Publications by authors named "Kristoffer Lassen"

48 Publications

The tube, the pancreatoduodenectomy-and the dogma.

BJS Open 2021 11;5(6)

HPB-Surgery, Oslo University Hospital at Rikshospitalet, Oslo, Norway.

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http://dx.doi.org/10.1093/bjsopen/zrab113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684476PMC
November 2021

Secondary effects of the COVID-19 pandemic on surgical management of hepatopancreatobiliary malignancies in the Nordic capitals.

Br J Surg 2021 12;109(1):e8-e9

Karolinska University Hospital, Department of Upper Gastrointestinal Diseases, and Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.

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http://dx.doi.org/10.1093/bjs/znab405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8690271PMC
December 2021

Increased sensitivity to SMAC mimetic LCL161 identified by longitudinal ex vivo pharmacogenomics of recurrent, KRAS mutated rectal cancer liver metastases.

J Transl Med 2021 09 8;19(1):384. Epub 2021 Sep 8.

Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P. O. Box 4953, 0424, Oslo, Norway.

Tumor heterogeneity is a primary cause of treatment failure. However, changes in drug sensitivity over time are not well mapped in cancer. Patient-derived organoids (PDOs) may predict clinical drug responses ex vivo and offer an opportunity to evaluate novel treatment strategies in a personalized fashion. Here we have evaluated spatio-temporal functional and molecular dynamics of five PDO models established after hepatic re-resections and neoadjuvant combination chemotherapies in a patient with microsatellite stable and KRAS mutated metastatic rectal cancer. Histopathological differentiation phenotypes of the PDOs corresponded with the liver metastases, and ex vivo drug sensitivities generally reflected clinical responses and selection pressure, assessed in comparison to a reference data set of PDOs from metastatic colorectal cancers. PDOs from the initial versus the two recurrent metastatic settings showed heterogeneous cell morphologies, protein marker expression, and drug sensitivities. Exploratory analyses of a drug screen library of 33 investigational anticancer agents showed the strongest ex vivo sensitivity to the SMAC mimetic LCL161 in PDOs of recurrent disease compared to those of the initial metastasis. Functional analyses confirmed target inhibition and apoptosis induction in the LCL161 sensitive PDOs from the recurrent metastases. Gene expression analyses indicated an association between LCL161 sensitivity and tumor necrosis factor alpha signaling and RIPK1 gene expression. In conclusion, LCL161 was identified as a possible experimental therapy of a metastatic rectal cancer that relapsed after hepatic resection and standard systemic treatment.
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http://dx.doi.org/10.1186/s12967-021-03062-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424985PMC
September 2021

Prognostic Impact of Resection Margin Status in Distal Pancreatectomy for Ductal Adenocarcinoma.

Ann Surg Oncol 2022 Jan 22;29(1):366-375. Epub 2021 Jul 22.

The Intervention Centre, Rikshospitalet, Oslo University Hospital, Oslo, Norway.

Background: Resection margin status is considered one of the few surgeon-controlled parameters affecting prognosis in pancreatic ductal adenocarcinoma (PDAC). While studies mostly focus on resection margins in pancreatoduodenectomy, little is known about their role in distal pancreatectomy (DP). This study aimed to investigate resection margins in DP for PDAC.

Methods: Patients who underwent DP for PDAC between October 2004 and February 2020 were included (n = 124). Resection margins and associated parameters were studied in two consecutive time periods during which different pathology examination protocols were used: non-standardized (period 1: 2004-2014) and standardized (period 2: 2015-2020). Microscopic margin involvement (R1) was defined as ≤1 mm clearance.

Results: Laparoscopic and open resections were performed in 117 (94.4%) and 7 (5.6%) patients, respectively. The R1 rate for the entire cohort was 73.4%, increasing from 60.4% in period 1 to 83.1% in period 2 (p = 0.005). A significantly higher R1 rate was observed for the posterior margin (35.8 vs. 70.4%, p < 0.001) and anterior pancreatic surface (based on a 0 mm clearance; 18.9 vs. 35.4%, p = 0.045). Pathology examination period, poorly differentiated PDAC, and vascular invasion were associated with R1 in the multivariable model. Extended DP, positive anterior pancreatic surface, lymph node ratio, perineural invasion, and adjuvant chemotherapy, but not R1, were significant prognostic factors for overall survival in the entire cohort.

