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1. Prospective multicentre study of indications for surgery in patients with idiopathic acute pancreatitis following endoscopic ultrasonography (PICUS).

Author

Umans, D.S., Timmerhuis, H.C., Anten, M.G.F., Bhalla, A., Bijlsma, R.A., Boxhoorn, L., Brink, Maaike, Bruno, M.J., Curvers, W.L., Eijck, B.C. van, Erkelens, G.W., Geenen, E.J.M. van, Hazen, W.L., Hoge, C.V., Hol, L., Inderson, A., Kager, L.M., Kuiken, S.D., Perk, L.E., Quispel, R., Römkens, T.E.H., Sperna Weiland, C.J., Thijssen, A.Y., Venneman, N.G., Verdonk, R.C., Wanrooij, R.L.J. van, Witteman, B.J., Besselink, M.G.H., Hooft, Jeanin E. van, Umans, D.S., Timmerhuis, H.C., Anten, M.G.F., Bhalla, A., Bijlsma, R.A., Boxhoorn, L., Brink, Maaike, Bruno, M.J., Curvers, W.L., Eijck, B.C. van, Erkelens, G.W., Geenen, E.J.M. van, Hazen, W.L., Hoge, C.V., Hol, L., Inderson, A., Kager, L.M., Kuiken, S.D., Perk, L.E., Quispel, R., Römkens, T.E.H., Sperna Weiland, C.J., Thijssen, A.Y., Venneman, N.G., Verdonk, R.C., Wanrooij, R.L.J. van, Witteman, B.J., Besselink, M.G.H., and Hooft, Jeanin E. van

Abstract

Contains fulltext : 300159.pdf (Publisher’s version ) (Open Access), BACKGROUND: Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP). METHODS: This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up. RESULTS: After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life. CONCLUSION: EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study.

Published
2023

4. Pain patterns in chronic pancreatitis

Author

Kempeneers, M.A., Issa, Y., Verdonk, R.C., Bruno, M., Fockens, P., Goor, H. van, Alofs, E., Bollen, T.L., Bouwense, S., Dalen, A.S.H.M. van, Dieren, S. van, Dullemen, H.M. van, Geenen, E.J. van, Hoge, C., Hooft, J.E. van, Kager, L.M., Keulemans, Y., Nooijen, L.E., Poley, J.W., Seerden, T.C.J., Tan, A., Thijs, W., Timmer, R., Vleggaar, F., Witteman, B., Ali, U.A., Besselink, M.G., Boermeester, M.A., Santvoort, H.C. van, Dutch Pancreatitis Study Grp, Graduate School, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Other Research, Surgery, APH - Methodology, Center for Liver, Digestive and Metabolic Diseases (CLDM), Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: FHML non-thematic output, and Gastroenterology & Hepatology

Subjects
Male, Bio Process Engineering, PROGNOSIS, Nutrition and Disease, MULTICENTER, GUIDELINES, 0302 clinical medicine, Quality of life, INSUFFICIENCY, intractable pain, QUALITY-OF-LIFE, Risk Factors, EXOCRINE, Surveys and Questionnaires, Voeding en Ziekte, Longitudinal Studies, Prospective Studies, pancreatic surgery, Longitudinal cohort, Netherlands, Pain Measurement, medicine.diagnostic_test, Gastroenterology, Middle Aged, ENDOSCOPIC TREATMENT, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], 030220 oncology & carcinogenesis, Neuropathic pain, 030211 gastroenterology & hepatology, DUCT, Female, medicine.medical_specialty, Visual analogue scale, SURGICAL DRAINAGE, QUESTIONNAIRE, Pain, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], chronic pancreatitis, 03 medical and health sciences, Internal medicine, Pancreatitis, Chronic, medicine, Humans, endoscopy, business.industry, medicine.disease, Endoscopy, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Pain patterns, quality of life, Pancreatitis, Intractable pain, business
Abstract

