Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial

Daniël P. V. Lambrichts, Sandra Vennix, Gijsbert D. Musters, Irene M. Mulder, Hilko A. Swank, Anton G. M. Hoofwijk, Eric H. J. Belgers, Hein B. A. C. Stockmann, Quirijn A. J. Eijsbouts, Michael F. Gerhards, Bart A. van Wagensveld, Anna A. W. van Geloven, Rogier M. P. H. Crolla, Simon W. Nienhuijs, Marc J. P. M. Govaert, Salomone di Saverio, André J. L. D'Hoore, Esther C. J. Consten, Wilhelmina M. U. van Grevenstein, Robert E. G. J. M. Pierik & 156 others Philip M. Kruyt, Joost A. B. van der Hoeven, Willem H. Steup, Fausto Catena, Joop L. M. Konsten, Jefrey Vermeulen, S. van Dieren, Willem A. Bemelman, Johan F. Lange, W. C. Hop, B. C. Opmeer, J. B. Reitsma, R. A. Scholte, E. W. H. Waltmann, D. A. Legemate, J. F. Bartelsman, D. W. Meijer, Ünlü, A. B. Kluit, Y. el-Massoudi, R. Vuylsteke, P. J. Tanis, R. Matthijsen, S. W. Polle, S. M. Lagarde, S. S. Gisbertz, O. Wijers, J. D. W. van der Bilt, M. A. Boermeester, R. Blom, J. A. H. Gooszen, M. H. F. Schreinemacher, T. van der Zande, M. M. N. Leeuwenburgh, S. A. L. Bartels, W. L. E. M. Hesp, L. Koet, G. P. van der Schelling, E. van Dessel, M. L. P. van Zeeland, M. M. A. Lensvelt, H. Nijhof, S. Verest, M. Buijs, J. H. Wijsman, L. P. S. Stassen, M. Klinkert, M. F. G. de Maat, G. Sellenraad, J. Jeekel, G. J. Kleinrensink, T. Tha-in, W. N. Nijboer, M. J. Boom, P. C. M. Verbeek, C. Sietses, M. W. J. Stommel, P. J. van Huijstee, J. W. S. Merkus, D. Eefting, J. S. D. Mieog, D. van Geldere, G. A. Patijn, M. de Vries, M. Boskamp, A. Bentohami, T. S. Bijlsma, N. de Korte, D. Nio, H. Rijna, J. Luttikhold, M. H. van Gool, J. F. Fekkes, G. J. M. Akkersdijk, G. Heuff, E. H. Jutte, B. A. Kortmann, J. M. Werkman, W. Laméris, L. Rietbergen, P. Frankenmolen, W. A. Draaisma, M. A. W. Stam, M. S. Verweij, T. M. Karsten, L. C. de Nes, S. Fortuin, S. M. de Castro, A. Doeksen, M. P. Simons, G. I. Koffeman, E. P. Steller, J. B. Tuynman, P. Boele van Hensbroek, M. Mok, S. R. van Diepen, K. W. E. Hulsewé, J. Melenhorst, J. H. M. B. Stoot, S. Fransen, M. N. Sosef, J. van Bastelaar, Y. L. J. Vissers, T. P. D. Douchy, C. E. Christiaansen, R. Smeenk, A. M. Pijnenburg, V. Tanaydin, H. T. C. Veger, S. H. E. M. Clermonts, M. Al-Taher, E. J. R. de Graaf, A. G. Menon, M. Vermaas, H. A. Cense, E. Jutte, M. J. Wiezer, A. B. Smits, M. Westerterp, H. A. Marsman, E. R. Hendriks, O. van Ruler, E. J. C. Vriens, J. M. Vogten, C. C. van Rossem, D. Ohanis, E. Tanis, J. van Grinsven, J. K. Maring, J. Heisterkamp, M. G. H. Besselink, I. H. M. Borel Rinkes, I. Q. Molenaar, J. J. A. Joosten, V. Jongkind, G. M. P. Diepenhorst, M. C. Boute, M. Smeenge, K. Nielsen, J. J. Harlaar, M. D. P. Luyer, G. van Montfort, J. F. Smulders, F. Daams, E. van Haren, G. A. P. Nieuwenhuijzen, G. J. Lauret, I. T. A. Pereboom, R. A. Stokmans, A. Birindelli, E. Bianchi, S. Pellegrini, I. Terrasson, A. Wolthuis, A. de Buck van Overstraeten, S. Nijs