Conclusions: Pathology examination is a key determinant of resection margin status following DP for PDAC. A high R1 rate is to be expected when pathology examination is meticulous and standardized. Involvement of the anterior pancreatic surface affects prognosis.
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http://dx.doi.org/10.1245/s10434-021-10464-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677636PMC
January 2022

Gastro- or Duodenojejunostomy Leaks After Pancreatoduodenectomy: Single Center Experience and Narrative Literature Review.

J Gastrointest Surg 2021 12 15;25(12):3130-3136. Epub 2021 Jun 15.

Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Background And Methods: Gastro- or duodenojejunostomy leaks after pancreatoduodenectomy is rare. This study aims to analyze the incidence, management, and outcome of gastro- or duodenojejunostomy leaks after pancreatoduodenectomy based on a single center experience from 2004 to 2020 with a narrative literature review.

Results: Of a total of 1494 pancreatoduodenectomies, eight patients with gastrojejunostomy (n=1) or duodenojejunostomy (n=7) leak were identified from the institutional pancreatic database. All leaks were treated operatively. In two patients dismantling of the duodenojejunostomy, distal gastrectomy, and closure of the pyloric and jejunal side, a percutaneous endoscopic gastrostomy and a feeding jejunostomy ultimately had to be performed after an unsuccessful attempt of gastrojejunostomy and suture of the duodenojejunostomy, respectively. The literature search revealed three more studies specifically addressing this complication after pancreatoduodenectomy (36 patients of a total of 4739 pancreatoduodenectomies). Based on an analysis of the current study and the literature review, the overall incidence of gastro- or duodenojejunostomy leaks after pancreatoduodenectomy was 0.71 % (44/6233 pancreatoduodenectomies). The occurrence of a gastro- or duodenojejunostomy leak was associated with a concomitant postoperative pancreatic fistula in 50 % of the cases, an increased length of hospital stay, and a mortality rate of 15.9 %. Surgical treatment was performed in 84 % of the cases.

Conclusion: Gastro- or duodenojejunostomy leak is a rare complication after pancreatoduodenectomy. Prompt diagnosis and early repair is important. In most cases, a surgical intervention is necessary for a good outcome. Under salvage conditions, a bailout strategy may be to temporarily dismantle the gastro- or duodenojejunal anastomosis.
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http://dx.doi.org/10.1007/s11605-021-05058-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654710PMC
December 2021

Evolution of laparoscopic liver surgery: 20-year experience of a Norwegian high-volume referral center.

Surg Endosc 2021 May 25. Epub 2021 May 25.

The Intervention Centre, Oslo University Hospital - Rikshospitalet, 0027, Oslo, Norway.

Background: Laparoscopic liver surgery has evolved to become a standard surgical approach in many specialized centers worldwide. In this study we present the evolution of laparoscopic liver surgery at a single high-volume referral center since its introduction in 1998.

Methods: Patients who underwent laparoscopic liver resection (LLR) between August 1998 and December 2018 at the Oslo University Hospital were analyzed. Perioperative outcomes were compared between three time periods: early (1998 to 2004), middle (2005 to 2012) and recent (2013-2018).

Results: Up to December 2020, 1533 LLRs have been performed. A total of 1232 procedures were examined (early period, n = 62; middle period, n = 367 and recent period, n = 803). Colorectal liver metastasis was the main indication for surgery (68%). The rates of conversion to laparotomy and hand-assisted laparoscopy were 3.2% and 1.4%. The median operative time and blood loss were 130 min [interquartile range (IQR), 85-190] and 220 ml (IQR, 50-600), respectively. The total postoperative complications rate was 20.3% and the 30-day mortality was 0.3%. The median postoperative stay was two (IQR, 2-4) days. When comparing perioperative outcomes between the three time periods, shorter operation time (median, from 182 to 120 min, p < 0.001), less blood loss (median, from 550 to 200 ml, p = 0.023), decreased rate of conversions to laparotomy (from 8 to 3%) and shorter postoperative hospital stay (median, from 3 to 2 days, p < 0.001) was observed in the later periods, while the number of more complex liver resections had increased.

Conclusion: During the last two decades, the indications, the number of patients and the complexity of laparoscopic liver procedures have expanded significantly. Initially being an experimental approach, laparoscopic liver surgery is now safely implemented across our unit and has become the method of choice for surgical treatment of most liver tumors.
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http://dx.doi.org/10.1007/s00464-021-08570-3DOI Listing
May 2021

Better overview of pancreatic cancer in Norway.

Tidsskr Nor Laegeforen 2021 01 6;141(1). Epub 2021 Jan 6.

