Author: "Ubels S." - Searchworks@Jio Institute Digital Library Search Results

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1. Anastomotic leak after esophagectomy: Towards evidence-based treatment.

Author: Ubels, S. and Ubels, S.
Subjects: Radboudumc 14: Tumours of the digestive tract., Radboudumc 14: Tumours of the digestive tract Surgery.
Published: 2024

2. Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients

Author: Greijdanus, N, Wienholts, K, Ubels, S, Talboom, K, Hannink, G, Wolthuis, A, de Lacy, F, Lefevre, J, Solomon, M, Frasson, M, Rotholtz, N, Denost, Q, Perez, R, Konishi, T, Panis, Y, Rutegard, M, Hompes, R, Rosman, C, van Workum, F, Tanis, P, de Wilt, J, Bremers, A, Ferenschild, F, de Vriendt, S, D'Hoore, A, Bislenghi, G, Farguell, J, Lacy, A, Atienza, P, van Kessel, C, Parc, Y, Voron, T, Collard, M, Muriel, J, Cholewa, H, Mattioni, L, Frontali, A, Polle, S, Polat, F, Obihara, N, Vailati, B, Kusters, M, Tuynmann, J, Hazen, S, Gruter, A, Amano, T, Fujiwara, H, Salomon, M, Ruiz, H, Gonzalez, R, Estefania, D, Avellaneda, N, Carrie, A, Santillan, M, Pachajoa, D, Parodi, M, Gielis, M, Binder, A, Gurtler, T, Riedl, P, Badiani, S, Berney, C, Morgan, M, Hollington, P, da Silva, N, Nair, G, Ho, Y, Lamparelli, M, Kapadia, R, Kroon, H, Dudi-Venkata, N, Liu, J, Sammour, T, Flamey, N, Pattyn, P, Chaoui, A, Vansteenbrugge, L, van den Broek, N, Vanclooster, P, de Gheldere, C, Pletinckx, P, Defoort, B, Dewulf, M, Slavchev, M, Belev, N, Atanasov, B, Krastev, P, Sokolov, M, Maslyankov, S, Gribnev, P, Pavlov, V, Ivanov, T, Karamanliev, M, Filipov, E, Tonchev, P, Aigner, F, Mitteregger, M, Allmer, C, Seitinger, G, Colucci, N, Buchs, N, Ris, F, Toso, C, Gialamas, E, Vuagniaux, A, Chautems, R, Sauvain, M, Daester, S, von Flue, M, Guenin, M, Taha-Mehlitz, S, Hess, G, Martinek, L, Skrovina, M, Machackova, M, Bencurik, V, Uluk, D, Pratschke, J, Dittrich, L, Guel-Klein, S, Perez, D, Grass, J, Melling, N, Mueller, S, Iversen, L, Eriksen, J, Baatrup, G, Al-Najami, I, Bjorsum-Meyer, T, Teras, J, Teras, R, Monib, F, Ahmed, N, Alkady, E, Ali, A, Khedr, G, Abdelaal, A, Ashoush, F, Ewedah, M, Elshennawy, E, Hussein, M, Fernandez-Martinez, D, Garcia-Florez, L, Fernandez-Hevia, M, Suarez-Sanchez, A, Aretxabala, I, Docampo, I, Zabala, J, Tejedor, P, Morales Bernaldo de Quiros, J, Quiroga, I, Navarro-Sanchez, A, Darias, I, Fernandez, C, de La Cruz Cuadrado, C, Sanchez-Guillen, L, Lopez-Rodriguez-Arias, F, Soler-Silva, A, Arroyo, A, Bernal-Sprekelsen, J, Gomez-Abril, S, Gonzalvez, P, Torres, M, Sanchez, T, Antona, F, Lara, J, Montero, J, Mendoza-Moreno, F, Diez-Alonso, M, Matias-Garcia, B, Quiroga-Valcarcel, A, Colas-Ruiz, E, Tasende-Presedo, M, Fernandez-Hurtado, I, Cifuentes-Rodenas, J, Suarez, M, Losada, M, Hernandez, M, Alonso, A, Dieguez, B, Serralta, D, Quintana, R, Lopez, J, Pinto, F, Nieto-Moreno, E, Bonito, A, Santacruz, C, Marcos, E, Septiem, J, Calero-Lillo, A, Alanez-Saavedra, J, Munoz-Collado, S, Lopez-Lara, M, Martinez, M, Herrero, E, Borda, F, Villar, O, Escartin, J, Blas, J, Ferrer, R, Egea, J, Rodriguez-Infante, A, Minguez-Ruiz, G, Carreno-Villarreal, G, Pire-Abaitua, G, Dziakova, J, Rodriguez, C, Aranda, M, Huguet, J, Borda-Arrizabalaga, N, Enriquez-Navascues, J, Echaniz, G, Ansorena, Y, Estaire-Gomez, M, Martinez-Pinedo, C, Barbero-Valenzuela, A, Ruiz-Garcia, P, Kraft, M, Gomez-Jurado, M, Pellino, G, Espin-Basany, E, Cotte, E, Panel, N, Goutard, C, de Angelis, N, Lauka, L, Shaikh, S, Osborne, L, Ramsay, G, Nichita, V, Bhandari, S, Sarmah, P, Bethune, R, Pringle, H, Massey, L, Fowler, G, Hamid, H, de