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. Methods: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. Findings: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7–100] vs 71·7% [95% CI 60·1–83·3], hazard ratio 2·79 [95% CI 1·86–4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). Interpretation: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). Funding: Netherlands Organisation for Health Research and Development.
Original languageEnglish
Pages (from-to)599-610
JournalThe Lancet Gastroenterology and Hepatology
Volume4
Issue number8
DOIs
Publication statusPublished - 2019

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Lambrichts, Daniël P. V. ; Vennix, Sandra ; Musters, Gijsbert D. ; Mulder, Irene M. ; Swank, Hilko A. ; Hoofwijk, Anton G. M. ; Belgers, Eric H. J. ; Stockmann, Hein B. A. C. ; Eijsbouts, Quirijn A. J. ; Gerhards, Michael F. ; van Wagensveld, Bart A. ; van Geloven, Anna A. W. ; Crolla, Rogier M. P. H. ; Nienhuijs, Simon W. ; Govaert, Marc J. P. M. ; di Saverio, Salomone ; D'Hoore, André J. L. ; Consten, Esther C. J. ; van Grevenstein, Wilhelmina M. U. ; Pierik, Robert E. G. J. M. ; Kruyt, Philip M. ; van der Hoeven, Joost A. B. ; Steup, Willem H. ; Catena, Fausto ; Konsten, Joop L. M. ; Vermeulen, Jefrey ; van Dieren, S. ; Bemelman, Willem A. ; Lange, Johan F. ; Hop, W. C. ; Opmeer, B. C. ; Reitsma, J. B. ; Scholte, R. A. ; Waltmann, E. W. H. ; Legemate, D. A. ; Bartelsman, J. F. ; Meijer, D. W. ; Ünlü ; Kluit, A. B. ; el-Massoudi, Y. ; Vuylsteke, R. ; Tanis, P. J. ; Matthijsen, R. ; Polle, S. W. ; Lagarde, S. M. ; Gisbertz, S. S. ; Wijers, O. ; van der Bilt, J. D. W. ; Boermeester, M. A. ; Blom, R. ; Gooszen, J. A. H. ; Schreinemacher, M. H. F. ; van der Zande, T. ; Leeuwenburgh, M. M. N. ; Bartels, S. A. L. ; Hesp, W. L. E. M. ; Koet, L. ; van der Schelling, G. P. ; van Dessel, E. ; van Zeeland, M. L. P. ; Lensvelt, M. M. A. ; Nijhof, H. ; Verest, S. ; Buijs, M. ; Wijsman, J. H. ; Stassen, L. P. S. ; Klinkert, M. ; de Maat, M. F. G. ; Sellenraad, G. ; Jeekel, J. ; Kleinrensink, G. J. ; Tha-in, T. ; Nijboer, W. N. ; Boom, M. J. ; Verbeek, P. C. M. ; Sietses, C. ; Stommel, M. W. J. ; van Huijstee, P. J. ; Merkus, J. W. S. ; Eefting, D. ; Mieog, J. S. D. ; van Geldere, D. ; Patijn, G. A. ; de Vries, M. ; Boskamp, M. ; Bentohami, A. ; Bijlsma, T. S. ; de Korte, N. ; Nio, D. ; Rijna, H. ; Luttikhold, J. ; van Gool, M. H. ; Fekkes, J. F. ; Akkersdijk, G. J. M. ; Heuff, G. ; Jutte, E. H. ; Kortmann, B. A. ; Werkman, J. M. ; Laméris, W. ; Rietbergen, L. ; Frankenmolen, P. ; Draaisma, W. A. ; Stam, M. A. W. ; Verweij, M. S. ; Karsten, T. M. ; de Nes, L. C. ; Fortuin, S. ; de Castro, S. M. ; Doeksen, A. ; Simons, M. P. ; Koffeman, G. I. ; Steller, E. P. ; Tuynman, J. B. ; Boele van Hensbroek, P. ; Mok, M. ; van Diepen, S. R. ; Hulsewé, K. W. E. ; Melenhorst, J. ; Stoot, J. H. M. B. ; Fransen, S. ; Sosef, M. N. ; van