Search

Background Diabetic neuropathy is common in type 2 diabetic patients (T2DM) but tight glycemic control does not improve the symptoms. In contrast, Roux-Y gastric bypass (RYGB) has a positive effect on active neuropathic symptoms, independent from glycemic control. The purpose of the present study was to identify potential mechanisms of improved diabetic neuropathic symptoms after RYGB. Methods A prospective cohort of 20 patients with insulin-dependent T2DM and BMI 2 were treated with RYGB. Nineteen patients had complete follow-up. Fasting glucose, HbA1c (glycated hemoglobin), markers for nitrosative, carbonyl, and oxidative stress (nitrotyrosine, carboxylated-lysine (CML), methylglyoxal, oxidized low-density-lipoprotein (oxLDL)) as well as Neuropeptid Y and Neurokinin A were investigated over 12 months. Neuropathy was assessed using the Neuropathy Deficit Score (NDS). Results The preoperative NDS improved within twelve months (5.1±0.6 to 2.6±0.4, P = .010). Fasting glucose and HbA1c also improved compared to preoperative values (201.1±16.6 mg/dL to 128±8.7 mg/dL, P = .004 and 8.5±0.3% (53±3.3 mmol/mol) to 7±0.3% (67±3.3 mmol/mol), P = .001, respectively). Nitrotyrosine, CML, and methylglyoxal all 3 decreased postoperatively (1067.3±266.9 nM to 355.8±36.4 nM, P = .003; 257.1±10.2 ng/ml to 215.3±18.3 ng/ml, P = .039; 402.3±3.9 nM to 163.4±10.3 nM, P = .002). OxLDL remained unchanged. Fasting glucose and HbA1c did not correlate with improved neuropathy. The decrease in nitrotyrosine correlated with improvement in the NDS after 6 and twelve months (r = .9 , P P = .03). The decrease in methylglyoxal after 6 months correlated with decrease in NDS after twelve months (r = 0.897, P = .003). Conclusion RYGB seems to improve oxidative, nitrosative and carbonyl stress, known to have a causal role in diabetic neuropathy.

Background The effect of bariatric surgery on weight loss and improvement of co-morbidities is no longer doubted. However, little attention has been given to the treatment goals from the patient's point of view (patient expectations). The objective of this study was to examine patients' expectations of bariatric surgery and identify gender differences. Methods Bariatric patients were asked to complete a questionnaire. Statistical analysis was performed using chi-square, Pearson correlation coefficient, and Wilcoxon rank sum test. Results Overall, 248 patients participated in this study (69.4% females). The male patients (45.2 yr, SD±11.1) were significantly older than the female (41.8 yr, SD±12.0; P = .04) and suffered significantly more often from diabetes, hypertension, hypercholesterolemia, and sleep apnea. One hundred thirty patients (52.4%) expected to lose at least 45 kg and 39 patients (15.7%)>70 kg. The mean expected excess weight loss was 71.8%. Females expected significantly more often that surgery alone would induce weight loss ( P = .03). "Improved co-morbidity" was by far the highest ranked parameter. Conclusion The male bariatric surgery patients were older and suffered from more co-morbidities. Most of the patients had unrealistic weight loss goals and overestimated the effect of the surgical intervention. However, for both female and male patients, "improved co-morbidity" was the most important issue.

To evaluate improvement in gastrointestinal (GI) symptoms and health-related quality of life (HRQoL) in liver transplant recipients switched from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS).A multicenter, open-label, single-arm study was undertaken in maintenance liver transplant recipients who reported GI complications with MMF therapy. The patients were switched to equimolar doses of EC-MPS at baseline. The primary end point was the change in the Gastrointestinal Symptom Rating Scale (GSRS) total score after 6 to 8 weeks of treatment with EC-MPS. Other key assessments for GI symptoms and HRQoL included the GSRS subscores, the Gastrointestinal Quality of Life Index (GIQLI), the Psychological General Well-Being Index, and the Overall Treatment Effect (OTE). Paired t-test was used to assess the difference in the mean score changes over time.A total of 34 patients were enrolled and switched to equimolar doses of EC-MPS. After 6 to 8 weeks of EC-MPS treatment, mean GSRS total score improved significantly from 2.88 ± 0.66 to 2.10 ± 0.78. Mean improvement in GSRS total score (-0.77 score points; P = .001) exceeded the minimal clinically important difference. Significant improvements were observed in all GSRS subscales (P.05), GIQLI total scores (P = .001), and GIQLI subscales "GI symptoms" (P.001) and "physical function" (0.013). Patients who continued EC-MPS reported sustained benefits compared with patients who switched back to MMF after 6 to 8 weeks of treatment with EC-MPS. On the OTE scale, improvement in symptoms was reported in 76.5% and 61.8% of the patients as perceived by the physicians and the patients. Improvement in HRQoL was reported by 41.2% of the patients. No deaths, biopsy proven acute rejections, or graft losses were reported during the study.Conversion from MMF to EC-MPS was associated with a significant improvement in GI symptoms and HRQoL in liver transplant recipients.