Simone, B, Kynaston, J, Bradley, N, Stienstra, R, Gurjar, S, Mukherjee, T, Chandio, A, Ahmed, S, Singh, B, Runau, F, Chaudhri, S, Siaw, O, Sarveswaran, J, Miu, V, Ashmore, D, Darwich, H, Singh-Ranger, D, Singh, N, Shaban, M, Gareb, F, Petropolou, T, Polydorou, A, Dattani, M, Afzal, A, Bavikatte, A, Sebastian, B, Ward, N, Mishra, A, Manatakis, D, Agalianos, C, Tasis, N, Antonopoulou, M, Karavokyros, I, Charalabopoulos, A, Schizas, D, Baili, E, Syllaios, A, Karydakis, L, Vailas, M, Balalis, D, Korkolis, D, Plastiras, A, Rompou, A, Xenaki, S, Xynos, E, Chrysos, E, Venianaki, M, Christodoulidis, G, Perivoliotis, K, Tzovaras, G, Baloyiannis, I, Ho, M, Ng, S, Mak, T, Futaba, K, Santak, G, Simlesa, D, Cosic, J, Zukanovic, G, Kelly, M, Larkin, J, Mccormick, P, Mehigan, B, Connelly, T, Neary, P, Ryan, J, Mccullough, P, Al-Juaifari, M, Hammoodi, H, Abbood, A, Calabro, M, Muratore, A, La Terra, A, Farnesi, F, Feo, C, Fabbri, N, Pesce, A, Fazzin, M, Roscio, F, Clerici, F, Lucchi, A, Vittori, L, Agostinelli, L, Ripoli, M, Sambucci, D, Porta, A, Sinibaldi, G, Crescentini, G, Larcinese, A, Picone, E, Persiani, R, Biondi, A, Pezzuto, R, Lorenzon, L, Rizzo, G, Coco, C, D'Agostino, L, Spinelli, A, Sacchi, M, Carvello, M, Foppa, C, Maroli, A, Palini, G, Garulli, G, Zanini, N, Delrio, P, Rega, D, Carbone, F, Aversano, A, Pirozzolo, G, Recordare, A, D'Alimonte, L, Vignotto, C, Corbellini, C, Sampietro, G, Lorusso, L, Manzo, C, Ghignone, F, Ugolini, G, Montroni, I, Pasini, F, Ballabio, M, Bisagni, P, Armao, F, Longhi, M, Ghazouani, O, Galleano, R, Tamini, N, Oldani, M, Nespoli, L, Picciariello, A, Altomare, D, Tomasicchio, G, Lantone, G, Catena, F, Giuffrida, M, Annicchiarico, A, Perrone, G, Grossi, U, Santoro, G, Zanus, G, Iacomino, A, Novello, S, Passuello, N, Zucchella, M, Puca, L, Degiuli, M, Reddavid, R, Scabini, S, Aprile, A, Soriero, D, Fioravanti, E, Rottoli, M, Romano, A, Tanzanu, M, Belvedere, A, Mariani, N, Ceretti, A, Opocher, E, Gallo, G, Sammarco, G, de Paola, G, Pucciarelli, S, Marchegiani, F, Spolverato, G, Buzzi, G, Di Saverio, S, Meroni, P, Parise, C, Bottazzoli, E, Lapolla, P, Brachini, G, Cirillo, B, Mingoli, A, Sica, G, Siragusa, L, Bellato, V, Cerbo, D, de Pasqual, C, de Manzoni, G, di Cosmo, M, Alrayes, B, Qandeel, M, Hani, M, Rabadi, A, el Muhtaseb, M, Abdeen, B, Karmi, F, Zilinskas, J, Latkauskas, T, Tamelis, A, Pikuniene, I, Slenfuktas, V, Poskus, T, Kryzauskas, M, Jakubauskas, M, Mikalauskas, S, Jakubauskiene, L, Hassan, S, Altrabulsi, A, Abdulwahed, E, Ghmagh, R, Deeknah, A, Alshareea, E, Elhadi, M, Abujamra, S, Msherghi, A, Tababa, O, Majbar, M, Souadka, A, Benkabbou, A, Mohsine, R, Echiguer, S, Moctezuma-Velazquez, P, Salgado-Nesme, N, Vergara-Fernandez, O, Sainz-Hernandez, J, Alvarez-Bautista, F, Zakaria, A, Zakaria, Z, Wong, M, Ismail, R, Ibrahim, A, Abdullah, N, Julaihi, R, Bhat, S, O'Grady, G, Bissett, I, Lamme, B, Musters, G, Dinaux, A, Grotenhuis, B, Steller, E, Aalbers, A, Leeuwenburgh, M, Rutten, H, Burger, J, Bloemen, J, Ketelaers, S, Waqar, U, Chawla, T, Rauf, H, Rani, P, Talsma, A, Scheurink, L, van Praagh, J, Segelman, J, Nygren, J, Anderin, K, Tiefenthal, M, de Andres, B, Beltran de Heredia, J, Vazquez, A, Gomez, T, Golshani, P, Kader, R, Mohamed, A, Westerterp, M, Marinelli, A, Niemer, Q, Doornebosch, P, Shapiro, J, Vermaas, M, de Graaf, E, van Westreenen, H, Zwakman, M, van Dalsen, A, Vles, W, Nonner, J, Toorenvliet, B, Janssen, P, Verdaasdonk, E, Amelung, F, Peeters, K, Bahadoer, R, Holman, F, Heemskerk, J, Vosbeek, N, Leijtens, J, Taverne, S, Heijnen, B, El-Massoudi, Y, de Groot-Van Veen, I, Hoff, C, Jou-Valencia, D, Consten, E, Burghgraef, T, Geitenbeek, R, Hulshof, L, Slooter, G, Reudink, M, Bouvy, N, Wildeboer, A, Verstappen, S, Pennings, A, van