Bastelaar, J. ; Vissers, Y. L. J. ; Douchy, T. P. D. ; Christiaansen, C. E. ; Smeenk, R. ; Pijnenburg, A. M. ; Tanaydin, V. ; Veger, H. T. C. ; Clermonts, S. H. E. M. ; Al-Taher, M. ; de Graaf, E. J. R. ; Menon, A. G. ; Vermaas, M. ; Cense, H. A. ; Jutte, E. ; Wiezer, M. J. ; Smits, A. B. ; Westerterp, M. ; Marsman, H. A. ; Hendriks, E. R. ; van Ruler, O. ; Vriens, E. J. C. ; Vogten, J. M. ; van Rossem, C. C. ; Ohanis, D. ; Tanis, E. ; van Grinsven, J. ; Maring, J. K. ; Heisterkamp, J. ; Besselink, M. G. H. ; Borel Rinkes, I. H. M. ; Molenaar, I. Q. ; Joosten, J. J. A. ; Jongkind, V. ; Diepenhorst, G. M. P. ; Boute, M. C. ; Smeenge, M. ; Nielsen, K. ; Harlaar, J. J. ; Luyer, M. D. P. ; van Montfort, G. ; Smulders, J. F. ; Daams, F. ; van Haren, E. ; Nieuwenhuijzen, G. A. P. ; Lauret, G. J. ; Pereboom, I. T. A. ; Stokmans, R. A. ; Birindelli, A. ; Bianchi, E. ; Pellegrini, S. ; Terrasson, I. ; Wolthuis, A. ; de Buck van Overstraeten, A. ; Nijs, S. / Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial. In: The Lancet Gastroenterology and Hepatology. 2019 ; Vol. 4, No. 8. pp. 599-610.
@article{4d91b73d434f492cb083a7b5afcf2163,
title = "Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial",
abstract = "Background: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. Methods: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. Findings: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27{\%}) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6{\%} [95{\%} CI 88·7–100] vs 71·7{\%} [95{\%} CI 60·1–83·3], hazard ratio 2·79 [95{\%} CI 1·86–4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44{\%}] of 66 patients vs 25 [39{\%}] of 64, p=0·60; mortality: two [3{\%}] vs four [6{\%}], p=0·44). Interpretation: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). Funding: Netherlands Organisation for Health Research and Development.",
author = "Lambrichts, {Dani{\"e}l P. V.} and Sandra Vennix and Musters, {Gijsbert D.} and Mulder, {Irene M.} and Swank, {Hilko A.} and Hoofwijk, {Anton G. M.} and Belgers, {Eric H. J.} and Stockmann, {Hein B. A. C.} and Eijsbouts, {Quirijn A. J.} and Gerhards, {Michael F.} and {van Wagensveld}, {Bart A.} and {van Geloven}, {Anna A. W.} and Crolla, {Rogier M. P. H.} and Nienhuijs, {Simon W.} and Govaert, {Marc J. P. M.} and {di Saverio}, Salomone and D'Hoore, {Andr{\'e} J. L.} and Consten, {Esther C. J.} and {van Grevenstein}, {Wilhelmina M. U.} and Pierik, {Robert E. G. J. M.} and Kruyt, {Philip M.} and {van der Hoeven}, {Joost A. B.} and Steup, {Willem H.} and Fausto Catena and Konsten, {Joop L. M.} and Jefrey Vermeulen and {van Dieren}, S. and Bemelman, {Willem A.} and Lange, {Johan F.} and Hop, {W. C.} and Opmeer, {B. C.} and Reitsma, {J. B.} and Scholte, {R. A.} and Waltmann, {E. W. H.} and Legemate, {D. A.} and Bartelsman, {J. F.} and Meijer, {D. W.} and {\"U}nl{\"u} and Kluit, {A. B.} and Y. el-Massoudi and R. Vuylsteke and Tanis, {P. J.} and R. Matthijsen and Polle, {S. W.} and Lagarde, {S. M.