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.

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.

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.

The synthesis and characterization of the organotriboroxinate salts [Me3NCH2CH2OH][B3O4Ph4] (1) and [NEt3H][B3O3Ph3(OH)] (3) are reported. Compound 3 contains the first example of a hybrid inorganic/organic triboroxinate anion. Compounds 1 and 3 have been structurally characterized by single-crystal X-ray diffraction studies, which reveal H-bond ion-pair interactions between anions and cations in both 1 and 3, and additional anion–anion H-bond interactions in 3. Compound 3 exists as a dimer in the solid-state. A single crystal X-ray diffraction study of the triarylboroxine, (4-MeOC6H4)3B3O3, is also reported.

The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. The study assesses ifosfamide (IFO) and trofosfamide (TRO) for treating IOL.We prospectively evaluated the efficacy and aqueous penetration of intravenous IFO, oral TRO and their active 4-hydroxy (4-OH) metabolites in 10 patients with IOL. Doses varied from 1500 to 2000 mg/m2/day on days 1-3 for IFO and from 150 to 400 mg/day (continuous or intermittent administration) for TRO. Four patients had newly diagnosed disease, and six had relapsed after pretreatment.All patients responded to first treatment with IFO or TRO, and both of two patients responded to re-treatment with IFO on ocular relapse. Progression-free survival from the first treatment with IFO or TRO wasor = 6-18 months. In six of six patients, 4-OH metabolites were detected in the aqueous humor at a concentration of 0.32-1.56 microM immediately after IFO infusion with an aqueous/serum ratio of 0.19-0.54. 4-OH metabolites could be detected in one of three patients at a concentration of 7.2 microM 3-16 h after ingestion of TRO.IFO and TRO are active in IOL. IOL patients evidence aqueous penetration of 4-OH metabolites after intravenous administration of IFO.

The dose of high-dose methotrexate (HDMTX) in elderly patients often has to be reduced, resulting in a loss of treatment efficacy. We evaluated HDMTX-related toxicity with special regard to age distribution in patients with primary central nervous system lymphoma (PCNSL) in a phase IV multicenter trial.One hundred and fifty-four patients (median age 61 years; 89 patients60 years old, 21 patients70 years old) received 619 HDMTX cycles. Toxicity was evaluated prospectively using the WHO classification. Unless a reduced dose was required after calculating a decreased glomerular filtration rate (GFR), the patients received 4 g/m(2) HDMTX followed by leucovorin rescue.Toxicity was generally mild with toxicities of WHO gradeor =3 usually10%. The differences in the incidence and severity of toxicity were not statistically significant between patients60 years andor =60 years old. The same was true for therapy termination owing to MTX toxicity and for delayed serum MTX clearance. Dose reduction significantly differed between patientsor =60 years and those60 years old (18% versus 44%; P = 0.001).HDMTX is a safe treatment for PCNSL patients regardless of age, with adherence to dose reduction determined by calculating the GFR before each treatment cycle.

Although ATG is frequently used in hematopoietic stem cell transplantation and solid organ transplantation, little is known on its effects on NK cells, which mediate important functions in post-transplantation immunology. We incubated peripheral blood lymphocytes of healthy donors with Thymoglobulin, Lymphoglobulin or ATG-Fresenius. Cell death and apoptosis of NK cells and T cells were determined by flow cytometry using propidium iodide and Annexin V. As expected, there were no significant differences between the different ATGs regarding their T cell toxicity. Surprisingly, we found profound differences between the different ATGs regarding their impact on NK cells: In clinically relevant concentrations Lymphoglobulin had less toxic effects on NK cells as compared to Thymoglobulin or ATG-Fresenius: the median percentages of apoptotic or necrotic NK cells in response to 1 mug/ml Lymphoglobulin, ATG-Fresenius and Thymoglobulin were 2%, 35% and 38%, respectively (p

Lymphoma manifestations of the dura mater are extremely rare and have mostly been attributed to extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type. We report a patient with an isolated meningeal tumor, identified as a B-cell lymphoproliferative disorder with typical B-cell chronic lymphocytic leukemia immunophenotype. Because of the subclinical detection of trisomy 3 in the bone marrow by cytogenetic analysis and interphase fluorescence in situ hybridization, CD5(+) MALT is an important differential diagnosis; however, to our knowledge, this entity has never been reported in the context of dural lymphoma.

