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51. Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial.

Author

Janssen, Q. P., van Dam, J. L., Bonsing, B. A., Bos, H., Bosscha, K. P., Coene, P. P. L. O., van Eijck, C. H. J., de Hingh, I. H. J. T., Karsten, T. M., van der Kolk, M. B., Patijn, G. A., Liem, M. S. L., van Santvoort, H. C., Loosveld, O. J. L., de Vos-Geelen, J., Zonderhuis, B. M., Homs, M. Y. V., van Tienhoven, G., Besselink, M. G., and Wilmink, J. W.

Subjects
PANCREATIC cancer, CHEMORADIOTHERAPY, PANCREATIC surgery, QUALITY of life, NEOADJUVANT chemotherapy, PROGRESSION-free survival, CANCER patients
Abstract

Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients.Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. 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 inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up.Discussion: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer.Trial Registration: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004. [ABSTRACT FROM AUTHOR]

Published
2021
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53. Nationwide comprehensive gastro-intestinal cancer cohorts : The 3P initiative

Author

van den Braak, R. R. J. Coebergh, van Rijssen, L. B., van Kleef, J. J., Vink, G. R., Berbee, M., Henegouwen, M. I. van Berge, Bloemendal, H. J., Bruno, M. J., Burgmans, M. C., Busch, O. R. C., Coene, P. P. L. O., Coupe, V. M. H., Dekker, J. W. T., van Eijck, C. H. J., Elferink, M. A. G., Erdkamp, F. L. G., van Grevenstein, W. M. U., de Groot, J. W. B., van Grieken, N. C. T., de Hingh, I. H. J. T., Hulshof, M. C. C. M., Ijzermans, J. N. M., Kwakkenbos, L., Lemmens, V. E. P. P., Los, M., Meijer, G. A., Molenaar, I. Q., Nieuwenhuijzen, G. A. P., de Noo, M. E., van de Poll-Franse, L. V., Punt, C. J. A., Rietbroek, R. C., Roeloffzen, W. W. H., Rozema, T., Ruurda, J. P., van Sandick, J. W., Schiphorst, A. H. W., Schipper, H., Siersema, P. D., Slingerland, M., Sommeijer, D. W., Spaander, M. C. W., Sprangers, M. A. G., Stockmann, H. B. A. C., Strijker, M., van Tienhoven, G., Timmermans, L. M., Tjin-a-Ton, M. L. R., van der Velden, A. M. T., Verhaar, M. J., Verkooijen, H. M., Vles, W. J., de Vos-Geelen, J. M. P. G. M., Wilmink, J. W., Zimmerman, D. D. E., van Oijen, M. G. H., Koopman, M., Besselink, M. G. H., van Laarhoven, H. W. M., van den Braak, R. R. J. Coebergh, van Rijssen, L. B., van Kleef, J. J., Vink, G. R., Berbee, M., Henegouwen, M. I. van Berge, Bloemendal, H. J., Bruno, M. J., Burgmans, M. C., Busch, O. R. C., Coene, P. P. L. O., Coupe, V. M. H., Dekker, J. W. T., van Eijck, C. H. J., Elferink, M. A. G., Erdkamp, F. L. G., van Grevenstein, W. M. U., de Groot, J. W. B., van Grieken, N. C. T., de Hingh, I. H. J. T., Hulshof, M. C. C. M., Ijzermans, J. N. M., Kwakkenbos, L., Lemmens, V. E. P. P., Los, M., Meijer, G. A., Molenaar, I. Q., Nieuwenhuijzen, G. A. P., de Noo, M. E., van de Poll-Franse, L. V., Punt, C. J. A., Rietbroek, R. C., Roeloffzen, W. W. H., Rozema, T., Ruurda, J. P., van Sandick, J. W., Schiphorst, A. H. W., Schipper, H., Siersema, P. D., Slingerland, M., Sommeijer, D. W., Spaander, M. C. W., Sprangers, M. A. G., Stockmann, H. B. A. C., Strijker, M., van Tienhoven, G., Timmermans, L. M., Tjin-a-Ton, M. L. R., van der Velden, A. M. T., Verhaar, M. J., Verkooijen, H. M., Vles, W. J., de Vos-Geelen, J. M. P. G. M., Wilmink, J. W., Zimmerman, D. D. E., van Oijen, M. G. H., Koopman, M., Besselink, M. G. H., and van Laarhoven, H. W. M.

Published
2018

54. Nationwide comprehensive gastro-intestinal cancer cohorts: The 3P initiative

Author

Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, MS CGO, Trialbureau Beeld, Epi Kanker Team A, Circulatory Health, JC onderzoeksprogramma Kanker, van den Braak, R. R. J. Coebergh, van Rijssen, L. B., van Kleef, J. J., Vink, G. R., Berbee, M., Henegouwen, M. I. van Berge, Bloemendal, H. J., Bruno, M. J., Burgmans, M. C., Busch, O. R. C., Coene, P. P. L. O., Coupe, V. M. H., Dekker, J. W. T., van Eijck, C. H. J., Elferink, M. A. G., Erdkamp, F. L. G., van Grevenstein, W. M. U., de Groot, J. W. B., van Grieken, N. C. T., de Hingh, I. H. J. T., Hulshof, M. C. C. M., Ijzermans, J. N. M., Kwakkenbos, L., Lemmens, V. E. P. P., Los, M., Meijer, G. A., Molenaar, I. Q., Nieuwenhuijzen, G. A. P., de Noo, M. E., van de Poll-Franse, L. V., Punt, C. J. A., Rietbroek, R. C., Roeloffzen, W. W. H., Rozema, T., Ruurda, J. P., van Sandick, J. W., Schiphorst, A. H. W., Schipper, H., Siersema, P. D., Slingerland, M., Sommeijer, D. W., Spaander, M. C. W., Sprangers, M. A. G., Stockmann, H. B. A. C., Strijker, M., van Tienhoven, G., Timmermans, L. M., Tjin-a-Ton, M. L. R., van der Velden, A. M. T., Verhaar, M. J., Verkooijen, H. M., Vles, W. J., de Vos-Geelen, J. M. P. G. M., Wilmink, J. W., Zimmerman, D. D. E., van Oijen, M. G. H., Koopman, M., Besselink, M. G. H., van Laarhoven, H. W. M., Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, MS CGO, Trialbureau Beeld, Epi Kanker Team A, Circulatory Health, JC onderzoeksprogramma Kanker, van den Braak, R. R. J. Coebergh, van Rijssen, L. B., van Kleef, J. J., Vink, G. R., Berbee, M., Henegouwen, M. I. van Berge, Bloemendal, H. J., Bruno, M. J., Burgmans, M. C., Busch, O. R. C., Coene, P. P. L. O., Coupe, V. M. H., Dekker, J. W. T., van Eijck, C. H. J., Elferink, M. A. G., Erdkamp, F. L. G., van Grevenstein, W. M. U., de Groot, J. W. B., van Grieken, N. C. T., de Hingh, I. H. J. T., Hulshof, M. C. C. M., Ijzermans, J. N. M., Kwakkenbos, L., Lemmens, V. E. P. P., Los, M., Meijer, G. A., Molenaar, I. Q., Nieuwenhuijzen, G. A. P., de Noo, M. E., van de Poll-Franse, L. V., Punt, C. J. A., Rietbroek, R. C., Roeloffzen, W. W. H., Rozema, T., Ruurda, J. P., van Sandick, J. W., Schiphorst, A. H. W., Schipper, H., Siersema, P. D., Slingerland, M., Sommeijer, D. W., Spaander, M. C. W., Sprangers, M. A. G., Stockmann, H. B. A. C., Strijker, M., van Tienhoven, G., Timmermans, L. M., Tjin-a-Ton, M. L. R., van der Velden, A. M. T., Verhaar, M. J., Verkooijen, H. M., Vles, W. J., de Vos-Geelen, J. M. P. G. M., Wilmink, J. W., Zimmerman, D. D. E., van Oijen, M. G. H., Koopman, M., Besselink, M. G. H., and van Laarhoven, H. W. M.

