50 research outputs found
Volume-Function Analysis (LiMAx Test) in Patients with HCC and Cirrhosis Undergoing TACE-A Feasibility Study
Background Transarterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC) in cirrhosis. In particular in advanced cirrhosis, post-TACE hepatic failure liver (PTHF) failure may develop. Currently, there is no
standardization for the periinterventional risk assessment. The liver maximum capacity (LiMAx) test assesses the functional
liver capacity, but has not been investigated in this setting.
Aims The aim of this study was to prospectively evaluate periinterventional LiMAx and CT volumetry measurements in
patients with cirrhosis and HCC undergoing repetitive TACE.
Methods From 06/2016 to 11/2017, eleven patients with HCC and cirrhosis undergoing TACE were included. LiMAx
measurements (n=42) were conducted before and after each TACE. Laboratory parameters were correlated with the volumeâfunction data.
Results The median LiMAx levels before (276±166 ”g/kg/h) were slightly reduced after TACE (251 ±122 ”g/kg/h;
p=0.08). This corresponded to a median drop of 7.1%. Notably, there was a signifcant correlation between LiMAx levels
before TACE and bilirubin (but not albumin nor albuminâbilirubin [ALBI] score) increase after TACE (p=0.02, k=0.56).
Furthermore, a signifcantly higher increase in bilirubin in patients with LiMAxâ€150 ”g/kg/h was observed (p=0.011).
LiMAx levels at diferent time points in single patients were similar (p=0.2).
Conclusion In our prospective pilot study in patients with HCC and cirrhosis undergoing multiple TACE, robust and reliable LiMAx measurements were demonstrated. Lower LiMAx levels before TACE were associated with surrogate markers
(bilirubin) of liver failure after TACE. Specifc subgroups at high risk of PTHF should be investigated. This might facilitate
the future development of strategies to prevent occurrence of PTHF
Laparoscopic Management of Gastric Band Migration with Acute Gastric Perforation - a Video Vignette
Laparoscopic adjustable gastric banding (LAGB) was once considered to be a safe and effective surgical treatment for morbid obesity. Over the past years, its long-term efficacy and safety came into question by the occurrence of complications such as intragastric band migration. The incidence of intragastric band migration is reported to be between 0.4 and 3.8% [1,2,3,4]. The incidence of gastric perforations is 0.1â0.8% [5,6,7]. Removal of the band in case of migration is always required and often possible via upper endoscopy [2]. Overall, septic complications are rare. However, when they do occur they can be life-threatening
Salvage Surgery for Severe Post-Bariatric Hypoglycemia After Multiple Bariatric Revisions: Reversing Roux-en-Y Gastric Bypass to Sleeve with Roux Limb as Henley-Longmire Interposition
Despite excellent weight loss and resolution of comorbidities experienced by most patients, Roux-en-Y gastric bypass
(RYGB) is known to cause long-term complications that may
necessitate revisional intervention or surgery. Post-bariatric
hypoglycemia (PBH) is an increasingly recognized RYGB
complication afecting 0.1â34% of patients [1â3], which
can impact their quality of life [4]. In rare cases, reversing
RYGB and restoring normal food passage may be considered
due to severe PBH that is refractory to extensive therapeutic
interventions [1, 5, 6]. However, reversal procedures carry a
high risk of complications and usually require long operative
times [7â10]
Darbepoetin-α increases the blood volume flow in transplanted pancreatic islets in mice
Aims
The minimal-invasive transplantation of pancreatic islets is a promising approach to treat diabetes mellitus type 1. However, islet transplantation is still hampered by the insufficient process of graft revascularization, leading to a poor clinical outcome. Accordingly, the identification of novel compounds, which accelerate and improve the revascularization of transplanted islets, is of great clinical interest. Previous studies have shown that darbepoetin (DPO)-α, a long lasting analogue of erythropoietin, is capable of promoting angiogenesis. Hence, we investigated in this study whether DPO improves the revascularization of transplanted islets.
