Benjamin Müssle

A Comprehensive MicroRNA Expression Profile of Liver and Lung Metastases of Colorectal Cancer with Their Corresponding Host Tissue and Its Prognostic Impact on Survival

MicroRNAs are small non-coding RNAs with a length of 18–25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations—tumor, associated stroma, and host tissue—can provide new insights into the complex tumor biology of colorectal cancer. Frozen tissue samples of colorectal liver (n = 25) and lung metastases (n = 24) were laser microdissected to separate tumor cells and the adjacent tumor-associated stroma cells. Additionally, normal lung and liver tissue was collected from the same patients. We performed a microarray analysis in four randomly selected liver metastases and four randomly selected lung metastases, analyzing a total of 939 human miRNAs. miRNAs with a significant change >2-fold between the tumor, tumor stroma, and host tissue were analyzed in all samples using RT-qPCR (11 miRNAs) and correlated with the clinical data. We found a differential expression of several miRNAs between the tumor, the tumor-associated stroma, and the host tissue compartment. When comparing liver and lung metastases, miR-194 showed a 1.5-fold; miR-125, miR-127, and miR-192 showed a 2.5-fold; miR-19 and miR-215 a 3-fold; miR-145, miR-199-3, and miR-429 a 5-fold; miR-21 a 7-fold; and, finally, miR-199-5 a 12.5-fold downregulation in liver metastases compared to lung metastases. Furthermore miR-19, miR-125, miR-127, miR-192, miR-194, miR-199-5, and miR-215 showed a significant upregulation in the normal liver tissue compared to the normal lung tissue. Univariate analysis identified an association of poor survival with the expression of miR-125 (p = 0.05), miR-127 (p = 0.001), miR-145 (p = 0.005), miR-192 (p = 0.015), miR-194 (0.003), miR-199-5 (p = 0.008), miR-215 (p < 0.001), and miR-429 (p = 0.03) in the host liver tissue of the liver metastases. Colorectal liver and lung metastases have a unique miRNA expression profile. miRNA expression in the host tissue of colorectal liver metastases seems to be able to influence tumor progression and survival. These findings can be used in the development of tailored therapies.

Use of Activity Tracking in Major Visceral Surgery—the Enhanced Perioperative Mobilization Trial: a Randomized Controlled Trial

BackgroundEarly mobilization is one essential item within the enhanced recovery after surgery (ERAS) concept, but lacks solid evidence and a standardized assessment. The aim was to monitor and increase the postoperative mobilization of patients after major visceral surgery by providing a continuous step count feedback using activity tracking wristbands.MethodsThe study was designed as a randomized controlled single-center trial (NCT02834338) with two arms (open and laparoscopic surgery). Participants were randomized to either receive feedback of their step counts using an activity tracker wristband or not. The primary study endpoint was the mean step count during the first 5 postoperative days (PODs).ResultsA total of 132 patients were randomized. After laparoscopic operations, the average step count during PODs 1–5 was significantly increased by the feedback compared with the control group (P < 0.001); the cumulative step count (9867 versus 6103, P = 0.037) and activity time were also significantly increased. These results could not be confirmed in the open surgery arm. Possible reasons were a higher age and significantly more comorbidities in the open intervention group. Patients who achieved more than the median cumulative step count had a significantly shorter hospital stay and lower morbidity in both arms. The average step count also correlated with the length of hospital stay (R = − 0.341, P < 0.001).ConclusionThis study is the first randomized controlled trial investigating the use and feasibility of activity tracking to monitor and enhance postoperative mobilization in abdominal surgery. Our results demonstrate that activity tracking can enhance perioperative mobilization after laparoscopic surgery.Trial RegistrationClinicalTrials.gov: NCT02834338

Reproducibility of preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula

Abstract Background: A postoperative pancreatic fistula (POPF) is the most common and potentially life-threatening surgical complication in pancreatic surgery. One possible pharmacological treatment could be the endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi to prevent POPF. Promising data reported a significantly reduced rate of clinically relevant POPF. We analyzed the effect of BTX injection in our patients undergoing distal pancreatectomy (DP). Methods: A retrospective analysis of patients undergoing DP was performed. Patients with preoperative endoscopic injection of BTX into the sphincter of Oddi were included. The end points were postoperative outcomes including POPF. BTX patients were compared with a historical cohort and matched in a 1:1 ratio using a propensity score analysis. Results: A total of 19 patients were treated with endoscopic injection of BTX before open (n=8) or laparoscopic (n=11) DP. The median age of the patients was 67 years and the mean body mass index was 25.9 kg/m2. In median, the intervention was performed 1 day (range, 0–14 days) before the operation. There were no intervention-related complications. The incidence of POPF was not statistically different between the two groups: a clinically relevant POPF grade (B/C) occurred in 32% (BTX) and 42% (control; p=0.737). Likewise, there were no significant differences in postoperative drain fluid amylase levels, morbidity, and mortality. Conclusion: The present study could not reproduce the published results of a significant lowering of grade B/C POPF. The explanations could be the timing of BTX injection before surgery and the endoscopic technique of BTX injection. However, the conflicting results after BTX injection in two high-volume centers prompt a randomized controlled multicenter trial with trained endoscopists.