[Show abstract][Hide abstract] ABSTRACT: SirWe thank Dr. Mangano and his colleagues for their recognition of our modest piece of work and for their valuable and important comments on biostatistics.Generally, it is indeed difficult to draw conclusions from nonsignificant statistical tests as they are designed to control the alpha error, not the beta error. The latter, or the statistical power (which is 1-beta), can only be calculated a priori, not post hoc. The statistical power, as defined a priori, corresponds to the probability to detect a given true difference with the calculated sample size. Because our study was not designed as a randomized controlled trial (RCT), we did not define a primary endpoint, which is the precondition of sample size and power calculations.It is not true, however, that no conclusions can be drawn from significant statistical tests without a power analysis. As already noted, these tests are designed to control the alpha error, if significant. They do this irrespective of the beta error. Our conclu ...
World Journal of Surgery 09/2014; 38(11). DOI:10.1007/s00268-014-2723-8 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ischemic preconditioning (IP) and intermittent clamping (IC) increase the ischemic tolerance of the liver. The underlying mechanisms are not completely understood. Heat shock proteins protect cellular integrity in stress and have been discussed as mediators in preconditioning. IP and IC in rat livers were compared with respect to HSP induction and postischemic microcirculation.
All animals were exposed to 70min of partial warm liver ischemia. Different clamping protocols were used: in control animals (C) 70min continuous ischemia was applied. IP was performed by 5min ischemia and 10min reperfusion before the 70min ischemia time. In IC-groups, ischemia time of 70min was divided into four intervals. Each group included 21 animals with 3 different reperfusion intervals; either 30min, 12 or 36h. Intravital microscopy was performed after 30min of reperfusion. AST-levels and HSP induction were analysed 90min, 12 and 36h after reperfusion.
IP and IC significantly improved sinusoidal perfusion (IP: 83.4±2.8%; IC: 84.4±4.6% vs. C: 60.4±3.9%; p<0.001) and leucocyte adherence in sinusoids (IP: 51.9±12.0, IC: 40.9±4.7 vs. C: 90.1±17.7/mm(2) liver surface; p<0.001) and postsinusoidal venules. AST-levels were minimized in IP and IC compared to controls (12h after reperfusion: IP: 969±934U/l, IC: 675±562U/l vs. C: 2373±792U/l; p=0.004). In the course of reperfusion HSP70 protein expression doubled between 90min and 12h in IC (0.529±0.227 vs. 0.992±0.246; p<0.05) and control-groups (0.572±0.314 vs. 1.106±0.309; p<0.05) whereas it remained unchanged in the IP-group (0.437±0.383 vs. 0.412±0.439; n.s.).
Microcirculation is similarly preserved by IP and IC. The early protection derived by IP prevents further induction of HSP70 in opposite to IC. Therefore, IP may offer a more comprehensive protection against I/R on a cellular and transcriptional level.
Microvascular Research 12/2010; 80(3):365-71. DOI:10.1016/j.mvr.2010.05.005 · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ischemia/reperfusion injury is an unavoidable complication in liver surgery and transplantation. Hemodilution with colloids can reduce postischemic injury but limits oxygen transport. Hemoglobin-based oxygen carriers have been evaluated as blood substitute and provide a plasma-derived oxygen transport. It was the aim of our study to evaluate the combined benefits of hemodilution with a better oxygen supply to reperfused liver tissue by the use of HBOC-201 (Hemopure).
A model of partial warm liver ischemia in the rat was used. One group served as untreated control, the other groups were hemodiluted either with Ringer's lactate, Dextran-70, HBOC-201 or a mixture of Dextran and HBOC-201. After reperfusion, intravital microscopy studies were done and tissue pO(2) levels and transaminases measured. Statistical analysis was done by one- and two-way ANOVA, followed by pairwise comparison.
Hemodilution with Ringer's lactate did not show any improvement compared to the control group. Dextran and HBOC group were superior to the Ringer and control animals in all parameters studied. Leucocyte adherence in postsinusoidal venules improved from 569.03+/-171.87 and 364.52+/-167.32 in control and Ringer group to 131.68+/-58.34 and 68.44+/-20.31/mm(2) endothelium in Dextran and HBOC group (p<0.001). Concerning tissue pO(2) levels, HBOC (23.4+/-5.0 mmHg) proved to be superior to Dextran (7.9+/-4.4 mmHg; p=0.007).
HBOC was equivalent to Dextran in reducing I/R injury in the liver, but improved oxygenation of postreperfusion liver tissue.