} and Gisbertz, {S. S.} and O. Wijers and {van der Bilt}, {J. D. W.} and Boermeester, {M. A.} and R. Blom and Gooszen, {J. A. H.} and Schreinemacher, {M. H. F.} and {van der Zande}, T. and Leeuwenburgh, {M. M. N.} and Bartels, {S. A. L.} and Hesp, {W. L. E. M.} and L. Koet and {van der Schelling}, {G. P.} and {van Dessel}, E. and {van Zeeland}, {M. L. P.} and Lensvelt, {M. M. A.} and H. Nijhof and S. Verest and M. Buijs and Wijsman, {J. H.} and Stassen, {L. P. S.} and M. Klinkert and {de Maat}, {M. F. G.} and G. Sellenraad and J. Jeekel and Kleinrensink, {G. J.} and T. Tha-in and Nijboer, {W. N.} and Boom, {M. J.} and Verbeek, {P. C. M.} and C. Sietses and Stommel, {M. W. J.} and {van Huijstee}, {P. J.} and Merkus, {J. W. S.} and D. Eefting and Mieog, {J. S. D.} and {van Geldere}, D. and Patijn, {G. A.} and {de Vries}, M. and M. Boskamp and A. Bentohami and Bijlsma, {T. S.} and {de Korte}, N. and D. Nio and H. Rijna and J. Luttikhold and {van Gool}, {M. H.} and Fekkes, {J. F.} and Akkersdijk, {G. J. M.} and G. Heuff and Jutte, {E. H.} and Kortmann, {B. A.} and Werkman, {J. M.} and W. Lam{\'e}ris and L. Rietbergen and P. Frankenmolen and Draaisma, {W. A.} and Stam, {M. A. W.} and Verweij, {M. S.} and Karsten, {T. M.} and {de Nes}, {L. C.} and S. Fortuin and {de Castro}, {S. M.} and A. Doeksen and Simons, {M. P.} and Koffeman, {G. I.} and Steller, {E. P.} and Tuynman, {J. B.} and {Boele van Hensbroek}, P. and M. Mok and {van Diepen}, {S. R.} and Hulsew{\'e}, {K. W. E.} and J. Melenhorst and Stoot, {J. H. M. B.} and S. Fransen and Sosef, {M. N.} and {van Bastelaar}, J. and Vissers, {Y. L. J.} and Douchy, {T. P. D.} and Christiaansen, {C. E.} and R. Smeenk and Pijnenburg, {A. M.} and V. Tanaydin and Veger, {H. T. C.} and Clermonts, {S. H. E. M.} and M. Al-Taher and {de Graaf}, {E. J. R.} and Menon, {A. G.} and M. Vermaas and Cense, {H. A.} and E. Jutte and Wiezer, {M. J.} and Smits, {A. B.} and M. Westerterp and Marsman, {H. A.} and Hendriks, {E. R.} and {van Ruler}, O. and Vriens, {E. J. C.} and Vogten, {J. M.} and {van Rossem}, {C. C.} and D. Ohanis and E. Tanis and {van Grinsven}, J. and Maring, {J. K.} and J. Heisterkamp and Besselink, {M. G. H.} and {Borel Rinkes}, {I. H. M.} and Molenaar, {I. Q.} and Joosten, {J. J. A.} and V. Jongkind and Diepenhorst, {G. M. P.} and Boute, {M. C.} and M. Smeenge and K. Nielsen and Harlaar, {J. J.} and Luyer, {M. D. P.} and {van Montfort}, G. and Smulders, {J. F.} and F. Daams and {van Haren}, E. and Nieuwenhuijzen, {G. A. P.} and Lauret, {G. J.} and Pereboom, {I. T. A.} and Stokmans, {R. A.} and A. Birindelli and E. Bianchi and S. Pellegrini and I. Terrasson and A. Wolthuis and {de Buck van Overstraeten}, A. and S. Nijs",
year = "2019",
doi = "10.1016/S2468-1253(19)30174-8",
language = "English",
volume = "4",
pages = "599--610",
journal = "The Lancet Gastroenterology and Hepatology",
issn = "2468-1253",
publisher = "Elsevier Ltd",
number = "8",

