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Bruns H, Hillebrand N, Schneider T, Hinz U, Fischer L, Schmidt J, Goldschmidt AJW, Schemmer P. LabMELD-based organ allocation increases total costs of liver transplantation: a single-center experience. Clin Transplant 2011: 25: E558–E565. © 2011 John Wiley & Sons A/S. Abstract: Introduction: In 2006, model for end-stage liver disease (MELD)-based allocation was implemented in the Eurotransplant (ET) region. Sick patients, who in general require more resources, are prioritized. In this analysis, the effect of MELD on costs for liver transplantation (LTx) was assessed. Methods: Total costs for LTx before and after implementation of MELD were identified in 256 patients from January 2005–December 2007. Forty-nine patients (Re-LTx, HU listings, and 30-d mortality) were excluded from further analysis. The costs of LTx in 207 patients have been correlated with their corresponding labMELD; 84 and 123 LTx before and after implementation of MELD were compared, and patient survival was monitored. Results: A positive correlation exists between labMELD and costs (r2 = 0.28; p 24), with an increase of €15.672 ± 2.233 between each group (p

Background Pancreatic surgery requires extensive preparation and tissue dissection. Therefore, LigaSure (Valleylab, Boulder, CO) provides an alternative to conventional dissection techniques. The aim of the present study was to describe the feasibility, safety, and cost efficiency of LigaSure in pancreatoduodenectomy. Methods Seven patients underwent surgery with the Ligasure and 7 patients underwent surgery with conventional dissection techniques. The patients were investigated for surgical time, intraoperative blood loss, complications, mortality, duration of hospital stay, and surgery-related costs. Results Surgical time was 207 minutes in the LigaSure group and 255 minutes in the conventional group (P = .020). Intraoperative blood loss was 271 and 771 mL, respectively (P = .010). Other perioperative outcomes were comparable. The respective surgery-related costs averaged €4,125 and €4,931 (P = .023). Conclusions The use of LigaSure in pancreatoduodenectomy seems to be feasible and safe. In addition, it might lead to a reduction in the surgery-related costs.

Background: The aim of this trial was to confirm previous results demonstrating the efficacy and safety of a fixed combination tissue sealant versus argon beam coagulation (ABC) treatment in liver resection. Methods: This trial was designed as an international, multicenter, randomized, controlled surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of ≥1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondaty hemostasis. Secondary end points were drainage duration, volume, and content. Adverse events were collected to evaluate the safety of treatments. The trial was registered internationally (Eudract number 2008-006407-23). Results: Among 119 patients (60 TachoSil and 59 ABC) randomized in 10 tertiary care centers in Europe, the mean time to hemostasis was less when TachoSil was used (3.6 minutes) compared with ABC (5.0 minutes; P = .0018). The estimated ratio of mean time to hemostasis for TachoSil/ABC ws 0.61 (95% confidence interval, 0.47-0.80; P = .0003). Postoperative drainage volume, drainage fluid, and drainage duration did not differ between the 2 groups. Mortality (2 vs. 4 patients) and adverse reactions (24 vs. 28 patients) for TachoSil versus ABC did not differ. Conclusion: This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC. Postoperative morbidity and mortality remained unchanged between both groups.

One would have hoped that the publication of Michael Hofmann’s superb translation of Fred Wander’s novel The Seventh Well (New York 2008) might finally help secure Wander’s text the attention it deserves, alas, as yet to no avail. Fred Wander, probably best known (if at all) as the widower and executor of Maxie Wander, was a survivor of Auschwitz and Buchenwald. First published in East Berlin in 1971, The Seventh Well is a semi-fictionalized account of his experiences in the camps (and an attempt to lend those of his peers who did not survive a posthumous voice).

For scholars of Jewish/non-Jewish relations in the modern German (and Austrian) context these are truly exciting times. Until quite recently, the body of scholarship of genuine substance focusing on this topic could be quite easily surveyed. Each new monograph in the field was long awaited and treated as though it could reasonably be expected to resolve once and for all the perennial controversy between those who assume Jewish/non-Jewish relations in modern Germany and Austria, on balance, to have been either predominantly productive or consistently dysfunctional—between those, in other words, whom for brevity’s sake we might call “optimists” and “pessimists.” As demonstrated not least by the rich crop of publications under review here, the last decade or so has seen a veritable explosion of scholarship in this field, so much so that it is becoming increasingly difficult even for specialists to keep track. We are finally moving from a literature of individual stepping stones, as it were, toward a genuine critical mass of scholarship, and this process is facilitating a far-reaching refinement and differentiation in both methodology and content.

Medical Education 2010: 44: 936–940 Objectives Three-dimensional (3-D) representation is thought to improve understanding of complex spatial interactions and is being used more frequently in diagnostic and therapeutic procedures. It has been suggested that males benefit more than females from 3-D presentations. There have been few randomised trials to confirm these issues. We carried out a randomised trial, based on the identification of complex surgical liver anatomy, to evaluate whether 3-D presentation has a beneficial impact and if gender differences were evident. Methods A computer-based teaching module (TM) was developed to test whether two-dimensional (2-D) computed tomography (CT) images or 3-D presentations result in better understanding of liver anatomy. Following a PowerPoint lecture, students were randomly selected to participate in computer-based testing which used either 2-D images presented as consecutive transversal slices, or one of two 3-D variations. In one of these the vessel tree of portal and hepatic veins was shown in one colour (3-D) and in the other the two vessel systems were coloured differently (3-Dc). Participants were asked to answer 11 medical questions concerning surgical anatomy and four questions on their subjective assessment of the TM. Results Of the 160 Year 4 and 5 medical students (56.8% female) who participated in this prospective randomised trial, students exposed to 3-D presentation performed significantly better than those exposed to 2-D images (p 0.1). Male students gave significantly more correct answers in the 3-D and 3-Dc modalities than female students (p

