Knut Jørgen Labori

• Yaqub, Sheraz; Valberg, Morten; Bjørnbeth, Bjørn Atle; Angelsen, Jon-Helge; Brudvik, Kristoffer Watten & Eilertsen, Ina [Vis alle 43 forfattere av denne artikkelen] (2026). Aspirin after curative-intent treatment of colorectal cancer liver metastases (ASAC): a multicentre, phase 3, randomised, double-blind, placebo-controlled trial. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. doi: 10.1016/s2468-1253(26)00260-8. Fulltekst i vitenarkiv Vis sammendrag

  Background Colorectal cancer frequently metastasises to the liver. Recurrence after curative-intent treatment of colorectal cancer liver metastases is common. Aspirin has shown preventive and antitumour effects in colorectal cancer, but its role after treatment of metastatic disease is uncertain. We aimed to establish whether adjuvant aspirin improves disease-free survival after curative-intent treatment of colorectal cancer liver metastases. Methods In this phase 3, randomised, double-blind, placebo-controlled trial conducted at 14 centres in Norway, Sweden, and Denmark, patients who had undergone curative-intent treatment for colorectal cancer liver metastases were randomly assigned (1:1), stratified by study site using a centrally generated computerised sequence with variable block sizes, to aspirin 160 mg per day or matching placebo for up to 3 years or until recurrence, death, or treatment discontinuation. The primary outcome was disease-free survival in the full analysis set, comprising all patients who initiated study treatment. The trial is completed and this is the final analysis. This trial is registered with ClinicalTrials.gov, NCT03326791, and EudraCT, 2014-003601-15. Findings Between Dec 15, 2017, and Jan 27, 2022, 466 patients were randomly assigned, of whom 428 initiated study treatment and were included in the full analysis set (217 assigned aspirin and 211 assigned placebo); 272 (64%) were male, 156 (36%) were female, and the mean age was 62·2 years. 269 disease-free survival events occurred (138 in the aspirin group and 131 in the placebo group). Aspirin did not improve disease-free survival (hazard ratio [HR] for recurrence or death 1·08 [95·44% CI 0·85–1·38]; p=0·58). Median disease-free survival was 1·13 years (95·44% CI 0·92–1·44) with aspirin and 1·40 years (1·11–1·69) with placebo. Overall survival at 36 months was 76% (95% CI 69·4–82·7) with aspirin and 85% (79·5–90·8) with placebo (HR for death 1·64 [95% CI 1·01–2·65]; p=0·045). Time to recurrence did not differ between groups (adjusted cause-specific HR 1·06 [95% CI 0·83–1·35]; p=0·64). 24 serious adverse events occurred in 17 (8%) of 217 patients in the aspirin group and five serious adverse events occurred in four (2%) of 211 patients in the placebo group. Clinically relevant adverse events and serious adverse events that occurred more commonly in the aspirin group than in the placebo group were myocardial infarction (two vs 0), epistaxis (four vs 0), duodenal ulcer (two vs 0), and cerebral haemorrhage (two vs 0). There were no treatment-related deaths. Interpretation Adjuvant aspirin did not improve disease-free survival and was associated with lower overall survival and more serious adverse events. These findings do not support routine use of aspirin after curative-intent treatment of colorectal cancer liver metastases.

• Lucocq, James; Haugk, Beate; White, Steven; Marchegiani, Giovanni; Holmberg, Marcus & Zerbi, Alessandro [Vis alle 65 forfattere av denne artikkelen] (2026). Contemporary Adjuvant Chemotherapy for Intraductal Papillary Mucinous Neoplasms. JAMA Network Open. 9(3), s. e263688–e263688. doi: 10.1001/jamanetworkopen.2026.3688. Fulltekst i vitenarkiv
• Romandini, Elisa; Perri, Giampaolo; Maekawa, Aya; Bannone, Elisa; Sahakyan, Mushegh & Kleive, Dyre [Vis alle 17 forfattere av denne artikkelen] (2026). Postpancreatectomy acute pancreatitis after distal pancreatectomy: tri-institutional international cohort. BJS Open. 10(4). doi: 10.1093/bjsopen/zrag069. Fulltekst i vitenarkiv
• Veshi, Laura; Ghotbi, Mohammad Jacob; Waage, Anne & Labori, Knut Jørgen (2026). Reoperation after pancreatoduodenectomy: indications, surgical approaches, outcomes, and temporal trends. HPB. ISSN 1365-182X. doi: 10.1016/j.hpb.2026.04.452. Fulltekst i vitenarkiv
• Amrutkar, Manoj; Vefferstad, Anette; Labori, Knut Jørgen; Verbeke, Caroline Sophie & Gladhaug, Ivar Prydz (2026). Proteomic characterization of primary pancreatic fibroblasts derived from neoadjuvant chemotherapy treated versus treatment-naïve PDAC. Journal of Proteomics. ISSN 1874-3919. 328. doi: 10.1016/j.jprot.2026.105660. Fulltekst i vitenarkiv
• Bonsdorff, Akseli; Wennerblom, Johanna; Wigmore, Stephen J.; Williamsson, Caroline; Kjeseth, Trond & Kirkegård, Jakob [Vis alle 28 forfattere av denne artikkelen] (2026). Comparing Hand-Sewn Closure to Stapler Closure for Pancreatic Stump Management in Left Pancreatectomy: A Retrospective International Multicenter Propensity Score-Matched Study. Journal of the American College of Surgeons. ISSN 1072-7515. 242(5), s. 1348–1358. doi: 10.1097/XCS.0000000000001724. Fulltekst i vitenarkiv Vis sammendrag

  Background: Postoperative pancreatic fistula (POPF) is the most important complication after left pancreatectomy. Superiority of hand-sewn closure or stapler closure of pancreatic stump in terms of short-term outcomes is not established. The aim of this study was to compare short-term surgical outcomes between the 2 modalities after left pancreatectomy. Study design: An international, multicenter, retrospective cohort study was conducted, including patients undergoing left pancreatectomy. Patients with multivisceral resection other than splenectomy were excluded. POPF, as defined by the International Study Group for Pancreatic Surgery, was the main outcome. Patients undergoing hand-sewn closure were matched to stapler patients in a 1:1 ratio using propensity score matching. Results: Altogether 2,183 patients were included, and 219 (10.0%) underwent hand-sewn closure. The overall POPF incidence was 470 (21.5%). In the matched cohort of 438 patients (219 per group), POPF incidence was significantly higher in the hand-sewn group (72 [32.9%] vs 46 |21.0%], p = 0.007). In addition, the reoperation rate was higher, and the length of hospital stay was longer in the hand-sewn group. These results were reproducible in most of the different subgroups defined by, for example, pancreatic thickness, duct diameter, and histology. Conclusions: Hand-sewn closure is associated with worse short-term outcomes, mainly increased POPF incidence, compared with stapler closure.

• Giuliani, Tommaso; Siriwardena, Ajith K.; Vollmer, Charles M.; Hilal, Mohammed Abu; Adham, Mustapha & Barreto, Savio George [Vis alle 43 forfattere av denne artikkelen] (2026). The International Study Group for Pancreatic Surgery (ISGPS) Definition and Classification of Postpancreatectomy Mortality. Annals of Surgery. ISSN 0003-4932. doi: 10.1097/SLA.0000000000007019. Fulltekst i vitenarkiv
• Holm, Maia Blomhoff; Dorg, Linda Trobe; Rootwelt-Revheim, Mona-Elisabeth; Labori, Knut Jørgen & Verbeke, Caroline Sophie (2026). Expression of glycolytic markers in cancer and stromal cells of treatment-naïve and neoadjuvantly treated pancreatic ductal adenocarcinoma. Virchows Archiv. ISSN 0945-6317. doi: 10.1007/s00428-026-04478-2. Fulltekst i vitenarkiv
• Amrutkar, Manoj; Guttorm, Sander Johannes Thorbjørnsen; Labori, Knut Jørgen; Rootwelt, Helge; Elgstøen, Katja B. Prestø & Gladhaug, Ivar Prydz [Vis alle 7 forfattere av denne artikkelen] (2026). Reduced lipid metabolite abundance in human pancreatic cancer and matched serum samples following neoadjuvant FOLFIRINOX treatment | Metabolomics | Springer Nature Link. Metabolomics. ISSN 1573-3882. 22. doi: 10.1007/s11306-025-02388-z. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Exploiting the full potential of neoadjuvant treatment (NAT) in pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of biomarkers for treatment response. Dysregulated lipid metabolism has been suggested to promote PDAC growth and resistance to therapy. Objectives To investigate lipid metabolic changes in PDAC following NAT. Methods Cross-sectional study of mass spectrometry-based global lipidomic profiling of tumour tissue (n = 35) and paired serum samples (n = 35) from treatment-naïve (TN; n = 18) and neoadjuvant FOLFIRINOX-treated (NAT; n = 17) PDAC patients was conducted. Pre- and post-treatment CA 19–9 levels were available from 15 NAT patients. Differentially abundant lipids (DALs) in NAT versus TN were assessed for correlation with various clinical parameters and the performance of all serum DALs to distinguish NAT from TN samples was explored using receiver operating characteristic analysis. Results A total of 40 tissue and 35 serum DALs were identified, which mainly belonged to glycerophospholipids and sphingolipids in tissue and glycerolipids, glycerophospholipids, and fatty acyls in serum. All 19 serum glycerolipids were less abundant in NAT and 18 of these were triacylglycerols. The abundance of 26 tissue and 11 serum DALs correlated moderately with % reduction in serum CA 19–9 following NAT. The top five of 23 serum DALs with moderate discriminatory potential (AUC = 0.66–0.87) ‒ PI(18:0_20:3), AcCa(13:0), PC(O-42:6), TG(49:6), TG(66:14), performed better together (AUC = 0.93 and 95% CI = 0.79‒1) and combined with CA 19–9 (AUC = 0.99 and 95% CI = 0.81‒1). Conclusions Both tumour tissue and serum samples from PDAC patients showed lower abundance of lipid metabolites following neoadjuvant FOLFIRINOX treatment. Moreover, a biomarker panel of CA 19–9 together with five serum DALs could potentially be used to assess NAT response in PDAC but requires further validation.

• Christiansen, Gyda G.; Farnes, Ingvild; Hjermstad, Marianne Jensen & Labori, Knut Jørgen (2025). Association between baseline quality of life and survival in patients with non-metastatic, advanced pancreatic cancer. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 61(1), s. 53–60. doi: 10.1080/00365521.2025.2585113. Fulltekst i vitenarkiv
• Stoop, Thomas F.; Wu, Y. H.Andrew; Oba, Atsushi; Ali, Mahsoem; Feld, Isabel M. & Al-Musawi, Mohammed H. [Vis alle 65 forfattere av denne artikkelen] (2025). Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study. British Journal of Cancer. ISSN 0007-0920. 133(1), s. 76–84. doi: 10.1038/s41416-025-03025-1. Fulltekst i vitenarkiv
• Ghotbi, Mohammad Jacob; Farnes, Ingvild & Labori, Knut Jørgen (2025). ASO Author Reflections: From BRPC to LAPC—Rethinking Resectability in Pancreatic Cancer. Annals of Surgical Oncology. ISSN 1068-9265. 32(12), s. 8919–8920. doi: 10.1245/s10434-025-17676-0. Fulltekst i vitenarkiv
• Bonsdorff, Akseli; Yu, William; Kirkegård, Jakob; Ponthaud, Charles de; Kjeseth, Trond & Ghorbani, Poya [Vis alle 29 forfattere av denne artikkelen] (2025). Classification of postoperative pancreatic fistula after left pancreatectomy: international multicentre cohort study. BJS Open. 9(6). doi: 10.1093/bjsopen/zraf149. Fulltekst i vitenarkiv Vis sammendrag

  Background: Postoperative pancreatic fistula (POPF) is a major complication after left pancreatectomy. The current International Study Group of Pancreatic Surgery classification has limitations, including heterogeneity in morbidity and high interobserver variability. This study aimed to assess POPF-related morbidity after left pancreatectomy and propose a refined classification system. Methods: Patients undergoing left pancreatectomy at nine high-volume centres between January 2010 and April 2023 were included. All postoperative treatments and interventions related to POPF were collected. The Comprehensive Complication Index (CCI) was used to assess total cumulative morbidity. The International Study Group of Pancreatic Surgery B POPF was subclassified (B1 = prolonged drainage, B2 = pharmacological intervention, B3 = percutaneous intervention, B4 = endoscopic or angiographic intervention). A new POPF grading system was developed by combining subclasses with similar morbidity. Results: Among 2284 patients, 497 (21.8%) had B (B1: 48 (2.1%), B2: 135 (5.9%), B3: 175 (7.7%), B4: 99 (4.3%)) or C (40 (1.8%)) POPF. Median (interquartile range) POPF-related CCI was 33.5 (22.6–39.7). A significant overlap existed between B and C POPF in terms of CCI. Median CCI (i.q.r.) increased with the B POPF subclasses (B1–B4), 8.7 (8.7-8.7) – 22.6 (20.9-22.6) – 33.5 (33.5-34.6) – 47.4 (39.7-52.1) (P < 0.001), but no difference between B4 POPF and C POPF was observed (median CCI 47.4 versus 50.2; P = 0.265). The refined POPF grading system consists of grades 0 (including biochemical leak and B1), A (including B2), B (including B3), and C (including B4 and C) reflecting worsening morbidity. Conclusion: The current International Study Group of Pancreatic Surgery classification includes highly heterogeneous grade B POPF cases, ranging from minimal to severe morbidity. The refined grading system improves classification and clinical relevance by aligning POPF severity with morbidity and short-term outcomes.

