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Background: Multimodal optimized perioperative management (mPOM, fast-track, enhanced recovery after surgery, ERAS) leads to a significantly accelerated recovery of patients with elective colorectal resections. Nevertheless, fast-track surgery has not yet become established in everyday clinical practice in Germany. We present the results of a structured fast-track implementation in five German hospitals., Methods: Prospective data collection in the context of a 13-month structured fast-track implementation. All patients ≥ 18 years undergoing elective colorectal resection and who gave informed consent were included. After 3 months of preparation (pre-FAST), fast-track treatment was initiated and continued for 10 months (FAST). Outcome criteria were adherence to internationally recommended fast-track elements, postoperative complications, functional recovery, and postoperative hospital stay., Results: Data from 192 pre-FAST and 529 FAST patients were analyzed. Age, sex, patient risk, location, and type of disease were not different between both groups. The FAST patients were more likely to have undergone minimally invasive surgery (82% vs. 69%). Fast-track adherence increased from 52% (35-65%) under traditional treatment to 83% (65-96%) under fast-track treatment (p < 0.01). The duration until the end of infusion treatment, removal of the bladder catheter, first bowel movement, oral solid food, regaining autonomy, suitability for discharge and postoperative length of stay were significantly lower in the FAST group. Complications, reoperations, and readmission rates did not differ., Conclusion: Fast-track adherence rates > 75% can also be achieved in German hospitals through structured fast-track implementation and the recovery of patients can be significantly accelerated., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Complex abdominal wall hernia repair (CAWHR) is a challenging procedure. Mesh prosthesis is indicated, but the use of synthetic mesh in a contaminated area may add to overall morbidity. Biological meshes may provide a solution, but little is known about long-term results. The aim of our study was to evaluate clinical efficacy and patient satisfaction following Strattice™ (PADM) placement., Methods: In this cohort study, all patients operated for CAWHR with PADM in three large community hospitals in Germany were included. Patients underwent abdominal examination, an ultrasound was performed, and patients completed quality-of-life questionnaires. The study was registered in ClinicalTrials.gov under Identifier NCT02168231., Results: Twenty-seven patients were assessed (14 male, age 67.5 years, follow-up 42.4 months). The most frequent postoperative complication was wound infection (39.1%). In no case, the PADM had to be removed. Four patients had passed away. During outpatient clinic visit, six out of 23 patients (26.1%) had a recurrence of hernia, one patient had undergone reoperation. Five patients (21.7%) had bulging of the abdominal wall. Quality-of-life questionnaires revealed that patients judged their scar with a median 3.5 out of 10 points (0 = best) and judged their restrictions during daily activities with a median of 0 out of 10.0 (0 = no restriction)., Conclusions: Despite a high rate of wound infection, no biological mesh had to be removed. In some cases, therefore, the biological meshes provided a safe way out of desperate clinical situations. Both the recurrence rate and the amount of bulging are high (failure rate 47.8%). The reported quality of life is good after repair of these complex hernias.

Background: Complete mesocolic excision is gradually becoming an established oncologic surgical principle for right hemicolectomy. However, the procedure is technically demanding and carries the risk of serious complications, especially when performed laparoscopically. A standardized procedure that minimizes technical hazards and facilitates teaching is, therefore, highly desirable., Methods: An expert group of surgeons and one anatomist met three times. The initial aim was to achieve consensus about the surgical anatomy before agreeing on a sequence for dissection in laparoscopic CME. This proposal was evaluated and discussed in an anatomy workshop using post-mortem body donors along with videos of process-informed procedures, leading to a definite consensus., Results: In order to provide a clear picture of the surgical anatomy, the "open book" model was developed, consisting of symbolic pages representing the corresponding dissection planes (retroperitoneal, ileocolic, transverse mesocolic, and mesogastric), vascular relations, and radicality criteria. The description of the procedure is based on eight preparative milestones, which all serve as critical views of safety. The chosen sequence of the milestones was designed to maximize control during central vascular dissection. Failure to reach any of the critical views should alert the surgeon to a possible incorrect dissection and to consider converting to an open procedure., Conclusion: Combining the open-book anatomical model with a clearly structured dissection sequence, using critical views as safety checkpoints, may provide a safe and efficient platform for teaching laparoscopic right hemicolectomy with CME.