Physiological stimulation of pancreatic acinar cells by cholecystokinin and acetylcholine activate a spatial-temporal pattern of cytosolic [Ca(+2)] changes that are regulated by a coordinated response of inositol 1,4,5-trisphosphate receptors (IP(3)Rs), ryanodine receptors (RyRs) and calcium-induced calcium release (CICR). For the present study, we designed experiments to determine the potential role of Bcl-2 proteins in these patterns of cytosolic [Ca(+2)] responses. We used small molecule inhibitors that disrupt the interactions between prosurvival Bcl-2 proteins (i.e. Bcl-2 and Bcl-xl) and proapoptotic Bcl-2 proteins (i.e. Bax) and fluorescence microfluorimetry techniques to measure both cytosolic [Ca(+2)] and endoplasmic reticulum [Ca(+2)]. We found that the inhibitors of Bcl-2 protein interactions caused a slow and complete release of intracellular agonist-sensitive stores of calcium. The release was attenuated by inhibitors of IP(3)Rs and RyRs and substantially reduced by strong [Ca(2+)] buffering. Inhibition of IP(3)Rs and RyRs also dramatically reduced activation of apoptosis by BH3I-2'. CICR induced by different doses of BH3I-2' in Bcl-2 overexpressing cells was markedly decreased compared with control. The results suggest that Bcl-2 proteins regulate calcium release from the intracellular stores and suggest that the spatial-temporal patterns of agonist-stimulated cytosolic [Ca(+2)] changes are regulated by differential cellular distribution of interacting pairs of prosurvival and proapoptotic Bcl-2 proteins.

The technical development of computer tomography (CT) imaging has experienced great progress. As consequence, CT data to be used for 3D visualization is not only based on 4 row CTs and 16 row CTs but also on 64 row CTs, respectively. The main goal of this study was to examine whether the increased amount of CT detector rows is correlated with improved quality of the 3D images.All CTs were acquired during routinely performed preoperative evaluation. Overall, there were 12 data sets based on 4 detector row CT, 12 data sets based on 16 detector row CT, and 10 data sets based on 64 detector row CT. Imaging data sets were transferred to the DKFZ Heidelberg using the CHILI teleradiology system. For the analysis all CT scans were examined in a blinded fashion, i.e. both the name of the patient as well as the name of the CT brand were erased. For analysis, the time for segmentation of liver, both portal and hepatic veins as well as the branching depth of portal veins and hepatic veins was recorded automatically. In addition, all results were validated in a blinded fashion based on given quality index.Segmentation of the liver was performed in significantly shorter time (p0.01, Kruskal-Wallis test) in the 16 row CT (median 479 s) compared to 4 row CT (median 611 s), and 64 row CT (median 670 s), respectively. The branching depth of the portal vein did not differ significantly among the 3 different data sets (p=0.37, Kruskal-Wallis test). However, the branching depth of the hepatic veins was significantly better (p=0.028, Kruskal-Wallis test) in the 4 row CT and 16 row CT compared to 64 row CT. The grading of the quality index was not statistically different for portal veins and hepatic veins (p=0.80, Kruskal-Wallis test). Even though the total quality index was better for the vessel tree based on 64 row CT data sets (mean scale 2.6) compared to 4 CT row data (mean scale 3.25) and 16 row CT data (mean scale 3.0), these differences did not reach statistical difference (p=0.53, Kruskal-Wallis test).Even though 3D visualization is useful in operation planning, the quality of the 3D images appears to be not dependent of the number of CT detector rows.

The number of large slope failures in some high-mountain regions such as the European Alps has increased during the past two to three decades. There is concern that recent climate change is driving this increase in slope failures, thus possibly further exacerbating the hazard in the future. Although the effects of a gradual temperature rise on glaciers and permafrost have been extensively studied, the impacts of short-term, unusually warm temperature increases on slope stability in high mountains remain largely unexplored. We describe several large slope failures in rock and ice in recent years in Alaska, New Zealand and the European Alps, and analyse weather patterns in the days and weeks before the failures. Although we did not find one general temperature pattern, all the failures were preceded by unusually warm periods; some happened immediately after temperatures suddenly dropped to freezing. We assessed the frequency of warm extremes in the future by analysing eight regional climate models from the recently completed European Union programme ENSEMBLES for the central Swiss Alps. The models show an increase in the higher frequency of high-temperature events for the period 2001–2050 compared with a 1951–2000 reference period. Warm events lasting 5, 10 and 30 days are projected to increase by about 1.5–4 times by 2050 and in some models by up to 10 times. Warm extremes can trigger large landslides in temperature-sensitive high mountains by enhancing the production of water by melt of snow and ice, and by rapid thaw. Although these processes reduce slope strength, they must be considered within the local geological, glaciological and topographic context of a slope.

Hitler’s Priests. Catholic Clergy and National Socialism by Kevin P. Spicer, DeKalb, Northern Illinois University Press in association with the United States Holocaust Memorial Museum, 2008, xv + 3...

The frequency of meningeal dissemination (MD) in primary CNS lymphoma (PCNSL), its prognostic impact, and optimal management have not been defined thus far. In 69 of 92 (75%) immunocompetent patients, primarily diagnosed with PCNSL at our institution between January 1994 and February 2007, cerebrospinal fluid was analyzed for MD. MD was found by cytomorphology in 7/63 (11%), by immunophenotyping in 1/32 (3%), and by PCR of the IgH CDR III region in 6/37 (16%). Neuroradiologic examination revealed MD in 3 of 69 patients (4%). Median event-free survival (EFS) of patients with MD diagnosed by any of the methods was 26 months, of those without MD 34.1 months (P = .24); median overall survival (OAS) of these two patients' groups was 45.5 and 42.5 months, respectively (P = .34). Patients with cytomorphologic proof of MD had a median EFS of 15.4 months and OAS of 18.5 months, those without MD 34.3 and 45 months (P = .018 and .017, respectively). We found a low frequency of MD despite the use of putatively sensitive diagnostic methods. No impact on outcome was seen for MD, diagnosed by any of the methods used; however, patients with cytomorphologic proof of MD had a significantly shorter median EFS and OAS.