• Farnes, Ingvild; Verbeke, Caroline Sophie; Kleive, Dyre; Waage, Anne; Tholfsen, Tore & Hagen, Milada [Vis alle 9 forfattere av denne artikkelen] (2025). Surgical, Histopathological, and Quality of Life Outcomes Following Neoadjuvant Chemotherapy and Pancreatectomy for Borderline Resectable and Locally Advanced Pancreatic Cancer. Cancers. 17(15), s. 1–17. doi: 10.3390/cancers17152505. Fulltekst i vitenarkiv Vis sammendrag

  Background/Objectives: Treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer involves neoadjuvant chemotherapy followed by complex surgery, posing significant risks of toxicity, complications, and changes in quality of life (QoL). This study aims to investigate the impact of neoadjuvant chemotherapy followed by resection on overall survival (OS) and QoL. Methods: Consecutive patients with BRPC and LAPC included in a population-based study (NORPACT-2) from January 2018 to December 2020 were reviewed. Results: A total of 54 patients (BRPC; n = 43, LAPC; n = 11) underwent neoadjuvant chemotherapy followed by pancreatectomy. The majority (66.7%) received (m)FOLFIRINOX. Forty-six (85.2%) patients underwent pancreatoduodenectomy. Vascular resection was performed in 32 (59.3%) patients. Fourteen (25.9%) patients experienced major complications. The majority of the resected specimens demonstrated T2 (63%), N+ (79.6%), and R1 (85.2%) status. Median OS was 31 (CI 24.7–37.3) months. In multivariate analysis, only CAP 3 (p = 0.035) predicted worse survival. Forty (74.1%) patients experienced recurrence. Global QoL (p = 0.031), social and role functioning (p = 0.024, p = 0.031), improved three months after surgery. Pain (p = 0.042), dyspnea (p = 0.004), appetite loss (p = 0.028), and diarrhea (p = 0.007) improved post-resection. Conclusions: Patients with BRPC and LAPC undergoing neoadjuvant chemotherapy and resection have survival comparable to primary resectable pancreatic cancer. Postoperative morbidity was acceptable, and QoL recovered post-surgery. CAP grade was the only independent negative prognostic factor.

• Ghotbi, Mohammad Jacob; Farnes, Ingvild; Kleive, Dyre; Verbeke, Caroline Sophie; Issa-Epe, Aart Imran & Fosby, Bjarte [Vis alle 8 forfattere av denne artikkelen] (2025). Anatomical Classification and Staging Systems of Borderline Resectable and Locally Advanced Pancreatic Cancer—A Subgroup Analysis of the NORPACT-2 Trial. Annals of Surgical Oncology. ISSN 1068-9265. 32(12), s. 8856–8869. doi: 10.1245/s10434-025-17527-y. Fulltekst i vitenarkiv Vis sammendrag

  Background This study aims to provide a detailed understanding of resectability and prognosis within anatomical subgroups of borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) on the basis of established classification systems. Patients and Methods Patients with BRPC/LAPC, defined by National Comprehensive Cancer Network (NCCN) criteria, were prospectively included from 2018 to 2020. BRPC was subcategorized by vascular involvement and LAPC by the Louisville (Lv) classification system, and both cohorts were reclassified according to the Dutch (DPCG) criteria. NCCN-defined primary resectable pancreatic cancer (PC) cases that met DPCG-BRPC criteria were included in the analysis. Results In total, 228 patients (96 NCCN-BRPC, 92 NCCN-LAPC, and 40 reclassified from NNCN primary resectable PC to DPCG-BRPC) were included. NCCN-BRPC exhibiting both venous and arterial involvement had a lower resection rate (odds ratio (OR) 0.22, p = 0.038). Isolated vein involvement and baseline cancer antigen (CA)19–9 levels < 500 kU/L predicted resectability (OR 5.99, p = 0.005) and survival (hazard ratio (HR) 0.47, p = 0.024). DPCG-BRPC demonstrated higher resectability rates (67.4% versus 46.9%, p = 0.004) and fewer vascular resections (37% versus 58%, p = 0.031) compared with NCCN-BRPC. While the NCCN only predicted resectability, DPCG also predicted survival. No patients with Lv type IIIc2–4 (nonreconstructable invasion of the portomesenteric vein combined with arterial involvement) underwent resection, and this subgroup had worse survival (HR 2.08, p = 0.021). Conclusions Variations within established classification systems for BRPC/LAPC impact prediction of survival and resectability. A more detailed understanding of the anatomical subgroups in BRPC and LAPC, alongside CA19–9 levels, could enhance patient stratification regarding tumor resectability and neoadjuvant strategies.

• Rangelova, E.; Stoop, T.F.; Ramshorst, Ramshorst van; Ali, M.; Bodegraven, Bodegraven van & Javed, A.A. [Vis alle 188 forfattere av denne artikkelen] (2025). The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Annals of Oncology. ISSN 0923-7534. 36(5), s. 529–542. doi: 10.1016/j.annonc.2024.12.015. Fulltekst i vitenarkiv Vis sammendrag

  Background Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. Patients and methods This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. Results Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. Conclusions Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

• Stoop, Thomas F.; Sugawara, Toshitaka; Oba, Atsushi; Feld, Isabel M.; Roessel, Stijn Van & Veldhuisen, Eran Van [Vis alle 55 forfattere av denne artikkelen] (2025). Adjuvant Chemotherapy after Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX. JAMA Oncology. ISSN 2374-2437. 11(3), s. 276–287. doi: 10.1001/jamaoncol.2024.5917. Fulltekst i vitenarkiv
• Rompen, Ingmar F.; Stoop, Thomas F.; Roessel, Stijn van; Veldhuisen, Eran van; Janssen, Quisette P. & Alseidi, Adnan [Vis alle 45 forfattere av denne artikkelen] (2025). Validation of the PANAMA Score for Survival and Benefit of Adjuvant Therapy in Patients With Resected Pancreatic Cancer after Neoadjuvant FOLFIRINOX. Annals of Surgery. ISSN 0003-4932. 281(5), s. 852–860. doi: 10.1097/SLA.0000000000006650. Fulltekst i vitenarkiv Vis sammendrag

  Objective: To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA) score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX. Background: The PANAMA score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy. Methods: This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association. Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy. Results: Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. Discrimination in median overall survival (OS) was observed stratified by risk groups (48.5, 27.6, and 22.3 months, log-rank Plow-intermediate = 0.004, log-rank Pintermediate-high = 0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group [hazard ratio (HR): 1.50, 95% CI: 0.92–2.50], whereas improved OS was observed in the intermediate (HR: 0.58, 95% CI: 0.34–0.97) and high-risk groups (HR: 0.47, 95% CI: 0.24–0.94; P interaction = 0.008). Conclusions: The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available through pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefits associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS.

• Bonsdorff, Akseli; Kjeseth, Trond; Kirkegård, Jakob; Ponthaud, Charles de; Ghorbani, Poya & Wennerblom, Johanna [Vis alle 30 forfattere av denne artikkelen] (2025). International multicentre validation of the left pancreatectomy pancreatic fistula prediction models and development and validation of the combined DISPAIR-FRS prediction model. British Journal of Surgery. ISSN 0007-1323. 112(3). doi: 10.1093/bjs/znae313. Fulltekst i vitenarkiv Vis sammendrag

  Background: Every fifth patient undergoing left pancreatectomy develops a postoperative pancreatic fistula (POPF). Accurate POPF risk prediction could help. Two independent preoperative prediction models have been developed and externally validated: DISPAIR and D-FRS. The aim of this study was to validate, compare, and possibly update the models. Methods: Patients from nine high-volume pancreatic surgery centres (8 in Europe and 1 in North America) were included in this retrospective cohort study. Inclusion criteria were age over 18 years and open or minimally invasive left pancreatectomy since 2010. Model performance was assessed with discrimination (receiver operating characteristic (ROC) curves) and calibration (calibration plots). The updated model was developed with logistic regression and internally-externally validated. Results: Of 2284 patients included, 497 (21.8%) developed POPF. Both DISPAIR (area under the ROC curve (AUC) 0.62) and D-FRS (AUC 0.62) performed suboptimally, both in the pooled validation cohort combining every centre’s data and centre-wise. An updated model, named DISPAIR-FRS, was constructed by combining the most stable predictors from the existing models and incorporating other readily available patient demographics, such as age, sex, transection site, pancreatic thickness at the transection site, and main pancreatic duct diameter at the transection site. Internal-external validation demonstrated an AUC of 0.72, a calibration slope of 0.93, and an intercept of −0.02 for the updated model. Conclusion: The combined updated model of DISPAIR and D-FRS named DISPAIR-FRS demonstrated better performance and can be accessed at www.tinyurl.com/the-dispair-frs.

• Ghadimi, Michael; Pelzer, Uwe; Besselink, Marc G.; Siveke, Jens; Telgmann, Ralph & Braren, Rickmer [Vis alle 22 forfattere av denne artikkelen] (2025). Study protocol of the METAPANC trial - intensified treatment in patients with local operable but oligometastatic pancreatic cancer - multimodal surgical treatment versus chemotherapy alone: a randomized controlled trial. BMC Cancer. 25(1). doi: 10.1186/s12885-025-13573-7. Fulltekst i vitenarkiv
• Bonsdorff, Akseli; Kjeseth, Trond; Sahakyan, Mushegh; Kirkegård, Jakob; Ponthaud, Charles de & Ghorbani, Poya [Vis alle 28 forfattere av denne artikkelen] (2025). Impact of neoadjuvant therapy on short-term outcomes after left pancreatectomy: A propensity score-matched international multicenter study. Surgery. ISSN 0039-6060. 185. doi: 10.1016/j.surg.2025.109552. Fulltekst i vitenarkiv Vis sammendrag

  Background: Neoadjuvant therapy is protective of postoperative pancreatic fistula in pancreatoduodenectomy. However, the effect of neoadjuvant therapy after left pancreatectomy remains unclear. The aim of this international multicenter study was to evaluate the impact of neoadjuvant therapy on short term outcomes after left pancreatectomy for pancreatic ductal adenocarcinoma. Methods: Patients undergoing left pancreatectomy from January 2010 to April 2023 at 9 high-volume centers were included. Patients treated with neoadjuvant therapy were compared to patients with upfront surgery. Propensity score matching in 1:1 fashion was used. The primary outcome was postoperative pancreatic fistula. Results: Six-hundred-fifty patients underwent resection due to pancreatic ductal adenocarcinoma, of which 70 patients (10.8%) received neoadjuvant therapy. In the matched cohort (upfront surgery, 66 patients; neoadjuvant therapy, 66 patients), the rate of postoperative pancreatic fistula was similar in patients undergoing upfront surgery versus patients receiving neoadjuvant therapy (16 [24.2%] vs 13 [19.7%], P = .674, respectively). No statistically significant differences were observed between neoadjuvant therapy and upfront surgery group with respect to grade C-POPF, readmission, reoperation, postpancreatectomy hemorrhage, 90-day mortality, and severe complications. Conclusion: Neoadjuvant therapy was not associated with decreased rate of postoperative pancreatic fistula in patients undergoing left pancreatectomy.

• Braadland, Peder Rustøen; Farnes, Ingvild; Kure, Elin Wenche Hegland; Yaqub, Sheraz; McCann, Adrian & Ueland, Per Magne [Vis alle 8 forfattere av denne artikkelen] (2024). Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer. Frontiers in Oncology. 14. doi: 10.3389/fonc.2024.1488749. Fulltekst i vitenarkiv Vis sammendrag

  Background/Aims: It was recently reported that a higher concentration of the bacterially produced metabolite indole 3-acetate (3-IAA) in blood was linked to a better response to chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to extend these observations to patients diagnosed with non-metastatic PDAC. Method: We measured circulating 3-IAA in samples from a prospective population-based cohort of 124 patients with borderline resectable or locally advanced PDAC, collected before initiating neoadjuvant chemotherapy. The majority (61%) of the patients were treated with FOLFIRINOX. We used univariable and multivariable Cox proportional hazards regression to estimate the association between pre-treatment 3-IAA and overall survival. Results: The median serum 3-IAA concentration before chemotherapy was 290 (interquartile range 203–417) ng/mL. The unadjusted hazard ratio (HR) for pre-treatment log2(3-IAA) was 0.93, 95% confidence interval (CI) [0.74–1.16], p=0.52. When adjusting for age, ECOG, CA19-9 and tumor classification, the HR for log2(3-IAA) was 0.87, 95% CI [0.68–1.12], p=0.28. Conclusion: Our findings suggest that the potentiating effect of 3-IAA observed in metastatic PDAC undergoing chemotherapy may not translate to borderline resectable or locally advanced PDAC. We recommend additional clinical validation of 3-IAA’s predictive value in different categories of PDAC before implementation attempts in human studies are initiated.