Incisional hernias remain a surgical challenge when balancing surgical morbidity, functional restoration, and risk of recurrence. Laparoscopic intraperitoneal onlay mesh (IPOM) placement reduces postoperative wound infections and allows fast patient recovery. Yet, current IPOM techniques do not achieve closure of the midline hernia gap, thereby increasing the risk of persistent mesh bulging with poor abdominal wall function. We propose a novel triple-step hernia repair technique that includes tension-free midline reconstruction. It is achieved through laparoscopic dorsal component separation and laparoscopic suture closure of the midline with a 1.0 polydioxanone suture sling. Combining dorsal abdominal wall component separation, a midline closure with adequate suture strength, and IPOM reinforcement merges the benefits of open and laparoscopic hernia repair. This triple-step technique allows static and functional laparoscopic abdominal wall reconstruction.

Purpose: Wound infections affect not only the individual patient but lead to an increase in medical costs. After ileostomy reversal, surgical site infections are a common problem. The objective of the study was to compare the infection rates of purse-string and conventional skin closure techniques in a high volume setting., Methods: Patients undergoing ileostomy reversal at the Goethe University Hospital between January 2009 and August 2012 were retrospectively analysed regarding surgical site infections and associated risk factors. Patients received either conventional skin closure (running, interrupted or stapled suturing; group C) or subcuticular purse-string suture (group PS)., Results: In total, 114 patients have been analysed. Conventional wound closure was performed in 81 patients and 33 patients received purse-string skin closure. The groups did not differ regarding age, gender, indication for ileostomy, previous chemotherapy, and operation time. Median hospital stay was 7 days (3-34) in group PS and 8 (3-53) in group C (p = 0.15). Wound infections only occurred in groups C (n = 10, 12 %) compared to group PS (n = 0; 0 %; p = 0.034), and the wound closure technique was the only significant factor associated with surgical site infection. Surgery performed by a resident under supervision was not a risk factor for complications compared to the procedure done by a senior surgeon (p = 0.73)., Conclusion: This study reveals an advantage of the purse-string skin closure technique in ileostomy reversals analysing a large cohort of patients. Therefore, we recommend the use of the purse-string skin closure in ileostomy reversals as one way to lower wound infection rates.

Purpose: The diagnosis of acute appendicitis remains a challenge in daily clinical practice. The aim of the present study was to determine clinical criteria for a careful and cost-effective integration of computed tomography (CT) scans in the clinical pathway for the diagnosis of acute appendicitis., Methods: In this retrospective study, we analyzed all patients who were admitted to our hospital with suspected appendicitis (2008-2011). We included all patients who had an appendectomy with or without preoperative CT. Furthermore, we analyzed all patients who received a CT because of suspected appendicitis but did not have an appendectomy., Results: A total of 367 patients were included in this study. A CT was performed in 35 % of the patients with suspected appendicitis. Women had a significantly higher rate of negative appendectomy (NA) (16.5 %) than men (5.3 %). The frequency of NA was 5.7 % in the group of patients who were imaged, whereas it was 11.8 % (p = 0.075) among those who were not imaged. Thereby, CT scans helped to reduce total hospital expenses (1,317.44 (no CT scan) to 675.85 (CT scan and no operation). Furthermore, CT scans can be avoided in men with normal white blood cell counts who should be observed if not operated immediately., Conclusion: CT can be effectively applied for the diagnosis of acute appendicitis. We propose a diagnostic algorithm which helps to simultaneously avoid unnecessary operations and radiation exposure.