}

Lambrichts, DPV, Vennix, S, Musters, GD, Mulder, IM, Swank, HA, Hoofwijk, AGM, Belgers, EHJ, Stockmann, HBAC, Eijsbouts, QAJ, Gerhards, MF, van Wagensveld, BA, van Geloven, AAW, Crolla, RMPH, Nienhuijs, SW, Govaert, MJPM, di Saverio, S, D'Hoore, AJL, Consten, ECJ, van Grevenstein, WMU, Pierik, REGJM, Kruyt, PM, van der Hoeven, JAB, Steup, WH, Catena, F, Konsten, JLM, Vermeulen, J, van Dieren, S, Bemelman, WA, Lange, JF, Hop, WC, Opmeer, BC, Reitsma, JB, Scholte, RA, Waltmann, EWH, Legemate, DA, Bartelsman, JF, Meijer, DW, Ünlü, Kluit, AB, el-Massoudi, Y, Vuylsteke, R, Tanis, PJ, Matthijsen, R, Polle, SW, Lagarde, SM, Gisbertz, SS, Wijers, O, van der Bilt, JDW, Boermeester, MA, Blom, R, Gooszen, JAH, Schreinemacher, MHF, van der Zande, T, Leeuwenburgh, MMN, Bartels, SAL, Hesp, WLEM, Koet, L, van der Schelling, GP, van Dessel, E, van Zeeland, MLP, Lensvelt, MMA, Nijhof, H, Verest, S, Buijs, M, Wijsman, JH, Stassen, LPS, Klinkert, M, de Maat, MFG, Sellenraad, G, Jeekel, J, Kleinrensink, GJ, Tha-in, T, Nijboer, WN, Boom, MJ, Verbeek, PCM, Sietses, C, Stommel, MWJ, van Huijstee, PJ, Merkus, JWS, Eefting, D, Mieog, JSD, van Geldere, D, Patijn, GA, de Vries, M, Boskamp, M, Bentohami, A, Bijlsma, TS, de Korte, N, Nio, D, Rijna, H, Luttikhold, J, van Gool, MH, Fekkes, JF, Akkersdijk, GJM, Heuff, G, Jutte, EH, Kortmann, BA, Werkman, JM, Laméris, W, Rietbergen, L, Frankenmolen, P, Draaisma, WA, Stam, MAW, Verweij, MS, Karsten, TM, de Nes, LC, Fortuin, S, de Castro, SM, Doeksen, A, Simons, MP, Koffeman, GI, Steller, EP, Tuynman, JB, Boele van Hensbroek, P, Mok, M, van Diepen, SR, Hulsewé, KWE, Melenhorst, J, Stoot, JHMB, Fransen, S, Sosef, MN, van Bastelaar, J, Vissers, YLJ, Douchy, TPD, Christiaansen, CE, Smeenk, R, Pijnenburg, AM, Tanaydin, V, Veger, HTC, Clermonts, SHEM, Al-Taher, M, de Graaf, EJR, Menon, AG, Vermaas, M, Cense, HA, Jutte, E, Wiezer, MJ, Smits, AB, Westerterp, M, Marsman, HA, Hendriks, ER, van Ruler, O, Vriens, EJC, Vogten, JM, van Rossem, CC, Ohanis, D, Tanis, E, van Grinsven, J, Maring, JK, Heisterkamp, J, Besselink, MGH, Borel Rinkes, IHM, Molenaar, IQ, Joosten, JJA, Jongkind, V, Diepenhorst, GMP, Boute, MC, Smeenge, M, Nielsen, K, Harlaar, JJ, Luyer, MDP, van Montfort, G, Smulders, JF, Daams, F, van Haren, E, Nieuwenhuijzen, GAP, Lauret, GJ, Pereboom, ITA, Stokmans, RA, Birindelli, A, Bianchi, E, Pellegrini, S, Terrasson, I, Wolthuis, A, de Buck van Overstraeten, A & Nijs, S 2019, 'Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial' The Lancet Gastroenterology and Hepatology, vol. 4, no. 8, pp. 599-610. https://doi.org/10.1016/S2468-1253(19)30174-8

Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial. / Lambrichts, Daniël P. V.; Vennix, Sandra; Musters, Gijsbert D.; Mulder, Irene M.; Swank, Hilko A.; Hoofwijk, Anton G. M.; Belgers, Eric H. J.; Stockmann, Hein B. A. C.; Eijsbouts, Quirijn A. J.; Gerhards, Michael F.; van Wagensveld, Bart A.; van Geloven, Anna A. W.; Crolla, Rogier M. P. H.; Nienhuijs, Simon W.; Govaert, Marc J. P. M.; di Saverio, Salomone; D'Hoore, André J. L.; Consten, Esther C. J.; van Grevenstein, Wilhelmina M. U.; Pierik, Robert E. G. J. M.; Kruyt, Philip M.; van der Hoeven, Joost A. B.; Steup, Willem H.; Catena, Fausto; Konsten, Joop L. M.; Vermeulen, Jefrey; van Dieren, S.; Bemelman, Willem A.; Lange, Johan F.; Hop, W. C.; Opmeer, B. C.; Reitsma, J. B.; Scholte, R. A.; Waltmann, E. W. H.; Legemate, D. A.; Bartelsman, J. F.; Meijer, D. W.; Ünlü; Kluit, A. B.; el-Massoudi, Y.; Vuylsteke, R.; Tanis, P. J.; Matthijsen, R.; Polle, S. W.; Lagarde, S. M.; Gisbertz, S. S.; Wijers, O.; van der Bilt, J. D. W.; Boermeester, M. A.; Blom, R.; Gooszen, J. A. H.; Schreinemacher, M. H. F.; van der Zande, T.; Leeuwenburgh, M. M. N.; Bartels, S. A. L.; Hesp, W. L. E. M.; Koet, L.; van der Schelling, G. P.; van Dessel, E.; van Zeeland, M. L. P.; Lensvelt, M. M. A.; Nijhof, H.; Verest, S.; Buijs, M.; Wijsman, J. H.; Stassen, L. P. S.; Klinkert, M.; de Maat, M. F. G.; Sellenraad, G.; Jeekel, J.; Kleinrensink, G. J.; Tha-in, T.; Nijboer, W. N.; Boom, M. J.; Verbeek, P. C. M.; Sietses, C.; Stommel, M. W. J.; van Huijstee, P. J.; Merkus, J. W. S.; Eefting, D.; Mieog, J. S. D.; van Geldere, D.; Patijn, G. A.; de Vries, M.; Boskamp, M.; Bentohami, A.; Bijlsma, T. S.; de Korte, N.; Nio, D.; Rijna, H.; Luttikhold, J.; van Gool, M. H.; Fekkes, J. F.; Akkersdijk, G. J. M.; Heuff, G.; Jutte, E. H.; Kortmann, B. A.; Werkman, J. M.; Laméris, W.; Rietbergen, L.; Frankenmolen, P.; Draaisma, W. A.; Stam, M. A. W.; Verweij, M. S.; Karsten, T. M.; de Nes, L. C.; Fortuin, S.; de Castro, S. M.; Doeksen, A.; Simons, M. P.; Koffeman, G. I.; Steller, E. P.; Tuynman, J. B.; Boele van Hensbroek, P.; Mok, M.; van Diepen, S. R.; Hulsewé, K. W. E.; Melenhorst, J.; Stoot, J. H. M. B.; Fransen, S.; Sosef, M. N.; van Bastelaar, J.; Vissers, Y. L. J.; Douchy, T. P. D.; Christiaansen, C. E.; Smeenk, R.; Pijnenburg, A. M.; Tanaydin, V.; Veger, H. T. C.; Clermonts, S. H. E. M.; Al-Taher, M.; de Graaf, E. J. R.; Menon, A. G.; Vermaas, M.; Cense, H. A.; Jutte, E.; Wiezer, M. J.; Smits, A. B.; Westerterp, M.; Marsman, H. A.; Hendriks, E. R.; van Ruler, O.; Vriens, E. J. C.; Vogten, J. M.; van Rossem, C. C.; Ohanis, D.; Tanis, E.; van Grinsven, J.; Maring, J. K.; Heisterkamp, J.; Besselink, M. G. H.; Borel Rinkes, I. H. M.; Molenaar, I. Q.; Joosten, J. J. A.; Jongkind, V.; Diepenhorst, G. M. P.; Boute, M. C.; Smeenge, M.; Nielsen, K.; Harlaar, J. J.; Luyer, M. D. P.; van Montfort, G.; Smulders, J. F.; Daams, F.; van Haren, E.; Nieuwenhuijzen, G. A. P.; Lauret, G. J.; Pereboom, I. T. A.; Stokmans, R. A.; Birindelli, A.; Bianchi, E.; Pellegrini, S.; Terrasson, I.; Wolthuis, A.; de Buck van Overstraeten, A.; Nijs, S.