BACKGROUND: Interleukin-15 (IL-15) has been associated with the growth, survival and biological behavior of leukemic cells and response to therapy. We determined the expression of IL-15 in lymphoblasts and evaluated its potential impact on the outcome in adult acute lymphoblastic leukemia (ALL). METHODS: Between June 1999 and June 2006, ALL samples were collected from 87 adult patients before initiation of antineoplastic therapy. These patients were enrolled in the German Multicenter Acute Lymphoblastic Leukemia June 1999 and July 2003 study trials. The expression of IL-15 in leukemic cells was analyzed by real-time polymerase chain reaction. RESULTS: The expression of IL-15 correlated with the immunophenotype: T-lineage ALL had a more than 4-fold higher IL-15 mRNA expression as compared with B-cell precursor (BCP)-ALL (P < .001). Patients with BCR-ABL+-BCP-ALL had lower IL-15 expression compared with BCR-ABL−-BCP-ALL (P = .041). Furthermore, higher expression of IL-15 was associated with mediastinal (P = .001) and lymph node infiltration (P = .051), but not with hepatomegaly and splenomegaly. Notably, high IL-15 expression in BCP-ALL was associated with an inferior relapse-free survival (RFS) at 5 years (0.17 ± 0.13 vs 0.47 ± 0.13) (P = .008), but there was no impact on overall survival (P = .249). CONCLUSIONS: Differential expression of IL-15 in adult ALL at diagnosis was associated with clinical features and outcome, in particular, RFS. It remains to be evaluated whether IL-15 might be a relevant therapy target, or might be used for risk stratification. Cancer 2010. © 2010 American Cancer Society.

Knot tying is regarded as a basic surgical skill. However, there is no consensus in the literature on the best/safest technique. The aim of this study was to survey the various techniques used by German surgeons at the different stages of their training. A knot tying technique was defined based on three criteria, i.e., both thread ends are crossed at the beginning at least two throws tied pulling at the same free end of the thread (standing part) and at least one knot tied changing the standing part. The knot tying techniques of 192 randomly chosen German surgeons practicing in 102 different hospitals were compared against this standard. Besides the status of the participating surgeons, the type of hospital in which they were currently working was recorded. Of the192 participants, 69 were consultants, 56 fellows, and 67 residents. Forty-three surgeons (22.4%) worked in primary care centers (PCC), 81 (42.2%) in secondary care centers (SCC), and 68 (35.4%) in tertiary care centers (TCC). 62.5% crossed both thread ends at the beginning, 75.5% performed at least two identical throws keeping the same standing part, and 45.3% changed the standing part. Assessed against the technique defined as standard, 19.8% of all surgeons performed similar surgical knots. Even though consultants crossed both thread ends at the beginning and changed the standing part significantly more often (p = 0.007 and p = 0.031 respectively, Fisher’s exact test), the overall rate of identical knots was independent of the status of participants and the type of hospital (p > 0.1, Fisher’s exact test). This explorative study detected a high variability of knot tying techniques among German surgeons. In the absence of any evidence of the superiority of one particular technique, continuing education should focus on the quality of each single knot and perfect the details of the technique used.

We study a single-item periodic review (r, s, q) inventory policy. Customer demands arrive on a discrete (e.g. daily) time axis. The replenishment lead times are discrete random variables. This is the time model underlying the majority of the Advanced Planning Software systems used for supply chain management in industrial practice. We present an approximation of the probability distribution of the customer waiting time, which is a customer-oriented performance criterion that captures supplier–customer relationships of adjacent nodes in supply chains. The quality of the approximation is demonstrated with the help of a simulation experiment.

Background Thoracic epidural anesthesia (TEA) protects the intestinal microcirculation and improves perioperative outcomes. TEA also reduces mortality in acute experimental pancreatitis. Its impact on hepatic microcirculation, however, in health and critical illness is unknown. Therefore, the authors studied the effect of TEA on the liver in healthy rats and in experimental severe acute pancreatitis. Methods TEA was induced by 15 microl/h bupivacaine, 0.5%. Necrotizing pancreatitis was induced by intraductal infusion of 2 ml/kg taurocholic acid, 5%. Twenty-eight rats were assigned to either Sham operation, Sham + TEA, Pancreatitis, or Pancreatitis + TEA. After 15 h, mean arterial pressure, heart rate, and respiratory function were recorded. Sinusoidal width and perfusion rate and the intrahepatic leukocyte adhesion were assessed by intravital microscopy. In an additional 22 rats randomly assigned to Sham, Pancreatitis, and Pancreatitis + TEA, hepatic apoptosis was evaluated by staining for single-stranded DNA and Fas ligand-positive cells. Results TEA did not affect hepatic microcirculation and leukocyte adhesion in healthy rats. Blood pressure remained unchanged in the Sham + TEA group. In Pancreatitis, mean arterial pressure decreased from 141 + or - 6 mmHg to 127 + or - 13 mmHg but remained stable in Pancreatitis + TEA. The sinusoidal diameter decreased from 5.4 + or - 0.1 microm to 5.0 + or - 0.2 microm in Pancreatitis. This was restored in Pancreatitis + TEA. Intrahepatic leukocyte adhesion was not affected by TEA. The increased hepatocyte apoptosis in Pancreatitis was abolished in Pancreatitis + TEA. This might be mediated by inhibition of the Fas ligand pathway. Conclusion TEA reduces liver injury in necrotizing acute pancreatitis. This could be related to a regional sympathetic block. TEA could thus preserve liver function in systemic inflammatory disorders such as acute pancreatitis.