Background: The over-the-scope clip (OTSC) system was first used to close the access route in natural orifice transluminal endoscopic surgery and is increasingly used for other indications., Objective: We analyzed the use of the OTSC in intestinal bleeding and in closure of GI tract leaks., Design: Analysis of a consecutive series of patients., Setting: University hospital., Patients: Nineteen patients (group A: closure of GI leak site, n = 12; group B: complex GI bleeding, n = 7) were retrospectively enrolled in this study. We analyzed outcome and follow-up (6-68 weeks; group A: mean 37 weeks, standard deviation 24) in terms of treatment success (closure of the GI tract leak/durable hemostasis)., Intervention: Endoscopic application of OTSCs., Main Outcome Measurements: Resolution of leaks, closure of fistula (group A), or stopping bleeding (group B)., Results: In group A, durable closure was achieved in 8 of 12 patients. Sealing a postoperative/postinterventional leak was successful in 6 patients and failed in 3. A gastrocutaneous fistula was primarily closed successfully in 2 patients, but recurred in 1 of these patients. A gastric wall dehiscence in necrotizing pancreatitis was successfully closed in another patient. Group B patients had previous endoscopic treatment failure in 4 of 7 patients (through-the-scope clips, injection of Suprarenin or fibrin glue, others) and were deemed not treatable by through-the-scope clips in 3 of 7 patients. The primary success rate was 100% (7 of 7 patients); durable hemostasis was achieved in 4 of 7 patients, whereas surgery or angiography was necessary in the remaining patients., Limitations: Retrospective analysis., Conclusions: Leaks and fistulae are reliably closed with OTSCs in tissue flexible enough to be sucked into the attached cap (eg, in lesions caused <1 week before). GI bleeding may be stopped by OTSCs with reliable transient hemostasis, but durable hemostasis is less frequent., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Identification of patients at risk of a complicated course after liver resection is crucial for adapting post-operative care. In the present study, we investigated the diagnostic value of the plasma levels of various cytokines obtained immediately after surgery. IL-6, IL-10, IL-8, monokine induced by interferon-γ (MIG), monocyte chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) concentrations were measured in 26 patients after liver resection using a cytometric bead assay and were correlated with liver function, resectate weight, surgery duration, ischemia/reperfusion, hospitalization time and occurrence of complications. Patients with post-surgical complications showed distinctive patterns of IL-6 and IL-8 as early as minutes to hours after surgery. In addition, although pre-operative bilirubin in most patients remained within the normal range, a cut-off of 1 mg/dl separated the patients into groups with different profiles of IL-6, IL-8, and MCP-1 secretion and different likelihoods of experiencing post-operative complications (bilirubin levels ≥1.0 vs. <1.0 mg/dl; IL-6 (4 h): 701 vs. 265; IL-8 (6 h): 262 vs. 97 pg/ml; p<0.05 for both). Extended hospitalization, related to delayed recovery, was correlated with increased IL-8 and MCP-1 immediately after surgery. In conclusion, on the basis of these observations, we suggest that early measurement of post-operative levels of MCP-1, IL-6, and IL-8 can be used to identify individuals at risk of post-operative complications immediately after liver surgery.

Valproate (VPA) is a well-characterized histone deacetylase inhibitor with anti-neoplastic properties. We analyzed the growth blocking effects and the molecular mode of action of this compound in colorectal cancer cells in vitro and in vivo. Caco-2, SW-480, CX-1 or WIDR cell lines were exposed to VPA (0.25-2 mM) for various time periods. Cell growth, cell cycle progression and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide dye reduction assay and flow cytometry. Cell cycle- and apoptosis-regulating proteins and histone acetylation were assessed by Western blotting. In vivo tumor growth and regulating protein expression under VPA were investigated in a subcutaneous xenograft tumor model. VPA inhibited the growth of all cell lines with cell cycle arrest paralleled by the up-regulation of H3 and H4 acetylation. In vivo tumor growth was substantially depressed by VPA (200 mg/kg bw). Cell cycle proteins (cdk1, cdk2, cdk4, cyclin D, cyclin E, p19, p21 and p27) were differentially altered by VPA. Predominantly cdk1 was decreased and p27 was up-regulated in all models. Apoptosis-related proteins were altered in vivo with up-regulation of bax and down-regulation of bcl-2. VPA exerts anti-neoplastic activity in colorectal tumor cell lines in vitro and in vivo by altering cell cycle regulation.

