Translation and validation of the Norwegian version of the postoperative quality of recovery score QoR-15.

BACKGROUND: As patient-centered care gains more attention, assessing the patient's perspective on their recovery has become increasingly important. In response to the need for a reliable and valid patient reported outcome measurement tool for major surgical resections in Norway. The Norwegian Registry for Gastrointestinal Surgery (NORGAST) initiated a project to translate and evaluate QoR-15's psychometric properties for patients going through general, gastrointestinal (GI), and hepato-pancreato-biliary (HPB) resectional surgery. METHODS: After a translation and adaption of the original version of QoR-15 into Norwegian, the QoR-15NO was psychometrically evaluated including a confirmatory factor analysis to test for unidimensionality, as well as tests for content validity, internal consistency, measurement error, construct validity, feasibility, and responsiveness. This process included cognitive interviews using a structured interview guide. Further, patients who underwent various types of GI/HPB surgery at five hospitals in different parts of Norway completed the QoR-15NO before surgery and on the first or second day after surgery. The impact of surgery was classified according to Surgical Outcome Risk Tool v2 (SORT), in extra major/complex, major, intermediate, and minor. RESULTS: This study included 324 patients with 83% return rate with both pre- and postoperative forms. There were negative correlations between duration of surgery and postoperative QoR-15 score and the difference between post- and preoperative score (change score). Individuals who had gone through surgery with major impact had a lower postoperative mean QoR-15 score (97) than their counterparts who had experienced either medium (QoR-15: 110) or minor (QoR15: 119) impact surgery. Cronbach's alpha (0.88) and Omega Alpha Total (ωt = 0.90) indicate that the scale has good to very good internal consistency. Test-retest reliability was measured by Intra-class Correlation Coefficient to ICC = 0.70. Confirmatory factor analyses supported that a one-factor model with correlated residuals had a good fit to data. CONCLUSION: This study supports QoR-15NO as a valid, essentially unidimensional, feasible, and responsive instrument among patients undergoing general, GI, and HPB resectional surgery in Norway. The total QoR-15NO score provides important information that can be used in an everyday clinical setting and integrated into NORGAST.

Upper gastrointestinal endoscopy in the surgically altered patient.

As management of upper gastrointestinal malignancies improves, and with popularization of bariatric surgery, endoscopists are likely to meet patients with altered upper gastrointestinal anatomy. Short-term, the surgery can cause complications like bleeding, leaks, and fistulas, and longer-term problems such as intestinal or biliary anastomotic strictures or biliary stones can arise, all necessitating endoscopy. In addition, the usual upper gastrointestinal pathologies can also still occur. These patients pose unique challenges. To proceed, understanding the new layout of the upper gastrointestinal tract is essential. The endoscopist, armed with a clear plan for navigation, can readily diagnose and manage most commonly occurring conditions, such as marginal ulcers and proximal anastomotic strictures with standard endoscopic instruments. With complex reconstructions involving long segments of small bowel, such as Roux-en-Y gastric bypass, utilization of balloon-assisted enteroscopy may be necessary, mandating modification of procedures such as endoscopic retrograde cholangiopancreatography. Successful endoscopic management of patients with altered anatomy will require prior planning and preparation to ensure the appropriate equipment, setting, and skill set is provided.

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: a multicenter propensity score-matched study.

BACKGROUND: The role of laparoscopy in the treatment of intrahepatic cholangiocarcinoma (ICC) remains unclear. This multicenter study examined the outcomes of laparoscopic liver resection for ICC. METHODS: Patients with ICC who had undergone laparoscopic or open liver resection between 2012 and 2019 at four European expert centers were included in the study. Laparoscopic and open approaches were compared in terms of surgical and oncological outcomes. Propensity score matching was used for minimizing treatment selection bias and adjusting for confounders (age, ASA grade, tumor size, location, number of tumors and underlying liver disease). RESULTS: Of 136 patients, 50 (36.7%) underwent laparoscopic resection, whereas 86 (63.3%) had open surgery. Median tumor size was larger (73.6 vs 55.1 mm, p = 0.01) and the incidence of bi-lobar tumors was higher (36.6 vs 6%, p < 0.01) in patients undergoing open surgery. After propensity score matching baseline characteristics were comparable although open surgery was associated with a larger fraction of major liver resections (74 vs 38%, p < 0.01), lymphadenectomy (60 vs 20%, p < 0.01) and longer operative time (294 vs 209 min, p < 0.01). Tumor characteristics were similar. Laparoscopic resection resulted in less complications (30 vs 52%, p = 0.025), fewer reoperations (4 vs 16%, p = 0.046) and shorter hospital stay (5 vs 8 days, p < 0.01). No differences were found in terms of recurrence, recurrence-free and overall survival. CONCLUSION: Laparoscopic resection seems to be associated with improved short-term and with similar long-term outcomes compared with open surgery in patients with ICC. However, possible selection criteria for laparoscopic surgery are yet to be defined.