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http://dx.doi.org/10.4045/tidsskr.20.0869DOI Listing
January 2021

A man in his thirties with right ventricular heart failure, jaundice and abdominal pain.

Tidsskr Nor Laegeforen 2020 11 19;140(17). Epub 2020 Nov 19.

Background: The combination of jaundice and acute abdominal pain is a common clinical problem associated with a broad array of aetiologies.

Case Presentation: A 36-year-old male with Down's syndrome and Eisenmenger's syndrome presented with abdominal pain, jaundice and acute liver failure. Initial transabdominal ultrasound and subsequent magnetic resonance cholangiopancreatography (MRCP) revealed gallbladder stones, but no common bile duct stones. During the course of the patient's hospital admission, his liver chemistries were consistently elevated. Thus, endoscopic retrograde cholangiography (ERC) with sphincterotomy was performed, despite the anaesthesiological risk associated with his chronic heart failure. However, the ERC and sphincterotomy did not relieve the patient's symptoms and had no apparent effect on his abnormal liver chemistries. By the end of his hospital stay, the patient recovered spontaneously and was discharged with no final conclusion having been reached. An unexpected turn of events led us to conclude upon a diagnosis a few weeks later.

Interpretation: This case illustrates the challenges of a multidisciplinary approach in a complex patient, and an overlooked detail that became a lesson to learn from.
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http://dx.doi.org/10.4045/tidsskr.20.0191DOI Listing
November 2020

Guidelines for Perioperative Care for Pancreatoduodenectomy: Enhanced Recovery After Surgery (ERAS) Recommendations 2019.

World J Surg 2020 07;44(7):2056-2084

Department of Visceral Surgery, University Hospital Lausanne (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.

Background: Enhanced recovery after surgery (ERAS) pathways are now implemented worldwide with strong evidence that adhesion to such protocol reduces medical complications, costs and hospital stay. This concept has been applied for pancreatic surgery since the first published guidelines in 2012. This study presents the updated ERAS recommendations for pancreatoduodenectomy (PD) based on the best available evidence and on expert consensus.

Methods: A systematic literature search was conducted in three databases (Embase, Medline Ovid and Cochrane Library Wiley) for the 27 developed ERAS items. Quality of randomized trials was assessed using the Consolidated Standards of Reporting Trials statement checklist. The level of evidence for each item was determined using the Grading of Recommendations Assessment Development and Evaluation system. The Delphi method was used to validate the final recommendations.

Results: A total of 314 articles were included in the systematic review. Consensus among experts was reached after three rounds. A well-implemented ERAS protocol with good compliance is associated with a reduction in medical complications and length of hospital stay. The highest level of evidence was available for five items: avoiding hypothermia, use of wound catheters as an alternative to epidural analgesia, antimicrobial and thromboprophylaxis protocols and preoperative nutritional interventions for patients with severe weight loss (> 15%).

Conclusions: The current updated ERAS recommendations for PD are based on the best available evidence and processed by the Delphi method. Prospective studies of high quality are encouraged to confirm the benefit of current updated recommendations.
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http://dx.doi.org/10.1007/s00268-020-05462-wDOI Listing
July 2020

A man in his fifties with abdominal pain, itching and weight loss.

Tidsskr Nor Laegeforen 2020 02 10;140(3). Epub 2020 Feb 10.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease which can potentially affect any organ system. IgG4-related sclerosing cholangitis and inflammatory pseudotumour in the hepatobiliary system is rare, but is probably underdiagnosed.

Case Presentation: We present the case of a 52-year-old male who was admitted with obstructive jaundice and weight loss. He presented with a mass lesion in the porta hepatis mimicking hilar cholangiocarcinoma. The patient underwent extended right hepatectomy with hepaticojejunostomy. Severe liver failure developed postoperatively, and the patient underwent liver transplantation. The resected specimen showed infiltration of IgG4 positive plasma cells in the liver hilum, and immunohistochemical staining demonstrated a ratio of IgG4/IgG-positive plasma cells of more than 40 %. Postoperative serological testing showed elevated levels of serum IgG4 6.0 g/L (0.03-2.01), and the CT imaging revealed chronic pancreatitis and bilateral enlargement of the submandibular glands. The patient was ultimately diagnosed with IgG4-related disease.

Interpretation: It is difficult to distinguish benign bile duct strictures in the porta hepatis from hilar cholangiocarcinoma, and serum IgG4 is unreliable as a diagnostic marker due to low sensitivity and specificity. Greater awareness of IgG4-RD is needed in order to avoid surgery.
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http://dx.doi.org/10.4045/tidsskr.19.0390DOI Listing
February 2020

Centralization of Pancreatic Surgery in Europe: an Update.