ObjectivePain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing, we studied pain patterns in a prospective longitudinal nationwide study.Design1131 patients with chronic pancreatitis (fulfilling M-ANNHEIM criteria) were included between 2011 and 2018 in 30 Dutch hospitals. Patients with continuous or intermittent pain were compared for demographics, pain characteristics, quality of life (Short-Form 36), imaging findings, disease duration and treatment. Alternation of pain pattern and associated variables were longitudinally assessed using a multivariable multinomial logistic regression model.ResultsAt inclusion, 589 patients (52%) had continuous pain, 231 patients (20%) had intermittent pain and 311 patients (28%) had no pain. Patients with continuous pain had more severe pain, used more opioids and neuropathic pain medication, and had a lower quality of life. There were no differences between pain patterns for morphological findings on imaging, disease duration and treatment. During a median follow-up of 47 months, 552 of 905 patients (61%) alternated at least once between pain patterns. All alternations were associated with the Visual Analogue Scale pain intensity score and surgery was only associated with the change from pain to no pain.ConclusionContinuous and intermittent pain patterns in chronic pancreatitis do not seem to be the result of distinctly different pathophysiological entities. The subjectively reported character of pain is not related to imaging findings or disease duration. Pain patterns often change over time and are merely a feature of how severity of pain is experienced.

Published
2021

5. Pain patterns in chronic pancreatitis: a nationwide longitudinal cohort study

Author

Kempeneers, Marinus A., Issa, Y., Verdonk, R.C., Bruno, M., Fockens, P., Goor, H. van, Alofs, E., Bollen, T.L., Bouwense, S.A., Dalen, A. van, Dieren, S. van, Dullemen, H.M. van, Geenen, E.J.M. van, Hoge, C., Hooft, Jeanin E. van, Kager, L.M., Keulemans, Y., Nooijen, L.E., Poley, J.W., Seerden, T.C., Tan, A., Thijs, W., Timmer, R., Vleggaar, F., Witteman, B., Ali, U. Ahmed, Besselink, M.G.H., Boermeester, Marja A., Santvoort, H.C. van, Kempeneers, Marinus A., Issa, Y., Verdonk, R.C., Bruno, M., Fockens, P., Goor, H. van, Alofs, E., Bollen, T.L., Bouwense, S.A., Dalen, A. van, Dieren, S. van, Dullemen, H.M. van, Geenen, E.J.M. van, Hoge, C., Hooft, Jeanin E. van, Kager, L.M., Keulemans, Y., Nooijen, L.E., Poley, J.W., Seerden, T.C., Tan, A., Thijs, W., Timmer, R., Vleggaar, F., Witteman, B., Ali, U. Ahmed, Besselink, M.G.H., Boermeester, Marja A., and Santvoort, H.C. van

Abstract

Contains fulltext : 238452.pdf (Publisher’s version ) (Closed access), OBJECTIVE: Pain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing, we studied pain patterns in a prospective longitudinal nationwide study. DESIGN: 1131 patients with chronic pancreatitis (fulfilling M-ANNHEIM criteria) were included between 2011 and 2018 in 30 Dutch hospitals. Patients with continuous or intermittent pain were compared for demographics, pain characteristics, quality of life (Short-Form 36), imaging findings, disease duration and treatment. Alternation of pain pattern and associated variables were longitudinally assessed using a multivariable multinomial logistic regression model. RESULTS: At inclusion, 589 patients (52%) had continuous pain, 231 patients (20%) had intermittent pain and 311 patients (28%) had no pain. Patients with continuous pain had more severe pain, used more opioids and neuropathic pain medication, and had a lower quality of life. There were no differences between pain patterns for morphological findings on imaging, disease duration and treatment. During a median follow-up of 47 months, 552 of 905 patients (61%) alternated at least once between pain patterns. All alternations were associated with the Visual Analogue Scale pain intensity score and surgery was only associated with the change from pain to no pain. CONCLUSION: Continuous and intermittent pain patterns in chronic pancreatitis do not seem to be the result of distinctly different pathophysiological entities. The subjectively reported character of pain is not related to imaging findings or disease duration. Pain patterns often change over time and are merely a feature of how severity of pain is experienced.