Published
2018

55. Nationwide comprehensive gastro-intestinal cancer cohorts: The 3P initiative

Author

Coebergh Van Den Braak, R. R. J., Van Rijssen, L. B., Van Kleef, J. J., Vink, G. R., Berbee, M., Van Berge Henegouwen, M. I., Bloemendal, H. J., Bruno, M. J., Burgmans, M. C., Busch, O. R. C., Coene, P. P. L. O., Coupé, V. M. H., Dekker, J. W. T., Van Eijck, C. H. J., Elferink, M. A. G., Erdkamp, F. L. G., Van Grevenstein, W. M. U., De Groot, J. W. B., Van Grieken, N. C. T., De Hingh, I. H. J. T., Hulshof, M. C. C. M., Ijzermans, J. N. M., Kwakkenbos, L., Lemmens, V. E. P. P., Los, M., Meijer, G. A., Molenaar, I. Q., Nieuwenhuijzen, G. A. P., De Noo, M. E., van de Poll-Franse, L.V., Punt, C. J. A., Rietbroek, R. C., Roeloffzen, W. W. H., Rozema, T., Ruurda, J. P., Van Sandick, J. W., Schiphorst, A. H. W., Schipper, H., Siersema, P. D., Slingerland, M., Sommeijer, D. W., Spaander, M. C. W., Sprangers, M. A. G., Stockmann, H. B. A. C., Strijker, M., Van Tienhoven, G., Timmermans, L. M., Tjin-a-ton, M. L. R., Van Der Velden, A. M. T., Verhaar, M. J., Verkooijen, H. M., Vles, W. J., De Vos-geelen, J. M. P. G. M., Wilmink, J. W., Zimmerman, D. D. E., Van Oijen, M. G. H., Koopman, M., Besselink, M. G. H., Van Laarhoven, H. W. M., Coebergh Van Den Braak, R. R. J., Van Rijssen, L. B., Van Kleef, J. J., Vink, G. R., Berbee, M., Van Berge Henegouwen, M. I., Bloemendal, H. J., Bruno, M. J., Burgmans, M. C., Busch, O. R. C., Coene, P. P. L. O., Coupé, V. M. H., Dekker, J. W. T., Van Eijck, C. H. J., Elferink, M. A. G., Erdkamp, F. L. G., Van Grevenstein, W. M. U., De Groot, J. W. B., Van Grieken, N. C. T., De Hingh, I. H. J. T., Hulshof, M. C. C. M., Ijzermans, J. N. M., Kwakkenbos, L., Lemmens, V. E. P. P., Los, M., Meijer, G. A., Molenaar, I. Q., Nieuwenhuijzen, G. A. P., De Noo, M. E., van de Poll-Franse, L.V., Punt, C. J. A., Rietbroek, R. C., Roeloffzen, W. W. H., Rozema, T., Ruurda, J. P., Van Sandick, J. W., Schiphorst, A. H. W., Schipper, H., Siersema, P. D., Slingerland, M., Sommeijer, D. W., Spaander, M. C. W., Sprangers, M. A. G., Stockmann, H. B. A. C., Strijker, M., Van Tienhoven, G., Timmermans, L. M., Tjin-a-ton, M. L. R., Van Der Velden, A. M. T., Verhaar, M. J., Verkooijen, H. M., Vles, W. J., De Vos-geelen, J. M. P. G. M., Wilmink, J. W., Zimmerman, D. D. E., Van Oijen, M. G. H., Koopman, M., Besselink, M. G. H., and Van Laarhoven, H. W. M.

Abstract

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients.Material and methods: All patients aged 18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future.Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing.Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses

Published
2018

60. Erythrocyte sedimentation rate as an independent prognostic marker for mortality: a prospective population-based cohort study.

Author

Fest, J., Ruiter, R., Mooijaart, S.P., Ikram, M. A., Eijck, C. H. J., Stricker, B. H., and van Eijck, C H J

Subjects
BLOOD sedimentation, PROPORTIONAL hazards models, AGE groups, COHORT analysis, MORTALITY, COMORBIDITY
Abstract

Background: A very high erythrocyte sedimentation rate (ESR) is usually an indication of underlying pathology. Additionally, a moderately elevated ESR may also be attributable to biological ageing. Whether the ESR is a prognostic factor for mortality, regardless of age, has been scarcely investigated. Therefore, the objective was to analyse the association between elevated ESR levels and the risk of mortality in a prospective cohort of the general population.Methods: We studied data from the Rotterdam Study (1990-2014). ESR levels were measured at baseline and individuals were followed until death or end of study. Associations between moderately (20-50 mm h-1 ) and markedly (>50 mm h-1 ) elevated ESR levels and all-cause mortality were assessed using multivariate Cox proportional hazard models.Results: In total, 5226 participants were included, and the mean age was 70.3 years. During a median follow-up time of 14.9 years, 3749 participants died (71.7%). After adjustment, both a moderately elevated ESR and a markedly elevated ESR were associated with a significantly higher risk of overall mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12-1.35 and HR 1.89, 95% CI 1.38-2.60, respectively]. Although the ESR becomes higher with age, in a group aged above 75 years, without any comorbidities, an ESR > 20 mm h-1 remained associated with a significantly increased risk of mortality (HR 1.29, 95%CI 1.01-1.64).Conclusion: An elevated ESR is an independent prognostic factor for mortality. Despite the fact that ESR increases with age, it remains associated with an increased risk of mortality and warrants close follow-up. [ABSTRACT FROM AUTHOR]

Published
2019
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61. A Nationwide Population-Based Study on the Survival of Patients with Pancreatic Neuroendocrine Tumors in The Netherlands.