During initial stages of development of pancreatitis, co-localization of zymogens and lysosomal enzymes is observed in experimental models of pancreatitis. This leads to activation of trypsinogen to trypsin by cathepsin B. We have recently shown that these co-localized organelles are leaky thus resulting in the release of active trypsin and cathepsin B into cytosol. Whether and how active trypsin lead to acinar cell death during pancreatitis is not understood. The aim of the present study was to elucidate if trypsin or cathepsin B released into cytosol contributes to apoptotic cell death. Methods: Rat pancreatic acinar cells were prepared by collagenase digestion and stimulated with supramaximal concentrations of caerulein. These were permeabilzed using streptolysin O and separated into membrane and cytosolic fraction. In another set of experiments acinar cells were incubated with different concentrations of sphingosine (5-20μM), a lysosomotropic agent. Caspase 3 activation was measured by luminescence based assay. Trypsin and Cathepsin B activities were measured by fluorometric assays. Cytochrome c was detected by Western blotting. Results: Supramaximal stimulation of pancreatic acinar cells with caerulein resulted in significant increase in trypsin (12.3±2.1% of total) and cathepsin B (21.6±3.4% of total) activity in the cytosol. There was also significant increase in cytochrome c and caspase 3 (233.5±4.6 % of control) activities in the cytosolic fraction. Inhibition of cathepsin B resulted in significant decrease in caspase 3 activity. Addition of cathepsin B but not that of active trypsin to unstimulated permeabilzed acinar cells resulted in caspase 3 activation. Incubation of intact unstimulated pancreatic acinar cells with sphingosine resulted in permeability of lysosomes as measured by acridine orange fluorescence and release of cathepsin B into cytosol. This release again resulted in caspase 3 activation (203±4.4% over control) which was inhibited when cells were pretreated with cathepsin B inhibitor CA074me. Conclusion: Our results clearly show that release of cathepsin B into the cytosol of pancreatic acinar cells is sufficient for their apoptotic cell death throughmitochondrial pathway and trypsin doesn't directly participate in apoptosis observed during pancreatitis.

Introduction La transplantation hepatique donneur vivant (THDV) est devenue une alternative reconnue a la transplantation hepatique conventionnelle. Le but de cette etude a ete d’evaluer en l’absence de tout effet-centre, les resultats chez le receveur et les risques chez le donneur, a partir des donnees prospectives du Registre Europeen de Transplantation Hepatique (ELTR). Patients et Methodes D’octobre 1991 a juin 2007, 2 409 THDV (4 %) ont ete realisees parmi les 66 377 transplantations faites dans le meme temps dans 71 centres en Europe. Les donnees des THDV ont ete comparees a ceux de la transplantation conventionnelle/foie entier. Resultats Le nombre de THDV a augmente regulierement pendant 10 ans (de 17 en 1992 a 309 en 2002) pour atteindre un plateau, voire une discrete diminution plus recemment (279 en 2006). Initialement reservee aux enfants, la THDV est maintenant utilisee principalement chez l’adulte (2/3 des cas en 2006). Le foie droit a ete utilise dans 92 % des cas chez l’adulte et le lobe gauche dans 85 % des cas chez l’enfant. Chez le donneur, la mortalite post-operatoire a ete de 0,2 %, impliquant 5 des 2 409 donneurs, en rapport avec une embolie pulmonaire (1 cas), un sepsis (2 cas), une insuffisance cardiaque (1) ou une defaillance multi-organes associee a un myelome (1). Le taux de complications precoces (≤ 3 mois) a ete de 20 %, correle a l’importance de l’hepatectomie (27 % foie droit vs 11 % lobe gauche, p Conclusion La THDV represente 4 % des transplantations realisees en Europe. Elle est maintenant principalement utilisee chez l’adulte pour des indications qui ne sont pas tout a fait superposables a celles de la TH classique. Le risque de mortalite chez le donneur est de 0,2 % avec un taux de complications precoces de l’ordre de 20 %. Comparativement aux transplantations hepatiques conventionnelles, elle donne globalement de meilleurs resultats chez l’enfant et des resultants similaires chez l’adulte.