Thoracic epidural anesthesia (TEA) is most frequently used after major surgery. However, despite ongoing research, the influence of TEA on the intestinal perioperative pathophysiology is not fully understood.According to recent results, the splanchnic sympathetic activity is reduced during TEA both in animal models and in clinical TEA. The splanchnic sympathetic activity during high TEA is still unknown. Intestinal perfusion effects of TEA are still unclear as the technique and extent of TEA, hemodynamic alteration and size of measurement result in--seemingly--conflicting reports. Postoperative ileus after laparotomy is ameliorated by TEA. Recent findings suggest beneficial effects also after major laparoscopic procedures. Finally, the impact of TEA on the intestinal pathophysiology in critical illness is an area of growing clinical and scientific interest, although this knowledge is just at its beginning.Further research concerning the use of TEA in major laparoscopic procedures and its potential to improve or endanger anastomotic healing is warranted. The experimental studies of TEA in critical illness should be expanded.

Background The t(9;22) and t(4;11) chromosomal translocations, which generate the BCR-ABL and MLL-AF4 fusion genes, define high-risk subtypes of acute lymphoblastic leukemia in adults. However, the prognostic impact of other rarer fusion genes is less well established in adult acute lymphoblastic leukemia than in the childhood form.Design and Methods In the context of the German Multicenter Therapy Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) we used reverse transcriptase polymerase chain reaction to investigate 441 cases of BCR-ABL- and MLL-AF4-negative B-precursor acute lymphoblastic leukemia for the TCF3-PBX1 (E2A-PBX1) and ETV6-RUNX1 (TEL-AML1) fusion transcripts generated by the t(1;19)(q23;p13.3) and t(12;21)(p13;q22) translocations. Both are well-known molecular alterations in pediatric acute lymphoblastic leukemia in which they have favorable prognostic implications.Results We identified 23 adult patients with TCF3-PBX1 and ten with ETV6-RUNX1. In contrast to previous reports we found no significant difference in overall survival between TCF3-PBX1-positive and -negative patients. At 2 years after diagnosis all the ETV6-RUNX1-positive patients were alive and in continuous complete remission, but their long-term outcome was negatively affected by late relapses. TCF3-PBX1-positive patients exhibited a characteristic CD34−/CD33− and mostly cyIg+ immunophenotype. ETV6-RUNX1 only occurred in patients under 35 years old and was associated with a significantly lower white blood count.Conclusions In contrast to previous suggestions, adult patients with TCF3-PBX1-positive acute lymphoblastic leukemia do not appear to have a worse outcome than their negative counterparts. ETV6-RUNX1-positive patients had a very favorable performance status during the first few years but their long-term survival was negatively affected by late relapses. Both groups of patients are characterized by distinct clinicobiological features which facilitate their diagnostic identification.

Background Clinical benefits of thoracic epidural anesthesia (TEA) are partly ascribed to thoracic sympathetic block. However, data regarding sympathetic activity during TEA are scarce and contradictory. This prospective, randomized, double-blind study evaluated the segmental propagation of sympathetic block after low-concentration, high-volume TEA using digital thermography. Methods Twenty-four patients were included in the study. Thoracic epidural catheters were placed at a median insertion level of T8-T9. Patients were accommodated for 20 min to the room temperature of 23 degrees +/- 0.3 degrees C. Skin temperature was recorded by digital thermography. After baseline measurement of heart rate, arterial pressure, and core body and skin temperature, 10 ml saline (control group) or 10 ml bupivacaine, 0.25% (TEA group), respectively, was administered epidurally. Five minutes (t5) and 20 min (t20) after baseline measurements, hemodynamic parameters and core body temperature were again measured, and sensory block was identified by loss of cold-warm discrimination. In the thumb, the toe, and each thoracic dermatome, difference from baseline temperature was calculated at t5 and t20. Data were analyzed by Mann-Whitney U test. Results Baseline characteristics did not differ among groups. Median spread of sensory block at t20 was T5-L5. At both t5 and t20, skin temperature decreased more in the control group than in the TEA group in all thoracic dermatomes (P < 0.05). Toe temperature increased in the TEA group compared with the control group (P < 0.05), whereas thumb temperature remained unchanged. Conclusion TEA with 10 ml bupivacaine, 0.25%, induced thoracic and lumbar sympathetic block that precedes and exceeds sensory block. Caudal limit of sympathetic block could not be demonstrated in this study.

(2008). Public Knowledge of the Shoah in Nazi Germany. Holocaust Studies: Vol. 14, No. 3, pp. 142-162.

This historiographical discussion piece on the implication of Simon Petliura and the Directory in the pogroms during the ill‐fated struggle for Ukrainian independence between 1917 and 1920 focuses on four core issues. Firstly, it suggests that those committed to the current Ukrainian nation‐building agenda face a crucial paradox: for the Directory’s endeavours to qualify as a precedent in nation building, one has to talk up its ability to influence the developments in the territory under its control. Yet to get Petliura and the Directory off the hook as far as the pogroms are concerned, one has to talk down their ability to influence those same developments. Secondly, it fundamentally questions the juxtaposition of “Ukrainian” and “Jewish” approaches on which Henry Abramson’s claim to have achieved a new synthesis between these two positions hinges. Thirdly, it demonstrates just how crucial conceptual transparency is for any useful debate on the significance of antisemitism in this context. Finally, it re...

International audience; Patients with malignant central nervous system (CNS) involvement of lymphoma have a poor prognosis with intrathecal chemotherapy and radiation. In this paper, we report the results we obtained in such patients by intravenous chemotherapy with high-dose methotrexate and ifosfamide (HDMTX/IFO). The study involved a review of all patients who received HDMTX/IFO for CNS involvement of malignant lymphoma at our hospital. Therapy consisted of 4 g/m of MTX (4 h infusion on day 1) and 1.5–2 g/m/day of IFO (3 h infusion on days 3–5). The study included 20 patients with a median age of 65 years (range, 30–83) and CNS relapse of a malignant lymphoma. Seventeen patients had been pretreated with up to two chemotherapy regimens. The objective response rate was 90% with 12 complete or unconfirmed complete (CR and CRu) and six partial remissions. All patients had at least stabilization of their neurological symptoms. Myelosuppression was the most common toxicity. The median follow-up time was 14.9 months. The median time to neurological progression was 8.9 months. Twelve patients received subsequent therapy, including high-dose chemotherapy with autologous stem cell transplantation in five cases. The median overall survival was not reached. Systemic chemotherapy with HDMTX/IFO is a feasible and promising treatment modality for CNS relapse of a malignant lymphoma.