J Gastrointest Surg 2019 11 4;23(11):2322-2323. Epub 2019 Sep 4.

Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway.

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http://dx.doi.org/10.1007/s11605-019-04383-xDOI Listing
November 2019

Variation in use of open and laparoscopic distal pancreatectomy and associated outcome metrics in a universal health care system.

Pancreatology 2019 Sep 1;19(6):880-887. Epub 2019 Aug 1.

Institute of Clinical Medicine, the Arctic University of Norway, Tromsø, Norway; Department of Hepatobiliary and Pancreatic surgery, Oslo University Hospital, Oslo, Norway.

Background: Universal health care (UHC) should ensure equal access to and use of surgery, but few studies have explored variation in UHC systems. The objective was to describe practice of distal pancreatectomy in Norway covered exclusively by an UHC.

Methods: Data on all patients undergoing distal pancreatectomy from the Norwegian Patient Register over a 5-year period. Age- and gender-adjusted population-based resection rates (adj. per million/yr) for distal pancreatectomy were analysed across 4 regions and outcomes related to splenic salvage rate, hospital stay, reoperation, readmissions and 90-day mortality risk between regions. Risk is reported as odds ratio (OR) with 95% confidence interval (c.i.).

Results: Regional difference exist in terms of absolute numbers, with the majority of procedures done in one region (n = 331; 59.7%). Regional variation persisted for age- and gender-adjusted population-rates, with highest rate at 23.8/million/yr and lowest rate at 13.5/mill/yr (for a 176% relative difference; or an absolute difference of +10.3 resections/million/yr). Overall, a lapDP instead of an open DP was 3.5 times more likely in SouthEast compared to all other regions combined (lapDP rate: 83% vrs 24%, respectively; OR 15.4, 95% c.i. 10.1-23.5; P < 0.001). The splenic salvage rate was lower in SouthEast (19.9%) compared to all other regions (average 26.5%; highest in Central-region at 37.0%; P = 0.010 for trend). Controlled for other factors in multivariate regression, 'region' of surgery remained significantly associated with laparoscopic access.

Conclusion: Despite a universal health care system, considerable variation exists in resection rates, use of laparoscopy and splenic salvage rates across regions.
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http://dx.doi.org/10.1016/j.pan.2019.07.047DOI Listing
September 2019

Weight loss and BMI criteria in GLIM's definition of malnutrition is associated with postoperative complications following abdominal resections - Results from a National Quality Registry.

Clin Nutr 2020 05 20;39(5):1593-1599. Epub 2019 Jul 20.

Department of Research and Development, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.

Background & Aims: Although malnutrition is thought to be common among patients with intraabdominal diseases and is recognized as a risk factor for postoperative complications, diagnostic criteria for malnutrition have not been consistent. Thus, the Global Leadership Initiative in Malnutrition (GLIM) has recently published new criteria for malnutrition. The aims of this study were to investigate the prevalence of malnutrition according to weight loss and BMI criteria in GLIM's second step for the diagnosis and their association with severe postoperative complications in patients undergoing gastrointestinal resections.

Method: The current study includes adult patients who were prospectively included in the Norwegian Registry for Gastrointestinal Surgery in the period between 2015 and 2018. Exclusion criteria were acute surgery and lack of information regarding preoperative weight and/or postoperative complications. Severe surgical complications were classified according to the Revised Accordion Classification system and malnutrition with the GLIM criteria. Associations were assessed by logistic regression analyses, and the adjusted odds ratio included age (continuous), gender (male/female) and scores from the American Society of Anesthesiologists Physical Status Classification System and the Eastern Cooperative Oncology Group.

Results: Out of 6110 patients, 2161 (35.4%) were classified as with malnutrition, 1206 (19.7%) with moderate and 955 (15.6%) with severe malnutrition. Malnourished patients were 1.29 (95% CI: 1.13-1.47) times more likely to develop severe surgical complications, and 2.15 (95% CI: 1.27-3.65) times more likely to die within 30 days, as compared to those who were not.

Conclusion: Preoperative malnutrition is common among patients having gastrointestinal resections and is associated with an increased risk of severe surgical complications.
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http://dx.doi.org/10.1016/j.clnu.2019.07.003DOI Listing
May 2020

Contemporary practice and short-term outcomes after liver resections in a complete national cohort.