Author

Genc, C. G., Klümpen, H. J., van Oijen, M. G. H., van Eijck, C. H. J., and Nieveen van Dijkum, E. J. M.

Subjects
TREATMENT effectiveness, NEUROENDOCRINE tumors, PANCREATIC tumors, SURGICAL excision, TUMOR surgery, TUMOR treatment
Abstract

Background: Large population-based studies give insight into the prognosis and treatment outcomes of patients with pancreatic neuroendocrine tumors (pNETs). Therefore, we provide an overview of the treatment and related survival of pNET in the Netherlands. Methods: Patients diagnosed with pNET between 2008 and 2013 from the Netherlands Cancer Registry were included. Patient, tumors and treatment characteristics were reported. Survival analyses with log-rank testing were performed to compare survival. Results: In total, 611 patients were included. Median follow-up was 25.7 months, and all-cause mortality was 42%. Higher tumor grade and TNM stage were significantly associated with worse survival in both the overall and metastasized population. The effect of distant metastases on survival was more significant in lower tumor stages (T1-3 p < 0.05, T4 p = 0.074). Resection of the primary tumor was performed in 255 (42%) patients. Patients who underwent surgery had the highest 5-year survival (86%) compared to PRRT (33%), chemotherapy (21%), targeted therapy and somatostatin analogs (24%) (all p < 0.001). Patients with T1M0 tumors ( n = 115) showed favorable survival after surgical resection ( N = 95) compared to no therapy ( N = 20, p = 0.008). Resection also improved survival significantly in patients with metastases compared to other treatments (all p > 0.05). Without surgery, PRRT showed the best survival curves in patients with distant metastases. Grade 3 tumors and surgical resection were independently associated with survival (HR 7.23 and 0.12, respectively). Conclusion: Surgical resection shows favorable outcome for all pNET tumors, including indolent tumors and tumors with distant metastases. Prospective trials should be initiated to confirm these results. [ABSTRACT FROM AUTHOR]

Published
2018
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62. Centralisatie pancreaschirurgie reduceert postoperatieve sterfte in Nederland*

Author

de Wilde, R. F., Besselink, M. G. H., Borel Rinkes, I. H. M., de Hingh, I. H. J. T., van Eijck, C. H. J., Dejong, C. H. C., Porte, R. J., Gouma, D. J., Busch, O. R. C., Molenaar, I. Q., Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, and Cancer Center Amsterdam

Abstract

To analyse the extent of centralisation of pancreaticoduodenectomy (Whipple procedure) and changes in in-hospital mortality rates in the Netherlands. Retrospective analysis. Data on patients who had undergone pancreaticoduodenectomy (PD) during the 2004-2009 period was acquired from the Kiwa Prismant registry. Based on the number of procedures performed annually, hospitals were divided into 4 volume-categories: very-low (

Published
2012

63. Preoperatieve galwegdrainage voor pancreaskoptumoren: meer complicaties*

Author

van der Gaag, N. A., Rauws, E. A. J., van Eijck, C. H. J., Bruno, M. J., van der Harst, E., Kubben, F. J. G. M., Gerritsen, J. J. G. M., Greve, J. W., Gerhards, M. F., de Hingh, I. H. J. T., Klinkenbijl, J. H., Yung Nio, C., de Castro, S. M. M., Busch, O. R. C., van Gulik, T. M., Bosssuyt, P. M. M., Gouma, D. J., Other departments, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Gastroenterology and Hepatology, and Surgery

Published
2010

70. Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy

Author

UCL - MD/MINT - Département de médecine interne, UCL - (SLuc) Service de médecine nucléaire, Krenning, E. P., de Jong, M., Kooij, P. P. M., Breeman, W. A., Bakker, W. H., de Herder, W. W., van Eijck, C. H. J., Kwekkeboom, D. J., Jamar, François, Pauwels, Stanislas, Valkema, R., UCL - MD/MINT - Département de médecine interne, UCL - (SLuc) Service de médecine nucléaire, Krenning, E. P., de Jong, M., Kooij, P. P. M., Breeman, W. A., Bakker, W. H., de Herder, W. W., van Eijck, C. H. J., Kwekkeboom, D. J., Jamar, François, Pauwels, Stanislas, and Valkema, R.

Abstract

Peptide receptor scintigraphy with the radioactive somatostatin analogue, [111In-DTPA0]octreotide, is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer-types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy (PRRT) with repeated administrations of high doses of [111In-DTPA0)octreotide. 111In emits Auger and conversion electrons having a tissue penetration of 0.02-10 microns and 200 to 500 microns, respectively. Thirty end-stage patients with mostly neuroendocrine progressing tumours were treated with [111In-DTPA0]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. There were no major clinical side effects after up to two years treatment, except that in a few patients a transient decline in platelets counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight patients showed stabilisation of disease and six other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. PRRT is feasible, also with 111In as radionuclide. Depending on the homogeneity of distribution of tumour cells expressing peptide receptors and the size of the tumour, beta-emitting radionuclides, e.g., 90Y, labelled to DOTA-chelated peptides, are also attractive candidates for PRRT. The first PRRT trials with [90Y-DOTA0,Tyr3]octreotide started recently.

Published
1999

77. Operative Treatment of Primary Hyperparathyroidism in Daycare Surgery

Author

Dulfer, R. R., van Ginhoven, T. M., Geilvoet, W., de Herder, W. W., and van Eijck, C. H. J.

Abstract

Objective: The standard of care for primary hyperparathyroidism is surgical removal of hyperfunctional parathyroid tissue. Here, we describe 20 patients with primary hyperparathyroidism who were treated surgically in the setting of daycare surgery.Design: Prospective observational study.Methods: A total of 20 patients with primary hyperparathyroidism were operated between March 2005 and May 2010. The follow-up period had a median of 41?weeks (5–245 weeks). Results are presented as mean (± standard deviation) or median (minimum–maximum).Results: A total of 20 patients (15 women, mean age 54 ± 14?years) were included. Nine patients were provided with post-operative calcium supplementation. One of the patients visited the emergency department the next day with paresthesia and normocalcemia; this patient was sent home. Four patients, without prophylaxis, also reported themselves to the emergency department. Only one had mild hypocalcemia (2.09?mmol/L) and was supplemented. Comparing the emergency department group (n?=?5) with the others, we found that pre-operative calcium levels were similar (p?=?0.40); however, the emergency department group had significantly lower post-operative calcium levels (2.27?±?0.14 vs 2.55?±?0.25, p?=?0.008) and the decrease-percentage was significantly higher (17.5%?±?5.4% vs 10.5% ± 6.4%, p?=?0.21).Conclusion: Parathyroidectomy in the daycare setting is feasible and safe. However, many patients return to the emergency department. This could be related to the strict information that is provided or due to a large decrease in their calcium levels, albeit normocalcemia. Calcium supplementation is cheap and safe, so we will provide all future patients with calcium supplementation and herewith aim to reduce the amount of emergency department visits.