Protective hepatocellular responses to a hypoxic challenge are crucial to preserve liver function. The knowledge of affected metabolic functions could help assess and enhance hepatic ischemic tolerance. Here we studied adaptive mechanisms in human hepatocytes after hypoxia and reoxygenation using a proteomic approach. Proteins from primary hepatocytes were extracted after 6 h of hypoxia and 24 h of reoxygenation. The proteome was analyzed by 2D-electrophoresis. Densitometry and mass spectrometry (MALDI-TOF-MS) were used for protein identification. Two hundred and sixty-two spots were differentially analyzed and 33 spots displayed significant differences between hypoxic and normoxic cells. Seventeen proteins were identified by mass spectrometry. After hypoxia and reoxygenation the UTP-glucose-1-phosphate uridyltransferase, phosphoglycerate kinase1, fructose-1,6-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, fructose-1,6-bisphosphatase, thiosulfat-sulfurtransferase, thioredoxin peroxidase, peroxiredoxin III, and annexin A2 proteins were down-regulated. An increased expression was found for carbamoyl phosphate synthetase I, heat shock 70 kDa protein5, phosphoenolpyruvate carboxy-kinase, catalase isoform2, peroxiredoxin II, glutathione S-transferase, hydroxyacid oxidase1, and F1-ATP synthase, alpha subunit1. Hepatocellular adaptation to hypoxia and reoxygenation involve glucose metabolism, peroxisomal functions, and oxidative stress protection. The identified proteins can serve as possible diagnostic targets to monitor hepatic hypoxic tolerance e.g. in the context of liver surgery and transplantation.

Background: Complement activation contributes to the regulation of liver regeneration after liver resection (LR) in mice., Methods: We hypothesized that complement activation and changes in C5a-receptors (C5aR, C5L2) on polymorphonuclear cells (PMN) and monocytes are important in clinical LR. Anaphylatoxin and C5b9 plasma levels were measured (bead-array, ELISA) (25 patients) and receptor expression was assessed after LR (19 patients) (FACS). In vitro PMN C5a-dependent chemotactic response (7 patients) as well as L-selectin shedding and Mac-1 expression (3 patients) was determined., Results: C3a increased after LR (31.1 +/- 4 before LR vs. 41.6 +/- 5 ng/ml, 30 min after LR, P < 0.01), as did C5b9 (12.7 +/- 1 before LR vs. 26.9 +/- 3 ng/ml, 60 min after LR, P < 0.001). C4a and C5a decreased after LR, by 25% 24 h after LR and 30% 2 h after LR, respectively (P < 0.01). C5L2 expression decreased at 4 h, rising at 24 h after LR (PMN: 6.3 +/- 1 before LR, 3.1 +/- 1, 4 h, 8.3 +/- 2, 24 h; P < 0.01). The receptor-related changes accompanied a diminished C5a-dependent chemotactic response by PMN (42.1 +/- 17 before LR vs. 2.1 +/- 3 4 h after LR; P < 0.01) and a reduction of activation upon C5a-R stimulation as measured by L-selectin shedding and Mac-1 expression on PMN. Changes in C5L2 expression on monocytes paralleled postoperative impairment of liver function., Conclusions: These results indicate that complement components are released after clinical LR and subsequently PMN display altered C5a-dependent functional responses.

Complement effectors are known to contribute to host cell injury in several inflammatory diseases. Contrary to this paradigm, in this study utilizing surgical liver resection (partial hepatectomy) in various complement-deficient mice as a model, we have demonstrated that complement anaphylatoxins C3a and C5a are required for the survival of liver cells during regeneration. The mechanisms of these cytoprotective functions of complement were related to the regulation of IL-6 and TNF production or release after liver resection. Disturbances in the cytokine milieu, induced by a loss of complement activity, were found to alter prosurvival signaling, including the IL-6/STAT3 and PI3K/Akt/mammalian target of rapamycin pathways. In conclusion, this study documents functions of complement proteins as prosurvival factors that, through their interactions with cytokines, inhibit apoptotic signaling in proliferating cells of epithelial origin.

Objective: To illustrate the influence of pregnancy on primary umbilical endometriosis., Design: Case report., Setting: Gynecologic endocrinology outpatient department of a university hospital., Patient(s): 27-year-old nulliparous woman., Intervention(s): Surgical treatment with total excision of the umbilicus during early pregnancy., Main Outcome Measure(s): Progressive enlargement of endometriotic umbilical lesions during pregnancy., Result(s): At 3-month follow-up evaluation, there were no signs of recurrence of the disease., Conclusion(s): Spontaneous umbilicus endometriosis is a rare disease that can worsen during pregnancy.

