Till Hasenberg

Association between EGF, TGF-β1, VEGF gene polymorphism and colorectal cancer.

IntroductionUp to the present, EGF 61 A/G, TGF-β1 −509 T/C, and VEGF 936 T/C gene polymorphisms have been analyzed in other cancer entities than colorectal cancer. We have now investigated the frequency of these gene polymorphisms among colorectal cancer patients.Material and methods A total of 157 colorectal cancer patients and 117 cancer-free healthy people were recruited at the Surgical Department of the Universitätsklinikum Mannheim. All patients and healthy people are Caucasians. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP).ResultsThe distribution of EGF 61 G/G homozygotes among colorectal cancer patients was more frequent than that in the control group (33.1% versus 11.1%; Odds Ratio [OR]xa0=xa03.962; 95% Confidence Interval [CI]xa0=xa02.036–7.708). The frequency of the “G” allele in the colorectal cancer patient group was also higher than that in the control group (51.3% versus 33.3%; ORxa0=xa02.105; 95% CIxa0=xa01.482–2.988). No difference could be found for the TGF-β1 and VEGF genotypes among colorectal cancer patients and healthy controls.ConclusionsThe EGF 61 G/G genotype and the G allele are significantly related to colorectal cancer. The TGF-β1 −509 T/C and VEGF 936 T/C gene polymorphisms are not related to colorectal cancer.

Imaging Epidermal Growth Factor Receptor Phosphorylation in Human Colorectal Cancer Cells and Human Tissues

In tumor cells, high phosphorylation levels of receptor tyrosine kinases may occur in the absence of exogenous ligands due to autocrine signaling or enhanced tyrosine kinase activity. Here we show that the phosphorylation state of the endogenous epidermal growth factor receptor (EGFR) can be quantitatively imaged in tumor cells and tissues by detecting fluorescence resonance energy transfer between fluorophores conjugated to antibodies against the receptor and phosphotyrosine, respectively. Five different human colorectal cell lines were analyzed for activity and expression of EGFR. All cell lines exhibited basal EGFR phosphorylation under serum starvation conditions. Phosphorylation levels increased after stimulation with EGF or pervanadate, dependent on the level of basal EGFR phosphorylation in the respective cell lines. This basal activity correlated inversely with receptor expression. Using the acceptor photobleaching fluorescence resonance energy transfer imaging approach, a significantly higher phosphorylation state of EGFR was also found in resected human colorectal tumor samples as compared with adjacent healthy tissue. Imaging of EGFR phosphorylation may thus serve as a valuable tool to investigate the role of receptor tyrosine kinase activity in malignant cell growth.

Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Lead to Comparable Changes in Body Composition after Adjustment for Initial Body Mass Index

BackgroundBariatric surgery is a safe and established treatment option of morbid obesity. Mere percentage of excess weight loss (%EWL) should not be the only goal of treatment.MethodsOne hundred seventy-three obese patients were included in the study. They underwent either Roux-en-Y gastric bypass (RYGB; nu2009=u2009127, mean body mass index (BMI) 45.7u2009±u20095.7xa0kg/m2) or sleeve gastrectomy (SG; nu2009=u200946, mean BMI 55.9u2009±u20097.8xa0kg/m2) for weight reduction. Body weight and body composition were assessed periodically by bioelectrical impedance analysis.ResultsAfter 1xa0year of observation, %EWL was 62.9u2009±u200918.0xa0% in RYGB and 52.3u2009±u200915.0xa0% in SG (pu2009=u20090.0024). Body fat was reduced in both procedures with a slight preference for SG, and lean body mass was better preserved in the RYGB group. Due to significant differences in the initial BMI between the two groups, an analysis of covariance was performed, which demonstrated no significant differences in the %EWL as well as in the other parameters of body composition 1xa0year after surgery. Using percentage of total weight loss to evaluate the outcomes between the two procedures, no significant difference was found (31.7u2009±u20098.4xa0% in RYGB and 30.5u2009±u20097.6xa0% in SG patients, pu2009>u20090.4).ConclusionsExcess weight loss is highly influenced by the initial BMI. Total weight loss seems to be a better measurement tool abolishing initial weight differences. SG and RYGB do not differ in terms of body composition and weight loss 1xa0year after surgery.