• Perri, Giampaolo; Romandini, Elisa; Marchegiani, Giovanni; Ghorbani, Poya; Sahakyan, Mushegh & Holmberg, Marcus [Vis alle 17 forfattere av denne artikkelen] (2024). Postoperative Hyperamylasemia (POH) is an Early Predictor of Pancreatic Fistula Occurrence and Severity after Distal Pancreatectomy: Results from a European Multicentric Study. Annals of Surgery. ISSN 0003-4932. doi: 10.1097/SLA.0000000000006222. Fulltekst i vitenarkiv
• Amrutkar, Manoj; Guttorm, Sander; Vefferstad, Anette; Labori, Knut Jørgen; Eide, Lars & Rootwelt, Helge [Vis alle 9 forfattere av denne artikkelen] (2024). Global metabolomic profiling of tumor tissue and paired serum samples to identify biomarkers for response to neoadjuvant FOLFIRINOX treatment of human pancreatic cancer. Molecular Oncology. ISSN 1574-7891. 19(2), s. 391–411. doi: 10.1002/1878-0261.13759. Fulltekst i vitenarkiv Vis sammendrag

  Neoadjuvant chemotherapy (NAT) is increasingly used for the treatment of non-metastatic pancreatic ductal adenocarcinoma (PDAC) and is established as a standard of care for borderline resectable and locally advanced PDAC. However, full exploitation of its clinical benefits is limited by the lack of biomarkers that assess treatment response. To address this unmet need, global metabolomic profiling was performed on tumor tissue and paired serum samples from patients with treatment-naïve (TN; n = 18) and neoadjuvant leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX)-treated (NAT; n = 17) PDAC using liquid chromatography mass spectrometry. Differentially abundant metabolites (DAMs) in TN versus NAT groups were identified and their correlation with various clinical parameters was assessed. Metabolomics profiling identified 40 tissue and five serum DAMs in TN versus NAT PDAC. In general, DAMs associated with amino acid and nucleotide metabolism were lower in NAT compared to TN. Four DAMs—3-hydroxybutyric acid (BHB), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), glycochenodeoxycholate and citrulline—were common to both tissue and serum and showed a similar pattern of differential abundance in both groups. A strong positive correlation was observed between serum carbohydrate 19-9 antigen (CA 19-9) and tissue carnitines (C12, C18, C18:2) and N8-acetylspermidine. The reduction in CA 19-9 following NAT correlated negatively with serum deoxycholate levels, and the latter correlated positively with survival. This study revealed neoadjuvant-chemotherapy-induced changes in metabolic pathways in PDAC, mainly amino acid and nucleotide metabolism, and these correlated with reduced CA 19-9 following neoadjuvant FOLFIRINOX treatment.

• Bereska, Jacqueline; Zeeuw, Michiel; Wagenaar, Luuk; Jenssen, Håvard Bjørke; Wesdorp, Nina & Meulen, Delanie van der [Vis alle 50 forfattere av denne artikkelen] (2024). Development and external evaluation of a self-learning auto-segmentation model for Colorectal Cancer Liver Metastases Assessment (COALA). Insights into Imaging. 15(1). doi: 10.1186/s13244-024-01820-7. Fulltekst i vitenarkiv
• Stoop, Thomas F.; Oba, Atsushi; Wu, Y. H. Andrew; Beaty, Laurel E.; Colborn, Kathryn L. & Janssen, Boris V. [Vis alle 66 forfattere av denne artikkelen] (2024). Pathological Complete Response in Patients with Resected Pancreatic Adenocarcinoma after Preoperative Chemotherapy. JAMA Network Open. 7:e2417625(6), s. 1–19. doi: 10.1001/jamanetworkopen.2024.17625. Fulltekst i vitenarkiv Vis sammendrag

  Importance Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

• Yakub, Sheraz; Røsok, Bård Ingvald; Gladhaug, Ivar Prydz & Labori, Knut Jørgen (2024). Pancreatic duct occlusion with polychloroprene-based glue for the management of postoperative pancreatic fistula after pancreatoduodenectomy—an outdated approach? Frontiers in Surgery. 11. doi: 10.3389/fsurg.2024.1386708. Fulltekst i vitenarkiv Vis sammendrag

  Background: Managing postoperative pancreatic fistula (POPF) presents a formidable challenge after pancreatoduodenectomy. Some centers consider pancreatic duct occlusion (PDO) in reoperations following pancreatoduodenectomy as a pancreas-preserving procedure, aiming to control a severe POPF. The aim of the current study was to evaluate the short- and long-term outcomes of employing PDO for the management of the pancreatic stump during relaparotomy for POPF subsequent to pancreatoduodenectomy. Methods: Retrospective review of consecutive patients at Oslo University Hospital undergoing pancreatoduodenectomy and PDO during relaparotomy. Pancreatic stump management during relaparotomy consisted of occlusion of the main pancreatic duct with polychloroprene Faxan-Latex, after resecting the dehiscent jejunal loop previously constituting the pancreaticojejunostomy. Results: Between July 2005 and September 2015, 826 pancreatoduodenectomies were performed. Overall reoperation rate was 13.2% (n = 109). POPF grade B/C developed in 113 (13.7%) patients. PDO during relaparotomy was performed in 17 (2.1%) patients, whereas completion pancreatectomy was performed in 22 (2.7%) patients. Thirteen (76%) of the 17 patients had a persistent POPF after PDO, and the time from PDO until removal of the last abdominal drain was median 35 days. Of the PDO patients, 13 (76%) patients required further drainage procedures (n = 12) or an additional reoperation (n = 1). In-hospital mortality occurred in one patient (5.9%). Five (29%) patients developed new-onset diabetes mellitus, and 16 (94%) patients acquired exocrine pancreatic insufficiency. Conclusions: PDO is a safe and feasible approach for managing severe POPF during reoperation following pancreatoduodenectomy. A significant proportion of patients experience persistent POPF post-procedure, necessitating supplementary drainage interventions. The findings suggest that it is advisable to explore alternative pancreas-preserving methods before opting for PDO in the management of POPF subsequent to pancreatoduodenectomy.

• Labori, Knut Jørgen; Bratlie, Svein Olav; Andersson, Bodil; Angelsen, Jon-Helge; Biörserud, Christina & Björnsson, Bergthor [Vis alle 35 forfattere av denne artikkelen] (2024). Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 9(3), s. 205–217. doi: 10.1016/S2468-1253(23)00405-3. Fulltekst i vitenarkiv Vis sammendrag

  Background In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. Methods NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing. Findings Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49–71) in the neoadjuvant FOLFIRINOX group versus 73% (62–84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2–34·9) versus 38·5 months (27·6–not reached; hazard ratio [HR] 1·52 [95% CI 1·00–2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46–67) in the neoadjuvant FOLFIRINOX group versus 70% (55–83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2–34·9) versus 34·4 months (19·4–not reached; HR 1·46 [95% CI 0·99–2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event. Interpretation This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven.

• Waage, Anne; Khan, Ammar; Labori, Knut Jørgen; Birkeland, Kåre Inge; Scholz, Hanne & Jenssen, Trond [Vis alle 9 forfattere av denne artikkelen] (2024). Implementation of a nationwide program for total pancreatectomy and islet autotransplantation in chronic pancreatitis: A Scandinavian single-center observational study. Scandinavian Journal of Surgery. ISSN 1457-4969. doi: 10.1177/14574969241298985. Fulltekst i vitenarkiv
• Farnes, Ingvild; Lund-Iversen, Marius; Aabakken, Lars; Verbeke, Caroline Sophie & Labori, Knut Jørgen (2024). Molecular testing for personalized therapy is underutilized in patients with borderline resectable and locally advanced pancreatic cancer–real world data from the NORPACT-2 study. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 59(9), s. 1093–1096. doi: 10.1080/00365521.2024.2373115. Fulltekst i vitenarkiv Vis sammendrag

  Background International guidelines currently recommend the use of molecular testing in patients with advanced pancreatic cancer. The rate of actionable molecular alterations is low. The utility of molecular testing in patients with borderline resectable (BRPC) or locally advanced (LAPC) pancreatic cancer in real world clinical practice is unclear. Methods 188 consecutive patients included in a prospective, population-based study (NORPACT-2) in patients with BRPC and LAPC (2018–2020) were reviewed. Molecular testing was performed at the discretion of the treating oncologist and was not recommended as a routine investigation by the national guidelines. All patients were considered fit to undergo primary chemotherapy and potential surgical resection. The frequency and the results of molecular testing (microsatellite instability (MSI) and/or KRAS status) were assessed. Results Thirty patients (16%) underwent molecular testing. MSI tumour was detected in one (3.6%) of 28 tested patients. The patient received immunotherapy and subsequently underwent surgical resection. Histological assessment of the resected specimen revealed a complete response. KRAS wild type was detected in one (14.3%) of seven tested patient. Patients who initiated FOLFIRINOX as the primary chemotherapy regimen (p = 0.022), or were being treated at one of the eight hospital trusts (p = 0.001) were more likely to undergo molecular testing. Conclusions Molecular testing was rarely performed in patients with BRPC or LAPC. Routine molecular testing for all patients with BRPC and LAPC should be considered to increase identification of targetable mutations and improve outcomes.

• Ansari, Daniel; Søreide, Kjetil; Andersson, Bodil; Hansen, Carsten Palnæs; Seppänen, Hanna & Sparrelid, Ernesto [Vis alle 22 forfattere av denne artikkelen] (2024). Surveillance after surgery for pancreatic cancer: a global scoping review of guidelines and a nordic Survey of contemporary practice. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 59(9), s. 1097–1104. doi: 10.1080/00365521.2024.2378948. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. ‍This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. Materials and Methods A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. Results Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. Conclusion Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.

• Farnes, Ingvild; Kleive, Dyre; Verbeke, Caroline Sophie; Aabakken, Lars; Issa-Epe, Aart Imran & Småstuen, Milada Cvancarova [Vis alle 10 forfattere av denne artikkelen] (2023). Resection rates and intention-to-treat outcomes in borderline and locally advanced pancreatic cancer: real-world data from a population-based, prospective cohort study (NORPACT-2). BJS Open. 7:zrad137(6), s. 1–10. doi: 10.1093/bjsopen/zrad137. Fulltekst i vitenarkiv Vis sammendrag

  Background: Systemic chemotherapy is the initial treatment strategy for borderline resectable and locally advanced pancreatic cancer to facilitate curative resection. The aim of this study was to investigate the resection rates and overall survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer. Methods: Consecutive patients with borderline resectable pancreatic cancer/locally advanced pancreatic cancer discussed by Oslo University Hospital multidisciplinary team between 2018 and 2020, serving a population of 3.1 million within a geographically defined area in south-eastern Norway, were included in this prospective Norwegian Pancreatic Cancer Trial-2 study, according to intention-to-treat principles. The total number of patients with pancreatic cancer was sought from the Cancer Registry of Norway. Results: A total of 1178 patients were diagnosed with pancreatic cancer, of whom 618 were referred to Oslo University Hospital. After multidisciplinary team evaluation, 230 patients were considered to have borderline resectable pancreatic cancer/locally advanced pancreatic cancer. The final study group consisted of 188 patients (borderline resectable pancreatic cancer n = 96, locally advanced pancreatic cancer n = 92) who were fit to receive primary chemotherapy. Resection rates were 46.9% (45 of 96) for borderline resectable pancreatic cancer and 13% (12 of 92) for locally advanced pancreatic cancer (P <0.001). Median overall survival was 14.6 months (borderline resectable pancreatic cancer 16.4 months; locally advanced pancreatic cancer 13.7 months, (P = 0.2)). Adjusted for immortal time bias, median overall survival for patients undergoing resection versus only chemotherapy was 24.4 months versus 10.1 months (P <0.001) for borderline resectable pancreatic cancer and 28.4 months versus 12.6 months for locally advanced pancreatic cancer (P = 0.001). Conclusion: Resection rates and survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer treated at a high-volume centre in a universal healthcare system compare well with those treated at international expert centres.

