Predictive Factors for Delayed Gastric Emptying After Pancreatoduodenectomy: A Swedish National Registry-Based Study.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after pancreatoduodenectomy (PD). DGE causes prolonged hospital stay and a decrease in quality of life. This study analyzes predictive factors for development of DGE after PD, also in the absence of surgical complications. METHOD: Data from the Swedish National Pancreatic Cancer Registry for patients undergoing standard and pylorus preserving open PD from January 2010 until June 30, 2018, were collected. Data were analyzed in two groups, no DGE and DGE. A subgroup of patients with DGE but without surgical complications was compared to patients without DGE or any other surgical complication. RESULTS: In total, 2503 patients were included, of which 470 (19%) had DGE. In the DGE group, 238 had other coexisting surgical complications and 232 had not. Postoperative pancreatic fistula (OR = 4.22, p < 0.001), surgical infection (OR = 1.44, p = 0.013), heart disease (OR = 1.32, p = 0.023) and medical complications (OR = 1.35, p = 0.025) increased the risk for DGE. A standard PD compared with pylorus preserving resection (OR = 1.69, p = 0.001) and a reconstruction with a pancreaticojejunostomy compared with a pancreaticogastrostomy (OR = 1.83, p < 0.001) increased the risk. For patients without surgical complications, a standard PD and reconstruction with pancreaticojejunostomy still increased the risk for DGE. CONCLUSION: DGE is more common after standard PD compared to pylorus preserving PD and after reconstruction with PJ compared to PG in this national cohort, both in the presence of other surgical complications as well as in the absence of other complications.

Reinforced versus standard stapler transection on postoperative pancreatic fistula in distal pancreatectomy: multicentre randomized clinical trial.

BACKGROUND: Postoperative pancreatic fistula is the leading cause of morbidity after distal pancreatectomy. Strategies investigated to reduce the incidence have been disappointing. Recent data showed a reduction in postoperative pancreatic fistula with the use of synthetic mesh reinforcement of the staple line. METHODS: An RCT was conducted between May 2014 and February 2016 at four tertiary referral centres in Sweden. Patients scheduled for distal pancreatectomy were eligible. Enrolled patients were randomized during surgery to stapler transection with biological reinforcement or standard stapler transection. Patients were blinded to the allocation. The primary endpoint was the development of any postoperative pancreatic fistula. Secondary endpoints included morbidity, mortality, and duration of hospital stay. RESULTS: Some 107 patients were randomized and 106 included in an intention-to-treat analysis (56 in reinforced stapling group, 50 in standard stapling group). No difference was demonstrated in terms of clinically relevant fistulas (grade B and C): 6 of 56 (11 per cent) with reinforced stapling versus 8 of 50 (16 per cent) with standard stapling (P = 0.332). There was no difference between groups in overall postoperative complications: 45 (80 per cent) and 39 (78 per cent) in reinforced and standard stapling groups respectively (P = 0.765). Duration of hospital stay was comparable: median 8 (range 2-35) and 9 (2-114) days respectively (P = 0.541). CONCLUSION: Biodegradable stapler reinforcement at the transection line of the pancreas did not reduce postoperative pancreatic fistula compared with regular stapler transection in distal pancreatectomy. Registration number: NCT02149446 (http://www.clinicaltrials.gov).

Predictive Factors for Postoperative Pancreatic Fistula-A Swedish Nationwide Register-Based Study.

BACKGROUND: A serious complication after pancreatoduodenectomy (PD) is postoperative pancreatic fistula (POPF). The aim of this study was to analyse the incidence and predictive factors for POPF by using a large nationwide cohort. METHODS: Data from the Swedish National Registry for Pancreatic and Periampullary Cancer for all patients undergoing a PD from 2010 until 30th June 2018 were collected. The material was analysed in two groups, no POPF and clinically relevant (grade B and C) POPF. RESULTS: A total of 2503 patients underwent PD, of which 245 (10%) developed POPF. Patients with POPF had significantly more overall complications (Clavien Dindo ≥3a, 75% vs. 21%, p < 0.001) and longer hospital stay (median 23 [16-35] vs. 11 [8-15], p < 0.001) than patients without POPF. The risk of POPF was higher with increased BMI (OR 1.08, p < 0.001). Preoperative presence of diabetes (OR 0.52, p = 0.012) and preoperative biliary drainage (OR 0.34, p < 0.001) reduced the risk of POPF. Reconstruction with pancreaticojejunostomy caused a more than two folded increase in POPF compared with pancreaticogastrostomy (OR 2.41, p < 0.001). Weight gain ≥2 kg on postoperative day 1 was also a risk factor (OR 1.76, p < 0.001). CONCLUSION: A high BMI, a pancreaticojejunostomy and postoperative weight gain were risk factors for developing POPF. Diabetes or preoperative biliary drainage was protective.