Published
2015
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79. Correction to: Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Author

Giovinazzo, Francesco, Linneman, Ralph, Riva, Giulio Valentino Dalla, Greener, Daniele, Morano, Christopher, Patijn, Gijs A., Besselink, Mark G. H., Nieuwenhuijs, Vincent B., Abu Hilal, Mohammad, Artificial Intelligence Pancreatic Fistula Group, de Hingh, I. H., Kazemier, G., Festen, S., de Jong, K. P., van Eijck, C. H. J., Scheepers, J. J. G., van der Kolk, M., den Dulk, M., Bosscha, K., and Boerma, D.

Abstract

A correction to this paper has been published: https://doi.org/10.1007/s13304-021-01068-6 [ABSTRACT FROM AUTHOR]

Published
2021
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80. Pancreatic Fibrosis Correlates with Exocrine Pancreatic Insufficiency after Pancreatoduodenectomy.

Author

Tran, T. C. K., van ‘t Hof, G., Kazemier, G., Hop, W. C., Pek, C., van Toorenenbergen, A. W., van Dekken, H., and van Eijck, C. H. J.

Subjects
CYSTIC fibrosis, PANCREATICODUODENECTOMY, PANCREATIC surgery, SURGICAL complications, EXOCRINE glands, PANCREATIC duct, CANCER patients
Abstract

Background: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. Results: A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 μg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. Conclusion: The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2008
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81. The Post-Surgical Inflammatory Response Provokes Enhanced Tumour Recurrence: A Crucial Role for Neutrophils.

Author

van den Tol, M. P., ten Raa, S., van Grevenstein, W. M. U., van Rossen, M. E. E., Jeekel, J., and van Eijck, C. H. J.

Subjects
PERITONEAL dialysis, PREVENTION, NEUTROPHILS, THERAPEUTICS, EXPERIMENTS, CANCER, TUMORS, BLOOD cells
Abstract

Background/Aims: Peritoneal trauma activates a cascade of peritoneal defence mechanisms responsible for postoperative intra-abdominal tumour recurrence. After peritoneal trauma, inflammatory cells and soluble factors are present in the abdominal cavity and can be captured in lavage fluids. The present study evaluated which component enhances intra-abdominal tumour recurrence. Furthermore, we evaluated which inflammatory cells are present and studied the influence of anti-neutrophil serum (ANS) on peritoneal tumour recurrence. Methods: In a peritoneal trauma model in rats, postoperative lavage fluids were collected and separated into cellular and supernatant components. Both components were injected in naïve rats together with CC531s colon carcinoma cells. In a second experiment, rats were treated with one or three doses of ANS. Results: Intraperitoneal injection of naïve recipients with inflammatory cells or supernatant resulted in significant tumour recurrence. Severe peritoneal trauma provoked significant intra-abdominal neutrophil influx which could be prevented by ANS. Treatment with one dose did not affect blood cell counts and significantly reduced tumour recurrence. Treatment with three doses of ANS decreased blood lymphocytes, monocytes, and neutrophils and induced tumour load. Conclusions: Neutrophils play a crucial role in postoperative adhesion and growth of spilled tumour cells after surgical peritoneal trauma. Prevention of peritoneal neutrophil influx reduces local tumour recurrence. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2007
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82. Influence of Per-Operative Serum on Tumour Cell Adhesion in Vitro.

Author

Van Grevenstein, W. M. U., Hofland, L. J., Koetsveld, P. M., Jeekel, J., and Van Eijck, C. H. J.

Subjects
TUMORS, SERUM, CANCER cells, CELL adhesion, COLON cancer
Abstract

In case of massive tissue damage, the ensuing inflammatory reaction produces a potentially lethal cocktail of active mediators. Beside the influence of these local factors on local tumour recurrence, we hypothesize that during surgery systemically produced mediators are potential stimulators of tumour cell adhesion as well. The aim of this study was to investigate the influence of serum samples, obtained at eight different time periods before, during, and after surgery on the interaction between human colon carcinoma cells and mesothelial cells. In the control situation, the average adhesion of the Caco-2 cells to the mesothelial monolayers was 29%. No enhancement in adhesion was observed after incubation of the mesothelial cells with the pre- or postoperative serum of the patients. This study suggests that systemic factors produced directly after surgery are not influencing tumour adhesion to mesothelial monolayers. Therefore, local tumour recurrence is probably only influenced by locally produced factors. [ABSTRACT FROM AUTHOR]

Published
2007
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83. Delayed Closure of Complex Duodenal Injuries by a Foley Balloon Catheter Duodenostomy.

Author

Van Ginhoven, T., Schepers, T., Obertop, H., and Van Eijck, C. H. J.

Subjects
DUODENAL diseases, CATHETERS, DUODENOSCOPY, ENDOSCOPIC retrograde cholangiopancreatography, SURGICAL complications
Abstract

Less than 5% of abdominal injuries comprise the duodenum. Treatment is complex with high mortality and morbidity rates. These injuries are usually treated surgically and complications frequently occur. Three cases are presented in this communication in which the injury of the duodenum could not be repaired tension-free. In these cases a Foley balloon catheter was used to close the rupture. After a few weeks, patients were fed through the Foley catheter duodenostomy until a fistular track was formed. On removal of the catheter the fistular track closed spontaneously including the perforation of the duodenum. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2006
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84. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [[sup 177] Lu-DOTA[sup 0] ,Tyr[sup 3] ]octreotate.

Author

Kwekkeboom, D. J., Bakker, W. H., Kam, B. L., Teunissen, J. J. M., Kooij, P. P. M., de Herder, W. W., Feelders, R. A., van Eijck, C. H. J., de Jong, M., Srinivasan, A., Erion, J. L., and Krenning, E. P.

Subjects
NEUROENDOCRINE tumors, DRUG therapy, SOMATOSTATIN, TUMOR treatment
Abstract

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [[SUP90]Y-DOTA[SUP0],Tyr[SUP3]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA[SUP0],Tyr[SUP3]]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA[SUP0],Tyr[SUP3] octreotide. Also, labelled with the beta- and gamma-emitting radionuclide [SUP177]Lu, it has proved very successful in achieving tumour regression in animal models. The effects of [SUP177]Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi [SUP177]Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However,... [ABSTRACT FROM AUTHOR]

Published
2003
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85. Pigmented black neuroendocrine tumour of the pancreas diagnosed by fine needle aspiration cytology.