• Khan, Ammar; Fosby, Bjarte; Labori, Knut Jørgen; Lanari, Jacopo; Dorenberg, Eric & Line, Pål Dag (2023). Management of Coeliac and Hepatic Artery Aneurysms: A Single Institution Experience of 84 Cases. European Journal of Vascular and Endovascular Surgery. ISSN 1078-5884. 66(6), s. 814–820. doi: 10.1016/j.ejvs.2023.09.032. Fulltekst i vitenarkiv Vis sammendrag

  Objective To report outcomes following open or endovascular treatment of true hepatic and coeliac artery aneurysms at a single referral centre. Methods This was a retrospective cohort study of consecutive patients treated for true hepatic and coeliac artery aneurysms between May 2002 and December 2021. Outcome measures included complications, graft patency, and survival rate. Results Overall, 84 patients were included with a median age of 63 years (interquartile range 55, 79). The majority (76%) of the patients were men. Frequent comorbidities included a history of tobacco (69%), hypertension (65%), hyperlipidaemia (32%), and diabetes (15%). Multiple synchronous aneurysms were detected in 22 patients (26%). There were 33 (39%) symptomatic aneurysms (abdominal pain without rupture [n = 18], rupture [n = 10], and sepsis [n = 5]). Seventeen patients (20%) had mycotic aetiology. Fifty patients (60%) underwent endovascular treatment with either covered stent placement (n = 29) or coil embolisation (n = 21), and 34 patients (40%) were treated with open surgery using allogenic iliac artery (n = 15), autologous saphenous vein (n = 15), GoreTex graft (n = 2), or ligation (n = 2). The complication rate was 32% in the open group and 18% in the endovascular group (p = .048). The overall 90 day post-operative mortality rate was 1.2%, five year primary patency was 90.0%, five year survival rate was 81.2%, and mean follow up was 6.9 ± 4.2 years. Conclusion Endovascular treatment is the preferred approach whenever technically possible. Despite higher post-operative morbidity, an open approach with vascular reconstruction using autologous or allogenic vascular grafts yields acceptable long term results.

• Farnes, Ingvild; Paulsen, Vemund; Verbeke, Caroline Sophie; Tønnesen, Christer Julseth; Aabakken, Lars & Labori, Knut Jørgen (2023). Performance and safety of diagnostic EUS FNA/FNB and therapeutic ERCP in patients with borderline resectable and locally advanced pancreatic cancer - results from a population-based, prospective cohort study. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 59(4), s. 496–502. doi: 10.1080/00365521.2023.2290456. Fulltekst i vitenarkiv Vis sammendrag

  Objective: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS FNA/FNB) and potential endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression are indicated in patients with pancreatic cancer before initation of primary chemotherapy. This study aims to investigate the performance and safety of these two procedures in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). Methods: Endoscopy and pathology reports, and hospital records of consecutive patients with a radiological diagnosis of BRPC/LAPC included in a population based, protocol-driven study (NORPACT-2) were reviewed. Results: Of 251 patients, 223 (88.9%) underwent EUS-FNA/FNB, and 133 (53%) underwent ERCP. Repeated EUS attempts were performed in 33 (14.8%), eight (3.6%), and four (1.8%) patients. FNA was performed in 155 procedures, FNB in 30, and combined EUS-FNA/FNB in 83. Diagnostic accuracy was 86.1% for first EUS-FNA/FNB. The cumulative diagnostic accuracy for all attempts was 96%. False positive rate for malignancy was 0.9%. Of a total of 149 ERCP procedures, 122 (81.9%) were successful, and 27 (18.1%) were unsuccessful. Success rate of first ERCP attempt was 80.5% (107/133). Sixteen patients (12%) underwent a second attempt with a success rate of 93.8% (15 of 16). Combined EUS and ERCP was performed in 41 patients. Complications occurred in eight procedures (3%) after EUS-FNA/FNB, 23 procedures (15.3%) after ERCP, and four (9.8%) patients after combined EUS-FNA/FNB and ERCP. Conclusion: EUS-FNA/FNB and ERCP with biliary stenting in patients with BRPC/LAPC demonstrated acceptable performance and safety. Repeat procedures were performed with high success rates. Same session EUS-FNA/FNB and ERCP for biliary decompression is safe.

• Yakub, Sheraz; Tholfsen, Tore; Waage, Anne; Kleive, Dyre & Labori, Knut Jørgen (2023). Pancreatoduodenectomy after Roux-en-Y gastric bypass surgery: Single-center experience and literature review. Scandinavian Journal of Surgery. ISSN 1457-4969. 112, s. 98–104. doi: 10.1177/14574969231156350. Fulltekst i vitenarkiv Vis sammendrag

  Background and objective: Bariatric surgery with Roux-en-Y gastric bypass (RYGB) is widely used to treat morbid obesity and present diagnostic and therapeutic challenges in patients with pancreatic and periampullary tumors. The aim of this study was to describe diagnostic tools and challenges in performing pancreatoduodenectomy (PD) on patients with altered anatomy after RYGB. Methods: Patients undergoing PD after RYGB from April 2015 to June 2022 at a tertiary referral center were identified. Preoperative workup, operative techniques, and outcomes were reviewed. A literature search was performed to identify articles reporting PD in post-RYGB patients. Results: Of a total of 788 PDs, six patients had previous RYGB. The majority were women (n = 5), and median age was 59 years. The patients most commonly presented with pain (50%) and jaundice (50%) with a median of 5.5 years after RYGB. The gastric remnant was resected in all cases, and reconstruction of the pancreatobiliary drainage was achieved using the distal part of the pre-existing pancreatobiliary limb in all patients. Median follow-up was 60 months. The Clavien–Dindo grade ⩾3 complications occurred in two patients (33.3%), and 90 days mortality occurred in one patient (16.6%). The literature search revealed 9 articles reporting a total of 122 cases, specifically addressing PD after RYGB. Conclusions: Reconstruction after PD in post-RYGB patients may be challenging. Resection of the gastric remnant and use of the pre-existing biliopancreatic limb may be a safe strategy, but surgeons should be prepared for other reconstruction options for creation of a new pancreatobiliary limb.

• Amrutkar, Manoj; Verbeke, Caroline Sophie; Vefferstad, Anette; Dorg, Linda Trobe; Labori, Knut Jørgen & Gladhaug, Ivar Prydz (2022). Neoadjuvant chemotherapy is associated with an altered metabolic profile and increased cancer stemness in patients with pancreatic ductal adenocarcinoma. Molecular Oncology. ISSN 1574-7891. 17(1), s. 59–81. doi: 10.1002/1878-0261.13344. Fulltekst i vitenarkiv Vis sammendrag

  he modest clinical benefits of neoadjuvant chemotherapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) are associated with a lack of robust data on treatment-induced changes in the tumor. To this end, comparative proteomic profiling of tumor tissue samples from treatment-naïve (TN, n = 20) and NAT-treated (n = 22) PDACs was performed. Differentially expressed proteins were identified and correlation with overall survival (OS) was performed. Tumors were also examined for histopathological changes and expression of cancer stem cell (CSC) markers. Serum from 33 matched patients was analyzed for metabolic markers. Cytotoxicity, proliferation, and expression of CSC markers were assessed in chemoresistant Panc-1 and Mia PaCa-2 cells. Of the 2265 proteins identified, 227 and 144 proteins showed significantly altered expression and differential phosphorylation, respectively, in NAT compared with TN samples. The majority of these were metabolism-related proteins, and 14 of these correlated moderately with OS. NAT-treated tumors and chemoresistant cancer cells showed increased expression of CSC markers. Serum ALDH1A1 was higher in NAT compared with TN. Differentially phosphorylated proteins were mainly involved in cytoskeleton organization, cell locomotion, motility, and migration, and 17 of these showed a strong positive correlation with OS. This study provides evidence of the effects of NAT on PDAC metabolism at both the tumor and the systemic levels. NAT-treated tumors showed significantly lower expression of metabolic proteins, and patients who underwent NAT showed reduced serum lactate and high-density lipoprotein-cholesterol. Lastly, cancer cells that survived cytotoxic treatment expressed higher CSC markers, both in vivo and in vitro.

• Silwal-Pandit, Laxmi; Stålberg, Stina Margrethe; Johansson, Henrik J.; Mermelekas, Georgios; Lothe, Inger Marie Bowitz & Skrede, Martina Landschoof [Vis alle 14 forfattere av denne artikkelen] (2022). Proteome Analysis of Pancreatic Tumors Implicates Extracellular Matrix in Patient Outcome. Cancer Research Communications. 2(6), s. 434–446. doi: 10.1158/2767-9764.CRC-21-0100. Fulltekst i vitenarkiv Vis sammendrag

  Pancreatic cancer remains a disease with unmet clinical needs and inadequate diagnostic, prognostic, and predictive biomarkers. In-depth characterization of the disease proteome is limited. This study thus aims to define and describe protein networks underlying pancreatic cancer and identify protein centric subtypes with clinical relevance. Mass spectrometry–based proteomics was used to identify and quantify the proteome in tumor tissue, tumor-adjacent tissue, and patient-derived xenografts (PDX)-derived cell lines from patients with pancreatic cancer, and tissues from patients with chronic pancreatitis. We identified, quantified, and characterized 11,634 proteins from 72 pancreatic tissue samples. Network focused analysis of the proteomics data led to identification of a tumor epithelium–specific module and an extracellular matrix (ECM)-associated module that discriminated pancreatic tumor tissue from both tumor adjacent tissue and pancreatitis tissue. On the basis of the ECM module, we defined an ECM-high and an ECM-low subgroup, where the ECM-high subgroup was associated with poor prognosis (median survival months: 15.3 vs. 22.9 months; log-rank test, P = 0.02). The ECM-high tumors were characterized by elevated epithelial–mesenchymal transition and glycolytic activities, and low oxidative phosphorylation, E2F, and DNA repair pathway activities. This study offers novel insights into the protein network underlying pancreatic cancer opening up for proteome precision medicine development. Significance: Pancreatic cancer lacks reliable biomarkers for prognostication and treatment of patients. We analyzed the proteome of pancreatic tumors, nonmalignant tissues of the pancreas and PDX-derived cell lines, and identified proteins that discriminate between patients with good and poor survival. The proteomics data also unraveled potential novel drug targets.

• Latenstein, Anouk E.J.; Scholten, Lianne; Al-Saffar, Hasan Ahmad; Björnsson, Bergthor; Butturini, Giovanni & Capretti, Giovanni [Vis alle 36 forfattere av denne artikkelen] (2022). Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study. Annals of Surgery. ISSN 0003-4932. 276(5), s. E536–E543. doi: 10.1097/SLA.0000000000004551. Fulltekst i vitenarkiv
• Veldhuisen, Eran van; Klompmaker, Sjors; Janssen, Quisette P.; Hilal, Mohammed Abu; Alseidi, Adnan & Balduzzi, Alberto [Vis alle 42 forfattere av denne artikkelen] (2022). Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study. Annals of Surgical Oncology. ISSN 1068-9265. doi: 10.1245/s10434-022-12387-2. Fulltekst i vitenarkiv
• Ghotbi, Jacob; Sahakyan, Mushegh; Søreide, Kjetil; Fretland, Åsmund Avdem; Røsok, Bård Ingvald & Tholfsen, Tore [Vis alle 11 forfattere av denne artikkelen] (2022). Minimally Invasive Pancreatoduodenectomy: Contemporary Practice, Evidence, and Knowledge Gaps. Oncology and Therapy. ISSN 2366-1070. 10(2). doi: 10.1007/s40487-022-00203-6. Fulltekst i vitenarkiv Vis sammendrag

  Minimally invasive pancreatoduodenectomy has gained popularity throughout the last decade. For laparoscopic pancreatoduodenectomy, some high-level evidence exists, but with conflicting results. There are currently no published randomized controlled trials comparing robotic and open pancreatoduodenectomy. Comparative long-term data for patients with pancreatic ductal adenocarcinoma is lacking to date. Based on the existing evidence, current observed benefits of minimally invasive pancreatoduodenectomy over open pancreatoduodenectomy seem scarce, but retrospective data indicate the safety of these procedures in selected patients. As familiarity with the robotic platform increases, studies have shown an expansion in indications, also including patients with vascular involvement and even indicating favorable results in patients with obesity and high-risk morphometric features. Several ongoing randomized controlled trials aim to investigate potential differences in short- and long-term outcomes between minimally invasive and open pancreatoduodenectomy. Their results are much awaited.

• Waage, Anne; Holmquist, Olof Dan Sebastian; Labori, Knut Jørgen; Paulsen, Vemund; Lenz, Harald & Aabakken, Lars [Vis alle 9 forfattere av denne artikkelen] (2022). Tailored surgery in chronic pancreatitis after implementation of a multidisciplinary team assessment; a prospective observational study. HPB. ISSN 1365-182X. 24(12). doi: 10.1016/j.hpb.2022.09.007. Fulltekst i vitenarkiv Vis sammendrag

  Introduction - Optimal management of chronic pancreatitis involves several specialties. Selection of patients for surgery may benefit from evaluation by a multidisciplinary team (MDT), similar to cancer care. The aim of this study was to evaluate outcomes in patients selected for surgery after MDT decision. Methods - A prospective, observational study of consecutive patients operated for pain due to chronic pancreatitis after implementation of a MDT. The main outcome was Quality of life (QoL) assessed by EORTC-QLQ C30 and pain relief in patients followed >3 months. Complications were registered and predictive factors for pain relief analyzed. Results - Of 269 patients evaluated by the MDT, 60 (22%) underwent surgery. Postoperative surgical complications occurred in five patients (8.3%) and reoperation within 30 days in two. There was no 90-days mortality. Complete or partial pain relief was achieved in 44 of 50 patients followed >3 months (88%). Preoperative duration of pain predicted lower probability of success. Postoperative improvement in QoL was most prominent for pain, appetite and nausea. Conclusions - After MDT evaluation, one in five patients was selected for surgery. Pain relief was obtained in a majority of patients with improved QoL. A tailored approach through a MDT seems warranted and efficient.