Sustainability of an Enhanced Recovery Program for Pancreaticoduodenectomy with Pancreaticogastrostomy.

BACKGROUND:: Enhanced recovery program for pancreaticoduodenectomy have become standard care. Little is known about adherence rates and sustainability of the program, especially when pancreaticogastrostomy is used in reconstruction. The aim of this study was, therefore, to evaluate adherence rates and continued outcome, after implementation of an enhanced recovery program. METHODS:: Consecutive patients undergoing pancreaticoduodenectomy at the Department of Surgery, Skåne University Hospital, Lund, Sweden were followed, after implementation of enhanced recovery program, October 2012. In April 2015, some items in the enhanced recovery program were modified, namely earlier removal of nasogastric tubes and abdominal drain. The patients were analyzed in three groups, the implementation group (control) and two post-implementation groups; intermediate and modified group. Sustainability was assessed according to length of stay and adherence rate. RESULTS:: In total, 160 patients were identified. The overall protocol adherence rate increased from 65% to 72%, p = 0.035. While the pre- and intraoperative protocol items were fulfilled to more than >90%, the postoperative were lower, but increasing over time; 48%, 50%, and 58%, p = 0.033. Postoperative complications and hospital length of stay did not change significantly. CONCLUSION:: The positive outcome of an enhanced recovery program for pancreaticoduodenectomy was reasonably well sustained. Compliance with the protocol has increased, but strict adherence remains a challenge, especially with the postoperative items.

Intraductal Papillary Mucinous Neoplasms of The Pancreas: A Nationwide Registry-Based Study.

BACKGROUND AND AIMS:: To investigate the paraclinical and pathological features of surgically resected intraductal papillary mucinous neoplasms in Sweden. MATERIALS AND METHODS:: A review of prospectively collected data on patients undergoing pancreatic resection for a histopathologically verified intraductal papillary mucinous neoplasm between 2010 and 2016 was performed using the Swedish National Registry for Pancreatic and Periampullary Cancer. RESULTS:: A total of 3038 pancreatic resections were performed during the study period, of which 251 (8.3%) were due to intraductal papillary mucinous neoplasms. The intraductal papillary mucinous neoplasm cases comprised 227 noninvasive and 24 invasive lesions. There was an annual increase in the number of resected intraductal papillary mucinous neoplasms, from 13 in 2010 to 56 in 2016, and an increase in the proportion of intraductal papillary mucinous neoplasm to the total number of pancreatic resections (4.7%-11%). Biliary obstruction was the only independent predictor of invasive disease, with odds ratio 3.106 (p = 0.030). There was no difference in survival between low-, intermediate-, and high-grade dysplastic lesions (p = 0.417). However, once invasive, the prognosis was severely impacted (p < 0.001). Three-year survival was 90% for noninvasive intraductal papillary mucinous neoplasm and 39% for invasive intraductal papillary mucinous neoplasm. Survival was better in lymph node negative invasive intraductal papillary mucinous neoplasm (p = 0.021), but still dismal compared to noninvasive lesions (p < 0.001). CONCLUSION:: The number of surgically resected intraductal papillary mucinous neoplasms is increasing in Sweden. Biliary obstruction is associated with invasive disease. Low-to-high-grade dysplastic intraductal papillary mucinous neoplasm has an excellent prognosis, while invasive intraductal papillary mucinous neoplasm has a poor survival rate.

Hemorrhage after Major Pancreatic Resection: Incidence, Risk Factors, Management, and Outcome.