Transatlantic registries for minimally invasive liver surgery: towards harmonization.

BACKGROUND: Several registries focus on patients undergoing minimally invasive liver surgery (MILS). This study compared transatlantic registries focusing on the variables collected and differences in baseline characteristics, indications, and treatment in patients undergoing MILS. Furthermore, key variables were identified. METHODS: The five registries for liver surgery from North America (ACS-NSQIP), Italy, Norway, the Netherlands, and Europe were compared. A set of key variables were established by consensus expert opinion and compared between the registries. Anonymized data of all MILS procedures were collected (January 2014-December 2019). To summarize differences for all patient characteristics, treatment, and outcome, the relative and absolute largest differences (RLD, ALD) between the smallest and largest outcome per variable among the registries are presented. RESULTS: In total, 13,571 patients after MILS were included. Both 30- and 90-day mortality after MILS were below 1.1% in all registries. The largest differences in baseline characteristics were seen in ASA grade 3-4 (RLD 3.0, ALD 46.1%) and the presence of liver cirrhosis (RLD 6.4, ALD 21.2%). The largest difference in treatment was the use of neoadjuvant chemotherapy (RLD 4.3, ALD 20.6%). The number of variables collected per registry varied from 28 to 303. From the 46 key variables, 34 were missing in at least one of the registries. CONCLUSION: Despite considerable variation in baseline characteristics, indications, and treatment of patients undergoing MILS in the five transatlantic registries, overall mortality after MILS was consistently below 1.1%. The registries should be harmonized to facilitate future collaborative research on MILS for which the identified 46 key variables will be instrumental.

Preoperative Inflammatory Markers in Liver Resection for Colorectal Liver Metastases: A National Registry-Based Study.

BACKGROUND: Preoperative inflammatory markers were shown to be associated with prognosis following surgery for hepato-pancreato-biliary cancer. Yet little evidence exists about their role in patients with colorectal liver metastases (CRLM). This study aimed to examine the association between selected preoperative inflammatory markers and outcomes of liver resection for CRLM. METHODS: Data from the Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all liver resections performed in Norway within the study period (November 2015-April 2021). Preoperative inflammatory markers were Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS) and C-reactive protein to albumin ratio (CAR). The impact of these on postoperative outcomes, as well as on survival were studied. RESULTS: Liver resections for CRLM were performed in 1442 patients. Preoperative GPS ≥ 1 and mGPS ≥ 1 were present in 170 (11.8%) and 147 (10.2%) patients, respectively. Both were associated with severe complications but became non-significant in the multivariable model. GPS, mGPS, CAR were significant predictors for overall survival in the univariable analysis, but only CAR remained such in the multivariable model. When stratified by the type of surgical approach, CAR was a significant predictor for survival after open but not laparoscopic liver resections. CONCLUSIONS: GPS, mGPS and CAR have no impact on severe complications after liver resection for CRLM. CAR outperforms GPS and mGPS in predicting overall survival in these patients, especially following open resections. The prognostic significance of CAR in CRLM should be tested against other clinical and pathology parameters relevant for prognosis.

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

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.

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

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.

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

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.

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

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.

A man in his fifties with abdominal pain, itching and weight loss. / En mann i 50-årene med magesmerter, kløe og vekttap.

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.

A man in his thirties with right ventricular heart failure, jaundice and abdominal pain. / En mann i 30-årene med høyresidig hjertesvikt, ikterus og magesmerter.

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.

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

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.

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

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.

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

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 (r2 = 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.

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. 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.

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

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.

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.

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.