The objective of this study was to analyze factors leading to explantation of totally implanted access ports (TIAPs) and to assess its occurrence and clinical relevance. Of 438 patient consecutive patients with a port explantation, 385 were eligible for this retrospective cohort study. Reasons for explantation as well as demographic, clinical, and surgical characteristics were analyzed by univariate and multivariate models. The diagnoses leading to TIAP implantation were hematological malignancies in 142 patients (36.8%), breast cancer in 103 patients (26.8%), gastrointestinal cancer in 76 patients (19.8%), nonmalignant diseases in 46 patients (11.9%), and other malignant diseases in 18 patients (4.7%). The reasons for TIAP explantation were infection in 178 patients (46.2%), end of treatment in 129 patients (33.5%), thrombosis in 44 patients (11.4%), TIAP dysfunction in 22 patients (5.7%), and other reasons in 12 patients (3.2%). At the time of TIAP explantation, 115 patients (29.9%) were receiving chemotherapy, and 49 patients (12.7%) were considered immunocompromised. In case of TIAP explantation due to infection, the median length of TIAP in situ time was 303.3 days, whereas the cumulative 10-day and 30-day explantation rates were 2.8% and 10.6%, respectively. By multivariate models, TIAP explantation due to infection is statistically significantly decreased in patients with breast cancer (P

BACKGROUND. This retrospective, single-center study assessed the feasibility, outcome, and late side effects of the treatment of immunocompetent patients with primary central nervous system lymphoma (PCNSL) at the authors' institution. METHODS. All 72 consecutive patients diagnosed with PCNSL between January 1994 and February 2005 were scheduled to receive high-dose methotrexate (HDMTX)-based chemotherapy. RESULTS. The median age of the patients was 62 years and the median Karnofsky performance score (KPS) was 70. Twelve patients did not receive HDMTX-based chemotherapy because of poor physical condition or renal insufficiency. Of the 60 patients treated with HDMTX-based chemotherapy, the treatment of 9 was followed with whole-brain irradiation. Of 54 patients who were evaluable for response, 35 (65%) responded (52% with a complete response and 13% with a partial response), and 19 patients (35%) did not. At a median follow-up of 58.7 months, the median progression-free survival was 9 months and the median overall survival (OAS) was 41.4 months. According to the Memorial Sloan-Kettering Cancer Center (MSKCC) prognosis score, patients could be divided into 3 groups with significantly different OAS: 52.9 months for patients aged 70, and 5.2 months for patients aged ≥50 years and with a KPS

Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation (HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day +30 after allogeneic HSCT was assessed using the CD107a assay. Alemtuzumab and thymoglobulin were similarly very potent in inducing NK cell death in vitro. Even in low concentrations (1 microg/ml) the antibodies induced apoptosis and necrosis in a relevant percentage of NK cells (30%). However, the number of tumor reactive (CD107a+) NK cells was 13.16 per mul and 1.15 per microl (mean) in patients receiving T-cell depletion with 6 mg/kg thymoglobulin and in patients receiving 100 mg alemtuzumab, respectively (P=0.02). Although thymoglobulin and alemtuzumab are equally NK cell toxic in vitro, the recovery of NK cell frequency and anti-tumor reactivity is reduced in recipients of alemtuzumab. Our findings can be explained by a longer half-life of alemtuzumab as compared to active thymoglobulin under therapeutic conditions. Prolonged immunosuppression with increased risk of infections and tumor relapse are a potential threat to patients undergoing HCST and receiving alemtuzumab as T-cell depletion.

The antitumor activity of natural killer (NK) cells has recently been shown to be assessable at a single-cell level via flow cytometric detection of CD107a. We used this novel method to prospectively quantify and characterize tumor-reactive NK cells in patients undergoing myeloablative or nonmyeloablative conditioning and allogeneic hematopoietic stem cell transplantation (HSCT). Degranulation of NK cells in the peripheral blood of 34 patients after HSCT (day +30, day +90) was determined by evaluating CD107a expression after coincubation of the cells with tumor targets. The percentage of degranulating NK cells was higher after nonmyeloablative conditioning than after myeloablative conditioning (P < .001), indicating a higher activation state and increased antitumor activity of NK cells after nonmyeloablative conditioning. We were able to analyze NK cell subsets separately and found that CD56bright NK cells following HSCT are functionally different from CD56bright NK cells in healthy donors, as indicated by a high percentage of degranulating NK cells in response to tumor targets in patients after HSCT. The CD107a assay is a new and feasible method to quantify and characterize tumor-reactive NK cells after HSCT. Using this method, we found that NK cells had high antitumor cytotoxic activity after nonmyeloablative conditioning, which may contribute to the effectiveness of nonmyeloablative conditioning.

Summary The increasing complexity of hepato-biliary surgery, including major hepatic resections and living donor liver transplantation (LDLT), has lead to an increasing demand for sophisticated imaging modalities. Standard operation planning for hepatic resections and preoperative donor and recipient work-up for LDLT is based on two-dimensional computed tomography (CT) images and magnetic resonance imaging. However, even modern multidetector CT scanners are not able to perform routinely three-dimensional (3D) visualization needed for operation planning in liver surgery or LDLT. As a consequence, special-purpose computer-based operation planning systems have been developed that leverage the possibilities of modern image processing to improve surgical planning. The advances in technology enable surgeons to analyse and to visualize the anatomy of the human liver including the vascular structures within the human liver and define the exact volumetric data of the liver tissue to be resected or preserved. Furthermore, 3D visualization of the vessel architecture within the human liver allows a reliable estimation of the amount of liver tissue that could be at risk after resection because of inadequate hepatovenous drainage. Because of its clinical usefulness and real-time visualization capabilities we already use an operation planning system in selected patients prior to liver resection and before donor hepatectomy for LDLT as a standard.