Isolated human hepatocytes are of great value in investigating cell transplantation, liver physiology, pathology, and drug metabolism. Though hepatocytes possess a tremendous proliferative capacity in vivo, their ability to grow in culture is severely limited. We postulated that repeated medium change, common to most in vitro systems, may prevent long-term maintenance of hepato-specific functions and growth capacity. To verify our hypotheses we compared the DNA synthesis and differentiation status of isolated human hepatocytes, cultured in medium which was renewed every day or was not changed for 3 weeks ('autocrine' setting). Daily medium change led to rapid hepatocellular de-differentiation without any signs of DNA replication. In contrast, the autocrine setting allowed hepatocytes to become highly differentiated, demonstrated by an elevated ASGPr expression level, and increased albumin and fibrinogen synthesis and release. Cytokeratin 18 filaments were stably expressed, whereas cytokeratin 19 remained undetectable. Hepatocytes growing in an autocrine fashion were activated in the presence of hepatocyte growth factor (HGF), evidenced by c-Met phosphorylation. However, HGF response was not achieved when the culture medium was renewed daily. Furthermore, the autocrine setting evoked a late but strong interleukin 6 release into the culture supernatant, reaching maximum values after a 10-day cultivation period, and intense BrdU incorporation after a further 5-day period. Our data suggest that preservation of the same medium creates environmental conditions which allow hepatocytes to control their differentiation status and DNA synthesis in an autocrine fashion. Further studies are necessary to identify the key mediators involved in autocrine communication and to design the optimal culture configuration for clinical application.

Acceleration of liver regeneration could be of great clinical benefit in various liver-associated diseases. However, at present little is known about therapeutic interventions to enhance this regenerative process. Our limited understanding and the complexity of the mechanisms involved have prevented the identification of new targets for treatment. Here we propose a broad-range proteomic approach to this problem that makes possible the simultaneous study of different signaling and metabolic pathways on the liver proteome. Changes in protein expression in mouse livers (n = 5 per group) at 6 h and 12 h after partial hepatectomy and sham operation, as compared to untreated controls, were analyzed using two-dimensional gel electrophoresis, mass spectrometry (MS), and mass fingerprinting. Twelve proteins, identified by MS, were up-regulated by at least 2-fold after partial hepatectomy. These included adipose differentiation-related protein, gamma-actin, enoyl coenzyme A hydratase 1, serum amyloid A and eukaryotic translation initiation factor 3. These results indicate that liver regeneration following partial hepatectomy affects various signaling and metabolic pathways.

Gain-of-function mutations of the Cu/Zn superoxide dismutase (SOD1) gene cause dominantly inherited familial amyotrophic lateral sclerosis. The identification of differentially regulated proteins in spinal cords of paralyzed mice expressing SOD1(G93A) may contribute to understanding mechanisms of toxicity by mutant SOD1. Protein profiling showed dysregulation of Stathmin with a marked decrease of its most acidic and phosphorylated isoform, and up-regulation of heat shock proteins 25 and 27, peroxiredoxin 6, phosphatidylinositol transfer protein-alpha, apolipoprotein E, and ferritin heavy chain. Stathmin accumulated in the cytoplasm of 30% of spinal cord motor neurons with fragmented Golgi apparatus. Overexpression of Stathmin in HeLa cells was associated with collapse of microtubule networks and Golgi fragmentation. These results, together with the decrease of one Stathmin isoform, suggest a role of the protein in Golgi fragmentation. Mutant SOD1 co-precipitated and co-localized with Hsp25 in neurons and astrocytes. Mutant SOD1 may thus deprive cells of the anti-apoptotic and other protective activities of Hsp25. Astrocytes contained peroxiredoxin 6, a unique nonredundant antioxidant. The up-regulation of peroxiredoxin 6 probably constitutes a defense to oxidative stress induced by SOD1(G93A). Direct effects of SOD1(G93A) or sequential reactions triggered by the mutant may cause the protein changes.

Although the complement system has been implicated in liver regeneration after toxic injury and partial hepatectomy, the mechanism or mechanisms through which it participates in these processes remains ill-defined. In this study, we demonstrate that complement activation products (C3a, C3b/iC3b) are generated in the serum of experimental mice after CCl(4) injection and that complement activation is required for normal liver regeneration. Decomplementation by cobra venom factor resulted in impaired entry of hepatocytes into S phase of the cell cycle. In addition, livers from C3-deficient (C3(-/-)) mice showed similarly impaired proliferation of hepatocytes, along with delayed kinetics of both hepatocyte hyperplasia and removal of injured liver parenchyma. Restoration of hepatocyte proliferative capabilities of C3(-/-) mice through C3a reconstitution, as well as the impaired regeneration of C3a receptor-deficient mice, demonstrated that C3a promotes liver cell proliferation via the C3a receptor. These findings, together with data showing two waves of complement activation, indicate that C3 activation is a pivotal mechanism for liver regeneration after CCl(4) injury, which fulfills multiple roles; C3a generated early after toxin injection is relevant during the priming of hepatocytes, whereas C3 activation at later times after CCl(4) treatment contributes to the clearance of injured tissue.

