Steffen Wolk

Evaluation of central pancreatectomy and pancreatic enucleation as pancreatic resections--A comparison.

INTRODUCTION For minor pancreatic resection such as enucleation (PE) and central pancreatectomy (CP) comparative data are rare. These techniques provide parenchyma-sparing alternatives to major resections (e.g. pancreaticoduodenectomy) for neuroendocrine tumors, cystic tumors or metastases. This study retrospectively compares the morbidity and mortality of both techniques, with special regard to the formation of postoperative pancreatic fistulas (POPF). METHODS Between December 1996 and November 2013 the postoperative events and clinical outcomes of 17 patients after pancreatic enucleation and 26 patients after central pancreatectomy were retrospectively analyzed from a prospectively collected database. RESULTS Perioperative mortality was 0% in both groups. There was no significant difference in the overall peri-operative morbidity (CP 80.8% vs. PE 82.4%). The major cause of the high morbidity was the formation of a POPF with 26.9% of the patients after CP and 35.3% after PE. Univariate analysis showed a BMI over 30 kg/m(2) in the CP group to be an independent risk factor. Additional minor complications, e.g. urinary tract infection, pleural effusion, etc. furthermore contributed to the perioperative morbidity. CONCLUSION PE and central CP are feasible techniques for selected patients, but the indications are limited. Morbidity after these resections is high with the major cause being the development of a POPF.

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

Mir-132 controls beta cell proliferation and survival in mouse model through the PTEN/AKT/FOXO3 signaling

Aim and hypothesis microRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains a challenge. In this study we aimed to identify miRNAs and their downstream targets involved in regeneration of islet beta cells following partial pancreatectomy in mice. Methods RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in control of beta cell regeneration. Altered expression of selected miRNAs, including miR-132, was verified by RT-PCR. Potential targets of miR-132 were seleced through bioinformatic data mining. Predicted miR-132 targets were validated for their changed RNA and protein expression levels and signaling upon miR-132 knockdown or overexpression in MIN6 cells. The ability of miR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized miR-132-/- and control mice. Results Partial pancreatectomy significantly increased the number of BrdU+/insulin+ positive islet cells. Microarray profiling revealed 14 miRNAs, including miR-132 and -141, to be significantly upregulated in LCM islets of partially pancreatectomized compared to LCM islets of control mice. In the same comparison miR-760 was the only miRNA found to be downregulated. Changed expression of these miRNAs in islets of partially pancreatectomized mice was confirmed by RT-PCR only in the case of miR-132 and -141. Based on previous knowledge of its function, we chose to focus our attention on miR-132. Downregulation of miR-132 in MIN6 cells reduced proliferation while enhancing the expression of proapoptic genes, which was instead reduced in miR-132 overexpression MIN6 cells. Microarray profiling, RT-PCR and immunoblotting of miR-132 overexpressing MIN6 cells revealed their downregulated expression of Pten, with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb as well as inactivation of pro-apoptotic Foxo3 via its phosphorylation. Finally, we show that regeneration of beta cells following partial pancreatectomy was reduced in miR-132-/- mice compared to control mice. Conclusions/Interpretations Our study provides compelling evidence for upregulation of miR-132 being critical for regeneration of mouse islet beta cells in vivo through downregulation of its target Pten. Hence, the miR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass. Research in Context What is already known? Several miRNAs, including miR-132, are known to regulate beta cell function and mass in several mouse models of diabetes db/db, ob/ob and high fat-diet. What is the key question? Which are miRNAs implicated in control of beta cell regeneration upon partial pancreatectomy and how? What are the new findings? miR-132 is critical to promote regeneration of mouse beta cells in vivo following partial pancreatectomy In vitro studies in mouse MIN6 cells indicate that miR-132 fosters beta cell proliferation by down-regulating the expression of phosphatase Pten, thereby tilting the balance between anti-apoptotic factor Akt and pro-apoptotic factor Foxo3 activities towards proliferation through regulation of their phosphorylation. How might this impact on clinical practice in the foreseeable future? These findings strengthen the rationale for targeting the expression of miR-132 to increase beta cell mass in vivo (type 2 diabetes) or ex-vivo (islet transplantation in type 1 diabetes) for the treatment of diabetes.

Betazellregeneration transplantierter Inseln im Mausmodell

Background: Antiproliferative effects of immunosuppressants used in human islet transplantation interfere with the capability of the beta cells to balance cell renewal and cell loss. Consequently, longterm use of these drugs might contribute to graft dysfunction in islet transplant recipients. New immunosuppressive regimens are required to improve outcomes. Methods: Syngeneic islets (300 IEQ) were injected into the right liver lobes of C57BL/6 diabetic recipients. Osmotic pumps filled with Bromodeoxyuridine (group 1), Bromodeoxyuridine and Tacrolimus (group 2) or Bromodeoxyuridine and Everolimus (group 3) were implanted. Hepatectomy was performed after 4 weeks. Proliferation of beta cells was detected by BrdU incorporation. Results: In all transplanted animals normoglycemia was restored. Glucose tolerance was significantly improved after 4 weeks in group 1 (90 min: P < 0.012; 120 min: P < 0.045). This effect was not as strong when animals were treated with Tacrolimus. In contrast, mice that recieved Everolimus showed an impaired glucose tolerance. After 4 weeks 36.3 % of all beta cells in group 1 underwent at least on cycle of proliferation. In comparison, beta cells of group 2 had a significantly decreased proliferation rate (21.19 %), whereas beta cell proliferation in group 3 (38.36 %) remained unchanged. Conclusions: Beta cells of transplanted islets have a strong capability of self renewal when not affected by immunosuppression or immune assault. In this setting maintenance of glucose homeosstasis improves over time indicating an increase in beta cell mass. Exposure to Tacrolimus clearly inhibits beta cells replication. In contrast, Everolimus does not seem to affect beta cell proliferation, although having a negative impact on glucose tolerance. The use of Everolimus might lead to better long-term results in islet transplantation, due to the lacking inhibition of beta cell proliferation.