Although all bariatric procedures improve non-alcoholic fatty liver disease (NAFLD) in metabolically sick obese patients, it remains unclear whether different procedures achieve similar effects. Sleeve gastrectomy (SG) and Roux-Y-gastric bypass (RYGB) were compared for their effects on liver function tests (LFT) and glycemic control in a highly selected group of metabolically sick obese patients with both elevated alanine aminotransferase (ALT), a common marker for NAFLD and type 2 diabetes mellitus (T2DM). Thirty-four obese patients with a body mass index (BMI) >35 kg/m2, ALT > 35 U/L, and T2DM were well-matched from a prospective database and retrospectively analyzed. Seventeen patients each underwent RYGB and SG, respectively. The effects on LFT and glycemic control were evaluated over 12 months. Both procedures significantly lowered ALT and aspartate aminotransferase (AST) after 12 months, but SG improved both LFT significantly better than RYGB (ALT 17.8 ± 8.8 vs. 31.1 ± 11.2 U/L, p = 0.003; AST 17.0 ± 8.8 vs. 24.3 ± 7.5 U/L, p = 0.004). In contrast to RYGB, SG normalized elevated ALT levels completely (41 vs. 0 %, p = 0.007). Both SG and RYGB improved insulin resistance, glycemic control, and reduced the need of insulin significantly without any difference between the procedures. SG appears to improve LFT better than RYGB in well-matched obese patients with both elevated ALT and T2DM. This suggests that SG may have a better effect on NAFLD than RYGB with similar effects on glycemic control. The present findings should be verified in randomized controlled trials to obtain further evidence for the decision-making on the most appropriate bariatric procedure for metabolically sick patients.

OBJECTIVE Laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy (LMAH-C) might represent an alternative treatment of gastroesophageal reflux disease (GERD) and may provide durable reflux control without fundoplication. The expected benefit is the prevention of fundoplication-related side effects. Aim of the present trial was to compare LMAH-C with laparoscopic Nissen fundoplication (LNF) in patients with GERD. METHODS In a double-center randomized controlled trial (RCT) patients with proven GERD were eligible and assigned by central randomization to either LMAH-C (n = 46) or LNF (n = 44). The indigestion subscore of the Gastrointestinal Symptom Rating Scale questionnaire (GSRS) indicating gas-related symptoms as possible side effects of LNF was the primary endpoint. Secondary endpoints comprised pH testing and endoscopy and other symptoms measured by the GSRS, dysphagia, and the Gastrointestinal Quality of Life Index. The follow-up period was 36 months. RESULTS Indigestion subscore (LMAH-C 2.9 ± 1.5 vs LNF 3.7 ± 1.6; P = 0.031) but not dysphagia (2.8 ± 1.9 vs 2.3 ± 1.7; P = 0.302) and quality of life (106.9 ± 25.5 vs 105.8 ± 24.9; P = 0.838) differed between the groups at 36 months postoperatively. Although the reflux subscore improved in both groups, it was worse in LMAH-C patients (2.5 ± 1.6 vs 1.6 ± 1.0; P = 0.004) corresponding to a treatment failure of 77.3% in LMAH-C patients and of 34.1% in LNF patients (P

Purpose: The validated Objective Structured Assessment of Technical Skills (OSATS) score is used for evaluating laparoscopic surgical performance. It consists of two subscores, a Global Rating Scale (GRS) and a Specific Technical Skills (STS) scale. The OSATS has accepted construct validity for direct observation ratings by experts to discriminate between trainees' levels of experience. Expert time is scarce. Endoscopic video recordings would facilitate assessment with the OSATS. We aimed to compare video OSATS with direct OSATS. Methods: We included 79 participants with different levels of experience [58 medical students, 15 junior residents (novices), and 6 experts]. Performance of a cadaveric porcine laparoscopic cholecystectomy (LC) was evaluated with OSATS by blinded expert raters by direct observation and then as an endoscopic video recording. Operative time was recorded. Results: Direct OSATS rating and video OSATS rating correlated significantly (ρ = 0.33, p = 0.005). Significant construct validity was found for direct OSATS in distinguishing between students or novices and experts. Students and novices were not different in direct OSATS or video OSATS. Mean operative times varied for students (73.4 ± 9.0 min), novices (65.2 ± 22.3 min), and experts (46.8 ± 19.9 min). Internal consistency was high between the GRS and STS subscores for both direct and video OSATS with Cronbach's α of 0.76 and 0.86, respectively. Video OSATS and operative time in combination was a better predictor of direct OSATS than each single parameter. Conclusion: Direct OSATS rating was better than endoscopic video rating for differentiating between students or novices and experts for LC and should remain the standard approach for the discrimination of experience levels. However, in the absence of experts for direct rating, video OSATS supplemented with operative time should be used instead of single parameters for predicting direct OSATS scores.

