Scars arise in the late phase of wound healing and are characterized by fibroplasia. Previous controversial studies have discussed the regenerative wound healing capacity of Murphy Roths Large (MRL) mice. The aim of this study was to investigate the mechanisms of improved wound healing in a skin transplantation model. Skin grafts from MRL and haplotypically identical B10.BR mice were cross-transplanted. At day 10, B10.BR and MRL grafts on B10.BR recipients deposited collagen and showed severe apoptosis. Grafts of MRL recipients were not affected by such alterations and showed an enhanced healing progress. They were characterized by higher partial pressure of tissue oxygen, increased microcirculation, exceptionally intense neovascularization, and a blunted inflammatory response. This phenotype was accompanied by increased vascular endothelial growth factor expression, augmented by enhanced signal transducer and activator of transcription 3 (STAT3) phosphorylation. These effects were combined with a decreased STAT1 expression and phosphorylation. STAT1 pattern variation was associated with decreased Smad7 levels. Furthermore, MRL recipients showed improved stem cell recruitment to the wound area. The basic accelerated wound healing mechanism in MRL mice found in this skin transplantation model is improved engraftment; this is based on enhanced neovascularization and reduced inflammation. These effects are most likely due to higher vascular endothelial growth factor levels and changes in the STAT/Smad signal pathway, which may enhance transforming growth factor-β signaling, reducing proinflammatory responses.
Evaluation der Eignung eines Port-Staplers zur Erleichterung und Verbesserung der Portimplantation bei der laparoskopischen Magenbandimplantation.
BACKGROUND:The purpose of this study was to evaluate the applicability of a port stapling device to simplify and improve port implantation in laparoscopic adjustable gastric banding (LAGB).METHODS:From November 2005 to September 2006, a prospective study was conducted on 23 consecutive patients who underwent LAGB with Swedish adjustable gastric banding. Patients were randomized to either conventional titanium-port implantation or port stapling using the "Velocity" device.RESULTS:No differences in age, body weight, body mass index, fascia depth or incision length were reported between the groups. Port implantation time was significantly less using port stapling (90+/-24 s) compared to conventional port implantation (521+/-138 s). Port related complaints postoperatively and at follow-up were equal in both groups.CONCLUSIONS:Port stapling is an excellent tool to facilitate port implantation, particularly in massively obese patients with a thick abdominal wall.
Graft injury caused by warm ischemia in livers from non-heart-beating donors (NHBDs) strongly affects posttransplantation outcome and is associated with liver apoptosis, which is mediated by death receptors, such as Fas, a surface receptor of the tumor necrosis factor (TNF)-alpha family. The aim of this study was to test the ability of venous systemic oxygen persufflation (VSOP) to reduce apoptotic changes and Fas activation in the liver after warm ischemic insult in vivo. Livers of male Wistar rats were harvested 30 min after cardiac arrest from non-heart-beating donors (NHBD) with (NHBD + O2) or without (NHBD) application of gaseous oxygen during the cold storage period via the suprahepatic caval vein. After 24 h of storage in University of Wisconsin solution at 4 degrees C, viability of the livers was assessed upon isolated reperfusion in vitro. Conventional signs of tissue damage like enzyme release and bile production showed a significantly elevated nonspecific cell injury in the NHBD group. TUNEL staining revealed increased DNA fragmentation of sinusoidal endothelial cells in the NHBD group and more apoptotic hepatocytes than in the control group. All these alterations could be almost abrogated by the use of VSOP in the NHBD + O2 group. The immunohistochemical staining of Fas antigen expression showed a significantly elevated Fas receptor expression in the NHBD and NHBD + O2 groups, in accord with an eightfold increase of Fas receptor mRNA detected by real-time reverse-transcription polymerase chain reaction (RT-PCR). These results demonstrate that the postischemic apoptotic rate of sinusoidal endothelial cells in NHBD livers can be reduced by the use of VSOP. A significant improvement in liver integrity and viability was obtained with this technique, without influencing the expression of Fas expression.
