Expectations on mesenchymal stem cell (MSC) treatment are high, especially in the fields of sepsis, transplant medicine, and autoimmune diseases. Various pre-clinical studies have been conducted with encouraging results, although the mechanisms of action behind the observed immunomodulatory capacity of mesenchymal stem cells have not been fully understood. Previous studies have demonstrated that the immunomodulatory effect of MSCs is communicated via MSC-secreted cytokines and has been proven to rely on the local microenvironment as some of the observed effects depend on a pre-treatment of MSCs with inflammatory cytokines. Nonetheless, recent findings indicate that the cytokine-mediated effects are only one part of the equation as apoptotic, metabolically inactivated, or even fragmented MSCs have been shown to possess an immunomodulatory potential as well. Both cytokine-dependent and cytokine-independent mechanisms suggest a key role for regulatory T cells and monocytes in the overall pattern, but the principle as to why viable and non-viable MSCs have similar immunomodulatory capacities remains elusive. Here we review the current knowledge on cellular and molecular mechanisms involved in MSC-mediated immunomodulation and focus on the viability of MSCs, as there is still uncertainty concerning the tumorigenic potential of living MSCs.

Purpose: Prognostic inflammation-based parameters have been reported as useful tools in various oncologic diseases. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high mortality rate, making reliable prognostic markers highly desirable. However, there is still inconsistency in the literature regarding the efficacy of the different available scores. Methods: A total of 207 patients, who underwent primary resection of PDAC from January 2000 to December 2018 at the University Hospital of Erlangen, were included in this retrospective single-center study. Different biomarkers, including the preoperative neutrophil–lymphocyte ratio (NLR), the platelet–lymphocyte ratio (PLR), the c-reactive protein (CRP)–albumin ratio (CAR), the lymphocyte–CRP ratio (LCR), the prognostic nutritional index (PNI) and the modified Glasgow prognostic score (mGPS) were analyzed for their ability to predict overall survival (OS). Results: In our cohort, the median overall survival was 20.7 months. Among the investigated biomarkers, NLR and PNI were identified as independent prognostic markers (Hazard Ratio (HR) 1.6 (1.0–2.5), p = 0.048 and HR 0.6 (0.4–0.9), p = 0.018), whereas PLR, CAR, LCR and mGPS did not reach significance in the multivariate analysis. Subgroup analysis revealed that the prognostic value of NLR and PNI is particularly evident in locally advanced tumor stages (pT3/4 and pN+). Conclusions: The NLR and PNI could serve as valuable tools for estimating prognosis in patients with PDAC undergoing pancreatic resection in curative intention, especially in locally advanced tumor stages. However, conflicting results in the current literature highlight the need for further prospective studies to validate these findings.

Background/Objectives: This study aimed to determine the risk factors associated with postoperative major morbidity, anastomotic/suture leakage, re-surgery and mortality in patients undergoing emergency surgery for colonic perforation. Methods: A total of 204 adult patients treated surgically for colonic perforation from 2016 to 2021 at the University Hospital Erlangen were included in a retrospective analysis. Patient demographics and pre-, intra- and postoperative parameters were obtained and evaluated among various outcome groups (in-hospital major morbidity, anastomotic/suture leakage, re-surgery and 90-day mortality). Results: Postoperative in-hospital major morbidity, anastomotic/suture leakage, need of re-surgery and 90-day mortality occurred in 45%, 12%, 25% and 12% of the included patients, respectively. Independent risk factors for in-hospital major morbidity were identified and included the presence of any comorbidity, a significantly reduced preoperative general condition, the localization of perforation in the right hemicolon and the need for an intraoperative blood transfusion. The only independent risk factor for anastomotic/suture leakage was the presence of any comorbidity, whereas no independent risk factors for re-surgery were found. An age > 65 years, a significantly reduced preoperative general condition and the need for an intraoperative blood transfusion were independent risk factors for 90-day mortality. Conclusions: Our study identified risk factors impacting postoperative outcomes in patients undergoing emergency surgery for colonic perforation. These patients should receive enhanced postoperative care and may benefit from individualized and targeted therapeutic approaches.

: Background: Anastomotic leakages after esophagectomies continue to constitute significant morbidity and mortality. Intrathoracic anastomoses pose a high risk for mediastinitis, sepsis, and death, if a leak is not addressed timely and appropriately. However, there are no standardized treatment recommendations or algorithms as for how to treat these leakages. Methods: The study included all patients at the University Hospital Regensburg, who developed an anastomotic leakage after esophagectomy with gastric pull-up reconstruction from 2007 to 2022. Patients receiving conventional treatment options for an anastomotic leakage (stents, drainage tubes, clips, etc.) were compared to patients receiving endoscopic vacuum-assisted closure (eVAC) therapy as their mainstay of treatment. Treatment failure was defined as cervical esophagostomy formation or death. Results: In total, 37 patients developed an anastomotic leakage after esophagectomy with a gastric pull-up reconstruction. Twenty patients were included into the non-eVAC cohort, whereas 17 patients were treated with eVAC. Treatment failure was observed in 50% of patients (n = 10) in the non-eVAC cohort and in 6% of patients (n = 1) in the eVAC cohort (p < 0.05). The 90-day mortality in the non-eVAC cohort was 15% (n = 3) compared to 6% (n = 1) in the eVAC cohort. Cervical esophagostomy formation was required in 40% of cases (n = 8) in the non-eVAC cohort, whereas no patient in the eVAC cohort underwent cervical esophagostomy formation. Conclusion: eVAC therapy for leaking esophagogastric anastomoses appears to be superior to other treatment strategies as it significantly reduces morbidity and mortality. Therefore, we suggest eVAC as an essential component in the treatment algorithm for anastomotic leakages following esophagectomies, especially in patients with intrathoracic anastomoses.

Traditionally, esophageal oncological resections have been performed via open approaches with well-documented levels of morbidity and mortality complicating the postoperative course. In contemporary terms, minimally invasive approaches have garnered sustained support in all areas of surgery, and there has been an exponential adaptation of this technology in upper GI surgery with the advent of laparoscopic and robotic techniques. The current literature, while growing, is inconsistent in reporting on the benefits of minimally invasive esophagectomies (MIEs) and this makes it difficult to ascertain best practice. The objective of this review was to critically appraise the current evidence addressing the safety, efficacy, and cost-effectiveness of MIEs versus open esophagectomies. A systematic review of the literature was performed by searching nine electronic databases to identify any systematic reviews published on this topic and recommended Joanna Briggs Institute approach to critical appraisal, study selection, data extraction and data synthesis was used to report the findings. A total of 13 systematic reviews of moderate to good quality encompassing 143 primary trials and 36,763 patients were included in the final synthesis. Eleven reviews examined safety parameters and found a generalized benefit of MIE. Efficacy was evaluated by eight systematic reviews and found each method to be equivalent. There were limited data to judiciously appraise cost-effectiveness as this was only evaluated in one review involving a single trial. There is improved safety and equivalent efficacy associated with MIE when compared with open esophagectomy. Cost-effectiveness of MIE cannot be sufficiently supported at this point in time. Further studies, especially those focused on cost-effectiveness are needed to strengthen the existing evidence to inform policy makers on feasibility of increased assimilation of this technology into clinical practice.