den Hengel, B, Wijma, A, de Haan, J, de Nes, L, Heesink, V, Karsten, T, Heidsma, C, Koemans, W, Dekker, J, van der Zijden, C, Roos, D, Demirkiran, A, van der Burg, S, Oosterling, S, Hoogteijling, T, Wiering, B, Smeeing, D, Havenga, K, Lutfi, H, Tsimogiannis, K, Skoldberg, F, Folkesson, J, den Boer, F, van Schaik, T, van Gerven, P, Sietses, C, Hol, J, Boerma, E, Creemers, D, Schultz, J, Frivold, T, Riis, R, Gregussen, H, Busund, S, Sjo, O, Gaard, M, Krohn, N, Ersryd, A, Leung, E, Sultan, H, Hajjaj, B, Alhisi, A, Khader, A, Mendes, A, Semiao, M, Faria, L, Azevedo, C, da Costa Devesa, H, Martins, S, Jarimba, A, Marques, S, Ferreira, R, Oliveira, A, Ferreira, C, Pereira, R, Surlin, V, Graure, G, Ramboiu, S, Negoi, I, Ciubotaru, C, Stoica, B, Tanase, I, Negoita, V, Florea, S, Macau, F, Vasile, M, Stefanescu, V, Dimofte, G, Lunca, S, Roata, C, Musina, A, Garmanova, T, Agapov, M, Markaryan, D, Eduard, G, Yanishev, A, Abelevich, A, Bazaev, A, Rodimov, S, Filimonov, V, Melnikov, A, Suchkov, I, Drozdov, E, Kostromitskiy, D, Sjostrom, O, Matthiessen, P, Baban, B, Gadan, S, Jadid, K, Staffan, M, Park, J, Rydbeck, D, Lydrup, M, Buchwald, P, Jutesten, H, Darlin, L, Lindqvist, E, Nilsson, K, Larsson, P, Jangmalm, S, Kosir, J, Tomazic, A, Grosek, J, Bozic, T, Zazo, A, Zazo, R, Fares, H, Ayoub, K, Niazi, A, Mansour, A, Abbas, A, Tantoura, M, Hamdan, A, Hassan, N, Hasan, B, Saad, A, Sebai, A, Haddad, A, Maghrebi, H, Kacem, M, Yalkin, O, Samsa, M, Atak, I, Balci, B, Haberal, E, Dogan, L, Gecim, I, Akyol, C, Koc, M, Sivrikoz, E, Piyadeoglu, D, Avanagh, D, Sokmen, S, Bisgin, T, Gunenc, E, Guzel, M, Leventoglu, S, Yuksel, O, Kozan, R, Gobut, H, Cengiz, F, Erdinc, K, Acar, N, Kamer, E, Ozgur, I, Aydin, O, Keskin, M, Bulut, M, Kulle, C, Kara, Y, Sibic, O, Ozata, I, Bugra, D, Balik, E, Cakir, M, Alhardan, A, Colak, E, Aybar, A, Sari, A, Atici, S, Kaya, T, Dursun, A, Calik, B, Ozkan, O, Ulgur, H, Duzgun, O, Monson, J, George, S, Woods, K, Al-Eryani, F, Albakry, R, Coetzee, E, Boutall, A, Herman, A, Warden, C, Mugla, N, Forgan, T, Mia, I, Lambrechts, A, Greijdanus N. G., Wienholts K., Ubels S., Talboom K., Hannink G., Wolthuis A., de Lacy F. B., Lefevre J. H., Solomon M., Frasson M., Rotholtz N., Denost Q., Perez R. O., Konishi T., Panis Y., Rutegard M., Hompes R., Rosman C., van Workum F., Tanis P. J., de Wilt J. H. W., Bremers A. J. A., Ferenschild F. T., de Vriendt S., D'Hoore A., Bislenghi G., Farguell J., Lacy A. M., Atienza P. G., van Kessel C. S., Parc Y., Voron T., Collard M. K., Muriel J. S., Cholewa H., Mattioni L. A., Frontali A., Polle S. W., Polat F., Obihara N. J., Vailati B. B., Kusters M., Tuynmann J. B., Hazen S. J. A., Gruter A. A. J., Amano T., Fujiwara H., Salomon M., Ruiz H., Gonzalez R., Estefania D., Avellaneda N., Carrie A., Santillan M., Pachajoa D. A. P., Parodi M., Gielis M., Binder A. -D., Gurtler T., Riedl P., Badiani S., Berney C., Morgan M., Hollington P., da Silva N., Nair G., Ho Y. M., Lamparelli M., Kapadia R., Kroon H. M., Dudi-Venkata N. N., Liu J., Sammour T., Flamey N., Pattyn P., Chaoui A., Vansteenbrugge L., van den Broek N. E. J., Vanclooster P., de Gheldere C., Pletinckx P., Defoort B., Dewulf M., Slavchev M., Belev N., Atanasov B., Krastev P., Sokolov M., Maslyankov S., Gribnev P., Pavlov V., Ivanov T., Karamanliev M., Filipov E., Tonchev P., Aigner F., Mitteregger M., Allmer C., Seitinger G., Colucci N., Buchs N., Ris F., Toso C., Gialamas E., Vuagniaux A., Chautems R., Sauvain M. -O., Daester S., von Flue M., Guenin M. -O., Taha-Mehlitz S., Hess G. F., Martinek L., Skrovina M., Machackova