Published
2021

6. Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis The ESCAPE Randomized Clinical Trial

Author

Issa, Y., Kempeneers, M.A., Bruno, M.J., Fockens, P., Poley, J.W., Ali, U.A., Bollen, T.L., Busch, O.R., Dejong, C.H., Duijvendijk, P. van, Dullemen, H.M. van, Eijck, C.H. van, Goor, H. van, Hadithi, M., Haveman, J.W., Keulemans, Y., Nieuwenhuijs, V.B., Poen, A.C., Rauws, E.A., Tan, A.C., Thijs, W., Timmer, R., Witteman, B.J., Besselink, M.G., Hooft, J.E. van, Santvoort, H.C. van, Dijkgraaf, M.G., Boermeester, M.A., Honkoop, P., Thijssen, A.Y., Kooistra, T., Balkema, S., Bekkali, N., Boparai, K.S., Kager, L.M., Kloek, J.J., Takkenberg, R.B., Gouma, D.J., Gulik, T.M. van, Bemelman, W.A., Zwinderman, A.H., Bodelier, A.G.L., Seerden, T.C.J., Enckevort, C. van, Gils, N. van, Schoon, E., Vogelaar, L., Vries, R.S. de, Voorburg, A.M., Heisterkamp, J., Bezemer, G., Braat, H., Didden, P., Farahani, N., Flink, H.J., Koch, A.D., Postma, C., Putten, P.G. van, Reijnders, J.G.P., Roomer, R., Wiersema, U., Homans, G.L., Mares, W.G.N., Meiland, R., Erkelens, G.W., Maanen, H. van, Muller, G., Geenen, E. van, Perk, L.E., Raaf, J. de, Fransen, K., Hoedemaker, R., Meijssen, M.A.C., Hergelink, D.O., Munster, I.P. van, Romkes, T.E.H., Braat, A.E., Schaapherder, A.F.M., Kubben, F.J.G.M., Hoge, C., Masclee, A., Stassen, L.P.S., Brink, M.A., Vlerken, L. van, Kolkman, J.J., Venneman, N.G., Houdijk, A.P.J., Spek, B. van der, Jansen, J.M., The, O., Gerhards, M.F., Gooszen, H.G., Wilder-Smith, O., Hoekstra, J., Josemanders, D.F.G.M., Spanier, B.W.M., Boer, S.Y. de, Vries, E. de, Al-toma, A., Ramshorst, B. van, Weusten, B.L.A.M., Boerma, D., Bijlsma, A.R., Festen, E.A.M., Kerkhof, I., Kleibeuker, J.H., Kouw, E., Hofker, H.S., Ploeg, R., Beese, U., Siersema, P.D., Vleggaar, F.P., Molenaar, I.Q., Aktas, H., Guchelaar, I., Dutch Pancreatitis Study Grp, Gastroenterology & Hepatology, Surgery, RS: NUTRIM - R2 - Liver and digestive health, and MUMC+: MA Heelkunde (9)

Subjects
medicine.medical_specialty, Randomization, diagnosis, SURGICAL DRAINAGE, duodenum-preserving resection, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], duct, GUIDELINES, 01 natural sciences, law.invention, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Superiority Trial, All institutes and research themes of the Radboud University Medical Center, Quality of life, Randomized controlled trial, law, Internal medicine, medicine, MANAGEMENT, 030212 general & internal medicine, 0101 mathematics, Pancreatitis, chronic, therapy, medicine.diagnostic_test, business.industry, 010102 general mathematics, General Medicine, head, medicine.disease, Endoscopy, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Pancreatitis, Observational study, business
Abstract

Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function. Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes. Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018. Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed. Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality. Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P =.02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P =.10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P

