damaged sinusoids as well as in the necrotic areas. In chronically damaged livers glial fibrillary acidic protein was more detectable at the margins of the fibrotic septa, less inside the septa. All glial fibrillary acidic protein-positive cells were desmin-positive, but several desmin-positive cells were glial fibrillary acidic protein-negative (especially inside the septa). Among the different liver cell subpopulations tested in vitro, glial fibrillary acidic protein-gene expression was only detectable in Ito cells. During primary culture, glial fibrillary acidic protein-expression decreased in parallel to Ito cell activation. CONCLUSIONS: Glial fibrillary acidic protein is a new cell type specific marker for Ito cells, which might allow distinction between Ito cells and other fibroblastic liver cells (cells of the vessel walls). Cells located at the margins of fibrotic septa definitely represent Ito cells.