M., Bencurik V., Uluk D., Pratschke J., Dittrich L. S., Guel-Klein S., Perez D., Grass J. -K., Melling N., Mueller S., Iversen L. H., Eriksen J. D., Baatrup G., Al-Najami I., Bjorsum-Meyer T., Teras J., Teras R. M., Monib F. A., Ahmed N. E. A. E., Alkady E., Ali A. K., Khedr G. A. E., Abdelaal A. S., Ashoush F. M. B., Ewedah M., Elshennawy E. M., Hussein M., Fernandez-Martinez D., Garcia-Florez L. J., Fernandez-Hevia M., Suarez-Sanchez A., Aretxabala I. D. H., Docampo I. L., Zabala J. G., Tejedor P., Morales Bernaldo de Quiros J. T., Quiroga I. B., Navarro-Sanchez A., Darias I. S., Fernandez C. L., de La Cruz Cuadrado C., Sanchez-Guillen L., Lopez-Rodriguez-Arias F., Soler-Silva A., Arroyo A., Bernal-Sprekelsen J. C., Gomez-Abril S. A., Gonzalvez P., Torres M. T., Sanchez T. R., Antona F. B., Lara J. E. S., Montero J. A. A., Mendoza-Moreno F., Diez-Alonso M., Matias-Garcia B., Quiroga-Valcarcel A., Colas-Ruiz E., Tasende-Presedo M. M., Fernandez-Hurtado I., Cifuentes-Rodenas J. A., Suarez M. C., Losada M., Hernandez M., Alonso A., Dieguez B., Serralta D., Quintana R. E. M., Lopez J. M. G., Pinto F. L., Nieto-Moreno E., Bonito A. C., Santacruz C. C., Marcos E. B., Septiem J. G., Calero-Lillo A., Alanez-Saavedra J., Munoz-Collado S., Lopez-Lara M., Martinez M. L., Herrero E. F., Borda F. J. G., Villar O. G., Escartin J., Blas J. L., Ferrer R., Egea J. G., Rodriguez-Infante A., Minguez-Ruiz G., Carreno-Villarreal G., Pire-Abaitua G., Dziakova J., Rodriguez C. S. -C., Aranda M. J. P., Huguet J. M. M., Borda-Arrizabalaga N., Enriquez-Navascues J. M., Echaniz G. E., Ansorena Y. S., Estaire-Gomez M., Martinez-Pinedo C., Barbero-Valenzuela A., Ruiz-Garcia P., Kraft M., Gomez-Jurado M. J., Pellino G., Espin-Basany E., Cotte E., Panel N., Goutard C. -A., de Angelis N., Lauka L., Shaikh S., Osborne L., Ramsay G., Nichita V. -I., Bhandari S., Sarmah P., Bethune R. M., Pringle H. C. M., Massey L., Fowler G. E., Hamid H. K. S., de Simone B. D., Kynaston J., Bradley N., Stienstra R. M., Gurjar S., Mukherjee T., Chandio A., Ahmed S., Singh B., Runau F., Chaudhri S., Siaw O., Sarveswaran J., Miu V., Ashmore D., Darwich H., Singh-Ranger D., Singh N., Shaban M., Gareb F., Petropolou T., Polydorou A., Dattani M., Afzal A., Bavikatte A., Sebastian B., Ward N., Mishra A., Manatakis D., Agalianos C., Tasis N., Antonopoulou M. -I., Karavokyros I., Charalabopoulos A., Schizas D., Baili E., Syllaios A., Karydakis L., Vailas M., Balalis D., Korkolis D., Plastiras A., Rompou A., Xenaki S., Xynos E., Chrysos E., Venianaki M., Christodoulidis G., Perivoliotis K., Tzovaras G., Baloyiannis I., Ho M. -F., Ng S. S., Mak T. W. -C., Futaba K., Santak G., Simlesa D., Cosic J., Zukanovic G., Kelly M. E., Larkin J. O., McCormick P. H., Mehigan B. J., Connelly T. M., Neary P., Ryan J., McCullough P., Al-Juaifari M. A., Hammoodi H., Abbood A. H., Calabro M., Muratore A., La Terra A., Farnesi F., Feo C. V., Fabbri N., Pesce A., Fazzin M., Roscio F., Clerici F., Lucchi A., Vittori L., Agostinelli L., Ripoli M. C., Sambucci D., Porta A., Sinibaldi G., Crescentini G., Larcinese A., Picone E., Persiani R., Biondi A., Pezzuto R., Lorenzon L., Rizzo G., Coco C., D'Agostino L., Spinelli A., Sacchi M. M., Carvello M., Foppa C., Maroli A., Palini G. M., Garulli G., Zanini N., Delrio P., Rega D., Carbone F., Aversano A., Pirozzolo G., Recordare A., D'Alimonte L., Vignotto C., Corbellini C., Sampietro G. M., Lorusso L., Manzo C. A., Ghignone F., Ugolini G., Montroni I., Pasini F., Ballabio M., Bisagni P., Armao F. T., Longhi M., Ghazouani O., Galleano R., Tamini N., Oldani M., Nespoli L., Picciariello