• Yaqub, Sheraz; Jensenius, Mogens; Heieren, Ole E. B.; Drolsum, Anders; Pettersen, Frank O. & Labori, Knut Jørgen (2022). Echinococcosis in a non-endemic country–20-years’ surgical experience from a Norwegian tertiary referral Centre. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 57(8), s. 953–957. doi: 10.1080/00365521.2022.2046846. Fulltekst i vitenarkiv Vis sammendrag

  Background In Scandinavia, the incidence of cystic echinococcosis (CE) and alveolar echinococcosis (AE) is low and almost exclusively an imported disease following the trends of immigration. The aim of the study was to review available data on clinical management and outcome for patients treated at Oslo University Hospital, a referral centre for echinococcosis in Norway, with special emphasis on surgical treatment. Methods All patients admitted with echinococcosis between January 2000 and December 2020 were identified. Medical records were reviewed retrospectively concerning patient demographics, treatment strategy, surgical procedures, complications and outcomes. Results A total of 92 patients with median age 37 years (range 4-85) were identified. Sixty-eight patients (74%) were symptomatic. All patients, except for two, were immigrants to Norway and born in endemic areas. Ninety patients were diagnosed with CE and two with AE. Location of the cysts was most commonly in the liver (86%) followed by peritoneum, lungs, and spleen. All patients with active cysts were treated with albendazole. Surgical treatment was performed in 51 (56%) patients. The most common reason for abstaining from surgical treatment was that the diagnostic work-up revealed inactive cysts or interventional radiology was performed. Of the 51 patients who underwent surgery, a radical procedure was performed in 32 (64%) cases, a conservative procedure in 12 (24%), and a combination in six (12%). Clavien Dindo grade ≥3 complications occurred in 30%, and 90-day mortality was 2%. Bile leakage occurred in seven patients and was treated successfully with endoscopic retrograde cholangiopancreatography with biliary stent placement in all patients. Conclusion In a low-endemic area like Norway, management of echinococcus includes medical therapy, surgery, and/or interventional radiology. Surgical intervention seems to be effective, and is associated with acceptable morbidity rates.

• Hugenschmidt, Harald; Labori, Knut Jørgen; Borgen, Elin; Brunborg, Cathrine; Schirmer, Cecilie & Seeberg, Lars Thomas [Vis alle 8 forfattere av denne artikkelen] (2021). Preoperative CTC-Detection by CellSearch ® Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer. Cancers. 13(3). doi: 10.3390/cancers13030485. Fulltekst i vitenarkiv Vis sammendrag

  n patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5–10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future

• Sahakyan, Mushegh A.; Verbeke, Caroline S.; Tholfsen, Tore; Ignjatovic, Dejan; Kleive, Dyre & Buanes, Trond [Vis alle 10 forfattere av denne artikkelen] (2021). Prognostic Impact of Resection Margin Status in Distal Pancreatectomy for Ductal Adenocarcinoma. Annals of Surgical Oncology. ISSN 1068-9265. 29, s. 366–375. doi: 10.1245/s10434-021-10464-6. Fulltekst i vitenarkiv Vis sammendrag

  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.<p> <p>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 B1 mm clearance.<p> <p>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.<p> <p>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.

• Grut, Harald; Line, Pål Dag; Labori, Knut Jørgen; Schulz, Anselm & Dueland, Svein (2021). Survival after liver resection and liver transplantation for colorectal liver metastases: a comparative analysis stratified by metabolic tumor volume assessed by 18F-FDG PET/CT. HPB. ISSN 1365-182X. doi: 10.1016/j.hpb.2021.11.015. Fulltekst i vitenarkiv
• Labori, Knut Jørgen; Tholfsen, Tore; Yaqub, Sheraz; Lassen, Kristoffer; Kleive, Dyre & Waage, Anne (2021). Gastro- or Duodenojejunostomy Leaks After Pancreatoduodenectomy: Single Center Experience and Narrative Literature Review. Journal of Gastrointestinal Surgery. ISSN 1091-255X. s. 1–7. doi: 10.1007/s11605-021-05058-2. Fulltekst i vitenarkiv Vis sammendrag

  <i>Background and Methods</i> - 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.<br><br> <i>Results</i> - 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.<br><br> <i>Conclusion</i> - 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.

• Sahakyan, Mushegh; Røsok, Bård Ingvald; Tholfsen, Tore; Kleive, Dyre; Waage, Anne & Ignjatovic, Dejan [Vis alle 9 forfattere av denne artikkelen] (2021). Implementation and training with laparoscopic distal pancreatectomy: 23-year experience from a high-volume center. Surgical Endoscopy. ISSN 0930-2794. s. 1–12. doi: 10.1007/s00464-021-08306-3. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Distal pancreatectomy is the most common procedure in minimally-invasive pancreatic surgery. Data in the literature suggest that the learning curve flattens after performing up to 30 procedures. However, the exact number remains unclear. Methods The implementation and training with laparoscopic distal pancreatectomy (LDP) in a high-volume center were studied between 1997 and 2020. Perioperative outcomes and factors related to conversion were assessed. The individual experiences of four different surgeons (pioneer and adopters) performing LDP on a regular basis were examined. Results Six hundred forty LDPs were done accounting for 95% of all distal pancreatectomies performed throughout the study period. Conversion was needed in 14 (2.2%) patients due to intraoperative bleeding or tumor adherence to the major vasculature. Overall morbidity and mortality rates were 35 and 0.6%, respectively. Intra- and postoperative outcomes did not change for any of the surgeons within their first 40 cases. Operative time significantly decreased after the first 80 cases for the pioneer surgeon and did not change afterwards although the proportion of ductal adenocarcinoma increased. Tumor size increased after the first 80 cases for the first adopter without affecting the operative time. Conclusions In this nearly unselected cohort, no significant changes in surgical outcomes were observed throughout the first 40 LDPs for different surgeons. The exact number of procedures required to overcome the learning curve is difficult to determine as it seems to depend on patient selection policy and specifics of surgical training at the corresponding center.

• Lindholm, Espen; Bergmann, Gisli Björn; Haugaa, Håkon; Labori, Knut Jørgen; Yaqub, Sheraz & Bjørnbeth, Bjørn Atle [Vis alle 11 forfattere av denne artikkelen] (2021). Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study. HPB. ISSN 1365-182X. 24(6), s. 901–909. doi: 10.1016/j.hpb.2021.10.020. Fulltekst i vitenarkiv Vis sammendrag

  Background Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. Methods Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2–4 h thereafter. Results Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P < 0.01) in the microdialysate already in the first postoperative samples. Glycerol concentrations >400 μmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. Conclusion High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).

• Yaqub, Sheraz; Bjørnbeth, Bjørn Atle; Angelsen, Jon-Helge; Fristrup, Claus W.; Grønbech, Jon Erik & Hemmingsson, Oskar [Vis alle 29 forfattere av denne artikkelen] (2021). Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial. Trials. 22(1). doi: 10.1186/s13063-021-05587-w. Fulltekst i vitenarkiv Vis sammendrag

  Background: Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver. Methods: The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines. Discussion: The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness. Trial registration: ClinicalTrials.gov NCT03326791. Registered on 31 October 2017.

• Khan, Ammar; Kleive, Dyre; Aandahl, Einar Martin; Fosby, Bjarte; Line, Pål Dag & Dorenberg, Eric Jürgen [Vis alle 8 forfattere av denne artikkelen] (2020). Portal vein stent placement after hepatobiliary and pancreatic surgery. Langenbeck's Archives of Surgery. ISSN 1435-2443. 405, s. 657–664. doi: 10.1007/s00423-020-01917-9. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To evaluate the long-term outcomes of percutaneous transhepatic stent placement for portal vein (PV) stenosis after liver transplantation (LT) and hepato-pancreato-biliary (HPB) surgery. Methods Retrospective study of 455 patients who underwent LT and 522 patients who underwent resection of the pancreatic head between June 2011 and February 2016. Technical success, clinical success, patency, and complications were evaluated for both groups. Results A total of 23 patients were confirmed to have postoperative PV stenosis and were treated with percutaneous transhepatic PV stent placement. The technical success rate was 100%, the clinical success rate was 80%, and the long-term stent patency was 91.3% for the entire study population. Two procedure-related hemorrhages and two early stent thromboses occurred in the HPB group while no complications occurred in the LT group. A literature review of selected studies reporting PV stent placement for the treatment of PV stenosis after HPB surgery and LT showed a technical success rate of 78–100%, a clinical success rate of 72–100%, and a long-term patency of 57–100%, whereas the procedure-related complication rate varied from 0–33.3%. Conclusions Percutaneous transhepatic PV stent is a safe and effective treatment for postoperative PV stenosis/occlusion in patients undergoing LT regardless of symptoms. Due to increased risk of complications, the indication for percutaneous PV stent placement after HPB surgery should be limited to patients with clinical symptoms after an individual assessment.

• Nymo, Linn Såve; Kleive, Dyre; Waardal, Kim; Bringeland, Erling Audun; Søreide, Jon Arne & Labori, Knut Jørgen [Vis alle 9 forfattere av denne artikkelen] (2020). Centralizing a national pancreatoduodenectomy service: striking the right balance. BJS Open. 4(5), s. 904–913. doi: 10.1002/bjs5.50342. Fulltekst i vitenarkiv Vis sammendrag

  Background Centralization of pancreatic surgery is currently called for owing to superior outcomes in higher‐volume centres. Conversely, organizational and patient concerns speak for a moderation in centralization. Consensus on the optimal balance has not yet been reached. This observational study presents a volume–outcome analysis of a complete national cohort in a health system with long‐standing centralization. Methods Data for all pancreatoduodenectomies in Norway in 2015 and 2016 were identified through a national quality registry and completed through electronic patient journals. Hospitals were dichotomized (high‐volume (40 or more procedures/year) or medium–low‐volume). Results Some 394 procedures were performed (201 in high‐volume and 193 in medium–low‐volume units). Major postoperative complications occurred in 125 patients (31·7 per cent). A clinically relevant postoperative pancreatic fistula occurred in 66 patients (16·8 per cent). Some 17 patients (4·3 per cent) died within 90 days, and the failure‐to‐rescue rate was 13·6 per cent (17 of 125 patients). In multivariable comparison with the high‐volume centre, medium–low‐volume units had similar overall complication rates, lower 90‐day mortality (odds ratio 0·24, 95 per cent c.i. 0·07 to 0·82) and no tendency for a higher failure‐to‐rescue rate. Conclusion Centralization beyond medium volume will probably not improve on 90‐day mortality or failure‐to‐rescue rates after pancreatoduodenectomy.

• Labori, Knut Jørgen; Kleive, Dyre; Khan, Ammar; Farnes, Ingvild; Fosby, Bjarte & Line, Pål Dag (2020). Graft type for superior mesenteric and portal vein reconstruction in pancreatic surgery – A systematic review. HPB. ISSN 1365-182X. s. 1–12. doi: 10.1016/j.hpb.2020.11.008. Fulltekst i vitenarkiv Vis sammendrag

  Background Contemporary practice for superior mesenteric/portal vein (SMV-PV) reconstruction during pancreatectomy with vein resection involves biological (autograft, allograft, xenograft) or synthetic grafts as a conduit or patch. The aim of this study was to systematically review the safety and feasibility of the different grafts used for SMV-PV reconstruction. Methods A systematic search was performed in PubMed and Embase according to the PRISMA guidelines (January 2000–March 2020). Studies reporting on ≥ 5 patients undergoing reconstruction of the SMV-PV with grafts during pancreatectomy were included. Primary outcome was rate of graft thrombosis. Results Thirty-four studies with 603 patients were included. Four graft types were identified (autologous vein, autologous parietal peritoneum/falciform ligament, allogeneic cadaveric vein/artery, synthetic grafts). Early and overall graft thrombosis rate was 7.5% and 22.2% for synthetic graft, 5.6% and 11.7% for autologous vein graft, 6.7% and 8.9% for autologous parietal peritoneum/falciform ligament, and 2.5% and 6.2% for allograft. Donor site complications were reported for harvesting of the femoral, saphenous, and external iliac vein. No cases of graft infection were reported for synthetic grafts. Conclusion In selected patients, autologous, allogenic or synthetic grafts for SMV-PV reconstruction are safe and feasible. Synthetic grafts seems to have a higher incidence of graft thrombosis.