Methods
Islets were isolated from green fluorescent protein-positive FVB/N donor mice and transplanted into dorsal skinfold chambers of FVB/N wild-type animals, which were treated with DPO low dose (2.5 ”g/kg), DPO high dose (10 ”g/kg) or vehicle (control). The revascularization was assessed by repetitive intravital fluorescence microscopy over an observation period of 14 days. Subsequently, the cellular composition of the grafts was analyzed by immunohistochemistry.
Results
The present study shows that neither low- nor high-dose DPO treatment accelerates the revascularization of free pancreatic islet grafts. However, high-dose DPO treatment increased the blood volume flow of the transplanted islet.
Conclusions
These findings demonstrated that DPO treatment does not affect the revascularization of transplanted islets. However, the glycoprotein increases the blood volume flow of the grafts, which results in an improved microvascular function and may facilitate successful transplantation
Reduced NK-Cell Activity in Patients with Metastatic Colon Cancer
Natural killer cells (NK-cells) are believed to play an essential role in the immune surveillance against tumors and infectious diseases. The role of NK-cells in colon cancer remains obscure, since increased as well as decreased percentages and/or activity of NK-cells in comparison to control patients have been reported. Percentage and cytolytic activity of NKcells in the peripheral blood were analyzed in 42 patients with colon cancer before surgery and one year thereafter in comparison to control patients with non-malignant diseases. Patients without distant metastasis at the time of diagnosis displayed a significantly increased percentage of NK-cells as well as sustained NK-cell activity in the peripheral blood prior to surgery when compared to control patients. In contrast, patients with metastatic disease at the time of diagnosis displayed significantly decreased NK-cell activity in the peripheral blood when compared to control patients. One year after surgery, patients who remained free of metastasis still displayed sustained NK-cell activity, whereas patients who developed metastasis presented with profoundly decreased levels of NK-cell activity. Further analysis of these patients revealed that patients who developed metastasis within the first year after surgery already displayed reduced NK-cell activity prior to curative colorectal surgery. These observations indicate that metastatic spread of colorectal cancer is associated with decreased NK-cell activity. It remains speculative whether decreased NK-cell activity precedes the development of metastasis and thus may help to identify patients with a high risk of rapid tumor progression following curative colorectal surgery
Erythropoietin accelerates the revascularization of transplanted pancreatic islets
Background and Purpose
Pancreatic islet transplantation is a promising therapeutic approach for Type 1 diabetes. A major prerequisite for the survival of grafted islets is a rapid revascularization after transplantation. Erythropoietin (EPO), the primary regulator of erythropoiesis, has been shown to promote angiogenesis. Therefore, we investigated in this study whether EPO improves the revascularization of transplanted islets.
Experimental Approach
Islets from FVB/N mice were transplanted into dorsal skinfold chambers of recipient animals, which were daily treated with an intraperitoneal injection of EPO (500 IU·kgâ1) or vehicle (control) throughout an observation period of 14 days. In a second set of experiments, animals were only pretreated with EPO over a 6âday period prior to islet transplantation. The revascularization of the grafts was assessed by repetitive intravital fluorescence microscopy and immunohistochemistry. In addition, a streptozotocinâinduced diabetic mouse model was used to study the effect of EPOâpretreatment on the endocrine function of the grafts.
Key Results
EPO treatment slightly accelerated the revascularization of the islet grafts. This effect was markedly more pronounced in EPOâpretreated animals, resulting in significantly higher numbers of engrafted islets and an improved perfusion of endocrine tissue without affecting systemic haematocrit levels when compared with controls. Moreover, EPOâpretreatment significantly accelerated the recovery of normoglycaemia in diabetic mice after islet transplantation.