A., Altomare D. F., Tomasicchio G., Lantone G., Catena F., Giuffrida M., Annicchiarico A., Perrone G., Grossi U., Santoro G. A., Zanus G., Iacomino A., Novello S., Passuello N., Zucchella M., Puca L., deGiuli M., Reddavid R., Scabini S., Aprile A., Soriero D., Fioravanti E., Rottoli M., Romano A., Tanzanu M., Belvedere A., Mariani N. M., Ceretti A. P., Opocher E., Gallo G., Sammarco G., de Paola G., Pucciarelli S., Marchegiani F., Spolverato G., Buzzi G., Di Saverio S., Meroni P., Parise C., Bottazzoli E. I., Lapolla P., Brachini G., Cirillo B., Mingoli A., Sica G., Siragusa L., Bellato V., Cerbo D., de Pasqual C. A., de Manzoni G., di Cosmo M. A., Alrayes B. M. H., Qandeel M. W. M., Hani M. B., Rabadi A., el Muhtaseb M. S., Abdeen B., Karmi F., Zilinskas J., Latkauskas T., Tamelis A., Pikuniene I., Slenfuktas V., Poskus T., Kryzauskas M., Jakubauskas M., Mikalauskas S., Jakubauskiene L., Hassan S. Y., Altrabulsi A., Abdulwahed E., Ghmagh R., Deeknah A., Alshareea E., Elhadi M., Abujamra S., Msherghi A. A., Tababa O. W. E., Majbar M. A., Souadka A., Benkabbou A., Mohsine R., Echiguer S., Moctezuma-Velazquez P., Salgado-Nesme N., Vergara-Fernandez O., Sainz-Hernandez J. C., Alvarez-Bautista F. E., Zakaria A. D., Zakaria Z., Wong M. P. K., Ismail R., Ibrahim A. F., Abdullah N. A. N., Julaihi R., Bhat S., O'Grady G., Bissett I., Lamme B., Musters G. D., Dinaux A. M., Grotenhuis B. A., Steller E. J., Aalbers A. G. J., Leeuwenburgh M. M., Rutten H. J. T., Burger J. W. A., Bloemen J. G., Ketelaers S. H. J., Waqar U., Chawla T., Rauf H., Rani P., Talsma A. K., Scheurink L., van Praagh J. B., Segelman J., Nygren J., Anderin K., Tiefenthal M., de Andres B., Beltran de Heredia J. P., Vazquez A., Gomez T., Golshani P., Kader R., Mohamed A., Westerterp M., Marinelli A., Niemer Q., Doornebosch P. G., Shapiro J., Vermaas M., de Graaf E. J. R., van Westreenen H. L., Zwakman M., van Dalsen A. D., Vles W. J., Nonner J., Toorenvliet B. R., Janssen P. T. J., Verdaasdonk E. G. G., Amelung F. J., Peeters K. C. M. J., Bahadoer R. R., Holman F. A., Heemskerk J., Vosbeek N., Leijtens J. W. A., Taverne S. B. M., Heijnen B. H. M., El-Massoudi Y., de Groot-Van Veen I., Hoff C., Jou-Valencia D., Consten E. C. J., Burghgraef T. A., Geitenbeek R., Hulshof L. G. W. L., Slooter G. D., Reudink M., Bouvy N. D., Wildeboer A. C. L., Verstappen S., Pennings A. J., van den Hengel B., Wijma A. G., de Haan J., de Nes L. C. F., Heesink V., Karsten T., Heidsma C. M., Koemans W. J., Dekker J. -W. T., van der Zijden C. J., Roos D., Demirkiran A., van der Burg S., Oosterling S. J., Hoogteijling T. J., Wiering B., Smeeing D. P. J., Havenga K., Lutfi H., Tsimogiannis K., Skoldberg F., Folkesson J., den Boer F., van Schaik T. G., van Gerven P., Sietses C., Hol J. C., Boerma E. -J. G., Creemers D. M. J., Schultz J. K., Frivold T., Riis R., Gregussen H., Busund S., Sjo O. H., Gaard M., Krohn N., Ersryd A. L., Leung E., Sultan H., Hajjaj B. N., Alhisi A. J., Khader A. A. E., Mendes A. F. D., Semiao M., Faria L. Q., Azevedo C., da Costa Devesa H. M., Martins S. F., Jarimba A. M. R., Marques S. M. R., Ferreira R. M., Oliveira A., Ferreira C., Pereira R., Surlin V. M., Graure G. M., Ramboiu S. P. S. D., Negoi I., Ciubotaru C., Stoica B., Tanase I., Negoita V. M., Florea S., Macau F., Vasile M., Stefanescu V., Dimofte G. -M., Lunca S., Roata C. -E., Musina A. -M., Garmanova T., Agapov M. N., Markaryan D. G., Eduard G., Yanishev A., Abelevich A., Bazaev A., Rodimov S. V., Filimonov V. B., Melnikov A. A., Suchkov I. A., Drozdov E. S., Kostromitskiy D. N., Sjostrom O., Matthiessen P., Baban B., Gadan S., Jadid K. D., Staffan