Perioperative outcome of laparoscopic left lateral liver resection is improved by using a bioabsorbable staple line reinforcement material in a porcine model

Hypothesis Laparoscopic liver surgery is significantly limited by the technical difficulty encountered during transection of substantial liver parenchyma, with intraoperative bleeding and bile leaks. This study tested whether the use of a bioabsorble staple line reinforcement material would improve outcome during stapled laparoscopic left lateral liver resection in a porcine model. Study design A total of 20 female pigs underwent stapled laparoscopic left lateral liver resection. In group A (n = 10), the stapling devices were buttressed with a bioabsorbable staple line reinforcement material. In group B (n = 10), standard laparoscopic staplers were used. Operative data and perioperative complications were recorded. Necropsy studies and histopathological analysis were performed at 6 weeks. Data were compared between groups with the Student's t-test or the chi-square test. Results Operating time was similar in the two groups (64 +/- 11 min in group A versus 68 +/- 9 min in group B, p = ns). Intraoperative blood loss was significantly higher in group B (185 +/- 9 mL versus 25 +/- 5 mL, p <0.05). There was no mortality. There was no morbidity in the 6-week follow-up period; however, two animals in group B had subphrenic bilomas (20%) at necropsy. At necropsy, methylene blue injection via the main bile duct revealed leakage from the biliary tree in four animals in group B and none in group A (p <0.05). Histopathological examination of the resection site revealed minor abnormalities in group A while animals in group B demonstrated marked fibrotic changes and damaged vascular and biliary endothelium. Conclusion Use of a bioabsorbable staple line reinforcement material reduces intraoperative bleeding and perioperative bile leaks during stapled laparoscopic left lateral liver resection in a porcine model

MicroRNA profiling in B cell non-Hodgkin Lymphoma:focus on the role of MYC

Non-Hodgkinlymfoon is een kwaadaardige vorm van kanker die uitgaat van de lymfeklieren. De ziekte wordt gekenmerkt door specifieke chromosoomafwijkingen en door afwijkende patronen van genexpressie. Onderzoek naar miRNAs (MicroRNAs, moleculen die de expressie van genen reguleren tijdens cellulaire processen zoals celdeling en de vorming van nieuwe cellen) heeft bijgedragen aan een betere kennis van het ontstaan van de ziekte, maar er is nog veel onduidelijk. Jan Lukas Robertus onderzocht de rol van MicroRNAs in twee vormen van lymfklierkanker. Robertus deed onderzoek naar twee vormen van Non-Hodgkinlymfoom, het veel voorkomende diffuus grootcellig B-lymfoom (DLBCL) en het minder vaak voorkomende Burkitt lymfoom (BL). Hij wist twee specifieke miRNAs te identificeren waarmee een subgroep van DLBCL (namelijk die in de testikels en het centrale zenuwstelsel) gekarakteriseerd kan worden. Verder ontdekte de promovendus dat verschillende lymfoom-subtypes verschillende miRNA-expressieprofielen laten zien. Tot slot toonde hij de rol van zeven specifieke miRNAs aan die een belangrijke rol spelen in de groei van Burktitt Lymfoom-cellen.

Intratumoral macrophage phenotype and CD8(+) T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma

Objectives: In patients with malignant pleural mesothelioma (MPM), local tumor outgrowth (LTO) after invasive procedures is a well-known complication. Currently, no biomarker is available to predict the occurrence of LTO. This study aims to investigate whether the tumor macrophage infiltration and phenotype of and/or the infiltration of CD8(+) T-cells predicts LTO. Materials and methods: Ten mesothelioma patients who developed LTO were clinically and pathologically matched with 10 non-LTO mesothelioma patients. Immunohistochemistry was performed on diagnostic biopsies to determine the total TAM (CD68), the M2 TAM (CD163) and CD8(+) T-cell count (CD8). Results: The mean M2/total TAM ratio differed between the two groups: 0.90 +/- 0.09 in the LTO group versus 0.63 +/- 0.09 in patients without LTO (p < 0.001). In addition, the mean CD8(+) T-cell count was significantly different between the two groups: 30 per 0.025 cm(2) (range 2-60) in the LTO group and 140 per 0.025 cm(2) (range 23-314) in the patients without LTO (p < 0.01). Conclusion: This study shows that patients who develop LTO after a local intervention have a higher M2/total TAM ratio and lower CD8(+) cell count at diagnosis compared to patients who did not develop this outgrowth. We propose that the M2/total TAM ratio and the CD8(+) T-cell amount are potential tools to predict which MPM patients are prone to develop LTO. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Repeated Measurements of NT-pro-B-Type Natriuretic Peptide, Troponin T or C-Reactive Protein Do Not Predict Future Allograft Rejection in Heart Transplant Recipients