Microvascular Research 09/2009; 78(3):386-92. DOI:10.1016/j.mvr.2009.08.005 · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Changes in liver microcirculation are considered essential in assessing ischemia-reperfusion injury, which in turn has an impact on liver graft function and outcome following liver transplantation (LTx). The aim of this study was to introduce dynamic magnetic resonance imaging (dMRI) as a new technique for overall quantification of hepatic microcirculation and compare it to perfusion measured by laser Doppler flowmetry (LDF; hepatic artery/portal vein) and thermal diffusion (TD). The study included 3 groups, measuring hepatic blood flow and microcirculation with the help of TD, LDF, and dMRI. In group I (9 landrace pigs; 26 +/- 5 kg), the native liver before and after partial portal occlusion was studied; in group II (6 landrace pigs; 25.5 +/- 4.4 kg), the liver 24 hours after LTx was studied; and in group III (14 patients), the liver on days 4 to 7 following LTx was studied. A close correlation was found between dMRI measurements and TD (r = 0.7-0.9, P < 0.01) in 4 defined regions of interest. Portal blood flow and partial occlusion of the portal vein were accurately detected by LDF flowmetry and correlated well with dMRI (r = 0.95, P < 0.01). In the clinical setting, representative TD measurements in segment 4b of the transplanted liver correlated well with dMRI analysis in other segments. Quantification of the portal blood flow and imaging of the whole liver could be performed simultaneously by dMRI. In conclusion, dMRI has been proved to be a sensitive modality for the quantification of liver microcirculation and hepatic blood flow in experimental and clinical LTx. It allows for a synchronous, noninvasive assessment of macrocirculation and microcirculation of the liver and could become a valuable diagnostic tool in advanced liver surgery and transplantation.
[Show abstract][Hide abstract] ABSTRACT: Ischemia/reperfusion (I/R) injury is a variable yet unavoidable complication in liver surgery and transplantation. Selenium-dependent glutathione-peroxidases (GPx) and selenoproteins function as antioxidant defense systems. One target in preventing I/R injury is enhancing the capacity of endogenous redox defense. It was the aim of this study to analyze the effects of selenium substitution on liver microcirculation, hepatocellular injury and glutathione status in a model of partial warm liver ischemia in the rat.Sodium selenite was administered in three different dosages i.v.: 0.125 μg/g, 0.25 μg/g and 0.375 μg/g body weight and compared to an untreated control group (each n = 10). Intravital microscopy was performed after 70 min of partial warm liver ischemia and 90 min of reperfusion. Liver tissue and plasma samples were taken at the end of the experiment for laboratory analysis.Microcirculation improved significantly in all therapy groups in contrast to control animals. ALT levels decreased significantly whereas malondialdehyde levels remained unchanged. In liver tissue, selenium supplementation caused an increase in the amount of total and reduced glutathione without changes in oxidized glutathione. This effect is likely mediated by selenite itself and selenoprotein P rather than by modulating GPx activity.We were able to show that selenite substitution has an immediate protective effect on I/R injury after warm hepatic ischemia by acting as a radical scavenger and preserving the antioxidative capacity of the liver.
Microvascular Research 08/2008; 76(2-76):104-109. DOI:10.1016/j.mvr.2008.04.005 · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treatment of choice in recurrent and complicated diverticulitis is surgical resection of the inflamed bowel. Whereas it is accepted that recurrent diverticulitis (RD) can be handled laparoscopically, this is still not generally recommended for complicated diverticulitis (CD). Therefore, we analysed our results of laparoscopic sigmoidectomies concerning intraoperative course, conversion rate, morbidity and hospital stay in RD and CD.
Between 09/2002 and 01/2006, laparoscopic sigmoidectomies were offered to all patients suffering from recurrent or complicated diverticulitis (Hinchey I+II). All resections were performed in a four-port technique with the use of Ultracision and intraabdominal stapler anastomosis. Data were prospectively collected and retrospectively analysed in an intention-to-treat view.
Out of 127 laparoscopic colectomies, 58 were performed for diverticulitis (RD 32; CD 26). Eight patients with colovesical and one patient with colovaginal fistula are included. Three patients with abscesses underwent pretreatment by percutaneous drainage. Operative time was longer in CD than in RD (205+/-41 vs 147+/-34 min; p<0.001) and associated with higher blood loss, but conversion rate was low (RD, 2/32 vs CD, 3/26; p=0.64). There was one intraoperative complication in each group; postoperative major complications occurred in 3.13% (RD) vs 11.5% (CD; p=0.316). One anastomotic leakage occurred in the RD group. Length of hospital stay was shorter for RD than for CD (7.1+/-3.4 vs 10.7+/-6.4 days; p=0.02).
Laparoscopic resections should not be limited to recurrent diverticular disease but can be safely applied for complicated diverticulitis.
International Journal of Colorectal Disease 01/2008; 22(12):1515-21. DOI:10.1007/s00384-007-0359-y · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with hemophilia were at high risk of acquiring blood-borne infections transmitted by factor VIII or factor IX concentrates
which were not virus inactivated before 1986.