Background: Recombinant human growth hormone (hGH) therapy has a beneficial effect on catabolism and wound healing after major surgery. Polymorphonuclear neutrophils (PMN) play an important role in this context. In a prospective, double-blind, randomized, placebo-con trolled trial we studied the effect of perioperative hGH treatment on postoperative wound healing and oil changes in superoxide generation and susceptibility to apoptosis of PMN in elderly patients undergoing elective abdominal aortic aneurysm repair.Methods: Seven patients were treated with high-dose hGH (16 U/d) for nine days, seven patients with a placebo. IGF-1 neutrophil count, O-2-production induced by opsonized zymosan and apoptosis of PMN were measured and correlated with clinical outcome.Results: Perioperative hGH treatment more than doubled the O-2(-) production in PMN before and 24 h after surgery (p < 0.01). The long-term capacity of PMN to generate O-2 in vitro was prolonged (p < 0.001) in the hGH group. Spontaneous and Fas-inducible apoptosis was strongly down-regulated in PMN after surgery in all patients p < 0.01). hGH-treatment distinctly reduced apoptosis in PMN before and after surgery (p < 0.01). Clinical outcome was similar in both groups.Conclusion: Perioperative hGH treatment results in an enhanced O-2 production in PMN and in a prolongation of the functional life span of these cells. This may improve immune function and help to overcome the postoperative allergic state of the immune system especially in elderly individuals. (c) 2005 Elsevier Ltd. All rights reserved.
Auch 93 Jahre nach Durchführung der ersten partiellen Pankreatoduodenektomie durch den Königsberger Chirurgen Walter Kausch besteht bezüglich der optimalen Pankreasanastomose noch eine rege Diskussion. Die Mehrheit der Pankreaschirurgen bedient sich hierzu einer Jejunalschlinge, wohingegen von einigen die Magenhinterwand bevorzugt wird. Die Präsentation zeigt die Bonner Ergebnisse mit der Pankreato-Gastrostomie und gibt einen Überblick über die aktuelle Studienlage, insb. den Vergleich der beiden Verfahren.
Hintergrund: Die Adipositaschirurgie hat sich als effektive Maßnahme bei morbider Adipositas erwiesen. Überdies hat die Aufnahme der Adipositaschirurgie als anerkannte Therapiemaßnahme in die evidenzbasierten Leitlinien zur Adipositas-Behandlung (DAG, DDG, DGE) und die Entscheidung des BSG (02/2003) zu einer massiven Steigerung des Patientenaufkommens geführt. Ziel der Studie war die Optimierung der Patientenevaluation und -selektion in einer chirurgischen Adipositassprechstunde.
Background. Little is known about the local accumulation and function of immune cells in peritoneal fluid after elective surgery of the upper and lower gastrointestinal tract. Our study was designed to investigate whether systemic immune cell response mirrors the local response. We focused on the cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and on monocytes, natural killer (NK) cells, and T cells that play an important role in eliciting the innate and adaptive immune response.Methods. Blood samples were taken prospectively from 25 patients 24 It before surgery, as well as 24 h and 48 h afterward. Abdominal drainage fluids were collected intraoperatively 1 h after the abdomen was opened and 24 h and 48 h postoperatively. Apart from the white blood cells, intracellular T-helper-cell (TH1/ TH2) cytokine production (interferon-gamma, IL-2, IL-4, IL-13) and HILA-DR on monocytes were measured by four-color flow cytometry, IL-6, and TNF-alpha with the fast immunoluminescence method.Results. Cells of the innate immune system (NK cells, monocytes, NK-T cells, CD5(+) B cells) rapidly decreased in abdominal fluids (P < 0.05: +24 h; +48 h) after surgery, which was paralleled by a concomitant decline in peripheral blood. The percentage of abdominal interferon-gamma, IL-2, IL-4, and IL-13-producing TH cells increased in a way that distinctly counteracted the decrease of the natural immune cells. HILA-DR expression on monocytes in peripheral blood declined significantly (P < 0.05: +24 h; +48 h). In contrast, monocytes in abdominal fluids had high HLA-DR expression. Furthermore, abdominal fluids contained significantly higher concentrations of TNF-alpha (P < 0.05: +24 h; +48 h) and IL-6 (P < 0.05: +24 h) compared with peripheral blood.Conclusions. Specific immune cell recruitment and cytokine production play an important role in post-trauma events. Measuring distinct local immune cell repertoires and cytokines provides answers as to how the different phases of postoperative immune events proceed. The evaluation of the local response may provide additional criteria for the evaluation of operative trauma. This knowledge may be helpful in detecting postoperative pathological aberrancies. (C) 2005 Elsevier Inc. All rights reserved.