Background. Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. Methods. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 +/- 4 (mean +/- standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. Results. The mean age of the patients at HTx was 49 +/- 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after -12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. Conclusion. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx

Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma

Recent studies have shown that certain non-coding short RNAs, called miRNAs, play an important role in diffuse large B-cell lymphomas. Patients with diffuse large B-cell lymphoma have great diversity in both clinical characteristics, site of presentation and outcome. The aim of our study is to validate the differential expression in germinal center and non-germinal center diffuse large B-cell lymphoma,s and to study to the extent to which the primary site of differentiation is associated with the miRNA expression profile. We studied 50 cases of de novo diffuse large B-cell lymphoma for the expression of 15 miRNAs (miR-15a, miR-15b, miR-16, miR-17-3p, miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-92, miR-127, miR-155, miR-181a and miR-221). Apart from 19 nodal cases without extranodal dissemination (stages I and II), we selected two groups with unambiguous stages I and II extranodal presentation; 9 cases of primary central nervous system, II cases of primary testicular and II cases of other primary extranodal diffuse large B-cell lymphomas. All cases were analyzed with qRT-PCR. In situ hybridization for the most differentially expressed miRNAs was performed to show miRNA expression in tumor cells, but not in background cells. MiR-21 and miR-19b showed the highest expression levels. No significant differences were seen between germinal center and non- germinal center diffuse large B-cell lymphomas in either the total or the nodal group for any of the 15 miRNAs. Two miRNAs showed significant differences in expression levels for diffuse large B-cell lymphoma subgroups according to the site of presentation. MiR-17-5p showed a significant higher expression level in the central nervous system compared with testicular and nodal diffuse large B-cell lymphomas (P <0.05). MiR-127 levels were significantly higher in testicular than in central nervous system and in nodal diffuse large B-cell lymphomas (P <0.05). We conclude that the location of diffuse large B-cell lymphoma is an important factor in determining the differential expression of miRNAs

AT1-receptor blockade, but not renin inhibition, reduces aneurysm growth and cardiac failure in fibulin-4 mice

Aims:Increasing evidence supports a role for the angiotensin II-AT(1)-receptor axis in aneurysm development. Here, we studied whether counteracting this axis via stimulation of AT(2) receptors is beneficial. Such stimulation occurs naturally during AT(1)-receptor blockade with losartan, but not during renin inhibition with aliskiren.Methods and results:Aneurysmal homozygous fibulin-4(R/R) mice, displaying a four-fold reduced fibulin-4 expression, were treated with placebo, losartan, aliskiren, or the -blocker propranolol from day 35 to 100. Their phenotype includes cystic media degeneration, aortic regurgitation, left ventricular dilation, reduced ejection fraction, and fractional shortening. Although losartan and aliskiren reduced hemodynamic stress and increased renin similarly, only losartan increased survival. Propranolol had no effect. No drug rescued elastic fiber fragmentation in established aneurysms, although losartan did reduce aneurysm size. Losartan also increased ejection fraction, decreased LV diameter, and reduced cardiac pSmad2 signaling. None of these effects were seen with aliskiren or propranolol. Longitudinal micro-CT measurements, a novel method in which each mouse serves as its own control, revealed that losartan reduced LV growth more than aneurysm growth, presumably because the heart profits both from the local (cardiac) effects of losartan and its effects on aortic root remodeling.Conclusion:Losartan, but not aliskiren or propranolol, improved survival in fibulin-4(R/R) mice. This most likely relates to its capacity to improve structure and function of both aorta and heart. The absence of this effect during aliskiren treatment, despite a similar degree of blood pressure reduction and renin-angiotensin system blockade, suggests that it might be because of AT(2)-receptor stimulation