Author

Koljenovi, S., van Eijck, C. H. J., and den Bakker, M. A.

Subjects
*CASE studies, *ABDOMINAL pain, *SOMATOSTATIN, *IMMUNOCYTOCHEMISTRY, *POSITRON emission tomography, *ENDOCRINE gland tumors, *PATIENTS
Abstract

The article presents a case study of a 63-year-old female having a vague abdominal pain. Somatostatin receptor scintigraphy revealed unifocal accumulation in the pancreas region that is agreeable with a pancreatic endocrine tumour. Immunocytochemical analysis, made on spare air-dried smears, depicted strong positivity for cytokeratin 8/18.

Published
2010
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86. Enhanced Tumor Development after Surgery is Mainly due to Increased Adhesion of Tumor Cells.

Author

fen Raa, S., Oosterling, S. J., van der Kaaij, N. P., ten Kate, M., de Bruin, R. W. F., van den Tol, M. P., van Egmond, M., Beelen, R. H. J., van der Sijp, J. R. M., Meijer, S., van Eijck, C. H. J., and Jeekel, J.

Subjects
ABDOMINAL surgery, TUMOR surgery, IMMUNOSUPPRESSION, SURGERY, CANCER cells, IMMUNOLOGY
Abstract

Abdominal surgery induces an inflammatory reaction that activates a cascade of immunological events leading to increased postoperative intra-abdominal tumor recurrence. Subject for discussion is the mechanism by which postoperative intraabdominal tumor development is stimulated. Laparotomized groups enabled people to evaluate local and systemic effects of surgery on tumor development, whereas in thoracotomized groups only systemic effects were measured. The surgical intraperitoneal microenvironment enhances adhesion of free tumor cells rather than it affects growth of micrometastases. Additionally, local factors as well as systemic immune suppression as a result of surgery play an important role in facilitation of intra-abdominal tumor development.

Published
2004

87. The Influence of Reactive Oxygen Species on Adhesion of Pancreatic Tumor Cells to the Peritoneum.

Author

ten Raa, S., ten Kate, M., van't Hof, G., Sluiter, W., Hofland, L. J., Jeekel, J., and van Eijck, C. H. J.

Subjects
TUMORS, CANCER cells, PSYCHOANALYSIS, DEFENSE mechanisms (Psychology), EPITHELIUM, REACTIVE oxygen species
Abstract

Postoperative intra-abdominal tumor recurrence is significant clinical problem causing severe morbidity and mortality after "curative" resection of pancreatic carcinoma. Peroperative peritoneal trauma activates a cascade of peritoneal defense mechanisms responsible for postoperative intra-abdominal tumor recurrence. Reactive oxygen species (ROS) play a pivotal role in the post-operative inflammatory reaction. Conclusions: ROS appear to play an important role in the adhesion of pancreatic tumor cells to the mesothelium in vitro and therefore ROS can be held responsible for the enhanced post-operative intraabdominal tumor recurrence.

Published
2004

88. The Role of MMP-2 in Peritoneal Dissemination.

Author

Van't Hof, G., Ten Raa, S., Ten Kate, M., van Toorenenbergen, A. W., Hofland, L. J., Jeekel, J., and van Eijck, C. H. J.

Subjects
TUMOR surgery, CANCER cells, METALLOPROTEINASES, CANCER invasiveness, INFLAMMATION, NECROSIS
Abstract

Peritoneal dissemination after surgery for pancreatic carcinoma is one of the discouraging problems the clinician faces. Previous studies have shown that surgery leads to an inflammatory response that creates a mieroenvironment favourable for tumor cell adhesion. Several studies are performed to determine the role matrix metalloproteinases (MMP) play in the process of adhesion and tissue invasion. During the adhesion experiment the total concentration of MMP-2 increased tenfold in 24 h. The active fraction on the other hand was almost stable at a concentration of 0.2 ng/mL. Tumor-necrosis factor-alfa stimulates MMP-2 production of mesothelial cells. MMP-2 concentration seems not to be influenced by tumor cell adhesion.

Published
2004

90. Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis.

Author

Boxhoorn, L., van Dijk, S. M., van Grinsven, J., Verdonk, R. C., Boermeester, M. A., Bollen, T. L., Bouwense, S. A. W., Bruno, M. J., Cappendijk, V. C., Dejong, C. H. C., van Duijvendijk, P., van Eijck, C. H. J., Fockens, P., Francken, M. F. G., van Goor, H., Hadithi, M., Hallensleben, N. D. L., Haveman, J. W., Jacobs, M. A. J. M., and Jansen, J. M.

Abstract

BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P=0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. [ABSTRACT FROM AUTHOR]

Published
2021
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91. Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk

Author

Ye Lu, Chiara Corradi, Manuel Gentiluomo, Evangelina López de Maturana, George E. Theodoropoulos, Susanne Roth, Evaristo Maiello, Luca Morelli, Livia Archibugi, Jakob R. Izbicki, Patricia Sarlós, Vytautas Kiudelis, Martin Oliverius, Mateus Nóbrega Aoki, Yogesh Vashist, Casper H. J. van Eijck, Maria Gazouli, Renata Talar-Wojnarowska, Andrea Mambrini, Raffaele Pezzilli, Bas Bueno-de-Mesquita, Péter Hegyi, Pavel Souček, John P. Neoptolemos, Gregorio Di Franco, Cosimo Sperti, Emanuele F. Kauffmann, Viktor Hlaváč, Faik G. Uzunoğlu, Stefano Ermini, Ewa Małecka-Panas, Maurizio Lucchesi, Giuseppe Vanella, Frederike Dijk, Beatrice Mohelníková-Duchoňová, Franco Bambi, Maria Chiara Petrone, Krzysztof Jamroziak, Feng Guo, Katerina Kolarova, Giovanni Capretti, Anna Caterina Milanetto, Laura Ginocchi, Martin Loveček, Marta Puzzono, Hanneke W. M. van Laarhoven, Silvia Carrara, Audrius Ivanauskas, Konstantinos Papiris, Daniela Basso, Paolo G. Arcidiacono, Ferenc Izbéki, Roger Chammas, Pavel Vodicka, Thilo Hackert, Claudio Pasquali, Maria L. Piredda, Eithne Costello-Goldring, Giulia Martina Cavestro, Andrea Szentesi, Francesca Tavano, Barbara Włodarczyk, Hermann Brenner, Edita Kreivenaite, Xin Gao, Stefania Bunduc, Roel C. H. Vermeulen, Martin A. Schneider, Anna Latiano, Domenica Gioffreda, Sabrina G. G. Testoni, Juozas Kupcinskas, Rita T. Lawlor, Gabriele Capurso, Núria Malats, Daniele Campa, Federico Canzian, Sub IER overig, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Internal medicine, Surgery, Lu, Y., Corradi, C., Gentiluomo, M., Lopez de Maturana, E., Theodoropoulos, G. E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J. R., Sarlos, P., Kiudelis, V., Oliverius, M., Aoki, M. N., Vashist, Y., van Eijck, C. H. J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., Pezzilli, R., Bueno-de-Mesquita, B., Hegyi, P., Soucek, P., Neoptolemos, J. P., Di Franco, G., Sperti, C., Kauffmann, E. F., Hlavac, V., Uzunoglu, F. G., Ermini, S., Malecka-Panas, E., Lucchesi, M., Vanella, G., Dijk, F., Mohelnikova-Duchonova, B., Bambi, F., Petrone, M. C., Jamroziak, K., Guo, F., Kolarova, K., Capretti, G., Milanetto, A. C., Ginocchi, L., Lovecek, M., Puzzono, M., van Laarhoven, H. W. M., Carrara, S., Ivanauskas, A., Papiris, K., Basso, D., Arcidiacono, P. G., Izbeki, F., Chammas, R., Vodicka, P., Hackert, T., Pasquali, C., Piredda, M. L., Costello-Goldring, E., Cavestro, G. M., Szentesi, A., Tavano, F., Wlodarczyk, B., Brenner, H., Kreivenaite, E., Gao, X., Bunduc, S., Vermeulen, R. C. H., Schneider, M. A., Latiano, A., Gioffreda, D., Testoni, S. G. G., Kupcinskas, J., Lawlor, R. T., Capurso, G., Malats, N., Campa, D., Canzian, F., Pathology, AII - Cancer immunology, CCA - Cancer biology and immunology, Oncology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Linkage disequilibrium, In silico, pancreatic cancer, pancreatic ductal adenocarcinoma, Single-nucleotide polymorphism, Biology, QH426-470, susceptibility, genetic polymorphisms, miRNA, SDG 3 - Good Health and Well-being, Pancreatic cancer, medicine, Genetics, SNP, Genetics(clinical), 03.02. Klinikai orvostan, Gene, Genotyping, Genetics (clinical), Original Research, Heritability, medicine.disease, Molecular Medicine
Abstract

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case–Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07–1.17, p = 3.03 × 10−6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.

Published
2021

92. Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk

Author

Raffaele Pezzilli, Pavel Vodicka, Andrea Párniczky, George Theodoropoulos, Renata Talar-Wojnarowska, Paolo Giorgio Arcidiacono, Ugo Boggi, Bálint Erőss, Ewa Małecka-Panas, Martin Oliverius, Daniele Campa, Rita T. Lawlor, Faik G. Uzunoglu, Maria Chiara Petrone, Livia Archibugi, Stefania Bunduc, Edita Kreivenaite, Beatrice Mohelnikova-Duchonova, Manuel Gentiluomo, Maria Liliana Piredda, Giulia Peduzzi, Thilo Hackert, Francesco Perri, Giuseppe Vanella, Olivier R. Busch, Hermann Brenner, Pavel Soucek, John P. Neoptolemos, Martin Schneider, Sabrina Gloria Giulia Testoni, Luca Morelli, Krzysztof Jamroziak, Federico Canzian, Daniela Basso, Silvia Carrara, Maria Gazouli, Juozas Kupcinskas, Konstantinos Georgiou, Xīn Gào, Claudio Pasquali, Cosimo Sperti, Evaristo Maiello, Vytautas Kiudelis, Mara Götz, Martin Loos, Gabriele Capurso, Francesca Bazzocchi, Martin Lovecek, Bas Bueno-de-Mesquita, Viktor Hlavac, Niccola Funel, Roel Vermeulen, Maarten F. Bijlsma, Anna Caterina Milanetto, Ye Lu, Giulia Martina Cavestro, Stefano Ermini, Andrea Szentesi, Jakob R. Izbicki, William Greenhalf, Francesca Tavano, Feng Guo, Marta Puzzono, Domenica Gioffreda, Péter Hegyi, Eithne Costello, Casper H.J. van Eijck, Stefano Landi, Peduzzi, G., Gentiluomo, M., Tavano, F., Arcidiacono, P. G., Ermini, S., Vodicka, P., Boggi, U., Cavestro, G. M., Capurso, G., Morelli, L., Milanetto, A. C., Pezzilli, R., Lawlor, R. T., Carrara, S., Lovecek, M., Soucek, P., Guo, F., Hackert, T., Uzunoglu, F. G., Gazouli, M., Parniczky, A., Kupcinskas, J., Bijlsma, M. F., Bueno-De-Mesquita, B., Vermeulen, R., van Eijck, C. H. J., Jamroziak, K., Talar-Wojnarowska, R., Greenhalf, W., Gioffreda, D., Petrone, M. C., Landi, S., Archibugi, L., Puzzono, M., Funel, N., Sperti, C., Piredda, M. L., Mohelnikova-Duchonova, B., Lu, Y., Hlavac, V., Gao, X., Schneider, M., Izbicki, J. R., Theodoropoulos, G., Bunduc, S., Kreivenaite, E., Busch, O. R., Malecka-Panas, E., Costello, E., Perri, F., Giulia Testoni, S. G., Vanella, G., Pasquali, C., Oliverius, M., Brenner, H., Loos, M., Gotz, M., Georgiou, K., Eross, B., Maiello, E., Szentesi, A., Bazzocchi, F., Basso, D., Neoptolemos, J. P., Hegyi, P., Kiudelis, V., Canzian, F., Campa, D., Surgery, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Center of Experimental and Molecular Medicine, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Mitochondrial DNA, Pancreatic ductal adenocarcinoma, Nuclear gene, endocrine system diseases, Epidemiology, Biology, SUSCEPTIBILITY, Polymorphism, Single Nucleotide, SDG 3 - Good Health and Well-being, Pancreatic cancer, medicine, Humans, 03.02. Klinikai orvostan, Genetic variability, Carcinoma, Pancreatic Ductal, Case-Control Studies, Genetic Variation, Genome, Mitochondrial, Mitochondria, Pancreatic Neoplasms, Polymorphism, GENOME-WIDE ASSOCIATION, Gene, Genetics, Genome, GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY, Carcinoma, Single Nucleotide, Metabolism, medicine.disease, digestive system diseases, Mitochondrial, Oncology, Pancreatic Ductal
Abstract

Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported. Methods: We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software. Results: In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P < 0.05). In the second phase, none of the findings were replicated. In the gene-level analysis, we observed that three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial metabolism showed an association below the Bonferroni-corrected threshold of statistical significance (P = 0.05/1588 = 3.1 × 10−5). Conclusions: Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk. Impact: This large case–control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.