Background and aims Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN). This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN. Results were clinically correlated. Methods The study included biopsy samples from 87 patients who had been diagnosed with the following disease patterns: 47 invasive anal carcinoma, 33 AIN of varying severity and seven condylomatous lesions. In 52 of these cases, a tumour was clinically suspected. All biopsies were retrospectively examined for microscopic indications of HPV infection. After microdissection, additional HPV analysis via PCR was carried out. Results In 38 of 47 cases of anal carcinoma, HPV DNA could be detected via PCR (80.9%), the majority of which were HPV 16 (33/38=86.8%). In 29 of the 33 cases of AIN, HPV DNA was detected (87.9%), most of these in AIN III (15/16=93.8%). Histological markers of HPV infection were detected in all 87 cases. Discussion In our series, the clinical diagnosis of the invasive anal carcinoma had a high sensitivity of 93.6%, with a specificity of 80%. The positive predictive value was 84.6%, and the negative predictive value 91.4%. In contrast, AIN had been detected clinically in none of the cases. In this situation, especially with high-risk patients, our findings recommend anal HPV screening in combination with anal cytology and anoscopy. Conclusion Based on our results, we urgently recommend for any histological report on excision of anal lesions to include a statement whether histological markers of HPV infection were detected. In individual cases, validation via HPV PCR must be considered.
Pancreatogastrostomy is a safe reconstructive technique after pancreatoduodenectomy, even when performed as an educational operation in the hands of relatively inexperienced surgeons in a high-volume hospital. Sixteen surgeons with various case volumes operated on 190 consecutive patients and performed pancreatogastrostomy after pancreatoduodenectomy within the last 15 years in a university teaching hospital. Resections were performed for tumors localized in the head of the pancreas, the ampulla of Vater, or the distal common bile duct or duodenum (n = 169); for chronic pancreatitis (n = 16); and for miscellaneous reasons in five cases. The main outcome measures were postoperative mortality and morbidity, particularly the pancreatic leakage rate with special regard to the case volume of the performing surgeon. The overall mortality rate was 4.2% (n = 8), the 30-day mortality rate was 3.2% (n = 6), and mortality directly related to surgery was 2.6% (n = 5). Morbidity occurred in 45%, including severe surgical complications, which required reoperation (9%), and minor surgical complications that could be managed conservatively (30%). There were no significant differences in overall surgical morbidity rates when the groups with varying patient volume per surgeon were compared. The incidence of pancreatic leakage was 7.4%, which did not contribute to mortality in any case and showed no statistical differences between the surgical volume groups. We concluded that pancreatogastrostomy is safe and feasible even in the hands of inexperienced but supervised surgeons. The leakage rate is similar to the data from other high-volume centers. Once a leak is established, it can easily be managed conservatively, so it rarely contributes to severe complications or causes subsequent mortality. We recommend pancreatogastrostomy as a beneficial alternative to pancreatojejunostomy, even in the case of low surgical volume.
BACKGROUND AND AIMS:Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN). This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN. Results were clinically correlated. METHODS:The study included biopsy samples from 87 patients who had been diagnosed with the following disease patterns: 47 invasive anal carcinoma, 33 AIN of varying severity and seven condylomatous lesions. In 52 of these cases, a tumour was clinically suspected. All biopsies were retrospectively examined for microscopic indications of HPV infection. After microdissection, additional HPV analysis via PCR was carried out. RESULTS:In 38 of 47 cases of anal carcinoma, HPV DNA could be detected via PCR (80.9%), the majority of which were HPV 16 (33/38=86.8%). In 29 of the 33 cases of AIN, HPV DNA was detected (87.9%), most of these in AIN III (15/16=93.8%). Histological markers of HPV infection were detected in all 87 cases. DISCUSSION:In our series, the clinical diagnosis of the invasive anal carcinoma had a high sensitivity of 93.6%, with a specificity of 80%. The positive predictive value was 84.6%, and the negative predictive value 91.4%. In contrast, AIN had been detected clinically in none of the cases. In this situation, especially with high-risk patients, our findings recommend anal HPV screening in combination with anal cytology and anoscopy. CONCLUSION:Based on our results, we urgently recommend for any histological report on excision of anal lesions to include a statement whether histological markers of HPV infection were detected. In individual cases, validation via HPV PCR must be considered.