Background: Aspirin treatment has an undoubted beneficial impact on the progression of cardiovascular diseases. We hypothesized that aspirin also protects allograft function and survival in the context of chronic renal allograft dysfunction, which displays decisive pathophysiologic features that are similar to those involved in atherogenesis., Methods: A retrospective, multivariate analysis was performed to assess the effect of low-dose aspirin treatment (100 mg/day) on allograft function and survival of 830 renal transplant recipients. Allograft function was evaluated by serum creatinine levels, urine protein levels, and the presence of hematuria., Results: Median allograft survival time was significantly longer in patients receiving low-dose aspirin therapy compared with patients receiving no aspirin treatment (n=205, 13.8 +/- 2.6 vs. 7.8 +/- 0.3 years, n=625; adjusted relative risk=0.443, 95% confidence interval [0.323-0.608], P<0.0001). Statin treatment and a recent time point of transplantation, reflecting the qualitative advances of the applied immunosuppressive therapy, were further positive determinants of renal allograft survival. The number of antihypertensive agents, representing the extent of hypertension, was a negative determinant of allograft survival. Transplant function was better preserved in aspirin-treated patients, who displayed a slower increase of serum creatinine and less proteinuria and hematuria during the observation period. The duration of aspirin treatment was positively associated with better allograft function., Conclusions: Low-dose aspirin therapy substantially improves renal allograft function and allograft survival. These findings suggest that aspirin should be considered to complement long-term posttransplant medical treatment regimens.

Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNFalpha induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor-kappaB/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration.

Background: Patients with Wilson's disease may present with cirrhosis, acute hepatitis or fulminant hepatic failure. Without urgent orthotopic liver transplantation, a fulminant Wilson crisis has a mortality of 100%. We report on an 18-year-old female patient with fulminant hepatic failure due to Wilson crisis., Methods: The molecular adsorbent recirculating system (MARS) was used to eliminate albumin-bound toxins and to bridge waiting until an organ became available., Results: A total of 18 MARS sessions and 4 plasma exchange sessions were performed. Bilirubin levels and hepatic encephalopathy improved under MARS therapy. A total of 75 mg copper was removed until serum copper levels were within the normal range. Copper elimination was measured in 15 MARS treatments, which removed a total of 12.9 mg copper. Four plasma exchange sessions, with a total exchange of 11 liters of plasma, removed 12 mg copper. Urinary copper elimination with penicillamine was 50 mg., Conclusion: MARS was an effective method to stabilize a patient with Wilson crisis, contributed to copper elimination and gained time for liver transplantation. The risk of high-urgency transplantation could be avoided. Liver support was easy in the hands of nephrologists familiar with extracorporeal therapy., (Copyright 2003 S. Karger AG, Basel)

Excessive production of the complement activation product C5a appears to be harmful during the development of sepsis in rodents. Little is known about the role of the C5a receptor (C5aR) and its presence in different organs during sepsis. Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice. C5aR mRNA expression in these organs was also significantly increased during sepsis. Immunohistochemical analysis revealed patterns of increased C5aR expression in parenchymal cells in all four organs following CLP. Mice injected at the start of CLP with a blocking IgG to C5aR (alphaC5aR) showed dramatically improved survival when compared with animals receiving nonspecific IgG, as did mice injected with alphaC5a. In alphaC5aR-treated mice, serum levels of IL-6 and TNF-alpha and bacterial counts in various organs were significantly reduced during CLP when compared with control CLP animals. These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis.