Handgrip Strength as a Predictor for Post Bariatric Body Composition

BackgroundAfter bariatric surgery, the postoperative quality of weight loss is variable. The aim of weight loss treatment is to reduce fat mass while keeping fat free mass, in particular body cell mass (BCM), constant. Detection of low BCM is an important aspect of surgical follow up. Handgrip dynamometry is a rapid and inexpensive test to measure static muscle strength, which is an independent outcome indicator of various medical conditions. The objective of this study is to examine the change in handgrip strength after bariatric surgery and its predictive value for postoperative body composition. Furthermore, this study was carried out at the University Hospital, Germany.MethodsTwenty-five patients who underwent a bariatric procedure (laparoskopic Roux-Y gastric bypass nu2009=u200916 or sleeve resection nu2009=u20099) were included in this study. Bioelectrical impedance analysis and hand-grip strength were measured preoperatively and repeated every 6xa0weeks for 4xa0months. An analysis of variance was performed to observe the changes in these individual parameters.ResultsPostoperatively, all patients showed a significant decrease in the body mass index and body fat. The extracellular mass, BCM, and the lean mass of the patients remained constant. Handgrip strength showed no significant changes during the postoperative course. Nevertheless, the preoperative hand-grip strength showed a strong positive correlation with the postoperative body composition.ConclusionsThis study showed no changes in the static muscle force after bariatric surgery. The preoperative handgrip strength was strongly correlated with postoperative body composition and may be used to identify patients who need more attention before surgery and in the early postoperative phase.

Retraction Note: First Experiences with A Circular Stapled Gastro-Jejunostomy by a New Transorally Introducible Stapler System in Laparoscopic Roux-en-Y Gastric Bypass

BackgroundThe only effective treatment for patients with morbid obesity is surgery. Laparoscopic bariatric surgery has become quite popular in attempts to decrease the morbidity associated with laparotomy. The aim of this study was to assess the safety and efficiency by using SurgASSIST® for performing the gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass (RYGBP). The variables were compared with the results using the standard laparoscopic circular end-to-end anastomotic stapler (CEEA®).MethodsAfter randomization, the gastro-jejuostomy of RYGBP was performed in ten patients by transabdominal introduced circular stapler (group A) and in ten patients by transorally introduced circular stapler (SurgASSIST®; group B) via five-port laparoscopy. A prospective 12-month postoperative follow-up including documentation of minor and major complication as well as weight loss and body composition is done every 8xa0weeks.ResultsThe average body mass index (BMI, 52xa0kg/m2) and the other baseline characteristics were equally distributed in both groups. There was no difference in reduction of BMI, excess weight loss, and fat mass in both groups. The rate of port site wound infection in group A was significantly higher (pu2009=u20090.03) when compared to group B. There was no anastomotic leak or stricture postoperatively in both groups.ConclusionsPerforming of a gastrojejunostomy in RYGBP by SurgASSIST is a safe and feasible method in comparison to conventional circular stapler systems. The advantage of SurgASSIST is the avoidance to introduce the stapler through the abdominal wall and, by this, a possible port site wound infection. Further prospective studies have to be performed to verify the advantages of the SurgASSIST in comparison to conventional circular stapler systems.

The Phase Angle of the Bioelectrical Impedance Analysis as Predictor of Post-Bariatric Weight Loss Outcome

BackgroundBariatric surgery is proven to be the most effective therapy for obesity. However, the targeted weight reduction is not always achieved. Reliable predictors for postoperative success are rare. Also, most available predictors, such as gender and socioeconomic status, cannot be influenced. The aim of the study was to assess the reliability of the phase angle (PhA) as a predictor of weight reduction and body composition after bariatric surgery.MethodsOne hundred seventy-three patients (127 with Roux-en-Y gastric bypass and 46 with sleeve gastrectomy), treated between January 2004 and December 2012, were included into this prospective trial. Bioelectrical impedance analysis (BIA) was performed before and five times within the first year after the operation. Correlation between excess weight loss (EWL) was calculated using Pearson’s correlation coefficient and a receiver operating characteristic (ROC) curve.ResultsThe average weight loss was significant with a total weight loss of 30.1xa0%, while the PhA did not show any significant decrease during the first 12xa0months after surgery. The correlation between the preoperative PhA and the postoperative EWL was significant after 6xa0weeks and after 6, 9, and 12xa0months. The ROC curve has an area of 0.7. The best point of the curve is a PhA of 3.9° with a sensitivity of 81xa0% and a specificity of 54xa0%.ConclusionsPhA may be a useful predictor of EWL after bariatric surgery, and a PhA of 3.9° was calculated as the most suitable cut-off for a successful operation.