M., Park J. M., Rydbeck D., Lydrup M. -L., Buchwald P., Jutesten H., Darlin L., Lindqvist E., Nilsson K., Larsson P. -A., Jangmalm S., Kosir J. A., Tomazic A., Grosek J., Bozic T. K., Zazo A., Zazo R., Fares H., Ayoub K., Niazi A., Mansour A., Abbas A., Tantoura M., Hamdan A., Hassan N., Hasan B., Saad A., Sebai A., Haddad A., Maghrebi H., Kacem M., Yalkin O., Samsa M. V., Atak I., Balci B., Haberal E., Dogan L., Gecim I. E., Akyol C., Koc M. A., Sivrikoz E., Piyadeoglu D., Avanagh D. O., Sokmen S., Bisgin T., Gunenc E., Guzel M., Leventoglu S., Yuksel O., Kozan R., Gobut H., Cengiz F., Erdinc K., Acar N. C., Kamer E., Ozgur I., Aydin O., Keskin M., Bulut M. T., Kulle C. B., Kara Y., Sibic O., Ozata I. H., Bugra D., Balik E., Cakir M., Alhardan A., Colak E., Aybar A. B. C., Sari A. C., Atici S. D., Kaya T., Dursun A., Calik B., Ozkan O. F., Ulgur H. S., Duzgun O., Monson J., George S., Woods K., Al-Eryani F., Albakry R., Coetzee E., Boutall A., Herman A., Warden C., Mugla N., Forgan T., Mia I., Lambrechts A., Greijdanus, N, Wienholts, K, Ubels, S, Talboom, K, Hannink, G, Wolthuis, A, de Lacy, F, Lefevre, J, Solomon, M, Frasson, M, Rotholtz, N, Denost, Q, Perez, R, Konishi, T, Panis, Y, Rutegard, M, Hompes, R, Rosman, C, van Workum, F, Tanis, P, de Wilt, J, Bremers, A, Ferenschild, F, de Vriendt, S, D'Hoore, A, Bislenghi, G, Farguell, J, Lacy, A, Atienza, P, van Kessel, C, Parc, Y, Voron, T, Collard, M, Muriel, J, Cholewa, H, Mattioni, L, Frontali, A, Polle, S, Polat, F, Obihara, N, Vailati, B, Kusters, M, Tuynmann, J, Hazen, S, Gruter, A, Amano, T, Fujiwara, H, Salomon, M, Ruiz, H, Gonzalez, R, Estefania, D, Avellaneda, N, Carrie, A, Santillan, M, Pachajoa, D, Parodi, M, Gielis, M, Binder, A, Gurtler, T, Riedl, P, Badiani, S, Berney, C, Morgan, M, Hollington, P, da Silva, N, Nair, G, Ho, Y, Lamparelli, M, Kapadia, R, Kroon, H, Dudi-Venkata, N, Liu, J, Sammour, T, Flamey, N, Pattyn, P, Chaoui, A, Vansteenbrugge, L, van den Broek, N, Vanclooster, P, de Gheldere, C, Pletinckx, P, Defoort, B, Dewulf, M, Slavchev, M, Belev, N, Atanasov, B, Krastev, P, Sokolov, M, Maslyankov, S, Gribnev, P, Pavlov, V, Ivanov, T, Karamanliev, M, Filipov, E, Tonchev, P, Aigner, F, Mitteregger, M, Allmer, C, Seitinger, G, Colucci, N, Buchs, N, Ris, F, Toso, C, Gialamas, E, Vuagniaux, A, Chautems, R, Sauvain, M, Daester, S, von Flue, M, Guenin, M, Taha-Mehlitz, S, Hess, G, Martinek, L, Skrovina, M, Machackova, M, Bencurik, V, Uluk, D, Pratschke, J, Dittrich, L, Guel-Klein, S, Perez, D, Grass, J, Melling, N, Mueller, S, Iversen, L, Eriksen, J, Baatrup, G, Al-Najami, I, Bjorsum-Meyer, T, Teras, J, Teras, R, Monib, F, Ahmed, N, Alkady, E, Ali, A, Khedr, G, Abdelaal, A, Ashoush, F, Ewedah, M, Elshennawy, E, Hussein, M, Fernandez-Martinez, D, Garcia-Florez, L, Fernandez-Hevia, M, Suarez-Sanchez, A, Aretxabala, I, Docampo, I, Zabala, J, Tejedor, P, Morales Bernaldo de Quiros, J, Quiroga, I, Navarro-Sanchez, A, Darias, I, Fernandez, C, de La Cruz Cuadrado, C, Sanchez-Guillen, L, Lopez-Rodriguez-Arias, F, Soler-Silva, A, Arroyo, A, Bernal-Sprekelsen, J, Gomez-Abril, S, Gonzalvez, P, Torres, M, Sanchez, T, Antona, F, Lara, J, Montero, J, Mendoza-Moreno, F, Diez-Alonso, M, Matias-Garcia, B, Quiroga-Valcarcel, A, Colas-Ruiz, E, Tasende-Presedo, M, Fernandez-Hurtado, I, Cifuentes-Rodenas, J, Suarez, M, Losada, M, Hernandez, M, Alonso, A, Dieguez, B, Serralta, D, Quintana, R, Lopez, J, Pinto, F, Nieto-Moreno, E, Bonito, A, Santacruz, C, Marcos, E, Septiem, J, Calero-Lillo, A, Alanez-Saavedra, J, Munoz-Collado, S, Lopez-Lara, M, Martinez, M, Herrero, E, Borda, F, Villar, O, Escartin, J, Blas, J, Ferrer, R, Egea, J, Rodriguez-Infante, A, Minguez-Ruiz, G, Carreno-Villarreal, G, Pire-Abaitua, G, Dziakova, J, Rodriguez, C, Aranda, M, Huguet, J, Borda-Arrizabalaga, N, Enriquez-Navascues, J, Echaniz, G, Ansorena, Y, Estaire-Gomez, M, Martinez-Pinedo, C, Barbero-Valenzuela, A, Ruiz-Garcia, P, Kraft, M, Gomez-Jurado, M, Pellino, G, Espin-Basany, E, Cotte, E, Panel, N, Goutard, C, de