• Grut, Harald; Stern, Nadide; Dueland, Svein; Labori, Knut Jørgen; Dormagen, Johann Baptist & Schulz, Anselm (2020). Preoperative Preoperative 18F-FDG PET/computed tomography predicts survival following resection for colorectal liver metastases. Nuclear medicine communications. ISSN 0143-3636. 41(9), s. 916–923. doi: 10.1097/MNM.0000000000001235. Fulltekst i vitenarkiv
• Hugenschmidt, Harald; Labori, Knut Jørgen; Brunborg, Cathrine; Verbeke, Caroline Sophie; Seeberg, Lars Thomas & Schirmer, Cecilie [Vis alle 10 forfattere av denne artikkelen] (2020). Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information. BMC Cancer. 20:1107, s. 1–13. doi: 10.1186/s12885-020-07510-z. Fulltekst i vitenarkiv Vis sammendrag

  Background: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC). Methods: Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis. Results: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). Conclusions: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed.

• Roessel, Stijn; Veldhuisen, Eran; Klompmaker, Sjors; Janssen, Quisette; Hilal, Mohammed Abu & Alseidi, Adnan [Vis alle 44 forfattere av denne artikkelen] (2020). Evaluation of adjuvant chenotherapy in patients with resected pancreatic cancer after neoadjuvant FOLFIRINOX treatment. JAMA Oncology. ISSN 2374-2437. 6(11), s. 1733–1740. doi: 10.1001/jamaoncol.2020.3537. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Tholfsen, Tore; Kleive, Dyre; Waage, Anne; Buanes, Trond & Labori, Knut Jørgen [Vis alle 8 forfattere av denne artikkelen] (2020). Laparoscopic distal pancreatectomy in patients with poor physical status. HPB. ISSN 1365-182X. s. 1–5. doi: 10.1016/j.hpb.2020.10.004. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Tholfsen, Tore; Kleive, Dyre; Yaqub, Sheraz; Kazaryan, Airazat M. & Buanes, Trond [Vis alle 9 forfattere av denne artikkelen] (2020). Laparoscopic distal pancreatectomy following prior upper abdominal surgery (pancreatectomy and prior surgery). Journal of Gastrointestinal Surgery. ISSN 1091-255X. s. 1–8. doi: 10.1007/s11605-020-04858-2. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background and Purpose Previous abdominal surgery can be a risk factor for perioperative complications in patients undergoing laparoscopic procedures. Today, distal pancreatectomy is increasingly performed laparoscopically. This study investigates the consequences of prior upper abdominal surgery (PUAS) for laparoscopic distal pancreatectomy (LDP). Methods Patients who had undergone LDP from April 1997 to January 2020 were included. Based on the history and type of PUAS, these were categorized into three groups: minimally invasive (I), open (II), and no PUAS (III). To reduce possible confounding factors, the groups were matched in 1:2:4 fashion based on age, sex, body mass index (BMI) and American Society of Anesthesiology grade. Results After matching, 30, 60, and 120 patients were included in the minimally invasive, open and no PUAS groups, respectively. No statistically significant differences were found in terms of intraoperative outcomes. Postoperative morbidity, mortality and length of hospital stay were similar. Open PUAS was associated with higher Comprehensive Complication Index (33.7 vs 20.9 vs 26.2, p  = 0.03) and greater proportion of patients with ≥ 2 complications (16.7 vs 0 vs 6.7%, p  = 0.02) compared with minimally invasive and no PUAS. Male sex, overweight (BMI 25–29.9 kg/m 2 ), diagnosis of neuroendocrine neoplasia, and open PUAS were risk factors for severe morbidity in the univariable analysis. Only open PUAS was statistically significant in the multivariable model. Conclusions PUAS does not impair the feasibility and safety of LDP as its perioperative outcomes are largely comparable to those in patients without PUAS. However, open PUAS increases the burden and severity of postoperative complications.

• Søreide, Kjetil; Primavesi, Florian; Labori, Knut Jørgen; Watson, Martin & Stättner, Stefan (2019). Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy. European Surgery. ISSN 1682-8631. 51(3), s. 126–134. doi: 10.1007/s10353-019-0575-z. Fulltekst i vitenarkiv Vis sammendrag

  Background: Novel technology has enabled researchers to better characterize pancreatic cancers at the molecular level. We wanted to explore some of the emerging discoveries, such as molecular subclassification, use of liquid biopsy and use of organoids in cancer assessment. Methods: A literature review with a search specific to the topic, with recent reviews in major journals and a focus on the last 5 years (until December 2018), was done. Results: Pancreatic ductal adenocarcinoma (PDAC) may now be classified into clinical subgroups based on the predominant genomic profiles, but consensus on one classification system is lacking. Several subtypes have been suggested, including categories such as basal-like, stroma-activated, desmoplastic, pure classical and immune classical types. Further refinement may translate into clinically meaningful groups for therapeutic or prognostic purposes. Liquid biopsies (by means of circulating cancer cells, cell-free DNA, exosomes or other constituents of cancer cells in blood) may aid in earlier diagnosis, define prognostic groups and even predict therapy response and resistance. Organoids are increasingly used for the opportunity to investigate druggable and effective targets ex vivo and should facilitate personalized and precise, targeted therapy in the near future. While immunotherapy has not yet proved to be effective, a better understanding of molecular subgroups and specific immune profiles may help identify candidates for this approach in a more selective approach. Conclusion: Novel molecular techniques have the potential to accelerate the road to improved outcomes in patients with pancreatic cancer.

• Sandhu, Vandana; Labori, Knut Jørgen; Borgida, Ayelet; Lungu, Ilinca; Bartlett, John & Hafezi-Bakhtiari, Sara [Vis alle 15 forfattere av denne artikkelen] (2019). Meta-analysis of 1,200 transcriptomic profiles identifies a prognostic model for pancreatic ductal adenocarcinoma. JCO Clinical Cancer Informatics. 3, s. 1–16. doi: 10.1200/CCI.18.00102. Fulltekst i vitenarkiv Vis sammendrag

  PURPOSE With a dismal 8% median 5-year overall survival, pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy. Only 10% to 20% of patients are eligible for surgery, and more than 50% of these patients will die within 1 year of surgery. Building a molecular predictor of early death would enable the selection of patients with PDAC who are at high risk. MATERIALS AND METHODS We developed the Pancreatic Cancer Overall Survival Predictor (PCOSP), a prognostic model built from a unique set of 89 PDAC tumors in which gene expression was profiled using both microarray and sequencing platforms. We used a meta-analysis framework that was based on the binary gene pair method to create gene expression barcodes that were robust to biases arising from heterogeneous profiling platforms and batch effects. Leveraging the largest compendium of PDAC transcriptomic data sets to date, we show that PCOSP is a robust single-sample predictor of early death—1 year or less—after surgery in a subset of 823 samples with available transcriptomics and survival data. RESULTS The PCOSP model was strongly and significantly prognostic, with a meta-estimate of the area under the receiver operating curve of 0.70 (P = 2.6E−22) and d-index (robust hazard ratio) of 1.9 (range, 1.6 to 2.3; ( = 1.4E−04) for binary and survival predictions, respectively. The prognostic value of PCOSP was independent of clinicopathologic parameters and molecular subtypes. Over-representation analysis of the PCOSP 2,619 gene pairs—1,070 unique genes—unveiled pathways associated with Hedgehog signaling, epithelial–mesenchymal transition, and extracellular matrix signaling. CONCLUSION PCOSP could improve treatment decisions by identifying patients who will not benefit from standard surgery/chemotherapy but who may benefit from a more aggressive treatment approach or enrollment in a clinical trial.

• Kleive, Dyre; Sahakyan, Mushegh; Labori, Knut Jørgen & Lassen, Kristoffer (2019). Nasogastric Tube on Demand is Rarely Necessary After Pancreatoduodenectomy Within an Enhanced Recovery Pathway. World Journal of Surgery. ISSN 0364-2313. s. 1–7. doi: 10.1007/s00268-019-05045-4. Fulltekst i vitenarkiv Vis sammendrag

  <i>Background</i> - Evidence-based guidelines for enhanced recovery (ERAS) pathways after pancreatoduodenectomy (PD) are available. Routine use of nasogatric tube (NGT) after PD is not recommended. This study aims to evaluate the need for NGT reinsertion after PD performed within an ERAS setting.<p><p> <i>Methods</i> - It is a prospective observational study of all patients undergoing PD in a tertiary referral hospital within the study period from 2015 throughout 2016. Pre- and postoperative variables were collected. Patients requiring NGT reinsertion were identified. Comparative analysis of patients with and without a NGT reinsertion was performed, as well as multivariate analysis for risk factors for on-demand NGT reinsertion.<p><p> <i>Results</i> - Two-hundred and one patients were included. In total, 45 (22.4%) patients required NGT reinsertion after PD. A total of 32 (15.9%) patients underwent a relaparotomy. Reinsertion of NGT in patients not undergoing a relaparotomy occurred in 26 (15.4%) patients. The presence of a major postoperative complication was a risk factor for reinsertion of NGT, OR 5.27 (2.54–10.94, <i>p</i> = 0.001). Patients with the need for a NGT reinsertion had a higher frequency of major postoperative complications and relaparotomy compared to patients without the need of a NGT reinsertion, 26 (57.8%) versus 32 (20.5%), <i>p</i> < 0.001 and 19 (42.2%) versus 13 (8.3%), <i>p</i> < 0.001, respectively.<p><p> <i>Conclusion</i> - Routine use of NGT after PD is not justified within an ERAS setting. Immediate removal of the NGT after the procedure can be performed safely, and reinsertion on demand is rarely necessary in uncomplicated courses.

• Kleive, Dyre; Labori, Knut Jørgen; Line, Pål Dag; Gladhaug, Ivar Prydz & Verbeke, Caroline Sophie (2019). Pancreatoduodenectomy with venous resection for ductal adenocarcinoma rarely achieves complete (R0) resection. HPB. ISSN 1365-182X. 22(1), s. 50–57. doi: 10.1016/j.hpb.2019.05.005. Fulltekst i vitenarkiv Vis sammendrag

  Background Pancreatoduodenectomy with venous resection is considered standard of care for patients with tumour involvement of the superior mesenteric/portal vein (SMV/PV) and deemed justified if an R0-resection can be achieved. The aim of this study was to provide a detailed pathology assessment of the site and extent of margin involvement in specimens resulting from pancreatoduodenectomy with venous resection. Methods Retrospective observational study including patients undergoing pancreatoduodenectomy with or without venous resection for pancreatic ductal adenocarcinoma between 2015 and 2017. Detailed histopathological mapping of the tumour and its relationship to the margins was undertaken. Results 98 patients met the inclusion criteria. An R0-resection, based on 1 mm clearance, was achieved in 16 of 73 patients without venous resection and in 1 of 25 patients with venous resection ( p = 0.063). The surface of the SMV-groove was the most frequently involved margin (23 of 25 patients with venous resection, 37 of 73 patients without venous resection; p < 0.001). The broad invasive tumour front as well as the absence of peripancreatic fat at the SMV-groove were the reasons for these findings. Conlusion An R0-resection following pancreatoduodenectomy with venous resection for ductal adenocarcinoma can rarely be achieved due to microscopical involvement of the SMV-groove.

• Thorsen, Trygve; Solheim, Jon Magnus Aarstrand; Labori, Knut Jørgen; Line, Pål Dag & Aandahl, Einar Martin (2019). Liver transplantation as a lifesaving procedure for posthepatectomy liver failure and iatrogenic liver injuries. Langenbeck's Archives of Surgery. ISSN 1435-2443. doi: 10.1007/s00423-019-01780-3. Fulltekst i vitenarkiv Vis sammendrag

  Background Iatrogenic injuries to vital structures of the liver and posthepatectomy liver failure are associated with high mortality. The current donor situation in Norway allows liver transplantation of patients beyond conventional criteria. Methods From 1984 to 2017, a total of 1510 liver transplantations were performed. In this retrospective study, we report the results of 13 patients undergoing liver transplantation due to iatrogenic injuries to the liver vasculature or posthepatectomy liver failure. Results Twelve men and one woman with a median age of 55 years (range 22–69) were included. Seven patients underwent radical surgery for cancer prior to transplantation. The median follow-up time was 70.5 months (range 2.2–177). Three of the patients with malignant disease did not experience disease recurrence, whereas four patients had cancer recurrence and died 7, 24, 45, and 78 months after transplantation. Five of six patients with non-malignant disease fully recovered, but one patient died after 9 months due to infectious complications. Conclusions Liver transplantation for liver failure due to portal vein and hepatic artery injury in patients with non-malignant disease seems justified. However, it may be questioned whether patients with malignant disease beyond established criteria should be offered liver transplantation.