Published
2020

7. Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study

Author

Umans, D.S. (Devica S.), Timmerhuis, H.C. (Hester C.), Hallensleben, N.D.L. (Nora D.L.), Bouwense, S.A.W. (Stefan), Anten, M.-P.G.F. (Marie-Paule G.F.), Bhalla, A., Bijlsma, R.A. (Rina A.), Boermeester, M.A. (Marja), Brink, M.A. (Menno), Hol, L. (Lieke), Bruno, M.J. (Marco), Curvers, W.L. (Wouter L.), Dullemen, H.M. (Hendrik) van, Van Eijck, B.C. (B. C.), Erkelens, G.W. (G.Willemien), Fockens, P. (Paul), Geenen, E-J.M. (Erwin-Jan), Hazen, W.L. (Wouter L.), Hoge, C.V. (Chantal V.), Inderson, A. (Akin), Kager, L.M. (Liesbeth M.), Kuiken, S.D. (Sjoerd D.), Perk, L.E. (Lars E.), Poley, J.-W. (Jan-Werner), Quispel, R. (Rutger), Römkens, T.E.H., Santvoort, H.C. (Hjalmar) van, Tan, A.C. (Adriaan), Thijssen, A.Y. (Annemieke Y.), Venneman, N.G. (Niels), Vleggaar, F.P. (Frank), Voorburg, A.M. (Annet McJ), Wanrooij, R.L.J. (Roy) van, Witteman, B.J.M. (Ben), Verdonk, R.C. (Robert), Besselink, M.G. (Marc), Hooft, J.E. (Jeanin) van, Umans, D.S. (Devica S.), Timmerhuis, H.C. (Hester C.), Hallensleben, N.D.L. (Nora D.L.), Bouwense, S.A.W. (Stefan), Anten, M.-P.G.F. (Marie-Paule G.F.), Bhalla, A., Bijlsma, R.A. (Rina A.), Boermeester, M.A. (Marja), Brink, M.A. (Menno), Hol, L. (Lieke), Bruno, M.J. (Marco), Curvers, W.L. (Wouter L.), Dullemen, H.M. (Hendrik) van, Van Eijck, B.C. (B. C.), Erkelens, G.W. (G.Willemien), Fockens, P. (Paul), Geenen, E-J.M. (Erwin-Jan), Hazen, W.L. (Wouter L.), Hoge, C.V. (Chantal V.), Inderson, A. (Akin), Kager, L.M. (Liesbeth M.), Kuiken, S.D. (Sjoerd D.), Perk, L.E. (Lars E.), Poley, J.-W. (Jan-Werner), Quispel, R. (Rutger), Römkens, T.E.H., Santvoort, H.C. (Hjalmar) van, Tan, A.C. (Adriaan), Thijssen, A.Y. (Annemieke Y.), Venneman, N.G. (Niels), Vleggaar, F.P. (Frank), Voorburg, A.M. (Annet McJ), Wanrooij, R.L.J. (Roy) van, Witteman, B.J.M. (Ben), Verdonk, R.C. (Robert), Besselink, M.G. (Marc), and Hooft, J.E. (Jeanin) van

Abstract

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound

Published
2020
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8. Coagulation and fibrinolysis in tuberculosis, melioidosis and beyond

Author

Kager, L.M., van der Poll, T., van 't Veer, C., Wiersinga, W.J., and Faculteit der Geneeskunde

Abstract

The studies presented in this thesis significantly contribute to the current knowledge on the role of proteins involved in coagulation, anticoagulation and fibrinolysis during TB and melioidosis. We showed that during TB, although a chronic disease, the coagulation system becomes activated. The physiological significance of this activation, however, still is unclear and we failed to show a clear functional role for proteins involved in the PC system. With respect to melioidosis, we here demonstrated that some (components of) proteins involved in coagulation and fibrinolysis significantly contribute to the host defense against B. pseudomallei. This knowledge may add to further understanding of the pathophysiological processes during this severe septic disease and may serve as new targets for additional therapies.