Published
2021

94. Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival

Author

Chiara Corradi, Carsten Palnæs Hansen, Beatrice Mohelnikova-Duchonova, Maria Gazouli, Francesca Tavano, Paolo Giorgio Arcidiacono, Anna Caterina Milanetto, Pavel Soucek, Gabriele Capurso, Casper H.J. van Eijck, Dania Bozzato, Oliver Strobel, Federico Canzian, Thilo Hackert, Manuel Gentiluomo, Giuseppe Vanella, Erika Darvasi, Giulia Martina Cavestro, Andrea Szentesi, Juozas Kupcinskas, John P. Neoptolemos, Astrid Z. Johansen, Raffaele Pezzilli, Pavel Vodicka, Péter Hegyi, Eithne Costello, Renata Talar-Wojnarowska, Daniele Campa, Liliana Piredda, Julia S. Johansen, Inna Chen, Gentiluomo, M., Corradi, C., Vanella, G., Johansen, A. Z., Strobel, O., Szentesi, A., Milanetto, A. C., Hegyi, P., Kupcinskas, J., Tavano, F., Neoptolemos, J. P., Bozzato, D., Hackert, T., Pezzilli, R., Johansen, J. S., Costello, E., Mohelnikova-Duchonova, B., van Eijck, C. H. J., Talar-Wojnarowska, R., Hansen, C. P., Darvasi, E., Chen, I. M., Cavestro, G. M., Soucek, P., Piredda, L., Vodicka, P., Gazouli, M., Arcidiacono, P. G., Canzian, F., Campa, D., Capurso, G., and Surgery

Subjects
Oncology, Male, medicine.medical_specialty, Pancreatic disease, Pancreatic ductal adenocarcinoma, Science, Disease, Kaplan-Meier Estimate, Polymorphism, Single Nucleotide, Article, Gastrointestinal cancer, Cancer epidemiology, Internal medicine, Genotype, Biomarkers, Tumor, Cancer genomics, Aged, Carcinoma, Pancreatic Ductal, Chitinases, Female, Humans, Hyaluronan Receptors, Middle Aged, Pancreatic Neoplasms, Medicine, In patient, Polymorphism, Stage (cooking), Cancer genetics, Tumor, Multidisciplinary, biology, business.industry, Carcinoma, CD44, Single Nucleotide, medicine.disease, Pancreatic Ductal, Genetic marker, biology.protein, business, Biomarkers
Abstract

Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients’ response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58–15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.

Published
2021

95. A New Scoring System to Predict Recurrent Disease in Grade 1 and 2 Nonfunctional Pancreatic Neuroendocrine Tumors

Author

Anneke P. J. Jilesen, S. van Eeden, F. J. van Kemenade, Stefano Partelli, Francesca Muffatti, S. van Dieren, Cansu Guney Genc, J. Verheij, E. J. M. Nieveen van Dijkum, Massimo Falconi, C.H.J. van Eijck, Surgery, CCA - Cancer Treatment and Quality of Life, Pathology, APH - Methodology, AGEM - Digestive immunity, Genc, C. G., Jilesen, A. P., Partelli, S., Falconi, M., Muffatti, F., Van Kemenade, F. J., Van Eeden, S., Verheij, J., Van Dieren, S., Van Eijck, C. H. J., and Nieveen Van Dijkum, E. J. M.

Subjects
Oncology, Male, medicine.medical_specialty, Scoring system, recurrence, Non functional, Neuroendocrine tumors, Gastroenterology, nomogram, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Recurrence, Internal medicine, medicine, Recurrent disease, Humans, In patient, Neoplasm Invasiveness, Aged, Proportional Hazards Models, Retrospective Studies, Neoplasm Grading, pancreatic neuroendocrine tumors, Hepatology, Proportional hazards model, business.industry, Retrospective cohort study, Nomogram, Middle Aged, medicine.disease, Surgery, Pancreatic Neoplasms, Nomograms, 030220 oncology & carcinogenesis, Lymphatic Metastasis, 030211 gastroenterology & hepatology, Female, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Objective: The aim of this study was to predict recurrence in patients with grade 1 or 2 nonfunctioning pancreatic neuroendocrine tumors (NF-pNET) after curative resection. Background: Surgical resection is the preferred treatment for NF-pNET; however, recurrence occurs frequently after curative surgery, worsening prognosis of patients. Methods: Retrospectively, patients with NF-pNET of 3 institutions were included. Patients with distant metastases, hereditary syndromes, or grade 3 tumors were excluded. Local or distant tumor recurrence was scored. Independent predictors for survival and recurrence were identified using Cox-regression analysis. The recurrence score was developed to predict recurrence within 5 years after curative resection of grade 1 to 2 NF-pNET. Results: With a median follow-up of 51 months, 211 patients with grade 1 to 2 NF-pNET were included. Thirty-five patients (17%) developed recurrence. The 5- and 10-year disease-specific/overall survival was 98%/91% and 84%/68%, respectively. Predictors for recurrence were tumor grade 2, lymph node metastasis, and perineural invasion. On the basis of these predictors, the recurrence score was made. Discrimination [c-statistic 0.81, 95% confidence interval (95% CI) 0.75-0.87] and calibration (Hosmer Lemeshow Chi-square 11.25, P = 0.258) indicated that the ability of the recurrence score to identify patients at risk for recurrence is good. Conclusions: This new scoring system could predict recurrence after curative resection of grade 1 and 2 NF-pNET. With the use of the recurrence score, less extensive follow-up could be proposed for patients with low recurrence risk. For high-risk patients, clinical trials should be initiated to investigate whether adjuvant therapy might be beneficial. External validation is ongoing due to limited availability of adequate cohorts.

Published
2018

96. Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67

Author

Claudio Doglioni, Francesca Muffatti, Heinz-Josef Klümpen, E.J.M. Nieveen van Dijkum, S. van Eeden, C.H.J. van Eijck, Stefano Partelli, Massimo Falconi, Cansu Guney Genc, Genc, C. G., Falconi, M., Partelli, S., Muffatti, F., van Eeden, S., Doglioni, C., Klumpen, H. J., van Eijck, C. H. J., Nieveen van Dijkum, E. J. M., Surgery, Pathology, CCA - Imaging and biomarkers, AGEM - Digestive immunity, Oncology, and AGEM - Endocrinology, metabolism and nutrition

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Neuroendocrine tumors, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pancreatectomy, Surgical oncology, Internal medicine, Biomarkers, Tumor, Medicine, Humans, Neoplasm Invasiveness, Lymph node, Survival rate, Aged, Retrospective Studies, business.industry, Proportional hazards model, Retrospective cohort study, Pancreatic Tumors, Middle Aged, medicine.disease, Prognosis, Pancreatic Neoplasms, Survival Rate, Regimen, Neuroendocrine Tumors, medicine.anatomical_structure, Ki-67 Antigen, Oncology, 030220 oncology & carcinogenesis, Lymphatic Metastasis, 030211 gastroenterology & hepatology, Surgery, Female, Neoplasm Recurrence, Local, business, Adjuvant, Follow-Up Studies
Abstract

Background: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. Methods: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0–5 and Ki67 6–20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. Results: The study enrolled 241 patients (86%) with Ki67 0–5% and 39 patients (14%) with Ki67 6–20%. Recurrence was seen in 34 patients (14%) with Ki67 0–5% after a median period of 34months and in 16 patients (41%) with Ki67 6–20% after a median period of 16months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0–5% and respectively 55 and 26% for Ki67 6–20% (p < 0.001). The overall survival period after recurrence was 44.9months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4cm and lymph node metastases were independently associated with recurrence. Conclusions: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed.