• Klompmaker, Sjors; Peters, Niek A; Hilst, Jony van; Bassi, Claudio; Boggi, Ugo & Busch, Olivier R. [Vis alle 28 forfattere av denne artikkelen] (2019). Outcomes and Risk Score for Distal Pancreatectomy with Celiac Axis Resection (DP-CAR): An International Multicenter Analysis. Annals of Surgical Oncology. ISSN 1068-9265. 26(3), s. 772–781. doi: 10.1245/s10434-018-07101-0. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Labori, Knut Jørgen; Primavesi, Florian; Søreide, Kjetil; Stättner, Stefan & Edwin, Bjørn (2019). Minimally invasive pancreatic surgery-where are we going? European Surgery. ISSN 1682-8631. 51(3), s. 98–104. doi: 10.1007/s10353-019-0576-y. Fulltekst i vitenarkiv Vis sammendrag

  Background Introduced in the mid-1990s, minimally invasive pancreatic surgery (MIPS) developed slowly over the next two decades, and its real-life benefits remained unclear. Methods In this review, the current status and evidence on the most common types of MIPS, such as minimally invasive pancreatoduodenectomy (MIPD), distal pancreatectomy, enucleation, and central pancreatectomy are presented. Results Minimally invasive distal pancreatectomy (MIDP) is the most frequently used procedure among these, and its indications are nowadays expanding. MIDP for benign and low-grade malignant tumors is advantageous compared to the open approach, suggesting less intraoperative blood loss, shorter hospital stay, faster functional recovery, and better quality of life. The oncological adequacy of MIDP in pancreatic cancer is unclear, as no randomized trials have been published. In contrast, MIPD is a technically challenging procedure performed in a small number of centers and in a selected group of patients. Its use remains controversial, as conflicting data have been reported in the literature. Annual volume and learning curve seem to be the key determinants of safety in MIPD. Minimally invasive pancreatic enucleation and central pancreatectomy are less common. Although one randomized trial was published on minimally invasive vs. open central pancreatectomy, current evidence on these procedures is mostly based on retrospective, single-institution series clearly affected by selection bias and small sample size. Conclusion Well-designed prospective studies based on national registries are needed to expand knowledge on MIPS and determine its role in pancreatic surgery. To facilitate further development of MIPS, it has to integrate effectively with the outcome-improving effect of a dedicated pancreatic team.

• Ånonsen, Kim Vidar; Sahakyan, Mushegh; Kleive, Dyre; Waage, Anne; Verbeke, Caroline Sophie & Hauge, Truls [Vis alle 9 forfattere av denne artikkelen] (2019). Trends in management and outcome of cystic pancreatic lesions - analysis of 322 cases undergoing surgical resection. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 54(8), s. 1051–1057. doi: 10.1080/00365521.2019.1642379. Fulltekst i vitenarkiv Vis sammendrag

  Background: Several guidelines for the management of cystic pancreatic lesions (CPL) exists. From 2013, Oslo University Hospital adapted the European consensus guidelines (ECG) in the decision-making as to whether patients should be advised to have resection or observation for CPL. The aims of the study were to assess changes over time in the workup and diagnostic accuracy of resected CPL, and the short-term surgical outcome. Methods: Preoperative radiological workup, clinicopathological characteristics, and perioperative outcomes were retrospectively reviewed in three consecutive time periods (early: 2004–2008, intermediate: 2009–2012, late: 2013–2016). The rate of concordance between the ECG recommendations for resection (ECG+) or observation (ECG–) and the final histological diagnosis were assessed. Results: A total of 322 consecutive patients underwent resection for CPL (early: n = 89, intermediate: n = 108, late: n = 125). The most common diagnoses were intraductal papillary mucinous neoplasia (IPMN, 36.0%), serous cystic neoplasm (SCN, 23.9%), mucinous cystic neoplasm (10.6%), pseudocyst (9.6%), solid pseudopapillary neoplasm (7.8%), and cystic pancreatic neuroendocrine tumour (5.3%). The proportion of ECG+ CPL undergoing surgery increased significantly (42.7% vs. 60.7% vs. 70.4%, p < .001). The relative proportion of patients undergoing resection for SCN decreased (38.2% vs. 21.3% vs. 16.0%), whereas it increased for IPMN (31.5% vs. 30.6% vs. 44.0%). The use of magnetic resonance imaging and endoscopic ultrasound increased. There were no differences in postoperative severe complications (23.0% vs. 23.6%) or 90-day mortality (2.3% vs. 0.8%) between ECG+ and ECG– patients. Conclusion: Several changes in the management of CPL were revealed during time. Adherence to guidelines is important in order to avoid unnecessary surgery for CPL.

• Lothe, Inger Marie Bowitz; Kleive, Dyre; Pomianowska, Ewa; Småstuen, Milada Cvancarova; Kure, Elin Wenche Hegland & Dueland, Svein [Vis alle 8 forfattere av denne artikkelen] (2019). Clinical relevance of pancreatobiliary and intestinal subtypes of ampullary and duodenal adenocarcinoma: Pattern of recurrence, chemotherapy, and survival after pancreatoduodenectomy. Pancreatology (Print). ISSN 1424-3903. 19(2), s. 316–324. doi: 10.1016/j.pan.2019.01.019. Fulltekst i vitenarkiv Vis sammendrag

  Background. The clinical relevance of the classification of ampullary adenocarcinoma (AC) into pancreatobiliary (PB) or intestinal (Int) subtypes has not been resolved. Methods. Clinicopathological factors, survival, and localization and treatment of recurrence were investigated for patients with AC and duodenal adenocarcinoma (DC) treated by pancreatoduodenectomy from 2000 to 2015. Results. A total of 109 AC (45 PB, 64 Int) and 71 DC (all Int) were identified. Median overall survival (OS) for ACPB vs DC vs ACInt was 43.6 vs 51 vs 75 months, respectively. ACPB had significantly shorter OS than ACInt (p = 0.036). However, for AC stage (HR = 2.39; 95 %CI 1.23–4.64, p = 0.010) was the only factor associated with mortality risk in multivariate analysis. Localization of recurrence (n = 88) was predominantly distant (ACPB 81.5%; ACInt 92%; DC 91.7%, p = 0.371). Post-recurrence survival (PRS) for ACPB, ACInt and DC did not differ (6.9 vs 9.2 vs 7.5 months, p = 0.755). Best supportive care or palliative chemotherapy were offered for recurrent disease to 44.5%/48.1% for ACPB, 40%/56% for ACInt, and 41.7%/52.8% for DC (p = 0.947). The choice of chemotherapy regimen varied considerably. Five patients underwent surgical resection or ablation with curative intent. All deaths among ACPB were caused by recurrent disease, whereas 29.4% of ACInt and 23.1% of DC deaths was non-cancer related or caused by other specific cancer. Conclusion. ACPB, ACInt and DC have similar recurrence patterns and PRS. The difference in survival between ACPB and ACInt was not statistically significant when stratified by stage. The optimal chemotherapy in patients with recurrent AC remains undefined.

• Klompmaker, Sjors; Hilst, Jony van; Gerritsen, Sarah L.; Adham, Mustapha; Quer, M. Teresa Albiol & Bassi, Claudio [Vis alle 37 forfattere av denne artikkelen] (2018). Outcomes after distal pancreatectomy with celiac axis resection for pancreatic cancer: A pan-European retrospective cohort study. Annals of Surgical Oncology. ISSN 1068-9265. 25(5), s. 1440–1447. doi: 10.1245/s10434-018-6391-z. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Kleive, Dyre; Kazaryan, Airazat M.; Aghayan, Davit; Ignjatovic, Dejan & Labori, Knut Jørgen [Vis alle 8 forfattere av denne artikkelen] (2018). Extended laparoscopic distal pancreatectomy for adenocarcinoma in the body and tail of the pancreas: a single-center experience. Langenbeck's Archives of Surgery. ISSN 1435-2443. s. 1–8. doi: 10.1007/s00423-018-1730-x. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Haugvik, Sven-Petter; Røsok, Bård Ingvald; Kazaryan, Airazat M.; Ignjatovic, Dejan & Buanes, Trond [Vis alle 9 forfattere av denne artikkelen] (2018). Can standardized pathology examination increase the lymph node yield following laparoscopic distal pancreatectomy for ductal adenocarcinoma? HPB. ISSN 1365-182X. 20(2), s. 175–181. doi: 10.1016/j.hpb.2017.08.038. Fulltekst i vitenarkiv
• Hugenschmidt, Harald; Labori, Knut Jørgen; Brunborg, Cathrine; Verbeke, Caroline Sophie; Seeberg, Lars Thomas & Schirmer, Cecilie [Vis alle 10 forfattere av denne artikkelen] (2018). Circulating Tumor Cells are an Independent Predictor of Shorter Survival in Patients Undergoing Resection for Pancreatic and Periampullary Adenocarcinoma. Annals of Surgery. ISSN 0003-4932. 271(3), s. 549–558. doi: 10.1097/SLA.0000000000003035. Fulltekst i vitenarkiv
• Baekelandt, Bart Maria Gilbert; Fagerland, Morten; Hjermstad, Marianne Jensen; Heiberg, Turid; Labori, Knut Jørgen & Buanes, Trond (2018). Survival, Complications and Patient Reported Outcomes after Pancreatic Surgery. HPB. ISSN 1365-182X. doi: 10.1016/j.hpb.2018.07.023. Fulltekst i vitenarkiv Vis sammendrag

  Background: Long-term effects of complications in pancreatic surgery have not been systematically evaluated. The objectives were to assess potential effects of complications on survival and patient reported outcomes (PROs) as well as feasibility of PRO questionnaires in patients with periampullary and pancreatic tumors. Methods: From October 2008 to December 2011, 208 patients undergoing pancreatic surgery were included in a prospective observational study. ESAS, EORTC QLQ-C30 and QLQ-PAN26 questionnaires were completed at inclusion, then every third month. Complications were recorded according to the Clavien-Dindo (CD) classification and Comprehensive Complication Index (CCI). Results: 148 complications were registered in 100 patients (48%), 36 patients (17%) had CD IIIa or above. 125 patients (60%) completed baseline questionnaires, 80 (39%) responded after three and 54 (28%) after six months. Complications were associated with reduced long-term survival in patients with pancreatic ductal adenocarcinoma (PDAC) (p = 0.049) and other malignant diseases. No significant relationship was found between complications and PROs, except for anxiety, which was significantly increased in patients with complications. Conclusion: Postoperative complications led to increased anxiety at 3 months after surgery and were associated with reduced long-term survival in patients with malignancy. A short, patient derived, disease specific questionnaire is required in the clinical research context.

• Kleive, Dyre; Sahakyan, Mushegh; Søreide, Kjetil; Brudvik, Kristoffer Watten; Line, Pål Dag & Gladhaug, Ivar Prydz [Vis alle 7 forfattere av denne artikkelen] (2018). Risk for hemorrhage after pancreatoduodenectomy with venous resection. Langenbeck's Archives of Surgery. ISSN 1435-2443. s. 1–9. doi: 10.1007/s00423-018-1721-y. Fulltekst i vitenarkiv
• Brudvik, Kristoffer Watten; Røsok, Bård Ingvald; naresh, usha; Yaqub, Sheraz; Fretland, Åsmund Avdem & Labori, Knut Jørgen [Vis alle 8 forfattere av denne artikkelen] (2018). Survival after resection of colorectal liver metastases in octogenarians and sexagenarians compared to their respective age-matched national population. Hepatobiliary surgery and nutrition. ISSN 2304-3881. 7(4), s. 234–241. doi: 10.21037/hbsn.2017.09.03. Fulltekst i vitenarkiv
• Kleive, Dyre; Sahakyan, Mushegh; Khan, Ammar; Fosby, Bjarte; Line, Pål Dag & Labori, Knut Jørgen (2018). Incidence and management of arterial injuries during pancreatectomy. Langenbeck's Archives of Surgery. ISSN 1435-2443. 403(3), s. 341–348. doi: 10.1007/s00423-018-1666-1. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Edwin, Bjørn; Kazaryan, Airazat M.; Barkhatov, Leonid; Buanes, Trond & Ignjatovic, Dejan [Vis alle 8 forfattere av denne artikkelen] (2017). Perioperative outcomes and survival in elderly patients undergoing laparoscopic distal pancreatectomy. Journal of Hepato-Biliary-Pancreatic Sciences. ISSN 1868-6974. 24(1), s. 42–48. doi: 10.1002/jhbp.409. Fulltekst i vitenarkiv
• Ånonsen, Kim Vidar; Fagerland, Morten; Edwin, Bjørn; Labori, Knut Jørgen; Kure, E.H. & Hauge, Truls [Vis alle 7 forfattere av denne artikkelen] (2017). Cyst fluid CEA concentration discriminates between benign and premalignant/malignant pancreatic cystic lesions. A prospective cohort study. Short title: Diagnostic yield of pancreatic cyst fluid CEA analysis. EC Gastroenterology and Digestive System. ISSN 2276-1209. 02, s. 426–436. Fulltekst i vitenarkiv Vis sammendrag

  Background: The objective was to evaluate cyst fluid carcinoembryonic antigen (CEA) as a putative marker of malignant potential in cystic pancreatic lesions (CPLs). Methods: Prospective observational cohort study from October 2008 to September 2013. A total of 190 patients with CPL were in- cluded after signed informed consent. Endoscopic ultrasound and fine needle aspiration (EUS-FNA) of cyst fluid for analysis of CEA was performed as part of the multimodal preoperative workup. The diagnostic performance of cyst fluid CEA value for the selection of the right patients for surgery was evaluated by histological diagnosis as endpoint in operated patients. Diagnostic accuracy of cyst fluid CEA was assessed by receiver operating characteristics (ROC) analysis. Results: Surgical resection was performed in 65 patients (34.2%) after evaluation by the multidisciplinary team (MDT). Lesions with malignant potential or invasive carcinomas were found in 46 (70.8%) of resected cases. Area under the ROC curve (AUC) for cyst fluid CEA was 0.71 (95% CI 0.61 - 0.81). The optimal cut-off value was 36.3 ng/mL (sensitivity 74%, specificity 62%, PPV 51%, NPV 81%, accuracy 66%). A total of 125 patients (65.8%) were never operated, 15 because of unresectable carcinoma. None of the 110 patients undergoing conservative management developed malignancy at a median follow-up of 46.5 months (range 4 - 86 months). Conclusion: There is a significant diagnostic yield of cyst fluid CEA determination, when the indication for surgical exploration is focused.