INTRODUCTION:Perforation is a rare complication of intestinal endometriosis. We report on a 38-year-old patient with previously known rectovaginal and ileocecal endometriosis who was referred with an acute abdomen.CASE REPORT:On abdominal plain film an ileus of small intestine was diagnosed. The patient had fever, and the C-reactive protein was markedly increased. Upon emergency laparotomy an acute terminal ileitis with omentum-sealed perforation and a stenosis of the anterior wall of the rectum due to endometriosis were found. Partial resection of the ileum with end-to-end anastomosis, appendectomy, and short segmental rectum resection were performed. The postoperative course was uneventful. Histological examination corroborated the intraoperative diagnosis of fistulas, perforation and deep ulceration of the intestine consistent with transmural endometriosis.DISCUSSION:For proper care of these patients excellent cooperation between gynecologists and general surgeons is desirable. A short review of the literature concerning intestinal endometriosis is given.
Scars arise in the late phase of wound healing as a response to tissue injury and are characterised by fibroplasia. For the patient, the function deficiency is not only a cosmetic problem, in some cases it can present a life-threatening complication and lead to severe loss in health related quality of life. Current studies with the MRL mice could demonstrate an accelerated wound healing without the generation of scars as well as regenerative wound healing. The aim of the present study was to elucidate the mechanism of regenerative wound healing in a skin transplantation model. Material and Methods: Full skin grafts from MRL/+ and B10 mice were cross transplanted. 3 d and 10 d after transplantation we measured tissue pO2 (Licox-pO2), microcirculation (Laser Doppler), graft size and graft vascularization. In tissue slides, we evaluated the collagen thickness and cell apoptosis by the TUNEL-assay. Quantitative mRNA Analysis was performed with the Taqman method. Results: (Mean+/– SD; n = 5; *p < 0.05; T = 10 d; MRL vs. 0B10) Tissue pO2 was significantly higher in MRL mice (148 +/– 15.3* vs. 76 +/– 28.7 mm Hg), as was the microcirculation (233 +/– 65* vs. 77+/–33.2 aU) and the size of the full thickness skin graft (100+/–32 vs. 46+/– 17.6 mm2) which at 10 d was significantly larger than in the B10-group. The thickness of the collagen layer (298+/–32.82 vs. 545.6+/–39.2 µm) and the TUNEL reaction were significantly higher in the B10-group. The infiltration of the wound area with inflammatory cells (leucocytes) was markedly reduced in the MRL-group. Discussion: As possible mechanism for accelerated wound healing the SMAD pathway has been implicated. Our results showed that in MRL-mice, in contrast to B10 mice, the signal molecule SMAD7 expression is down regulated; therefore the signals from transforming growth factor beta are enhanced. Conclusions: The enhanced regenerative wound healing in MRL/+ mice is associated with improved vascularization and microcirculation. The inflammatory reaction is blunted. Causative for these results are most likely changes in the SMAD signal pathway.
Background. Up to 30% of all livers retrieved for organ transplantation exhibit steatotic transformations. Chronic organ-donor shortage has led to the acceptance of these organs for transplantation, although a higher risk of graft nonfunction is associated with the preservation of steatotic livers.Methods. A dietary steatosis was induced in Wistar rats by fasting them for 2 days and feeding them with a fat-free diet. Fatty livers (n=14) were retrieved and flushed with 60 mL of histidine, tryptophane, alpha-ketoglutarate (HTK) solution. In half of the experiments, L-carnitine (5 mM) was added to the HTK. Functional integrity of the livers was evaluated by isolated reperfusion with KHB in a recirculating system at 37degreesC for 45 minutes.Results. Addition of L-carnitine to the HTK promoted a significant reduction of the enzyme leakage from the livers upon reperfusion. Release of alanine-aminotransferase was reduced to one third (127+/-22 vs. 423+/-61 U/L), and the loss of glutamate dehydrogenase in the perfusate could be reduced significantly (42 7 vs. 542+/-134 U/L) when compared with livers stored without additional medication. Morphologic corroboration of these data was obtained by electron microscopy. Although normal appearance of liver mitochondria was preserved at the end of the cold ischemic storage, reperfusion of cold-stored fatty livers entailed massive alterations and frequent destruction of hepatic mitochondria. However, these morphologic impairments were remarkably mitigated in the carnitine-treated group.Conclusions. L-carnitine represents a feasible metabolic adjunct for a safe and more successful preservation of ischemia-reperfusion-sensitive steatotic livers.
