Systematic Review and Meta-analysis of Enhanced Recovery After Pancreatic Surgery with Particular Emphasis on Pancreaticoduodenectomies

Background

In the past decade, Enhanced Recovery after Surgery (ERAS) protocols have been implemented in several fields of surgery. With these protocols, a faster recovery and shorter hospital stay can be accomplished without an increase in morbidity or mortality. The purpose of this study was to review systematically the evidence for implementation of an ERAS protocol in pancreatic resections, with particular emphasis on pancreaticoduodenectomies (PDs).

Methods

A systematic search was performed in Medline, Embase, Pubmed, CINAHL, and the Cochrane library for papers describing an ERAS program in adult patients undergoing elective pancreatic surgery published between January 1966 and December 2012. The primary outcome measure was postoperative length of stay. Secondary outcome measures were time to recovery of normal function, overall postoperative complication rates, readmissions, and mortality. Subsequently, a meta-analysis of outcome measures focusing on PD was conducted. This systematic review and meta-analysis was performed according to the PRISMA statement.

Results

The literature search produced 248 potentially relevant papers. Of these, eight papers met the predefined inclusion criteria: five case-control studies, two retrospective studies, and one prospective study, describing a total of 1,558 patients. Only three of the studies reported data on discharge criteria and assessed time to recovery and return to normal function. Implementation of an ERAS protocol led in four of five comparative studies to a significant decrease in length of stay (reduction of 2–6 days in different studies). Meta-analysis of four studies focusing on PDs showed that there was a significant difference in complication rates in favor of the ERAS group (absolute risk difference 8.2 %, 95 % confidence interval (CI) 2.0–14.4, p = 0.008). Introduction of an ERAS protocol did not result in an increase in mortality or readmissions. Delayed gastric emptying and incidence of pancreatic fistula did not differ significantly between groups. All studies reporting on hospital costs showed a decrease after implementation of ERAS.

Conclusions

This systematic review suggests that using an ERAS protocol in pancreatic resections may help to shorten hospital length of stay without compromising morbidity and mortality. This seemed to apply to distal pancreatectomy, total pancreatectomy, and PD. Meta-analysis was performed for those studies focusing on PD and showed that there were no differences in readmission or mortality. Morbidity rates were significantly lower for patients managed according ERAS principles.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

The effect of centralization on short term outcomes of pancreatoduodenectomy in a universal health care system

Background

Centralization of pancreatic resections is advocated due to a volume-outcome association. Pancreatic surgery is in Norway currently performed only in five teaching hospitals. The aim was to describe the short-term outcomes after pancreatoduodenectomy (PD) within the current organizational model and to assess for regional disparities.

Inactivation of purified human alpha 2-antiplasmin and purified human C1 inhibitor by synthetic fibrinolytic agents

3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified alpha 2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125I-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of alpha 2-antiplasmin was abolished in a time-dependent and concentration- dependent manner. The influence of Flu-HPA on the ability of purified Cl inhibitor to inhibit purified plasma kallikrein and beta-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or beta-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either alpha 2-antiplasmin and plasmin of Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl- glutamic acid, also inactivated alpha 2-antiplasm and Cl inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating alpha 2- antiplasmin and Cl inhibitor.