Skeletal Muscle–Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study

Background and Aims: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle–derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy. Methods: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months. Results: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. Conclusions: Injection of a high dose of autologous skeletal muscle–derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32)

Stereotactic body radiotherapy using the CyberKnife® system in the treatment of patients with liver metastases: state of the art

Peter Ihnát,1,2 Eva Skácelíková,3 Milan Tesař,1,2 Igor Penka1,2 1Department of Surgery, University Hospital Ostrava, Ostrava, Czech Republic; 2Department of Surgical Studies, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; 3Department of Oncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic Background: The management of patients with liver metastases presents a challenging problem in clinical oncology. Patients with limited involvement of the liver may be suitable for surgical resection or local ablative techniques. Stereotactic body radiotherapy (SBRT) presents an emerging new technology that has shown high efficacy in ablating tumors at various disease sites.Methods: A comprehensive literature search was performed to identify articles in regard to the SBRT in the treatment of patients with liver metastases.Results: SBRT allows for the delivery of high-dose radiation in few fractions to the tumor with extreme accuracy, while minimizing the damage to normal surrounding tissue. The CyberKnife® system is an image-guided robotic system that delivers SBRT, tracks tumors during respiration, and automatically adjusts treatment for any patient movement. The most frequently used indications for CyberKnife® therapy are ≤5 liver metastases with maximum tumor sizes of 6 cm, no extrahepatic disease, good performance status, and adequate hepatic functions. Local control rates range from 70%–100% at 1 year and from 60%–90% at 2 years. Severe toxicity related to SBRT is uncommon – grade three side effects occur in less than 5% of cases. Despite excellent local control rates, out-of-field metastatic progression (out-of-field hepatic metastases and extrahepatic metastases) develops in a substantial proportion of patients after SBRT. Therefore, it seems essential to improve the selection of patients with liver metastases for SBRT.Conclusion: The CyberKnife® system presents an effective minimally invasive treatment modality for patients with hepatic oligometastases who are not suitable candidates for radical liver resection. The available data suggest that liver metastases can be treated by CyberKnife therapy with very low toxicity and excellent local control rates. Keywords: CyberKnife, liver metastases, stereotactic body radiotherapy, indications, clinical outcomes, toxicit

Surgical injury: comparing open surgery and laparoscopy by markers of tissue damage

Jan Máca,1 Matúš Peteja,2 Petr Reimer,1 Ondřej Jor,1 Věra Šeděnková,1 Lucie Panáčková,1 Peter Ihnát,2 Michal Burda,3 Pavel Ševčík1 1Department of Anesthesiology and Intensive Care Medicine, University Hospital Ostrava, Ostrava, Czech Republic; 2The Clinic of Surgery, University Hospital Ostrava, Ostrava, Czech Republic; 3Institute for Research and Applications of Fuzzy Modeling, Centre of Excellence IT4Innovations, University of Ostrava, Ostrava, Czech Republic Background: Major abdominal surgery (MAS) is high-risk intervention usually accompanied by tissue injury leading to a release of signaling danger molecules called alarmins. This study evaluates the surgical injury caused by two fundamental types of gastrointestinal surgical procedures (open surgery and laparoscopy) in relation to the inflammation elicited by alarmins. Patients and methods: Patients undergoing MAS were divided into a mixed laparoscopy group (LPS) and an open surgery group (LPT). Serum levels of alarmins (S100A8, S100A12, HMGB1, and HSP70) and biomarkers (leukocytes, C-reactive protein [CRP], and interleukin-6 [IL-6]) were analyzed between the groups. The secondary objectives were to compare LPT and LPS cancer subgroups and to find the relationship between procedure and outcome (intensive care unit length of stay [ICU-LOS] and hospital length of stay [H-LOS]). Results: A total of 82 patients were analyzed. No significant difference was found in alarmin levels between the mixed LPS and LPT groups. IL-6 was higher in the LPS group on day 2 (p=0.03) and day 3 (p=0.04). Significantly higher S100A8 protein levels on day 1 (p=0.02) and day 2 (p=0.01) and higher S100A12 protein levels on day 2 (p=0.03) were obtained in the LPS cancer subgroup. ICU-LOS and H-LOS were longer in the LPS cancer subgroup. Conclusion: The degree of surgical injury elicited by open MAS as reflected by alarmins is similar to that of laparoscopic procedures. Nevertheless, an early biomarker of inflammation (IL-6) was higher in the laparoscopy group, suggesting a greater inflammatory response. Moreover, the levels of S100A8 and S100A12 were higher with a longer ICU-LOS and H-LOS in the LPS cancer subgroup. Keywords: open surgery, laparoscopy, gastrointestinal surgery, alarmins, surgical injury, major surger