In: The Lancet Gastroenterology and Hepatology, Vol. 4, No. 8, 2019, p. 599-610.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial

AU - Lambrichts, Daniël P. V.

AU - Vennix, Sandra

AU - Musters, Gijsbert D.

AU - Mulder, Irene M.

AU - Swank, Hilko A.

AU - Hoofwijk, Anton G. M.

AU - Belgers, Eric H. J.

AU - Stockmann, Hein B. A. C.

AU - Eijsbouts, Quirijn A. J.

AU - Gerhards, Michael F.

AU - van Wagensveld, Bart A.

AU - van Geloven, Anna A. W.

AU - Crolla, Rogier M. P. H.

AU - Nienhuijs, Simon W.

AU - Govaert, Marc J. P. M.

AU - di Saverio, Salomone

AU - D'Hoore, André J. L.

AU - Consten, Esther C. J.

AU - van Grevenstein, Wilhelmina M. U.

AU - Pierik, Robert E. G. J. M.

AU - Kruyt, Philip M.

AU - van der Hoeven, Joost A. B.

AU - Steup, Willem H.

AU - Catena, Fausto

AU - Konsten, Joop L. M.

AU - Vermeulen, Jefrey

AU - van Dieren, S.

AU - Bemelman, Willem A.

AU - Lange, Johan F.

AU - Hop, W. C.

AU - Opmeer, B. C.

AU - Reitsma, J. B.

AU - Scholte, R. A.

AU - Waltmann, E. W. H.

AU - Legemate, D. A.

AU - Bartelsman, J. F.

AU - Meijer, D. W.

AU - Ünlü, null

AU - Kluit, A. B.

AU - el-Massoudi, Y.

AU - Vuylsteke, R.

AU - Tanis, P. J.

AU - Matthijsen, R.

AU - Polle, S. W.

AU - Lagarde, S. M.

AU - Gisbertz, S. S.

AU - Wijers, O.

AU - van der Bilt, J. D. W.

AU - Boermeester, M. A.

AU - Blom, R.

AU - Gooszen, J. A. H.

AU - Schreinemacher, M. H. F.

AU - van der Zande, T.

AU - Leeuwenburgh, M. M. N.

AU - Bartels, S. A. L.

AU - Hesp, W. L. E. M.

AU - Koet, L.

AU - van der Schelling, G. P.

AU - van Dessel, E.

AU - van Zeeland, M. L. P.

AU - Lensvelt, M. M. A.

AU - Nijhof, H.

AU - Verest, S.

AU - Buijs, M.

AU - Wijsman, J. H.

AU - Stassen, L. P. S.

AU - Klinkert, M.

AU - de Maat, M. F. G.

AU - Sellenraad, G.

AU - Jeekel, J.

AU - Kleinrensink, G. J.

AU - Tha-in, T.

AU - Nijboer, W. N.

AU - Boom, M. J.

AU - Verbeek, P. C. M.

AU - Sietses, C.

AU - Stommel, M. W. J.

AU - van Huijstee, P. J.

AU - Merkus, J. W. S.

AU - Eefting, D.

AU - Mieog, J. S. D.