Published
2018

98. Gender differences in tumor characteristics, treatment allocation and survival in stage I-III pancreatic cancer: a nationwide study.

Author

Gehrels AM, Wagner AD, Besselink MG, Verhoeven RHA, van Eijck CHJ, van Laarhoven HWM, Wilmink JW, and van der Geest LG

Subjects
Humans, Female, Male, Aged, Middle Aged, Netherlands epidemiology, Sex Factors, Registries statistics & numerical data, Healthcare Disparities statistics & numerical data, Aged, 80 and over, Survival Rate, Pancreatic Neoplasms mortality, Pancreatic Neoplasms therapy, Pancreatic Neoplasms pathology, Neoplasm Staging
Abstract

Introduction: Sex and gender are modulators of health and disease and may have impact on treatment allocation and survival in patients with cancer. In this study, we analyzed the impact of sex and gender on treatment allocation and overall survival in patients with stage I-III pancreatic cancer., Methods: Patients with stage I-III pancreatic cancer diagnosed between 2015 and 2020 were selected from the nationwide Netherlands Cancer Registry. Associations between sex and gender and the probability of receiving surgical and/or systemic treatment were examined with multivariable logistic regression analyses. Overall survival was assessed with log rank test and multivariable Cox proportional hazard analysis., Results: Among 6855 patients, 51.2 % were female. Multivariable logistic regression analyses with adjustment for known confounders (age, performance status, comorbidities, tumor location, tumor stage and previous malignancies) showed that females less often received systemic chemotherapy compared to males (OR 0.799, 95 %CI 0.703-0.909, p < .001). No difference was found in the probability for undergoing surgical resection. Furthermore, females had worse overall survival compared to males (median OS 8.5 and 9.2 months respectively, 95 %CI 8.669-9.731)., Conclusion: This nationwide study found that female patients with stage I-III pancreatic cancer significantly less often received systemic treatment and had worse overall survival as compared to males. Disparities in pancreatic cancer care can be decreased by recognizing and resolving potential obstacles or biases in treatment decision-making., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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99. Overexpression of the adhesion signaling pathway is linked to short-term survival in pancreatic ductal adenocarcinoma.

Author

Aziz MH, Saida L, van Eijck CHJ, and Mustafa DAM

Subjects
Humans, Prognosis, Signal Transduction, Integrins, Tumor Microenvironment, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal pathology
Abstract

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) is known for its unfavorable prognosis. Gaining insights into the molecular mechanisms that contribute to its progression is crucial for developing effective therapies. In this study, our objective was to investigate the molecular pathways associated with short-term survival in patients with PDAC., Methods: Immune profiles were analyzed from both long-term survivors (n = 10) and short-term survivors (n = 10) after surgical resection. Pathway scores were calculated to compare the two groups., Results: The "Adhesion" pathway emerged as the most significant pathway, exhibiting a notably higher score in the samples of short-term survivors (P < 0.009). Within this pathway, significant findings were observed in genes related to integrins and CEACAM., Conclusion: The role of integrins in the tumor microenvironment of pancreatic cancer is of utmost importance, as they are found to be overexpressed in short-term survivors. These findings provide valuable insights into the underlying biology of PDAC and have potential implications for the development of therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare no conflict of interests regarding any financial disclosures nor commercial associations., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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100. Dataset from a proteomics analysis of tumor antigens shared between an allogenic tumor cell lysate vaccine and pancreatic tumor tissue.

Author

Stingl C, Lau SP, van der Burg SH, Aerts JG, van Eijck CHJ, and Luider TM

Abstract

The data described was acquired as part of a clinical study with the aim to investigate the potential of tumor-reactive T-cell response as response to vaccination of pancreatic cancer patients with an allogenic tumor cell lysate vaccine (Lau et al., 2022). Proteomics analysis was carried out to identify tumor antigens that are shared between the allogeneic tumor cell lysate used for the vaccine and pancreatic ductal adenocarcinoma (PDAC) tissue samples. To this objective, cell lysates of the vaccine and of nine tissue samples were enzymatically digested and isotopically labeled with tandem mass tags (TMT) in a so-called six-plex manner (Thermo Fisher Scientific). Three pools were prepared by mixing the samples according to their TMT-labels. Subsequently, the three sample pools were fractionated into 24 fractions with high-pH reversed phase chromatography. These fractions were first analyzed on a nano-liquid chromatography (LC) system online coupled to a high-resolution Eclipse Orbitrap mass spectrometer (MS) equipped with a high-field asymmetric-waveform ion-mobility spectrometry (FAIMS) source using a data-dependent MS2 shotgun method. Overall, 126,618 unique peptide sequences, on basis of 768,638 peptide spectra matches and corresponding to 7,597 protein groups, were identified in the total sample set including 61 tumor antigens (Supplement Table S2 in Lau et al. 2022) that were prioritized by Cheever and co-workers as vaccine target antigens on basis of a series of objective criteria (Cheever et al., 2009). In the second phase of the experiment, this set of tumor antigens was targeted using a serial precursor selection (SPS) MS3 method. From this data, ion trap MS2 and Orbitrap MS3 fragment spectra were extracted for peptide identification (protein sequence database-dependent search) and relative quantification using the TMT labels, respectively. The dataset ultimately allowed the identification and quantification of 51 proteins and 163 related peptide precursors with the TMT labels (see Fig. 2B and Supplemental Fig. 8, Lau et al. 2022)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Please declare any financial interests/personal relationships which may be considered as potential competing interests here: J.G.A: Stock or other Ownership: Amphera. Consulting or Advisory Role: Eli-Lilly, MSD Oncology, Bristol-Myers Squibb, Roche, AstraZeneca. Rest of the authors have no relationship to disclose in relation to the submitted work., (© 2022 Published by Elsevier Inc.)

Published
2022
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