BACKGROUND AND AIMS: Hemorrhage is a rare but dreaded complication after pancreatic surgery. The aim of this study was to examine the incidence, risk factors, management, and outcome of postpancreatectomy hemorrhage in a tertiary care center. MATERIALS AND METHODS: A retrospective observational study was conducted on 500 consecutive patients undergoing major pancreatic resections at our institution. Postpancreatectomy hemorrhage was defined according to the International Study Group of Pancreatic Surgery criteria. RESULTS: A total of 68 patients (13.6%) developed postpancreatectomy hemorrhage. Thirty-four patients (6.8%) had a type A, 15 patients (3.0%) had a type B, and the remaining 19 patients (3.8%) had a type C bleed. Postoperative pancreatic fistula Grades B and C and bile leakage were significantly associated with severe postpancreatectomy hemorrhage on multivariable logistic regression. For patients with postpancreatectomy hemorrhage Grade C, the onset of bleeding was in median 13 days after the index operation, ranging from 1 to 85 days. Twelve patients (63.2%) had sentinel bleeds. Surgery lead to definitive hemostatic control in six of eight patients (75.0%). Angiography was able to localize the bleeding source in 8/10 (80.0%) cases. The success rate of angiographic hemostasis was 8/8. (100.0%). The mortality rate among patients with postpancreatectomy hemorrhage Grade C was 2/19 (10.5%), and both fatalities occurred late as a consequence of eroded vessels in association with pancreaticogastrostomy. CONCLUSION: Delayed hemorrhage is a serious complication after major pancreatic surgery.Sentinel bleed is an early warning sign. Postoperative pancreatic fistula and bile leakage are important risk factors for severe postpancreatectomy hemorrhage.

Impact of a fast-track surgery programme for pancreaticoduodenectomy.

BACKGROUND: Fast-track (FT) programmes are multimodal, evidence-based approaches to optimize patient outcome after surgery. The aim of this study was to evaluate the safety, clinical outcome and patients' experience of a FT programme after pancreaticoduodenectomy (PD) in a high-volume institution in Sweden. METHODS: Consecutive patients undergoing PD were studied before and after implementation of the FT programme. FT changes included earlier mobilization, standardized removal of the nasogastric tube and drain, and earlier start of oral intake. Patient experience was evaluated with European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26 questionnaires 2 weeks before and 4 weeks after surgery. RESULTS: Between 2011 and 2014, 100 consecutive patients undergoing PD were studied, of whom 50 received standard care (controls), followed by 50 patients treated after implementation of the FT programme. The nasogastric tube was removed significantly earlier in the FT group, and these patients were able fully to tolerate fluids and solid food sooner after PD. Delayed gastric emptying was significantly reduced in the FT group (26 versus 48 per cent; P = 0.030). Overall morbidity remained unchanged and there were no deaths in either group. Postoperative length of hospital stay was reduced from 14 to 10 days and hospital costs were decreased significantly. Health-related quality-of-life questionnaires showed similar patterns of change, with no significant difference between groups before or after surgery. CONCLUSION: The FT programme after PD was safe. Delayed gastric emptying, hospital stay and hospital costs were all reduced significantly. Although patients were discharged 4 days earlier in the FT group, this did not influence health-related quality of life compared with standard care.

In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.

The combination of two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.

Prevention of pleural adhesions by bioactive polypeptides - a pilot study.

OBJECTIVE: Postoperative pleural adhesions lead to major problems in repeated thoracic surgery. To date, no antiadhesive product has been proven clinically effective. Previous studies of differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG) have shown promising results reducing postoperative abdominal adhesions in experimental settings. This pilot study examined the possible pleural adhesion prevention by using the PL+PG concept after pleural surgery and its possible effect on key parameters; plasmin activator inhibitor-1 (PAI-1) and tissue growth factor beta 1 (TGFb) in the fibrinolytic process. METHODS: A total of 22 male rats were used in the study, one control group (n=10) and one experimental group (n=12). All animals underwent primary pleural surgery, the controls receiving saline in the pleural cavity and the experimental group the PL+PG solution administered by spray. The animals were evaluated on day 7. Macroscopic appearance of adhesions was evaluated by a scoring system. Histology slides of the adhesions and pleural biopsies for evaluation of PAI-1 and TGFb1 were taken on day 7. RESULTS: A significant reduction of adhesions in the PL+PG group (p<0.05) was noted at day 7 both regarding the length and severity of adhesions. There were no significant differences in the concentration of PAI-1 and TGFb1 when comparing the two groups. CONCLUSIONS: PL+PG may be used to prevent pleural adhesions. The process of fibrinolysis, and fibrosis was though not affected after PLPG administration.

Small bowel obstruction: early parameters predicting the need for surgical intervention.