OBJECTIVE:to evaluate local surgical trauma induced by endovascular (TPEG) and conventional infrarenal aortic aneurysm repair (AAA-C), the inflammatory response and changes in cell-mediated and antibody-mediated immunity as illustrated by the type-1/type-2 T-helper (TH1/TH2) cell balance were investigated.DESIGN:prospective study.PATIENTS AND METHODS:sixteen patients were included, eight patients underwent AAA-C and eight TPEG. Venous peripheral blood samples were collected 24h preoperatively and 24, 48, 72h, 5 and 7 days postoperatively. Besides the WBC, intracellular TH1/TH2 cytokines (IFN-gamma/IL-4) and the cell surface markers HLA-DR on monocytes and CD23 on B cells were measured by four colour flow cytometry.RESULTS:statistically significant higher values in the AAA-C group were demonstrated for neutrophiles. The TH1/TH2 immunobalance (expressed by forming the ratio of IFN-(gamma/IL-4 producing T cells as well as by the ratio of HLA-DR(pos) monocytes/CD23(pos) B-cells) showed a significant shift towards TH2 immunity in the AAA-C group whereas TPEG led to a significant lesser shift 24-72h after surgery (p < 0.05).CONCLUSIONS:TPEG leads to a minor distortion of the TH1/TH2 immunobalance. This implies that TPEG is a less stressing procedure, that is especially beneficial in patients whose conditions are considered less suitable for AAA-C due to age and serious comorbidity.
Beim Morbus Behçet handelt es sich um eine Vasculitis unklarer Genese, die sich meist durch okuläre und mucocutane Symptome äußert. In seltenen Fällen kommt es durch eine Vasculitis der Vasa vasorum großer Arterien zu Gefäßwandnekrosen mit konsekutiver Ausbildung von Aneurysmata spuria. Es wird der Fall eines 41 jährigen Patienten vorgestellt, der eine Ruptur eines infrarenalen Aneursyma spurium im Rahmen eines Morbus Behçet erlitt. Die Therapie bestand in der aorto-aortalen Interpostion einer Dacron-Prothese. Es wird anhand der Kasuistik die Diagnostik, die Therapie sowie Wert einer Sekundärprophylaxe bei Morbus Behçet diskutiert.
Behçet's disease is a vasculitis of unknown aetiology, which becomes apparent by ocular and mucocutaneous symptoms. In rare cases, owing to vasculitis of the vasa vasorum of large arteries, necrosis of the vascular wall and thus spurious aneurysms occur. The case of a 41-year-old patient is described who presented with a rupture of an infrarenal aortic aneurysm due to Behçet's disease. Therapy consisted of placement of an aortic-aortic Dacron prosthesis. On the basis of the case report, the diagnostic approach, the therapy and the value of secondary prophylaxis of Behçet's disease are discussed.
Background and aims: Lymphocyte apoptosis may influence immune responsiveness in systemic inflammation. Therefore, we investigated whether early signs of apoptosis (i.e., annexin-V binding and cell shrinkage) in peripheral lymphocytes were different among patients with severe sepsis, critically ill, nonseptic patients after major surgery, and healthy individuals. Patients/methods: Ten patients with severe sepsis and ten critically ill, nonseptic patients after major surgery admitted to a surgical intensive care unit in a university hospital were included in the study. In addition, ten healthy blood donors were included for comparison. We investigated early signs of apoptosis using flow cytometric measurement of annexin-V binding to the cell surface and cell shrinkage of peripheral lymphocytes. Results: The percentage of apoptotic lymphocytes determined as annexin-V positive and propidium iodide negative cells was increased in freshly prepared cells of patients with severe sepsis (11.4±0.5%) and critically ill, nonseptic patients after major surgery (18.5±2.0%) relative to healthy blood donors (4.4±0.5%) (P<0.05). No significant difference between patients with severe sepsis and patients after major surgery were found. Annexin-V binding increased significantly after OKT-3 stimulation of lymphocytes in patients with severe sepsis (34.4±1.6%), patients after major surgery (33.8±3.4%), and healthy blood donors (21.1±2.8%). No significant difference among groups was detected following OKT-3 stimulation. Furthermore, freshly isolated peripheral lymphocytes of patients with severe sepsis and critically ill, nonseptic patients after major surgery revealed a significantly higher proportion of cell shrinkage than in healthy blood donors (55.0±2.2%, 21.5±2.4% vs 3.6±0.7%; P<0.05). Conclusion: Circulating lymphocytes of critically ill patients show a high degree of early signs of cellular apoptosis. This may contribute to hyporesponsiveness of immune cells in systemic inflammation.