Background: En bloc kidneys from pediatric donors are regarded as questionable with respect to the safety and quality of the transplant outcome. Therefore, we retrospectively studied graft outcome and graft function of our 56 en bloc kidneys transplanted in paraaortal position between 1992 and 1999., Methods: Graft outcome of en bloc kidneys (group A) was compared with graft outcome of single cadaveric adult donor kidneys (group B). Matched pairs were generated regarding HLA-missmatch, cold ischemic time, recipient age, body mass index, and systolic arterial blood pressure., Results: Allograft survival rates of pediatric en bloc kidneys at 1, 3, and 5 years were significantly lower (group A: 78, 70, 70% vs. group B: 92, 92, 81%, P<0.05). Lower survival rate was caused by a higher number of graft losses in the early postoperative period (group A: 21% vs. group B: 4%, P<0.01) due to vascular complications. Main risk factor for graft loss was donor age of less than 12 months. Five years after transplantation serum creatinine of pediatric en bloc kidneys was significantly better than of adult kidneys (0.9+/-0.06 vs. 1.8+/-0.2 mg/dl, P<0.001)., Conclusion: En bloc kidneys show a high percentage of graft survival with excellent long-term graft function. However, the early postoperative period carries a higher risk of graft loss in very young donors due to vascular complications. In the face of donor shortage en bloc kidneys from pediatric donors can successfully be transplanted in a paraaortal position.

Background: Mortality or graft loss after renal transplantation might be influenced by hepatitis virus infection., Methods: Sera from time of transplantation of 927 renal transplant recipients were tested for hepatitis C (HCV) and hepatitis B virus (HBV) in order to investigate the impact of hepatitis virus infection on graft loss and mortality over an observation period of 20 yr., Results: One hundred and twenty three of 927 patients were HCV positive, 30 patients HBV positive and seven patients HBV and HCV positive. The observation period was 9.2 +/- 4.4 yr. Mortality was significantly higher in patients with hepatitis B (p = 0.0005), as well as in patients with concomitant B and C hepatitis (p < 0.0001) and in those who acquired HCV infection after transplantation (n = 30, p = 0.0192) compared with non-infected patients. Patients with replicating HBV infection (HBeAg positive) had the worst prognosis (p < 0.0001). In the multivariate analysis the presence of HBeAg (p < 0.0001), patients' age (p < 0.0001) and HCV infection after transplantation (p = 0.0453) were predictors for death. Graft survival was significantly shorter in patients with concomitant hepatitis B and C (p = 0.0087) as well as in HBeAg positive patients (p = 0.002). HCV infection or HBs antigenemia did not have a significant impact on graft survival compared with non-infected patients., Conclusion: HCV infection after transplantation is associated with a high mortality whereas chronic HCV infection before trans plantation does not have a significant impact on mortality. Patients with replicating HBV infection or concomitant HBV and HCV infection have a high risk of graft loss and mortality.

Severe osteoporosis frequently is observed after organ transplantation. In kidney transplantation, it adds to pre-existing renal bone disease and strategies to prevent osteoporosis are not established. Eighty kidney recipients were included in a randomized controlled prospective intervention trial. Treated patients (n = 40) received an injection of ibandronate, a bisphosphonate, immediately before and at 3, 6, and 9 mo after transplantation. The primary outcome measured was the change in bone mineral density. Secondary measures included graft outcome, spinal deformities, fracture rate, body height, and hormonal and metabolic data. Loss of spongy and cortical bone after transplantation was prevented by ibandronate. Changes of bone mineral density (ibandronate versus controls) were as follows: lumbar spine, -0.9 +/- 6.1% versus -6.5 +/- 5.4% (P < 0.0001); femoral neck, +0.5 +/- 5.2% versus -7.7 +/- 6.5% (P < 0.0001); and midfemoral shaft, +2.7 +/- 12.2% versus -4.0 +/- 10.9% (P = 0.024). Fewer spinal deformities developed with ibandronate (7 patients with 7 deformities versus 12 patients with 23 deformities; P = 0.047). Loss of body height was 0.5 +/- 1.0 cm versus 1.1 +/- 1.0 cm in control subjects (P = 0.040). Two bone fractures occurred in each group. There were fewer acute rejection episodes with ibandronate (11 versus 22; P = 0.009). Graft function after 1 yr was comparable. Bone loss, spinal deformation, and loss of body height during the first year after kidney transplantation are prevented by injection of ibandronate at intervals of 3 mo. The smaller number of rejection episodes of the ibandronate-treated group should be confirmed and its mechanism should be explored in additional studies.