Langenbecks Arch Surg 2019 Feb 5;404(1):11-19. Epub 2018 Dec 5.

Clinical Surgery, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK.

Background: Improved outcome after liver resections have been reported in several series, but outcomes from national cohorts are scarce. Our aim was to evaluate nationwide practice and short-term outcomes after liver surgery in a universal healthcare system.

Methods: A complete 5-year cohort of all liver resections from the Norwegian Patient Registry (NPR). Short-term outcomes were aggregated length of stay (a-LoS), reoperation and 90-day mortality.

Results: Of 2118 liver resections, 605 (28.6%) were major, median age was 65 years and 1184 (55%) were male. Most common indication was metastatic disease (n = 1554; 73.4%) and primary malignancy (n = 328; 15.3%). Laparoscopy was performed in 513 (33.9%) of minor and 37 (6.1%) of major liver resections and increased over time to 39.1% of minor resections in 2016. Median a-LoS was 12 days for major resections, 8 days for open minor and 3 days for laparoscopic minor resections. Reoperation was reported for 159 (7.4%) and 90-day mortality for 44 (2.1%). Primary malignancy, male gender, elderly patients and major resections were associated with poorer outcome.

Conclusions: In a national cohort, laparoscopy is used for a substantial proportion of minor resections and was associated with reduced a-LoS. Risk factors for reoperation and mortality were male gender, increased age and major resection for primary malignancy.
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http://dx.doi.org/10.1007/s00423-018-1737-3DOI Listing
February 2019

A nationwide cohort study of resection rates and short-term outcomes in open and laparoscopic distal pancreatectomy.

HPB (Oxford) 2019 06 1;21(6):669-678. Epub 2018 Nov 1.

Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway; Department of Hepatobiliary and Pancreatic Surgery, Oslo University Hospital, Oslo, Norway.

Background: Distal pancreatectomy (DP) is increasingly done by laparoscopy but data from routine practise are scarce. We describe practise in a national cohort.

Methods: Data from the Norwegian Patient Register of all patients undergoing DP from 2012 to 2016. National resection rates were analysed. Short-term outcomes include length of stay, reoperation, readmissions and 90-day mortality. Risk is reported as odds ratio (OR) with 95% confidence interval (c.i.).

Results: Of 554 procedures, 327 (59%) were laparoscopic. Median age was 66 years (iqr 55-72) and 52% were women. Resection rates increased during the period for all DP (from 1.76 to 2.39 per 100.000/yr), and significantly for laparoscopic DP (adjusted R-square 0.858; P = 0.015). Elderly patients had more resection (r = 0.11; P = 0.019). Splenectomy (n = 427; 77%) was less likely with laparoscopy (laparoscopy 72% vs open 84%, respectively; OR 0.64, 95% c.i. 0.42-0.97; P = 0.035). Multivisceral resections occurred more often in open DP (5.3% vs 1.2% for laparoscopy, OR 4.51, 1.44-14.2; P = 0.008). Reoperation occurred in 34 (6%), readmission in 109 (20%), and mortality in 8 (1.4%). Hospital stay was shorter for laparoscopic DP.

Conclusion: Use of DP increases in the population, particularly in the elderly, with use of laparoscopic access and an association with a reduced hospital stay.
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http://dx.doi.org/10.1016/j.hpb.2018.10.006DOI Listing
June 2019

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

HPB (Oxford) 2019 03 5;21(3):319-327. Epub 2018 Oct 5.

Department of Gastrointestinal Surgery, University Hospital of Northern Norway, Sykehusveien 38, 9019, Tromsø, Norway; Institute of Clinical Medicine, The Arctic University of Norway, Hansine Hansens Veg 18, 9019, Tromsø, Norway; Department of Hepatobiliary and Pancreatic Surgery, Oslo University Hospital, Postboks 4950 Nydalen, 0424, Oslo, Norway.

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.

Methods: All patients who underwent PD in Norway between 2012 and 2016 were identified. Mortality (90 days) and relaparotomy (30 days) were assessed for predictors including demographic data and multi-visceral or vascular resection. Aggregated length-of-stay and national and regional incidences of the procedure were also analysed.

Results: A total of 930 patients underwent PD during the study period. In-hospital mortality occurred in 20 patients (2%) and 34 patients (4%) died within 90 days. Male gender, age, multi-visceral resection and relaparotomy were independent predictors of 90-day mortality. Some 131 patients (14%) had a relaparotomy, with male gender and multi-visceral resection as independent predictors. There was no difference between regions in procedure incidence or 90-day mortality. There was a disparity within the regions in the use of vascular resection (p = 0.021).