Effects of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: Magnetic Resonance Imaging Is an Effective, Non-invasive Method to Evaluate Changes in the Liver Fat Fraction

IntroductionNon-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease worldwide and is highly associated with obesity. The prevalences of both conditions have markedly increased in the Western civilization. Bariatric surgery is the most effective treatment for morbid obesity and its comorbidities such as NAFLD.ObjectivesMeasure postoperative liver fat fraction (LFF) in bariatric patients by using in-opposed-phase MRI, a widely available clinical tool validated for the quantification of liver fatMethodsRetrospective analyses of participants, who underwent laparoscopic Roux-Y-gastric-bypass (17) or laparoscopic sleeve gastrectomy (2) were performed using magnetic resonance imaging (MRI), bioelectrical impedance analysis (BIA), and anthropometric measurements 1xa0day before surgery, as well as 6, 12, and 24xa0weeks after surgery, LFF was calculated from fat-only and water-only MR images.ResultsSix months after surgery, a significant decrease of LFF and liver volume has been observed along with weight loss, decreased waist circumference, and parameters obtained by body fat measured by BIA. LFF significantly correlated with liver volume in the postoperative course.ConclusionsMRI including in-opposed-phase imaging of the liver can detect the quantitative decrease of fatty infiltration within the liver after bariatric surgery and thus could be a valuable tool to monitor NAFLD/NASH postoperatively.

Effect of different liver resection methods on liver damage and regeneration factors VEGF and FGF-2 in mice

BACKGROUNDnDifferent approaches to study liver regeneration in murine models have been proposed. We investigated the effect of different liver resection models on liver damage and regeneration parameters in mice.nnnMETHODSnWe compared the technical aspect of the 2 most commonly used techniques of 50% and 70% liver resection. Liver damage, as determined by the change in serum alanine aminotransferase and aspartate aminotransferase, as well as the regeneration parameters VEGF and FGF-2 were analyzed at 6 time points. A postoperative vitality score was introduced.nnnRESULTSnCholestasis was not observed for either technique. Both resection techniques resulted in full weight recovery of the liver after 240 hours, with no significant difference between sham and resection groups. Postoperative animal morbidity and total protein levels did not differ significantly for either method, indicating early and full functional recovery. However, comparing the mitogenic growth factors FGF-2 and VEGF, a significant increase in serum levels and, therefore, increased growth stimulus, was shown in the extended resection group.nnnCONCLUSIONnExtended resection led to a greater response in growth factor expression. This finding is important since it shows that growth factor response differs acdording to the extent of resection. We have demonstrated the need to standardize murine hepatic resection models to adequately compare the resulting liver damage.

Letter to the Editor for the Manuscript the Complex Interplay of Physical Fitness, Protein Intake and Vitamin D Supplementation After Bariatric Surgery

Dear editor, We agree with the authors that postoperative body composition and maintenance of muscle mass has an influence on the results of bariatric surgery. Preoperative handgrip strength and phase angle (which is part of the bioelectrical impedance analysis, reflecting quality of the lean body mass) are strongly correlated with postoperative body composition changes and even weight loss— this means that physical functionality plays an important role [1, 2]. As the authors mentioned, there are multiple factors responsible for skeletal muscle atrophy and loss of bone mass. However, if the application of proteins and vitamin D will change something on the long-term course is completely unclear. Metcalf et al. showed that a postoperative exercise program can positively influence body composition, that means there are possibilities of influencing [3]. Long-term data does not exist. We agree that the overall supplementation in bariatric patients is not sufficient. Therefore, a structured postoperative follow-up, including frequent clinical examination and investigation of the vitamin serum levels is very important. Several published studies confirmed, that many patients are not adherent to a follow-up program [4]. As described, a structured follow-up program after bariatric surgery is crucial to improve and sustain weight loss [5]. Whether the body composition is influenced positively by such a program is unclear.