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17 results on '"Labori, K. J."'

1. Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial

Author

van Dam, J. L., Verkolf, E. M. M., Dekker, E. N., Bonsing, B. A., Bratlie, S. O., Brosens, L. A. A., Busch, O. R., van Driel, L. M. J. W., van Eijck, C. H. J., Feshtali, S., Ghorbani, P., de Groot, D. J. A., de Groot, J. W. B., Haberkorn, B. C. M., de Hingh, I. H., van der Holt, B., Karsten, T. M., van der Kolk, M. B., Labori, K. J., Liem, M. S. L., Loosveld, O. J. L., Molenaar, I. Q., Polée, M. B., van Santvoort, H. C., de Vos – Geelen, J., Wumkes, M. L., van Tienhoven, G., Homs, M. Y. V., Besselink, M. G., Wilmink, J. W., and Groot Koerkamp, B.

Published
2023
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3. Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3):study protocol for a multicenter randomized controlled trial

Author

van Dam, J. L., Verkolf, E. M.M., Dekker, E. N., Bonsing, B. A., Bratlie, S. O., Brosens, L. A.A., Busch, O. R., van Driel, L. M.J.W., van Eijck, C. H.J., Feshtali, S., Ghorbani, P., de Groot, D. J.A., de Groot, J. W.B., Haberkorn, B. C.M., de Hingh, I. H., van der Holt, B., Karsten, T. M., van der Kolk, M. B., Labori, K. J., Liem, M. S.L., Loosveld, O. J.L., Molenaar, I. Q., Polée, M. B., van Santvoort, H. C., de Vos-Geelen, J., Wumkes, M. L., van Tienhoven, G., Homs, M. Y.V., Besselink, M. G., Wilmink, J. W., Groot Koerkamp, B., van Dam, J. L., Verkolf, E. M.M., Dekker, E. N., Bonsing, B. A., Bratlie, S. O., Brosens, L. A.A., Busch, O. R., van Driel, L. M.J.W., van Eijck, C. H.J., Feshtali, S., Ghorbani, P., de Groot, D. J.A., de Groot, J. W.B., Haberkorn, B. C.M., de Hingh, I. H., van der Holt, B., Karsten, T. M., van der Kolk, M. B., Labori, K. J., Liem, M. S.L., Loosveld, O. J.L., Molenaar, I. Q., Polée, M. B., van Santvoort, H. C., de Vos-Geelen, J., Wumkes, M. L., van Tienhoven, G., Homs, M. Y.V., Besselink, M. G., Wilmink, J. W., and Groot Koerkamp, B.

Abstract

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

Published
2023

8. Outcomes and Risk Score for Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) : An International Multicenter Analysis

Author

Klompmaker, S., Peters, N. A., van Hilst, J., Bassi, C., Boggi, U., Busch, O. R., Niesen, W., Van Gulik, T. M., Javed, A. A., Kleeff, J., Kawai, M., Lesurtel, M., Lombardo, C., Moser, A. J., Okada, K. -I., Popescu, I., Prasad, R., Salvia, R., Sauvanet, A., Sturesson, C., Weiss, M. J., Zeh, H. J., Zureikat, A. H., Yamaue, H., Wolfgang, C. L., Hogg, M. E., Besselink, M. G., Gerritsen, S. L., Adham, M., Albiol Quer, M. T., Berrevoet, F., Cesaretti, M., Dalla Valle, R., Darnis, B., Diener, M. K., Del Chiaro, M., Hackert, T. H., Grutzmann, R., Dumitrascu, T., Friess, H., Hirono, S., Ivanecz, A., Karayiannakis, A., Fusai, G. K., Labori, K. J., Lopez-Ben, S., Mabrut, J. -Y., Miyazawa, M., Pardo, F., Perinel, J., Roeyen, G., Graduate School, CCA - Cancer Treatment and Quality of Life, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, AGEM - Endocrinology, metabolism and nutrition, Surgery, CCA - Cancer biology and immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and E-AHPBA DP-CAR Study Grp

Subjects
Male, medicine.medical_specialty, Pancreatic Neoplasms/pathology, SURGERY, medicine.medical_treatment, Pancreatectomy/mortality, Pancreatectomy, Celiac artery, Celiac Artery, Pancreatic cancer, medicine.artery, Medicine and Health Sciences, Aged, Female, Follow-Up Studies, Humans, Middle Aged, Pancreatic Neoplasms, Retrospective Studies, Survival Rate, Treatment Outcome, Patient Selection, Journal Article, Medicine, Survival rate, ARTERY, Framingham Risk Score, business.industry, Mortality rate, Celiac Artery/surgery, ADENOCARCINOMA, Retrospective cohort study, medicine.disease, Surgery, ddc, MODEL, Multicenter Study, DEFINITION, Oncology, Hepatobiliary Tumors, VOLUME, Adenocarcinoma, Human medicine, business
Abstract

Background Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000–2016) and three very-high-volume international centers in the United States and Japan (model validation 2004–2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2–11%) at 5 high-volume (≥ 1 DP-CAR/year) and 18% (95 CI, 9–30%) at 18 low-volume DP-CAR centers (P = 0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P = 0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19 months (95 CI, 15–25 months). Conclusions When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor. Electronic supplementary material The online version of this article (10.1245/s10434-018-07101-0) contains supplementary material, which is available to authorized users.