Angelis, N, Lauka, L, Shaikh, S, Osborne, L, Ramsay, G, Nichita, V, Bhandari, S, Sarmah, P, Bethune, R, Pringle, H, Massey, L, Fowler, G, Hamid, H, de Simone, B, Kynaston, J, Bradley, N, Stienstra, R, Gurjar, S, Mukherjee, T, Chandio, A, Ahmed, S, Singh, B, Runau, F, Chaudhri, S, Siaw, O, Sarveswaran, J, Miu, V, Ashmore, D, Darwich, H, Singh-Ranger, D, Singh, N, Shaban, M, Gareb, F, Petropolou, T, Polydorou, A, Dattani, M, Afzal, A, Bavikatte, A, Sebastian, B, Ward, N, Mishra, A, Manatakis, D, Agalianos, C, Tasis, N, Antonopoulou, M, Karavokyros, I, Charalabopoulos, A, Schizas, D, Baili, E, Syllaios, A, Karydakis, L, Vailas, M, Balalis, D, Korkolis, D, Plastiras, A, Rompou, A, Xenaki, S, Xynos, E, Chrysos, E, Venianaki, M, Christodoulidis, G, Perivoliotis, K, Tzovaras, G, Baloyiannis, I, Ho, M, Ng, S, Mak, T, Futaba, K, Santak, G, Simlesa, D, Cosic, J, Zukanovic, G, Kelly, M, Larkin, J, Mccormick, P, Mehigan, B, Connelly, T, Neary, P, Ryan, J, Mccullough, P, Al-Juaifari, M, Hammoodi, H, Abbood, A, Calabro, M, Muratore, A, La Terra, A, Farnesi, F, Feo, C, Fabbri, N, Pesce, A, Fazzin, M, Roscio, F, Clerici, F, Lucchi, A, Vittori, L, Agostinelli, L, Ripoli, M, Sambucci, D, Porta, A, Sinibaldi, G, Crescentini, G, Larcinese, A, Picone, E, Persiani, R, Biondi, A, Pezzuto, R, Lorenzon, L, Rizzo, G, Coco, C, D'Agostino, L, Spinelli, A, Sacchi, M, Carvello, M, Foppa, C, Maroli, A, Palini, G, Garulli, G, Zanini, N, Delrio, P, Rega, D, Carbone, F, Aversano, A, Pirozzolo, G, Recordare, A, D'Alimonte, L, Vignotto, C, Corbellini, C, Sampietro, G, Lorusso, L, Manzo, C, Ghignone, F, Ugolini, G, Montroni, I, Pasini, F, Ballabio, M, Bisagni, P, Armao, F, Longhi, M, Ghazouani, O, Galleano, R, Tamini, N, Oldani, M, Nespoli, L, Picciariello, A, Altomare, D, Tomasicchio, G, Lantone, G, Catena, F, Giuffrida, M, Annicchiarico, A, Perrone, G, Grossi, U, Santoro, G, Zanus, G, Iacomino, A, Novello, S, Passuello, N, Zucchella, M, Puca, L, Degiuli, M, Reddavid, R, Scabini, S, Aprile, A, Soriero, D, Fioravanti, E, Rottoli, M, Romano, A, Tanzanu, M, Belvedere, A, Mariani, N, Ceretti, A, Opocher, E, Gallo, G, Sammarco, G, de Paola, G, Pucciarelli, S, Marchegiani, F, Spolverato, G, Buzzi, G, Di Saverio, S, Meroni, P, Parise, C, Bottazzoli, E, Lapolla, P, Brachini, G, Cirillo, B, Mingoli, A, Sica, G, Siragusa, L, Bellato, V, Cerbo, D, de Pasqual, C, de Manzoni, G, di Cosmo, M, Alrayes, B, Qandeel, M, Hani, M, Rabadi, A, el Muhtaseb, M, Abdeen, B, Karmi, F, Zilinskas, J, Latkauskas, T, Tamelis, A, Pikuniene, I, Slenfuktas, V, Poskus, T, Kryzauskas, M, Jakubauskas, M, Mikalauskas, S, Jakubauskiene, L, Hassan, S, Altrabulsi, A, Abdulwahed, E, Ghmagh, R, Deeknah, A, Alshareea, E, Elhadi, M, Abujamra, S, Msherghi, A, Tababa, O, Majbar, M, Souadka, A, Benkabbou, A, Mohsine, R, Echiguer, S, Moctezuma-Velazquez, P, Salgado-Nesme, N, Vergara-Fernandez, O, Sainz-Hernandez, J, Alvarez-Bautista, F, Zakaria, A, Zakaria, Z, Wong, M, Ismail, R, Ibrahim, A, Abdullah, N, Julaihi, R, Bhat, S, O'Grady, G, Bissett, I, Lamme, B, Musters, G, Dinaux, A, Grotenhuis, B, Steller, E, Aalbers, A, Leeuwenburgh, M, Rutten, H, Burger, J, Bloemen, J, Ketelaers, S, Waqar, U, Chawla, T, Rauf, H, Rani, P, Talsma, A, Scheurink, L, van