The increasing prevalence of obese patients will lead to a more frequent use of bariatric procedures in the future. Compared to conservative medical therapy, bariatric procedures achieve greater weight loss and superior control of comorbidities, resulting in improved overall mortality.A search for current literature regarding mechanisms, indications, and outcomes of bariatric surgery was performed.In order to care for patients after bariatric surgery properly, it is important to understand its mechanisms of action and effects on gastrointestinal physiology. Recent investigations indicate that the beneficial effects of bariatric procedures are much more complex than simply limiting food intake or an associated malabsorption. Changes in gastrointestinal hormone secretion, energy expenditure, intestinal bacterial colonization, bile acid metabolism, and epigenetic modifications resulting in altered gene expression are likely responsible for the majority of the beneficial effects of bariatric surgery. Malabsorptive bariatric procedures divert the flow of bile and pancreatic enzymes from food and therefore limit the digestion and absorption of nutrients, resulting in reduced calorie intake and subsequent weight loss. Essential micronutrients such as vitamins and trace elements are also absorbed to a lesser extent, potentially leading to severe side effects.To prevent malnutrition, dietary supplementation and regular control of micronutrient levels are mandatory for patients undergoing malabsorptive bariatric procedures, in whom the fat-soluble vitamins A and D are commonly deficient.Die Zunahme an adipösen Patienten wird in Zukunft zu mehr bariatrischen Operationen führen. Diese Operationen sind effizient, um den erwünschten Gewichtsverlust und eine der konservativen medizinischen Therapie überlegenen Kontrolle von Komorbiditäten zu erreichen.Eine Recherche zur aktuellen Literatur bezüglich der Wirkmechanismen, Indikationen und Resultate bariatrischer Operationen wurde durchgeführt.Um Patienten nach bariatrischen Eingriffen gut behandeln zu können, sollten die Wirkmechanismen und die Auswirkungen auf die Physiologie des Magen-Darm-Trakts verstanden werden. Neuere Untersuchungen zeigen, dass bariatrische Operationen nicht nur über eine Restriktion der Nahrungszufuhr oder Malabsorption wirken, sondern zu komplexen Veränderungen der Sekretion gastrointestinaler Hormone, der Energieverbrennung, der bakteriellen Kolonisation des Darms, des Gallensäurestoffwechsels und epigenetischen Veränderungen, welche die Genexpression modulieren, führen. Diese Veränderungen sind wahrscheinlich hauptverantwortlich für die positiven Effekte bariatrischer Eingriffe. Malabsorptive bariatrische Operationen separieren die Galle sowie die Pankreasenzyme von der Nahrung und limitieren damit die Verdauung und Resorption von Nährstoffen. Durch die reduzierte Kalorienaufnahme wird der gewünschte Gewichtsverlust erreicht. Durch die Diversion des Verdauungsprozesses werden auch Vitamine und Spurenelemente ungenügend resorbiert, woraus eine potenziell gefährliche Mangelernährung resultieren kann.Um eine Unterernährung zu verhindern, ist es wichtig, dass Patienten nach malabsorptiven bariatrischen Eingriffen lebenslang Nahrungsergänzungsmittel zu sich nehmen und regelmäßige Kontrollen des Ernährungszustands durchführen, da vor allem die fettlöslichen Vitamine A und D sehr häufig unzureichend vorhanden sind.

Macrophages importantly contribute to sepsis-induced lung injury. As their impact on pulmonary endothelial injury and dysregulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear, we assessed pulmonary endothelial dysfunction and HPV by macrophage inhibition via gadolinium chloride (GC) pre-treatment in rats with peritonitis (cecal ligation and puncture [CLP]).The following four study groups were made: Group I: SHAM and group II: SHAM + GC (pre-treatment with NaCl 0.9% or GC 14 mg/kg body weight (b.w.) intravenously 24 hours prior to sham laparotomy); group III: CLP and group IV: CLP + GC (pre-treatment with NaCl 0.9% or GC 14 mg/kg b.w. 24 hours prior to induction of peritonitis). Exhaled nitric oxide (exNO), bradykinin-induced pulmonary vasoconstriction (=surrogate marker of endothelial dysfunction) and HPV were investigated in isolated and perfused lungs (n = 40). Using the same protocol wet to dry lung weight ratio and myeloperoxidase (MPO) activity were investigated in separate rats (n = 28). In additional rats (n = 12) of groups III and IV nitrite levels in alveolar macrophages (AM) were measured.In sepsis, GC pre-treatment significantly attenuated exNO levels, AM-derived nitrite levels, lung MPO activity, and restored blunted HPV, but severely enhanced endothelial dysfunction in healthy and septic animals.Macrophages exhibit a controversial role in sepsis-induced lung injury. The GC-induced restoration of inflammation parameters to sham levels is clearly limited by the negative impact on CLP-induced endothelial injury in this setting. The exact link between the GC-associated modulation of the NO pathway demonstrated and septic lung injury needs to be determined in future studies.

Due to its reliable effects on type 2 diabetes mellitus (T2DM) remission, Roux-en-Y gastric bypass (RYGB) has recently been investigated as a treatment option for nonseverely obese patients with T2DM (body mass index (BMI)35 kg/m(2)). The purpose of this study was to investigate whether RGYB induces malnutrition of macro- and micronutrients within 24 months in these patients.A prospective cohort of 20 patients with longstanding, insulin-dependent T2DM and a BMI of 25-35 kg/m(2) were treated with RYGB. The patients were supplemented with over-the-counter, multivitamin, and micronutrient supplements. Serum concentrations of albumin, vitamins, and trace elements, hemoglobin, and bone density were measured preoperatively and over a 24-month period (DRKS00004605).RYGB did not result in underweight or protein malnutrition. No new onset of deficiencies of water- or fat-soluble vitamins developed over the study period. However, serum selenium, zinc, and ferritin decreased significantly (selenium, 1.17 ± 0.13 to 0.89 ± 0.11 μmol/l, p = 0.018; zinc, 13.9 ± 0.5 to 10.8 ± 0.5 μmol/l, p = 0.012; ferritin, 171.7 ± 26.9 to 31.8 ± 11.2 μg/l, p = 0.018). Hemoglobin remained stable. Vitamin D (13.7 ± 1.8 to 19.1 ± 1.1 ng/ml, p = 0.017) and osteocalcin (15.3 ± 1.7 to 25.4 ± 2.7 ng/ml, p = 0.025) rose significantly, whereas the parathyroid hormone remained stable. Despite increased bone formation, bone density decreased (T score hip, 0.15 ± 0.25 to -0.71 ± 0.34, p = 0.005) resulting in a significant increase in osteopenia rates (18 to 50 %, p = 0.046).This is the first prospective cohort to investigate malnutrition after RYGB in nonseverely obese patients. These patients are at risk of developing iron, selenium, and zinc deficiencies within 24 months, as well as osteopenia despite an increase in bone formation.