Published
2019

9. 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

Author

Labori, K. J., primary, Guren, M. G., additional, Brudvik, K. W., additional, Røsok, B. I., additional, Waage, A., additional, Nesbakken, A., additional, Larsen, S., additional, Dueland, S., additional, Edwin, B., additional, and Bjørnbeth, B. A., additional

Published
2017
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14. Intravenous Bilirubin, Dibromosulfophthalein, and Bromosulfophthalein Infusions Uncouple Biliary Phospholipid and Cholesterol Secretion from Bile Acid Secretion by Inhibiting Hepatic Phosphoglycoprotein-3 Activity in Pigs.

Author

Labori, K. J., Bjørnbeth, B. A., Hvattum, E., Lyberg, T., and Ræder, M. G.

Subjects
*BILE acids, *BILIRUBIN, *WESTERN immunoblotting, *SECRETION
Abstract

Background: Biliary secretion of organic anions disturbs the proportional relationship normally pertaining between biliary lipid and bile acid secretion. The mechanism causing this uncoupling of biliary lipid from bile acid secretion is incompletely understood. Impaired micellization of membrane lipids by bile due to biliary contamination with organic anions or lowering of biliary bile acid concentration by enhanced bile acid-independent bile flow has been proposed as causative factors. Recently, we found that hepatic phosphoglycoprotein 3 (pgp3) activity was reduced in pigs during bilirubin-induced uncoupling of biliary lipid from bile acid secretion. Pgp3 is the phosphatidylcholine flippase in the canalicular membrane sustaining biliary phospholipid secretion in pigs. This investigation was undertaken to examine whether bilirubin, dibromosulfophthalein, and bromosulfophthalein uncouple biliary lipid from bile acid secretion by the same mechanism. Methods/Results: Hepatic bile was collected from 24 anesthetized pigs before and during infusion of 0.63 μmol·kg body wt[sup -1] · min[sup -1] intravenous bilirubin, dibromosulfophthalein, or bromosulfophthalein. Bile acid secretion was varied by intraportal cholic acid infusion. Hepatic pgp3 expression was measured by means of Western blot, using C219 antibody. Bilirubin > dibromosulfophthalein > bromosulfophthalein lowered biliary lipid secretion without altering hepatic pgp3 expression, increased bile acid-independent bile flow (bromosulfophthalein > dibromosulfophthalein > bilirubin), and enhanced the capacity of bile to micellize membrane lipids as assayed by means of erythrocyte lysis. Biliary bile acid concentration did not determine biliary lipid secretion. Conclusion: Bilirubin, dibromosulfophthalein, and bromosulfophthalein in bile uncouple biliary lipid from bile acid secretion by inhibiting hepatic pgp3 phosphatidylcholine flippase activity, putatively through diffusing into the pgp3 pore. [ABSTRACT FROM AUTHOR]

Published
2000
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15. Effect of Intravenous Bilirubin Infusion on Biliary Phospholipid Secretion, Hepatic P-Glycoprotein Expression, and Biliary Cytotoxicity in Pigs.

Author

Bjørnbeth, B. A., Labori, K. J., Hvattum, E., Lyberg, T., Christensen, T., Woldseth, B., and Ræder, M. G.

Subjects
*BILIRUBIN, *INTRAVENOUS therapy, *PHOSPHOLIPIDS
Abstract

Investigates the effects of intravenous bilirubin infusion on biliary phospholipid secretion in pigs. Increase in the biliary cytotoxicity; Alterations in hepatic P-glycoprotein expression; Use of gas chromatography in determining biliary phospholipid fatty acid profile.

Published
1999

16. Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment

Author

Marco Del Chiaro, Patrick M.M. Bossuyt, Giuseppe Malleo, Isabella Frigerio, A Nikov, Antonio Sa Cunha, Johan Gagnière, Rupaly Pande, Morgan Bonds, Mickael Lesurtel, Kevin C. Conlon, Per Pfeiffer, Giuseppe Fusai, Marc G. Besselink, Giovanni Butturini, Bas Groot Koerkamp, Claudio Bassi, Sjors Klompmaker, Ulla Klaiber, Stijn van Roessel, Massimo Falconi, Marco Vito Marino, Eran van Veldhuisen, Oonagh Griffin, Michael Bau Mortensen, Mohammed Abu Hilal, Tobias Keck, Timo Tarvainen, Frederik Berrevoet, Oliver Strobel, Asif Halimi, Thilo Hackert, Knut Jørgen Labori, Gianpaolo Balzano, Jörg Kleeff, Olivier R. Busch, Roberto Salvia, D. Pietrasz, Adnan Alseidi, Johanna W. Wilmink, Keith J. Roberts, Quisette P. Janssen, A. Balduzzi, Hanneke W. M. van Laarhoven, Surgery, Graduate School, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Personalized Medicine, APH - Methodology, Epidemiology and Data Science, Oncology, CCA -Cancer Center Amsterdam, Van Roessel, S., Van Veldhuisen, E., Klompmaker, S., Janssen, Q. P., Abu Hilal, M., Alseidi, A., Balduzzi, A., Balzano, G., Bassi, C., Berrevoet, F., Bonds, M., Busch, O. R., Butturini, G., Del Chiaro, M., Conlon, K. C., Falconi, M., Frigerio, I., Fusai, G. K., Gagniere, J., Griffin, O., Hackert, T., Halimi, A., Klaiber, U., Labori, K. J., Malleo, G., Marino, M. V., Mortensen, M. B., Nikov, A., Lesurtel, M., Keck, T., Kleeff, J., Pande, R., Pfeiffer, P., Pietrasz, D., Roberts, K. J., Sa Cunha, A., Salvia, R., Strobel, O., Tarvainen, T., Bossuyt, P. M., Van Laarhoven, H. W. M., Wilmink, J. W., Groot Koerkamp, B., and Besselink, M. G.