Conclusion: The short-term outcomes after PD in Norway are acceptable and the 90-day mortality rate is low. The outcomes may reflect centralization of pancreatic surgery.
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http://dx.doi.org/10.1016/j.hpb.2018.08.011DOI Listing
March 2019

Drain After Pancreatoduodenectomy: Methodological Issues.

Ann Surg 2018 03;267(3):e58

Oslo University Hospital, Oslo, Norway.

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http://dx.doi.org/10.1097/SLA.0000000000002103DOI Listing
March 2018

Priority and prejudice: does low socioeconomic status bias waiting time for endoscopy? A blinded, randomized survey.

Scand J Gastroenterol 2018 05 16;53(5):621-625. Epub 2017 Nov 16.

c Department of Gastrointestinal and Hepatopancreatobiliary Surgery , Oslo University Hospital , Rikshospitalet , Norway.

Introduction: An unwanted socioeconomic health gap is observed in Western countries with easily accessible, government-financed health care systems. Survival rates from several malignancies differ between socioeconomic clusters and the disparities remain after adjusting for major co-morbidities and health related behavior. The possibility of biased conduct among health care workers has been proposed as a contributing factor, but evidence is sparse.

Methods: A blinded, randomized online questionnaire survey was conducted among specialists in gastroenterology in Norway. Each respondent was asked to give priority for colonoscopy to three different referrals. By randomized sequence, half the referrals contained a discreet piece of information indicating low socioeconomic status (SES). The SES information given was focused on known low-status clusters in Norway, namely the morbidly obese and receivers of disability pensions.

Results: There were 107 respondents giving a response rate of 67%. A lower priority was consistently given to the referrals containing information on low SES, but the difference only reached statistical significance (p = .018) for one of the referrals.

Conclusion: Information on low SES may influence how referrals for endoscopy are prioritized.
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http://dx.doi.org/10.1080/00365521.2017.1402207DOI Listing
May 2018

Neoadjuvant chemotherapy versus surgery first for resectable pancreatic cancer (Norwegian Pancreatic Cancer Trial - 1 (NorPACT-1)) - study protocol for a national multicentre randomized controlled trial.

BMC Surg 2017 Aug 25;17(1):94. Epub 2017 Aug 25.

Department of Oncology, Oslo University Hospital, Oslo, Norway.

Background: Pancreatic cancer is the fourth leading cause of cancer-related death. While surgical resection remains the foundation for potentially curative treatment, survival benefit is achieved with adjuvant oncological treatment. Thus, completion of multimodality treatment (surgical resection and (neo)adjuvant chemotherapy) to all patients and early treatment of micrometastatic disease is the ideal goal. NorPACT-1 aims to test the hypothesis that overall mortality at one year after allocation of treatment can be reduced with neoadjuvant chemotherapy in surgically treated patients with resectable pancreatic cancer.

Methods/design: The NorPACT- 1 is a multicentre, randomized controlled phase III trial organized by the Norwegian Gastrointestinal Cancer Group for Hepato-Pancreato-Biliary cancer. Patients with resectable adenocarcinoma of the pancreatic head are randomized to receive either surgery first (Group 1: SF/control) or neoadjuvant chemotherapy (Group 2: NT/intervention) with four cycles FOLFIRINOX followed by resection. Both groups receive adjuvant chemotherapy with gemicitabine and capecitabine (six cycles in Group 1, four cycles in Group 2). In total 90 patients will be randomized in all the five Norwegian university hospitals performing pancreatic surgery. Primary endpoint is overall mortality at one year following commencement of treatment for those who ultimately undergo resection. Secondary endpoints are overall survival after date of randomization (intention to treat), overall survival after resection, disease-free survival, histopathological response, complication rates after surgery, feasibility of neoadjuvant and adjuvant chemotherapy, completion rates of all parts of multimodal treatment, and quality-of-life. Bolt-on to the study is a translational research program that aims at identifying factors that are predictive of response to NT, the risk of distant cancer spread, and patient outcome.

Discussion: NorPACT- 1 is designed to investigate the additional benefit of NT compared to standard treatment only (surgery + adjuvant chemotherapy) for resectable cancer of the pancreatic head to decrease early mortality (within one year) in resected patients.