Conclusion and Implications
These findings demonstrate that, particularly, shortâterm EPOâpretreatment represents a promising therapeutic approach to improve the outcome of islet transplantation, without an increased risk of thromboembolic events
Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis
Cellular senescence is an irreversible growth arrest that occurs as a result of damaging stimuli, including DNA damage and/or telomere shortening. Here, we investigate histone variant H2A.J as a new biomarker to detect senescent cells during human skin aging. Skin biopsies from healthy volunteers of different ages (18â90 years) were analyzed for H2A.J expression and other parameters involved in triggering and/or maintaining cellular senescence. In the epidermis, the proportions of H2A.J-expressing keratinocytes increased from â20% in young to â60% in aged skin. Inverse correlations between Ki67- and H2A.J staining in germinative layers may reflect that H2A.J-expressing cells having lost their capacity to divide. As cellular senescence is triggered by DNA-damage signals, persistent 53BP1-foci, telomere lengths, and telomere-associated damage foci were analyzed in epidermal keratinocytes. Only slight age-related telomere attrition and few persistent nuclear 53BP1-foci, occasionally colocalizing with telomeres, suggest that unprotected telomeres are not a significant cause of senescence during skin aging. Quantification of integrin-α6+ basal cells suggests that the number and function of stem/progenitor cells decreased during aging and their altered proliferation capacities resulted in diminished tissue renewal with epidermal thinning. Collectively, our findings suggest that H2A.J is a sensitive marker of epidermal aging in human skin
Evaluation of Electrochemotherapy with Bleomycin in the Treatment of Colorectal Hepatic Metastases in a Rat Model
Background: The available ablative procedures for the treatment of hepatic cancer have
contraindications due to the heat-sink effect and the risk of thermal injuries. Electrochemotherapy
(ECT) as a nonthermal approach may be utilized for the treatment of tumors adjacent to high-risk
regions. We evaluated the effectiveness of ECT in a rat model. Methods: WAG/Rij rats were
randomized to four groups and underwent ECT, reversible electroporation (rEP), or intravenous
injection of bleomycin (BLM) eight days after subcapsular hepatic tumor implantation. The fourth
group served as Sham. Tumor volume and oxygenation were measured before and five days after
the treatment using ultrasound and photoacoustic imaging; thereafter, liver and tumor tissue were
additionally analysed by histology and immunohistochemistry. Results: The ECT group showed
a stronger reduction in tumor oxygenation compared to the rEP and BLM groups; moreover, ECTtreated tumors exhibited the lowest levels of hemoglobin concentration compared to the other groups.
Histological analyses further revealed a significantly increased tumor necrosis of >85% and a reduced
tumor vascularization in the ECT group compared to the rEP, BLM, and Sham groups. Conclusion:
ECT is an effective approach for the treatment of hepatic tumors with necrosis rates >85% five days
following treatment
Prolyl hydroxylase domain 2 protein is a strong prognostic marker in human gastric cancer
Objective: According to recent research, prolyl hydroxylase domain 2 protein (PHD2) plays an important role in human carcinogenesis by inducing neovascularization and tumor growth. The aim of this study was to evaluate PHD2 expression patterns in primary gastric adenocarcinoma and to test for a potential predictive value of PHD2 expression in gastric cancer patients. Methods: In a total of 121 patients, PHD2 expression was investigated by immunohistochemistry in paraffin- embedded tissue and correlated with clinicopathological parameters and patient survival. Results: 64 of 121 gastric carcinomas (52.9%) showed PHD2 expression in tumor cell cytoplasm. In univariate analysis, PHD2- negative patients had a significantly shortened survival in compariso
Cellular model system to dissect the isoform-selectivity of Akt inhibitors
The protein kinase Akt plays a pivotal role in cellular processes. However, its isoformsâ distinct functions have not been resolved to date, mainly due to the lack of suitable biochemical and cellular tools. Against this background, we present the development of an isoform-dependent Ba/F3 model system to translate biochemical results on isoform specificity to the cellular level. Our cellular model system complemented by protein X-ray crystallography and structure-based ligand design results in covalent-allosteric Akt inhibitors with unique selectivity profiles. In a first proof-of-concept, the developed molecules allow studies on isoform-selective effects of Akt inhibition in cancer cells. Thus, this study will pave the way to resolve isoform-selective roles in health and disease and foster the development of next-generation therapeutics with superior on-target properties