AU - van Geldere, D.

AU - Patijn, G. A.

AU - de Vries, M.

AU - Boskamp, M.

AU - Bentohami, A.

AU - Bijlsma, T. S.

AU - de Korte, N.

AU - Nio, D.

AU - Rijna, H.

AU - Luttikhold, J.

AU - van Gool, M. H.

AU - Fekkes, J. F.

AU - Akkersdijk, G. J. M.

AU - Heuff, G.

AU - Jutte, E. H.

AU - Kortmann, B. A.

AU - Werkman, J. M.

AU - Laméris, W.

AU - Rietbergen, L.

AU - Frankenmolen, P.

AU - Draaisma, W. A.

AU - Stam, M. A. W.

AU - Verweij, M. S.

AU - Karsten, T. M.

AU - de Nes, L. C.

AU - Fortuin, S.

AU - de Castro, S. M.

AU - Doeksen, A.

AU - Simons, M. P.

AU - Koffeman, G. I.

AU - Steller, E. P.

AU - Tuynman, J. B.

AU - Boele van Hensbroek, P.

AU - Mok, M.

AU - van Diepen, S. R.

AU - Hulsewé, K. W. E.

AU - Melenhorst, J.

AU - Stoot, J. H. M. B.

AU - Fransen, S.

AU - Sosef, M. N.

AU - van Bastelaar, J.

AU - Vissers, Y. L. J.

AU - Douchy, T. P. D.

AU - Christiaansen, C. E.

AU - Smeenk, R.

AU - Pijnenburg, A. M.

AU - Tanaydin, V.

AU - Veger, H. T. C.

AU - Clermonts, S. H. E. M.

AU - Al-Taher, M.

AU - de Graaf, E. J. R.

AU - Menon, A. G.

AU - Vermaas, M.

AU - Cense, H. A.

AU - Jutte, E.

AU - Wiezer, M. J.

AU - Smits, A. B.

AU - Westerterp, M.

AU - Marsman, H. A.

AU - Hendriks, E. R.

AU - van Ruler, O.

AU - Vriens, E. J. C.

AU - Vogten, J. M.

AU - van Rossem, C. C.

AU - Ohanis, D.

AU - Tanis, E.

AU - van Grinsven, J.

AU - Maring, J. K.

AU - Heisterkamp, J.

AU - Besselink, M. G. H.

AU - Borel Rinkes, I. H. M.

AU - Molenaar, I. Q.

AU - Joosten, J. J. A.

AU - Jongkind, V.

AU - Diepenhorst, G. M. P.

AU - Boute, M. C.

AU - Smeenge, M.

AU - Nielsen, K.

AU - Harlaar, J. J.

AU - Luyer, M. D. P.

AU - van Montfort, G.

AU - Smulders, J. F.

AU - Daams, F.

AU - van Haren, E.

AU - Nieuwenhuijzen, G. A. P.

AU - Lauret, G. J.

AU - Pereboom, I. T. A.

AU - Stokmans, R. A.

AU - Birindelli, A.

AU - Bianchi, E.

AU - Pellegrini, S.

AU - Terrasson, I.

AU - Wolthuis, A.

AU - de Buck van Overstraeten, A.

AU - Nijs, S.

PY - 2019

Y1 - 2019

N2 - Background: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. Methods: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. Findings: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7–100] vs 71·7% [95% CI 60·1–83·3], hazard ratio 2·79 [95% CI 1·86–4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). Interpretation: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). Funding: Netherlands Organisation for Health Research and Development.

AB - Background: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. Methods: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. Findings: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7–100] vs 71·7% [95% CI 60·1–83·3], hazard ratio 2·79 [95% CI 1·86–4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). Interpretation: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). Funding: Netherlands Organisation for Health Research and Development.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068469357&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31178342

U2 - 10.1016/S2468-1253(19)30174-8

DO - 10.1016/S2468-1253(19)30174-8

M3 - Article

VL - 4

SP - 599

EP - 610

JO - The Lancet Gastroenterology and Hepatology

JF - The Lancet Gastroenterology and Hepatology

SN - 2468-1253

IS - 8

ER -