[Show abstract][Hide abstract] ABSTRACT: To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy.
Patients who developed biliary complications were analysed in detail for the clinical information, laboratory tests, treatment offered, response to it, follow up and outcomes. The profile of liver enzymes was determined. The safety, efficacy and outcomes of endoscopic retrograde cholangiography (ERC) were also analysed.
40 patients required ERC for 70 biliary complications. GGT was found to be > 3 times (388.1 +/- 70.9 U/mL vs 168.5 +/- 34.2 U/L, P=0.007) and SAP > 2 times (345.1 +/- 59.1 U/L vs 152.7 +/- 21.4 U/L, P=0.003) the immediate post OLT values. Most frequent complication was isolated anastomotic strictures in 28 (40%). Sustained success was achieved in 26 (81%) patients.
Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early, non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.
World Journal of Gastroenterology 05/2007; 13(20):2819-25. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Die chirurgische Therapie des hepatozellulren Karzinoms (HCC) mit vollstndiger Entfernung des Tumors oder die Lebertransplantation kann eine langfristige Heilung ermglichen. Beide Verfahren sind primr oder im Rahmen neoadjuvanter Konzepte durchfhrbar. In bestimmten Fllen kann ein lokoregionres Verfahren mit kurativer Zielsetzung angewandt werden. Die Zuordnung des Patienten zu einer primr chirurgisch kurativen, neoadjuvanten oder palliativen Vorgehensweise ist, neben der hepatischen und extrahepatischen Tumorausdehnung, von der vorbestehenden chronischen Leberschdigung abhngig. Die individuelle Grenze der Resektabilitt ergibt sich aus der notwendigen Radikalitt und dem fr eine suffiziente postoperative Leberfunktion erforderlichen Parenchymrest. Aus diesem Grund ist das Ausma der zirrhotischen Leberschdigung fr die Auswahl und die Sequenz der Therapiemanahmen entscheidend.Surgical treatment with complete resection of the hepatocellular carcinoma and liver transplantation can lead to a long term cure. If needed both surgical approaches can be incorporated into a neoadjuvant concept. In certain cases locoregional tumor treatment with curative intent can establish tumor control. Patients with established diagnosis are assigned to the corresponding surgical curative, neoadjuvant or palliative therapeutic approach according to the tumor stage and degree of parenchymal liver damage. The individual resection requirements to achieve tumor control and the acceptable limit of remnant liver volume to maintain liver function, define the individual feasibility of liver resection. For this reason sequence and choice of the therapeutic measures are determined by the extent of chronic functional impairment of the liver.
Der Gastroenterologe 12/2006; 2(1):20-26. DOI:10.1007/s11377-006-0053-6
[Show abstract][Hide abstract] ABSTRACT: Liver resection for colorectal metastases disease can be performed with curative intent at low morbidity and mortality. Only 15-30 % of liver metastases are amenable to potentially curative resection. Five year survival following primary and repeat liver resection has consistently been reported as 25-40 %. Future strategies focus at widening the indication and extending therapeutic options. The aim of neoadjuvant treatment of irresectable liver metastasis is the conversion to secondary resectability either via increasing residual liver mass (portal vein embolisation/2-stage resection) and/or reducing tumor load via chemotherapy ("down-sizing"). Current data suggest resectability following neoadjuvant chemotherapy in around 8 % of cases but varying between 1-33 %.
Zentralblatt für Chirurgie 05/2006; 131(2):140-7. · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The main cause of death for diabetic patients and patients on dialysis is coronary artery disease (CAD). The most common cause of graft loss following simultaneous pancreas and kidney transplantation (SPK) is death with a functioning graft due to CAD. Therefore, careful pretransplantation evaluation of CAD is mandatory. In our series, every patient undergoes a noninvasive cardiac function test like dobutamine stress echocardiography (DSE) or myocardial thallium scintigraphy using adenosine to induce medical stress. Thirty patients were evaluated for SPK: 15 patients with myocardial scintigraphy and 8 with DSE. Seven investigations showed pathological findings and we performed coronary angiograms, none of which showed coronary artery stenosis. Seven primary coronary angiograms were performed: four due to a history of CAD and three as a primary diagnostic. Following SPK one patient died at 21 days after transplantation due to myocardial infarction. He had a history of CAD with angioplasty and stent implantation. Noninvasive cardiac function tests like DSE or myocardial scintigraphy are reliable methods to evaluate CAD in patients with diabetic nephropathy awaiting SPK. In case of a suspicious finding or a history of CAD, a coronary angiogram should be performed to assess the need for revascularization. Following this algorithm we may further reduce the mortality of SPK.