Trial Registration: Trial open for accrual 01.02.2017. ClinicalTrials.gov Identifier: NCT02919787 . Date of registration: September 14, 2016.
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http://dx.doi.org/10.1186/s12893-017-0291-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389186PMC
August 2017

Systemic antibiotic prophylaxis prior to gastrointestinal surgery - is oral administration of doxycycline and metronidazole adequate?

Infect Dis (Lond) 2017 Nov - Dec;49(11-12):785-791. Epub 2017 Jun 28.

a Department of Gastrointestinal Surgery , University Hospital of North Norway , Tromsø , Norway.

Background: Antibiotic prophylaxis is recommended prior to a wide range of gastrointestinal operations to reduce the rate of surgical site infections (SSIs). Traditional intravenous (IV) drugs are costly and their preparation strains nursing resources at the wards. While oral administration may attenuate these limitations, its use remains limited. We aimed to assess whether a dual oral antibiotic prophylaxis regimen provides adequate serum concentrations throughout the surgical procedure.

Methods: We measured serum concentrations of doxycycline and metronidazole following single oral doses of 400 mg doxycycline and 1200 mg metronidazole at first incision and repeated at wound closure in a cohort of patients undergoing elective gastrointestinal surgery. Both drugs were dispensed at least two hours before skin incision. Serum concentrations were compared to minimum inhibitory concentrations (MIC) and epidemiological cut-off values (ECOFFs) for relevant pathogens.

Results: Mean serum concentrations of doxycycline at first incision and at wound closure were 5.75 mg/L and 4.66 mg/L and of metronidazole 18.88 mg/L and 15.56 mg/L, respectively. Metronidazole concentrations were above ECOFF (2 mg/L) for relevant anaerobic species in 103/104 of patients in both samples. Doxycycline serum concentrations were above the ECOFF for common Enterobacteriaceae species (4 mg/L) in both samples in 58/104 patients (55.8%).

Conclusions: A single dose of orally administered metronidazole provides adequate concentrations throughout surgery in a heterogeneous cohort of patients. Uncertainty persists regarding the adequacy of doxycycline concentrations, as the optimal serum level of doxycycline in a prophylactic setting has not been established.
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http://dx.doi.org/10.1080/23744235.2017.1342044DOI Listing
April 2018

Major postoperative complications are associated with impaired long-term survival after gastro-esophageal and pancreatic cancer surgery: a complete national cohort study.

BMC Surg 2016 May 18;16(1):32. Epub 2016 May 18.

Department of GI and HPB surgery, University Hospital of Northern Norway, 9038 Breivika, Tromsø, Norway.

Background: Some studies have reported an association between complications and impaired long-term survival after cancer surgery. We aimed to investigate how major complications are associated with overall survival after gastro-esophageal and pancreatic cancer surgery in a complete national cohort.

Methods: All esophageal-, gastric- and pancreatic resections performed for cancer in Norway between January 1, 2008, and December 1, 2013 were identified in the Norwegian Patient Registry together with data concerning major postoperative complications and survival.

Results: When emergency cases were excluded, there were 1965 esophageal-, gastric- or pancreatic resections performed for cancer in Norway between 1 January 2008, and 1 December 2013. A total of 248 patients (12.6 %) suffered major postoperative complications. Complications were associated both with increased early (90 days) mortality (OR = 4.25, 95 % CI = 2.78-6.50), and reduced overall survival when patients suffering early mortality were excluded (HR = 1.23, 95 % CI = 1.01-1.50).

Conclusions: Major postoperative complications are associated with impaired long-term survival after gastro-esophageal and pancreatic cancer surgery.
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http://dx.doi.org/10.1186/s12893-016-0149-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870774PMC
May 2016

Food at will after pancreaticoduodenectomies. Re. "Perioperative nutritional support of patients undergoing pancreatic surgery in the age of ERAS".

Nutrition 2015 Jul-Aug;31(7-8):1057-8. Epub 2015 Mar 20.

Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

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http://dx.doi.org/10.1016/j.nut.2015.02.013DOI Listing
September 2015

Functional recovery is considered the most important target: a survey of dedicated professionals.

Perioper Med (Lond) 2014 30;3. Epub 2014 Jul 30.

Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway ; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.

Background: The aim of this study was to survey the relative importance of postoperative recovery targets and perioperative care items, as perceived by a large group of international dedicated professionals.

Methods: A questionnaire with eight postoperative recovery targets and 13 perioperative care items was mailed to participants of the first international Enhanced Recovery After Surgery (ERAS) congress and to authors of papers with a clear relevance to ERAS in abdominal surgery. The responders were divided into categories according to profession and region.