Subjects
Male, Cancer Research, medicine.medical_specialty, FOLFIRINOX, Adjuvant Chemotherapy, medicine.medical_treatment, Leucovorin, Irinotecan, Gastroenterology, 03 medical and health sciences, Folinic acid, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Adjuvant therapy, Humans, 030212 general & internal medicine, Neoadjuvant therapy, Original Investigation, Retrospective Studies, Adjuvant Chemotherapy, Resected Pancreatic Cancer, Neoadjuvant FOLFIRINOX Treatment, business.industry, Neoadjuvant FOLFIRINOX Treatment, Middle Aged, medicine.disease, Chemotherapy regimen, Neoadjuvant Therapy, Gemcitabine, 3. Good health, Oxaliplatin, Pancreatic Neoplasms, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Resected Pancreatic Cancer, Fluorouracil, business, medicine.drug
Abstract

Importance: The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.Objective: To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.Design, Setting, and Participants: This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded.Exposures: The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise.Results: We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73).Conclusions and Relevance: These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.

Published
2020

17. Follow-up after curative surgery for pancreatic ductal adenocarcinoma: asymptomatic recurrence is associated with improved survival.

Author

Nordby T, Hugenschmidt H, Fagerland MW, Ikdahl T, Buanes T, and Labori KJ

Subjects
Abdominal Pain etiology, Adult, Aged, Aged, 80 and over, Analysis of Variance, Back Pain etiology, Carcinoma, Pancreatic Ductal complications, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal therapy, Chemotherapy, Adjuvant, Confounding Factors, Epidemiologic, Disease-Free Survival, Fatigue etiology, Female, Follow-Up Studies, Humans, Jaundice etiology, Kaplan-Meier Estimate, Lymphatic Metastasis, Male, Medical Records, Middle Aged, Nausea etiology, Neoplasm Grading, Neoplasm Staging, Pancreatic Neoplasms complications, Pancreatic Neoplasms pathology, Pancreatic Neoplasms therapy, Pancreaticoduodenectomy methods, Population Surveillance methods, Prognosis, Radiotherapy, Adjuvant, Recurrence, Retrospective Studies, Splenectomy, Tomography, X-Ray Computed, Weight Loss, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal surgery, Pancreatectomy methods, Pancreatic Neoplasms mortality, Pancreatic Neoplasms surgery
Abstract

Aim: There is no consensus on the optimal follow-up schedule of patients after surgery for pancreatic cancer. In this retrospective study, recurrence and survival were investigated for patients presenting with either symptomatic or asymptomatic recurrence. Patient, tumor and treatment characteristics that predicted the length of postrecurrence survival were identified., Methods: Clinical records of 164 patients who underwent a pancreatic resection (R0/R1) for pancreatic ductal adenocarcinoma from January 2000 to December 2010 were retrieved. Patients underwent a systematic follow-up program. Patient, tumor and treatment characteristics were compared between patients with asymptomatic and symptomatic recurrence., Results: Of 164 consecutive patients, 144 patients (88%) had recurrence (29 asymptomatic, 115 symptomatic). The most frequent reported symptoms were abdominal pain, fatigue/weakness, back pain, weight loss, nausea/loss of appetite and jaundice. Median time to recurrence was 12.0 months for asymptomatic and 7.0 months for symptomatic patients (P = 0.036). Median postrecurrence survival was 10.0 months for asymptomatic and 4.0 months for symptomatic patients (P < 0.0001). Median overall survival was 24.5 months for asymptomatic and 11.0 months for symptomatic patients (P < 0.0001). Symptomatic recurrence, disease free survival <12 months, and no adjuvant chemotherapy were the only independent predictors of poor postrecurrence survival. 72% of asymptomatic and 37% of symptomatic patients received oncological treatment., Conclusions: Patients with asymptomatic pancreatic cancer recurrence have improved recurrence-free, postrecurrence and overall survival. Symptoms when recurrence is diagnosed are a good surrogate marker of biological aggressiveness. Detection of asymptomatic recurrence may facilitate patient eligibility for investigational studies or other forms of treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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