Published
2014

9. Plasminogen activator inhibitor type I may contribute to transient, non-specific changes in immunity in the subacute phase of murine tuberculosis.

Author

Kager, L.M., Windt, G.J. van der, Wieland, C.W., Florquin, S., Veer, C. van't, Poll, T. van der, Kager, L.M., Windt, G.J. van der, Wieland, C.W., Florquin, S., Veer, C. van't, and Poll, T. van der

Abstract

1 augustus 2012, Item does not contain fulltext, Tuberculosis, caused by Mycobacterium (M.) tuberculosis, is a devastating infectious disease causing many deaths worldwide. Non-specific host defense mechanisms such as the coagulation and fibrinolytic system may give insight in possible new therapeutic targets. Plasminogen activator inhibitor type-1 (PAI-1), an important regulator of inflammation and fibrinolysis, might be of interest as tuberculosis patients have elevated plasma levels of PAI-1. In this study we set out to investigate the role of PAI-1 during tuberculosis in vivo. Wildtype (WT) and PAI-1 deficient (PAI-1(-/-)) mice were intranasally infected with M. tuberculosis H37rv and sacrificed after 2, 5 and 29 weeks. Five weeks post-infection, bacterial loads in lungs of PAI-1(-/-) mice were significantly higher compared to WT mice, while no differences were seen 2 and 29 weeks post-infection. At two weeks post-infection increased influx of macrophages and lymphocytes was observed. PAI-1 deficiency was associated with a reduced cytokine response in the lungs; however, upon stimulation with tuberculin purified protein derivative (PPD), PAI-1(-/-) splenocytes released increased levels of IFN-gamma compared to WT. No clear differences were found between PAI-1(-/-) and WT mice at 29 weeks after infection. In conclusion, these data suggest that PAI-1 contributes to transient, non-specific changes in immunity during the early phase of murine tuberculosis.

Published
2012

10. Expression and function of macrophage migration inhibitory factor (MIF) in melioidosis.

Author

Wiersinga, W.J., Calandra, T, Kager, L.M., Windt, G.J. van der, Roger, T., Roy, D. Le, Florquin, S., Peacock, S.J., Sweep, C.G.J., Poll, T. van der, Wiersinga, W.J., Calandra, T, Kager, L.M., Windt, G.J. van der, Roger, T., Roy, D. Le, Florquin, S., Peacock, S.J., Sweep, C.G.J., and Poll, T. van der

Abstract

Contains fulltext : 88613.pdf (publisher's version ) (Open Access), BACKGROUND: Macrophage migration inhibitory factor (MIF) has emerged as a pivotal mediator of innate immunity and has been shown to be an important effector molecule in severe sepsis. Melioidosis, caused by Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast-Asia. We aimed to characterize the expression and function of MIF in melioidosis. METHODOLOGY AND PRINCIPAL FINDINGS: MIF expression was determined in leukocytes and plasma from 34 melioidosis patients and 32 controls, and in mice infected with B. pseudomallei. MIF function was investigated in experimental murine melioidosis using anti-MIF antibodies and recombinant MIF. Patients demonstrated markedly increased MIF mRNA leukocyte and MIF plasma concentrations. Elevated MIF concentrations were associated with mortality. Mice inoculated intranasally with B. pseudomallei displayed a robust increase in pulmonary and systemic MIF expression. Anti-MIF treated mice showed lower bacterial loads in their lungs upon infection with a low inoculum. Conversely, mice treated with recombinant MIF displayed a modestly impaired clearance of B. pseudomallei. MIF exerted no direct effects on bacterial outgrowth or phagocytosis of B. pseudomallei. CONCLUSIONS: MIF concentrations are markedly elevated during clinical melioidosis and correlate with patients' outcomes. In experimental melioidosis MIF impaired antibacterial defense.

Published
2010

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