• Kleive, Dyre; Berstad, Audun Elnæs; Sahakyan, Mushegh; Verbeke, Caroline Sophie; Naper, Christian & Haugvik, Sven-Petter [Vis alle 9 forfattere av denne artikkelen] (2017). Portal vein reconstruction using primary anastomosis or venous interposition allograft in pancreatic surgery. Journal of Vascular Surgery: Venous and Lymphatic Disorders (JVS-VL). ISSN 2213-333X. 6(1), s. 66–74. doi: 10.1016/j.jvsv.2017.09.003. Fulltekst i vitenarkiv
• Labori, Knut Jørgen; Guren, Marianne; Brudvik, Kristoffer Watten; Røsok, Bård Ingvald; Waage, Anne & Nesbakken, Arild [Vis alle 10 forfattere av denne artikkelen] (2017). Resection of synchronous liver metastases between radiotherapy and definitive surgery for locally advanced rectal cancer: short-term surgical outcomes, overall survival and recurrence-free survival. Colorectal Disease. ISSN 1462-8910. 19(8), s. 731–738. doi: 10.1111/codi.13622. Fulltekst i vitenarkiv
• Kleive, Dyre; Sahakyan, Mushegh; Berstad, Audun Elnæs; Verbeke, Caroline Sophie; Gladhaug, Ivar Prydz & Edwin, Bjørn [Vis alle 9 forfattere av denne artikkelen] (2017). Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy. British Journal of Surgery. ISSN 0007-1323. 104(11), s. 1558–1567. doi: 10.1002/bjs.10603. Fulltekst i vitenarkiv
• Chellappa, Stalin; Hugenschmidt, Harald; Hagness, Morten; Subramani, Saranya; Melum, Espen & Line, Pål Dag [Vis alle 10 forfattere av denne artikkelen] (2017). CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer. Journal of Immunology. ISSN 0022-1767. 198(4), s. 1729–1739. doi: 10.4049/jimmunol.1600061. Fulltekst i vitenarkiv
• Gunasekaran, Stalin Chellappa; Hugenschmidt, Harald; Hagness, Morten; Subramani, Saranya; Melum, Espen & Line, Pål Dag [Vis alle 10 forfattere av denne artikkelen] (2017). CD8+ T cells that coexpress ROR?t and T-bet are functionally impaired and expand in patients with distal bile duct cancer. Journal of Immunology. ISSN 0022-1767. 198(4), s. 1729–1739. doi: 10.4049/jimmunol.1600061. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Kim, Song Cheol; Kleive, Dyre; Kazaryan, Airazat M.; Song, Ki Byung & Ignjatovic, Dejan [Vis alle 10 forfattere av denne artikkelen] (2017). Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: Long-term oncologic outcomes after standard resection. Surgery. ISSN 0039-6060. 162(4), s. 802–811. doi: 10.1016/j.surg.2017.06.009. Fulltekst i vitenarkiv
• Labori, Knut Jørgen; Lassen, Kristoffer; Hoem, Dag; Grønbech, Jon Erik; Søreide, Jon Arne & Mortensen, Kim Erlend [Vis alle 10 forfattere av denne artikkelen] (2017). 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 Surgery. 17(1). doi: 10.1186/s12893-017-0291-1. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Sandhu, Vandana; Lothe, Inger Marie Bowitz; Labori, Knut Jørgen; Skrede, Martina; Hamfjord, Julian & Larsen, Astrid Marie [Vis alle 14 forfattere av denne artikkelen] (2016). Differential expression of miRNAs in pancreatobiliary type of periampullary adenocarcinoma and its associated stroma. Molecular Oncology. ISSN 1574-7891. 10(2), s. 303–316. doi: 10.1016/j.molonc.2015.10.011. Fulltekst i vitenarkiv
• Søreide, Kjetil & Labori, Knut Jørgen (2016). Risk factors and preventive strategies for post-operative pancreatic fistula after pancreatic surgery: a comprehensive review. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 51(10), s. 1147–1154. doi: 10.3109/00365521.2016.1169317. Fulltekst i vitenarkiv Vis sammendrag

  Background: Pancreas surgery has developed into a fairly safe procedure in terms of mortality, but is still hampered by considerable morbidity. Among the most frequent and dreaded complications are the development of a post-operative pancreatic fistula (POPF). The prediction and prevention of POPF remains an area of debate with several questions yet to be firmly addressed with solid answers. Methods: A systematic review of systematic reviews/meta-analyses and randomized trials in the English literature (PubMed/MEDLINE, Cochrane library, EMBASE) covering January 2005 to December 2015 on risk factors and preventive strategies for POPF. Results: A total of 49 systematic reviews and meta-analyses over the past decade discussed patient, surgeon, pancreatic disease and intraoperative related factors of POPF. Non-modifiable factors (age, BMI, comorbidity) and pathology (histotype, gland texture, duct size) that indicates surgery are associated with POPF risk. Consideration of anastomotic technique and use of somatostatin-analogs may slightly modify the risk of fistula. Sealant products appear to have no effect. Perioperative bleeding and transfusion enhance risk, but is modifiable by focus on technique and training. Drains may not prevent fistulae, but may help in early detection. Early drain-amylase may aid in detection. Predictive scores lack uniform validation, but may have a role in patient information if reliable pre-operative risk factors can be obtained. Conclusions: Development of POPF occurs through several demonstrated risk factors. Anastomotic technique and use of somatostatin-analogs may slightly decrease risk. Drains may aid in early detection of leaks, but do not prevent POPF.

• Pozzi-Mucelli, Raffaella Maria; Rinta-Kiikka, Irina; Wünsche, Katharina; Laukkarinen, Johanna; Labori, Knut Jørgen & Ånonsen, Kim Vidar [Vis alle 9 forfattere av denne artikkelen] (2016). Pancreatic MRI for the surveillance of cystic neoplasms: comparison of a short with a comprehensive imaging protocol. European Radiology. ISSN 0938-7994. 27(1), s. 41–50. doi: 10.1007/s00330-016-4377-4. Fulltekst i vitenarkiv
• Gunasekaran, Stalin Chellappa; Hugenschmidt, Harald; Hagness, Morten; Line, Pål Dag; Labori, Knut Jørgen & Wiedswang, Gro [Vis alle 8 forfattere av denne artikkelen] (2016). Regulatory T cells that co-express RORγt and FOXP3 are pro-inflammatory and immunosuppressive and expand in human pancreatic cancer. Oncoimmunology. ISSN 2162-4011. 5(4). doi: 10.1080/2162402X.2015.1102828. Fulltekst i vitenarkiv
• Haugvik, Sven-Petter; Kaemmerer, Daniel; Gaujoux, Sebastien; Labori, Knut Jørgen; Verbeke, Caroline Sophie & Gladhaug, Ivar Prydz (2016). Pathology and Surgical Treatment of High-Grade Pancreatic Neuroendocrine Carcinoma: an Evolving Landscape. Current Oncology Reports. ISSN 1523-3790. 18(5). doi: 10.1007/s11912-016-0518-9. Fulltekst i vitenarkiv
• Sandhu, Vandana; Wedge, David C.; Lothe, Inger Marie Bowitz; Labori, Knut Jørgen; Dentro, Stefan C. & Buanes, Trond [Vis alle 16 forfattere av denne artikkelen] (2016). The genomic landscape of pancreatic and periampullary adenocarcinoma. Cancer Research. ISSN 0008-5472. 76(17), s. 5092–5102. doi: 10.1158/0008-5472.CAN-16-0658. Fulltekst i vitenarkiv
• Labori, Knut Jørgen; H, Katz Matthew; Tzeng, Ching; Bjørnbeth, Bjørn Atle; Småstuen, Milada Cvancarova & Edwin, Bjørn [Vis alle 11 forfattere av denne artikkelen] (2016). Impact of early disease progression and surgical complications on adjuvant chemotherapy completion rates and survival in patients undergoing the surgery first approach for resectable pancreatic ductal adenocarcinoma - A population-based cohort study. Acta Oncologica. ISSN 0284-186X. 55(3), s. 265–277. doi: 10.3109/0284186X.2015.1068445. Fulltekst i vitenarkiv
• Sahakyan, Mushegh; Yaqub, Sheraz; Kazaryan, Airazat M.; Villanger, Olaug; Berstad, Audun Elnæs & Labori, Knut Jørgen [Vis alle 8 forfattere av denne artikkelen] (2016). Laparoscopic Completion Pancreatectomy for Local Recurrence in the Pancreatic Remnant after Pancreaticoduodenectomy: Case Reports and Review of the Literature. Journal of Gastrointestinal Cancer. ISSN 1941-6628. 47(4), s. 509–513. doi: 10.1007/s12029-015-9796-y. Fulltekst i vitenarkiv

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• Labori, Knut Jørgen (2025). Prognostic and monitoring potential of circulating tumor DNA in resectable pancreatic cancer. Translational gastroenterology and hepatology (TGH). 10. doi: 10.21037/tgh-24-167. Fulltekst i vitenarkiv Vis sammendrag

• Labori, Knut Jørgen; Bratlie, Svein Olav; Dueland, Svein & Lassen, Kristoffer (2024). NORPACT-1: implications for future trials – Authors' reply. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. 9(5), s. 408–409. doi: 10.1016/S2468-1253(24)00079-7. Fulltekst i vitenarkiv
• Dam, Dam van; Verkolf, E.M.M.; Dekker, E.N.; Bonsing, B.A.; Bratlie, S.O. & Brosens, L.A.A. [Vis alle 31 forfattere av denne artikkelen] (2023). Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial. BMC Cancer. 23. doi: 10.1186/s12885-023-11141-5. Fulltekst i vitenarkiv Vis sammendrag

  Background Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. Methods This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. Discussion The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. Trial registration Clinical Trials: NCT04927780. Registered June 16, 2021.

• Labori, Knut Jørgen (2022). Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives. Frontiers in Surgery. 9. doi: 10.3389/fsurg.2022.839339. Fulltekst i vitenarkiv Vis sammendrag

  Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field.

• Fosheim, Ingrid Knutsdotter; Hårvig, Karina Roheim; Heldal, Kristian; Mariathasan, Anthony Burton; Lundesgaard, Kristoffer & BENTERUD, BJØRN PETTER [Vis alle 9 forfattere av denne artikkelen] (2021). En ung kvinne som ikke våknet etter omfattende operasjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(15), s. 1–8. doi: 10.4045/tidsskr.21.0184. Fulltekst i vitenarkiv
• Silwal-Pandit, Laxmi; Stålberg, Stina Margrethe; Mermelekas, G; Lothe, Inger Marie Bowitz; Skrede, Martina Landschoof & Dalsgaard, Astrid M. [Vis alle 11 forfattere av denne artikkelen] (2019). Proteomic Landscape of Pancreatic Ductal Adenocarcinoma. Fulltekst i vitenarkiv
• Klompmaker, Sjors; Hilst, Jony van; Gerritsen, Sarah L.; Adham, Mustapha; Quer, Albiol Teresa Albiol & Bassi, Claudio [Vis alle 37 forfattere av denne artikkelen] (2018). Correction to: Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study. Annals of Surgical Oncology. ISSN 1068-9265. 25, s. 988–988. doi: 10.1245/s10434-018-6442-5. Fulltekst i vitenarkiv
• Labori, Knut Jørgen & Brudvik, Kristoffer Watten (2017). Follow-up after surgery for pancreatic ductal adenocarcinoma. Pancreas. ISSN 0885-3177. 46(1), s. e2–e3. doi: 10.1097/MPA.0000000000000689. Fulltekst i vitenarkiv
• Labori, Knut Jørgen; Haugvik, Sven-Petter & Line, Pål Dag (2016). Letter to the editor: Multidisciplinary management of pancreatic neuroendocrine tumors - The importance of an aggressive surgical approach. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 51(3), s. 383–384. doi: 10.3109/00365521.2015.1094125. Fulltekst i vitenarkiv

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