Objective: This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy (WBRT) in primary therapy of primary CNS lymphoma (PCNSL) after a median follow-up of 81.2 months. Methods: Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate (HDMTX)–based chemotherapy alone or followed by WBRT. We hypothesized that the omission of WBRT would not compromise overall survival (OS; primary endpoint), using a noninferiority design with a margin of 0.9. Results: In the per-protocol population (n = 320), WBRT nonsignificantly prolonged progression-free survival (PFS) (median 18.2 vs 11.9 months, hazard ratio [HR] 0.83 [95% confidence interval (CI) 0.65–1.06], p = 0.14) and significantly PFS from last HDMTX (25.5 vs 12.0 months, HR 0.65 [95% CI 0.5–0.83], p = 0.001), but without OS prolongation (35.6 vs 37.1 months, HR 1.03 [95% CI 0.79–1.35], p = 0.82). In the intent-to-treat population (n = 410), there was a prolongation by WBRT of both PFS (15.4 vs 9.9 months, HR 0.79 [95% CI 0.64–0.98], p = 0.034) and PFS from last HDMTX (19.4 vs 11.9 months, HR 0.72 [95% CI 0.58–0.89], p = 0.003), but not of OS (32.4 vs 36.1 months, HR 0.98 [95% CI 0.79–1.26], p = 0.98). Conclusion: Although the statistical proof of noninferiority regarding OS was not given, our results suggest no worsening of OS without WBRT in primary therapy of PCNSL. Classification of evidence: This study provides Class II evidence that in PCNSL HDMTX-based chemotherapy followed by WBRT does not significantly increase survival compared to chemotherapy alone. The study lacked the precision to exclude an important survival benefit or harm from WBRT.

Background Acute pancreatitis has been linked to intestinal barrier dysfunction and systemic inflammatory response with high mortality. Thoracic epidural analgesia improves intestinal perfusion. The authors hypothesized that thoracic epidural analgesia influences microcirculation injury, inflammatory response, and outcome of acute pancreatitis in rats. Methods Control groups underwent a sham procedure or untreated pancreatitis induced by intraductal taurocholate injection. In the treatment groups, epidural analgesia was commenced immediately or after a 7-h delay. Fifteen hours after injury, the ileal mucosal perfusion was assessed by intravital microscopy. Thereby, the intercapillary area between all perfused capillaries and between continuously perfused capillaries only was used to differentially quantify total and continuous capillary mucosal perfusion. Villus blood flow and serum levels of amylase, lactate, and interleukin 6 were determined, and pancreatic injury was scored histologically. Seven-day survival was recorded in an additional 30 rats undergoing untreated pancreatitis or pancreatitis with epidural analgesia. Results In untreated pancreatitis, decreased total capillary perfusion increased the total intercapillary area by 24%. Furthermore, loss of continuous perfusion increased continuous intercapillary area to 228%. After immediate and delayed epidural analgesia, continuous perfusion was restored (P < 0.05). Blood flow decreased 50% in untreated pancreatitis but was preserved by epidural analgesia (P < 0.05). Biochemical and histologic signs of pancreatitis were not affected by epidural analgesia. Lactate and interleukin-6 levels increased in untreated pancreatitis, which was prevented in the treatment groups (P < 0.05). Epidural analgesia increased 7-day survival from 33% to 73% (P < 0.05). Conclusion Thoracic epidural analgesia attenuated systemic response and improved survival in severe acute pancreatitis. These effects might be explained by improved mucosal perfusion.

Full right hepatic grafts are most frequently used for adult-to-adult living donor liver transplantation (LDLT). One of the major problems is venous drainage of segments 5 and 8. Thus, this study was designed to provide information on venous drainage of right liver lobes for operation-planning. Fifty-six CT data sets from routine clinical imaging were evaluated retrospectively using a liver operation-planning system. We defined and analyzed venous drainage segments and the impact of anatomic variations of the middle hepatic vein (MHV) on venous outflow from segments 5 and 8. MHV variations led to significant shifts of segment 5 drainage between the middle and right hepatic vein. In cases with the most frequent MHV branching pattern (n = 33), a virtual hepatectomy closely right to the MHV intersected drainage vessels that provided drainage for 30% of the potential graft, not taking into account potential veno-venous shunts. In individuals with inferior MHV branches that extend far into segments 5 and 6 (n = 10), the overall graft volume at risk of impaired venous drainage increased by 5% (p < 0.001). If this is confirmed in clinical trials and correlated with intraoperative findings, the use of liver operation-planning systems would be beneficial to improve overall outcome after right lobe LDLT.

Background In patients treated with rituximab and alemtuzumab for lymphomas or CLL, antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of action. Therefore, assessment of ADCC is mandatory to understand the complex mechanisms leading to the anti-lymphoma effects of monoclonal antibodies (mAb). Due to methodical difficulties, little is yet known about the relevant cell subpopulations and effector mechanisms leading to tumor lysis in ADCC. Methods We used a novel flow cytometric assay that detects CD107a as a marker for NK-cell degranulation to characterize and quantify peripheral blood natural killer (NK) cells mediating ADCC in vitro and in vivo. Results We observed specific and dose-dependent NK-cell activation after administration of rituximab and alemtuzumab. The number of degranulating NK cells was closely related to the concentration of mAb and the effector:target ratio. We were able to quantify and characterize the peripheral blood NK cells mediating ADCC. The majority of degranulating NK cells had the phenotype: CD56 dim , CD69 + , NKG2D + , NKp30 − , NKp46 − , and CD94 − . Furthermore, we found that the CD107a assay can also visualize ADCC under clinical conditions as we observed increased numbers of NK cells degranulating in response to CD20 + lymphoma cell lines in patients with non-Hodgkin's lymphoma treated with rituximab. Conclusions We were able to quantify and characterize NK cells mediating ADCC with a new and feasible method. The CD107a assay may be useful for predicting treatment responses of individual patients and may help find the optimal dosage and timing for treatment with mAb.