Results: The recovery targets 'To be completely free of nausea', 'To be independently mobile' and 'To be able to eat and drink as soon as possible' received the highest score irrespective of the responder's profession or region of origin. Equally, the care items 'Optimizing fluid balance', 'Preoperative counselling' and 'Promoting early and scheduled mobilisation' received the highest score across all groups.

Conclusions: Functional recovery, as in tolerance of food without nausea and regained mobility, was considered the most important target of recovery. There was a consistent uniformity in the way international dedicated professionals scored the relative importance of recovery targets and care items. The relative rating of the perioperative care items was not dependent on the strength of evidence supporting the items.
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http://dx.doi.org/10.1186/2047-0525-3-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118075PMC
August 2014

Attitudes of patients and care providers to enhanced recovery after surgery programs after major abdominal surgery.

J Surg Res 2015 Jan 23;193(1):102-10. Epub 2014 Jun 23.

Department of Clinical Surgery, Royal Infirmary of Edinburgh, Edinburgh, Scotland, United Kingdom.

Background: Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies.

Materials And Methods: Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance.

Results: One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and care providers rated the majority of items as important and supported ERAS principles. Freedom from nausea (median, 10; interquartile range [IQR], 8-10) and pain at rest (median, 10; IQR, 8-10) were the care components rated the highest by both patients and care providers. Early return of bowel function (median, 7; IQR, 5-8) and avoiding preanesthetic sedation (median, 6; IQR, 3.75-8) were scored the lowest by care providers.

Conclusions: ERAS principles are supported by both patients and care providers. This is important when attempting to implement and maintain an ERAS program. Controversies still remain regarding the relative importance of individual ERAS components.
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http://dx.doi.org/10.1016/j.jss.2014.06.032DOI Listing
January 2015

Huge effect of arginine on survival in gastric cancer?

J Cancer Res Clin Oncol 2014 Apr 13;140(4):685. Epub 2014 Feb 13.

Department of GI/HPB Surgery, University Hospital Northern Norway, Tromsö, Norway,

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http://dx.doi.org/10.1007/s00432-014-1608-4DOI Listing
April 2014

Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS(®)) society recommendations.

Clin Nutr 2013 Dec 17;32(6):879-87. Epub 2013 Oct 17.

Dept of Urology, University Hospital of Lausanne, Switzerland.

Purpose: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery.

Objectives: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group.

Evidence Acquisition: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated.

Evidence Synthesis: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery.

Conclusions: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.
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http://dx.doi.org/10.1016/j.clnu.2013.09.014DOI Listing
December 2013

Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?

Eur Urol 2014 Feb 22;65(2):263-6. Epub 2013 Oct 22.

Academic Urology Unit, University of Sheffield, Sheffield, UK.

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes.
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http://dx.doi.org/10.1016/j.eururo.2013.10.011DOI Listing
February 2014

A systematic review of outcomes in patients undergoing liver surgery in an enhanced recovery after surgery pathways.

HPB (Oxford) 2013 Apr 28;15(4):245-51. Epub 2012 Sep 28.

Department of Surgery, University Hospital Maastricht, Maastricht 6202 AZ, the Netherlands.

Objectives: Enhanced recovery after surgery (ERAS) or fast-track protocols have been implemented in different fields of surgery to attenuate the surgical stress response and accelerate recovery. The objective of this study was to systematically review the literature on outcomes of ERAS protocols applied in liver surgery.

Methods: The MEDLINE, EMBASE, PubMed and Cochrane Library databases were searched for randomized controlled trials (RCTs), case-control studies and case series published between January 1966 and October 2011 comparing adult patients undergoing elective liver surgery in an ERAS programme with those treated in a conventional manner. The primary outcome measure was hospital length of stay (LoS). Secondary outcome measures were time to functional recovery, and complication, readmission and mortality rates.

Results: A total of 307 articles were found, six of which were included in the review. These comprised two RCTs, three case-control studies and one retrospective case series. Median LoS ranged from 4 days in an ERAS group to 11 days in a control group. Morbidity, mortality and readmission rates did not differ significantly between the groups. Only two studies assessed time to functional recovery. Functional recovery in these studies was reached 2 days before discharge.

Conclusions: This systematic review suggests that ERAS protocols can be successfully implemented in liver surgery. Length of stay is reduced without compromising morbidity, mortality or readmission rates.
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http://dx.doi.org/10.1111/j.1477-2574.2012.00572.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608977PMC
April 2013
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