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic pancreatic resection is rarely described. Telerobotic-assisted laparoscopy may offer some advantages for resection of the pancreatic tail. A 49-year-old woman was diagnosed with insulinoma located in the pancreatic tail. Telerobotic-assisted laparoscopic spleen-preserving resection of the pancreatic tail was performed. Operation time was 195 minutes. The postoperative course was uneventful. The previously described advantages of a telerobotic approach with extended range of motion and three-dimensional view make more complex operations like pancreatic resection possible and may offer extended indications for laparoscopic surgery.
[Show abstract][Hide abstract] ABSTRACT: The prevalence of methicillin-resistant Staphylococus aureus (MRSA) has increased worldwide and MRSA has emerged as an important cause of sepsis in cirrhotic patients and liver transplant recipients. In this retrospective study, the prevalence of MRSA colonization and its influence on infections following orthotopic liver transplantation (OLT) was investigated. From August, 2002 until November, 2004, 66 primary cadaver OLT were performed for adult recipients. Antibody induction used Daclizumab (n = 49) or ATG (n = 14). Maintenance immunosuppression consisted of tacrolimus and steroids, with 30 patients receiving mycophenolate mofetil and 4, rapamune. For perioperative anti-infectious prophylaxis cefotaxime, metronidazole, and tobramycin were administered for 48 hours. The preoperatively performed routine swabs revealed MRSA colonization in 12 of 66 (18.2%) patients. The stage of cirrhosis was equivalent for MRSA(-) patients according to Child score. The mean MELD score was significantly higher for MRSA(+) patients (24.3 versus 18.7, P = .036). More MRSA(+) patients were hospitalized at the time of transplantation (14/54 versus 8/12, P = .018). The incidence of posttransplant infections was not significantly different among the two groups. Within the first year 7 of 66 (10.6%) patients died: 3 of 12 (25%) MRSA(+) and 4 of 54 (7.4%) MRSA(-). The 1-year survival was lower in the MRSA(+) group (74.1% versus 94.1%). In conclusion, this study did not show that an MRSA-positive carrier status implies an increased risk for septic complications following OLT. Mortality was increased for MRSA(+), but failed to show a significant difference. A significantly higher MELD score and pretransplant hospitalization for MRSA(+) patients may contribute to the higher mortality and reflect sicker patients.
[Show abstract][Hide abstract] ABSTRACT: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs.
We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays) to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WI/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI).
Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context.
This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage.
World Journal of Gastroenterology 04/2005; 11(9):1303-16. DOI:10.3748/wjg.v11.i9.1303 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The outcome after live-donor kidney transplantation is influenced by many parameters. The aim of our study was to establish a multivariate prognostic model for calculating the recipient's creatinine clearance after transplantation. Basic immunological, donor-, recipient- and process-related variables were assessed in a series of 18 live-donor kidney transplant patients with an uncomplicated postoperative course. Multivariate analysis was carried out with automated forward and backward selection. The following four parameters were included in the predictive model: recipient age, recipient BMI, graft clearance and degree of relationship. The coefficient of determination (R(2)) was 0.67. It could be shown that a significant prediction of creatinine clearance after living related kidney transplantation can be made, based on simple variables. Therefore, this formula could help to detect early complications in the post-transplantation course if the recipient's creatinine clearance drops below the predicted result.
Transplant International 11/2004; 17(9):490-4. DOI:10.1007/s00147-004-0734-3 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although prothrombotic disorders (PTD) are known to increase the risk of graft failure in kidney transplantation only, there are no data on PTD in simultaneous pancreas and kidney transplantation (SPK).
Forty-seven SPK performed between September 2000 and July 2002 underwent routine screening for PTD. Data were retrospectively analyzed in view of complications (relaparotomy, graft thrombosis, pancreatitis, rejection) and graft function (HbA1c, serum creatinine) 3 months posttransplantation.
Twenty-five of forty-seven (53.2%) patients had 30 PTDs. Homozygous mutations of the MTHFR gene (C677T) were found in six, factor-V Leiden mutation (homo- or heterozygous G1691A) in seven, and prothrombin mutation (20210A) in one patient (group 1). Group 2 consists of deficiencies of protein C (n=1), of protein S (n=12), of antithrombin (n=1), and antiphospholipid syndromes (n=2). Overall, PTD had no influence on graft thrombosis (P=0.36) or rejection (P=0.56). In patients with homozygous mutations, relaparotomies were more often necessary than in patients without mutations (42.9% vs. 11.8%, P=0.046). In group 1, there was a trend toward a higher incidence of graft pancreatitis than in patients without mutations (38.5% vs. 14.7%, P=0.075). Three months posttransplantation, HbA1c was 6.0% in patients with and 5.5% in patients without PTD (P=0.023). With regard to serum creatinine, no significant differences were observed.
PTD are frequent in type-1 diabetics receiving SPK and may have a role in relaparotomies, graft pancreatitis, and pancreas graft function.