AIM: To study and identify early clinical and radiological findings that could help to predict operative intervention for small bowel obstruction. MATERIALS AND METHODS: One hundred and nine consecutive patients with small bowel obstruction who underwent small bowel follow-through examination with Gastrografin(®) during 2005-2006. The patients were divided into an operative group and a non-operative group, n = 44 and 65, respectively. Findings primarily noted were those which were possible to register within 1-4 h from hospital arrival. RESULTS: In univariate analyses, factors found to be significantly associated with surgical intervention were no prior abdominal surgery, the presence of radiological differential air fluid levels, and absence of flatulence 24 h prior to admission, CRP > 10 mg/L and dehydration at admission. In multivariate analyses, the presence of dehydration and radiological differentiated air fluid levels were independent predictive factors of significance. Absence of all factors significantly favored non-operative treatment, while operative treatment was significantly favored when two or more factors were present. CONCLUSIONS: The presence of two or more early predictive factors as defined above, available at admission, significantly correlates with a likelihood of complete obstruction and the need of surgical intervention.

Toxicity and dose response of intra-abdominally administered poly-L-alpha-lysine and poly-L-glutamate for postoperative adhesion protection.

BACKGROUND/AIMS: Two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), have previously been shown to reduce postoperative intra-abdominal adhesions. This study aims to investigate the possible toxic effects and to establish a lowest effective antiadhesive dose. METHODS: 152 mice were investigated with a well-known adhesion model and given different concentrations of the two differently charged polypeptides as well as only the cationic PL. RESULTS: For the first time, a probable toxic level of PL given intraperitoneally (40 mg/kg) and the lowest significant concentration of PL and PG for antiadhesive purposes (1.6 mg/kg) could be established. CONCLUSION: The gap between the possible toxicity level of PL and the lowest efficient antiadhesive dose is probably too narrow, and the shape and charge of PL warrant continuous research for another polycation in the concept of differently charged polypeptides used as antiadhesive agents.

Prevention of abdominal adhesions--present state and what's beyond the horizon?

Intra-abdominal adhesions are normally found after most surgical procedures. Many of the adhesions are asymptomatic, but in about 5% they will lead to readmission due to adhesion-related disorders, such as small bowel obstruction, pelvic pain and infertility. This review discusses possible ways to prevent abdominal adhesions and provides an update as comes to where we stand today in research regarding experimental and clinical use of various antiadhesive agents.

Long-term follow-up and cost analysis following surgery for small bowel obstruction caused by intra-abdominal adhesions.

BACKGROUND: This study examined the natural course of patients following surgery for small bowel obstruction (SBO) caused by abdominal adhesions. In addition, a cost analysis was performed. METHODS: A retrospective analysis was undertaken of 102 patients who underwent surgery between 1987 and 1992 for intestinal obstruction due to abdominal adhesions. RESULTS: Median follow-up was 14 years. The 102 patients experienced 273 episodes of intestinal obstruction after the index operation, of which 237 involved inpatient readmissions; 47.3 per cent of the episodes resulted in further surgery. Single band adhesions were more common in patients with no previous abdominal surgery (P < 0.001). Some 52.0 per cent of the patients had undergone only one operation for SBO. A mean of 2.7 episodes per patient occurred after the index operation. The cost of adhesion-related problems in this study was 1,588,594 euros or 6702 euros per inpatient episode. CONCLUSION: The readmission rate in a selected cohort of patients with proven intra-abdominal adhesions was higher than reported previously. The annual cost of adhesion-related problems in Sweden was estimated as 39.9-59.5 million euros, and the cost of inpatient readmissions was almost equal to that for gastric cancer.

Immunomodulation in surgical practice.

BACKGROUND: Immunomodulation may represent a potential way to improve surgical outcome. These types of interventions should be based on detailed knowledge of the underlying mechanisms involved. The aim of the present review is to summarize some experience on the acute phase response, potential ways of intervention and experiences from critical illness and HPB disease. DISCUSSION: Mechanisms of the acute phase response are discussed including the individual parameters and local changes that take part. Mechanisms involved in failure of the gut barrier are presented and include changes in gut barrier permeability, effects on gut-associated immunocompetent cells, and systemic implications. As examples of HPB disease, mechanisms of the acute phase response and potential ways of intervention in obstructive jaundice and acute pancreatitis are discussed. Nutritional pharmacology and lessons learned from immunomodulation and immunonutrition in critical illness and major abdominal surgery, including upper GI and HPB surgery, are referred to. Overall, immunomodulation represents a potential tool to improve results but requires a thorough mapping of underlying mechanisms in order to achieve individualized treatment or prevention based on patients' specific needs.