Praagh, J, Segelman, J, Nygren, J, Anderin, K, Tiefenthal, M, de Andres, B, Beltran de Heredia, J, Vazquez, A, Gomez, T, Golshani, P, Kader, R, Mohamed, A, Westerterp, M, Marinelli, A, Niemer, Q, Doornebosch, P, Shapiro, J, Vermaas, M, de Graaf, E, van Westreenen, H, Zwakman, M, van Dalsen, A, Vles, W, Nonner, J, Toorenvliet, B, Janssen, P, Verdaasdonk, E, Amelung, F, Peeters, K, Bahadoer, R, Holman, F, Heemskerk, J, Vosbeek, N, Leijtens, J, Taverne, S, Heijnen, B, El-Massoudi, Y, de Groot-Van Veen, I, Hoff, C, Jou-Valencia, D, Consten, E, Burghgraef, T, Geitenbeek, R, Hulshof, L, Slooter, G, Reudink, M, Bouvy, N, Wildeboer, A, Verstappen, S, Pennings, A, van den Hengel, B, Wijma, A, de Haan, J, de Nes, L, Heesink, V, Karsten, T, Heidsma, C, Koemans, W, Dekker, J, van der Zijden, C, Roos, D, Demirkiran, A, van der Burg, S, Oosterling, S, Hoogteijling, T, Wiering, B, Smeeing, D, Havenga, K, Lutfi, H, Tsimogiannis, K, Skoldberg, F, Folkesson, J, den Boer, F, van Schaik, T, van Gerven, P, Sietses, C, Hol, J, Boerma, E, Creemers, D, Schultz, J, Frivold, T, Riis, R, Gregussen, H, Busund, S, Sjo, O, Gaard, M, Krohn, N, Ersryd, A, Leung, E, Sultan, H, Hajjaj, B, Alhisi, A, Khader, A, Mendes, A, Semiao, M, Faria, L, Azevedo, C, da Costa Devesa, H, Martins, S, Jarimba, A, Marques, S, Ferreira, R, Oliveira, A, Ferreira, C, Pereira, R, Surlin, V, Graure, G, Ramboiu, S, Negoi, I, Ciubotaru, C, Stoica, B, Tanase, I, Negoita, V, Florea, S, Macau, F, Vasile, M, Stefanescu, V, Dimofte, G, Lunca, S, Roata, C, Musina, A, Garmanova, T, Agapov, M, Markaryan, D, Eduard, G, Yanishev, A, Abelevich, A, Bazaev, A, Rodimov, S, Filimonov, V, Melnikov, A, Suchkov, I, Drozdov, E, Kostromitskiy, D, Sjostrom, O, Matthiessen, P, Baban, B, Gadan, S, Jadid, K, Staffan, M, Park, J, Rydbeck, D, Lydrup, M, Buchwald, P, Jutesten, H, Darlin, L, Lindqvist, E, Nilsson, K, Larsson, P, Jangmalm, S, Kosir, J, Tomazic, A, Grosek, J, Bozic, T, Zazo, A, Zazo, R, Fares, H, Ayoub, K, Niazi, A, Mansour, A, Abbas, A, Tantoura, M, Hamdan, A, Hassan, N, Hasan, B, Saad, A, Sebai, A, Haddad, A, Maghrebi, H, Kacem, M, Yalkin, O, Samsa, M, Atak, I, Balci, B, Haberal, E, Dogan, L, Gecim, I, Akyol, C, Koc, M, Sivrikoz, E, Piyadeoglu, D, Avanagh, D, Sokmen, S, Bisgin, T, Gunenc, E, Guzel, M, Leventoglu, S, Yuksel, O, Kozan, R, Gobut, H, Cengiz, F, Erdinc, K, Acar, N, Kamer, E, Ozgur, I, Aydin, O, Keskin, M, Bulut, M, Kulle, C, Kara, Y, Sibic, O, Ozata, I, Bugra, D, Balik, E, Cakir, M, Alhardan, A, Colak, E, Aybar, A, Sari, A, Atici, S, Kaya, T, Dursun, A, Calik, B, Ozkan, O, Ulgur, H, Duzgun, O, Monson, J, George, S, Woods, K, Al-Eryani, F, Albakry, R, Coetzee, E, Boutall, A, Herman, A, Warden, C, Mugla, N, Forgan, T, Mia, I, Lambrechts, A, Greijdanus N. G., Wienholts K., Ubels S., Talboom K., Hannink G., Wolthuis A., de Lacy F. B., Lefevre J. H., Solomon M., Frasson M., Rotholtz N., Denost Q., Perez R. O., Konishi T., Panis Y., Rutegard M., Hompes R., Rosman C., van Workum F., Tanis P. J., de Wilt J. H. W., Bremers A. J. A., Ferenschild F. T., de Vriendt S., D'Hoore A., Bislenghi G., Farguell J., Lacy A. M., Atienza P. G., van Kessel C. S., Parc Y., Voron T., Collard M. K., Muriel J. S., Cholewa H., Mattioni L. A., Frontali A., Polle S. W., Polat F., Obihara N. J., Vailati B. B., Kusters M., Tuynmann J. B., Hazen S. J. A., Gruter A. A. J., Amano T., Fujiwara H., Salomon M., Ruiz H., Gonzalez R., Estefania D., Avellaneda N., Carrie A., Santillan M., Pachajoa D. A. P., Parodi M., Gielis M., Binder A. -D., Gurtler T., Riedl P., Badiani S., Berney C., Morgan M., Hollington P., da Silva N., Nair G., Ho Y. M., Lamparelli M., Kapadia R., Kroon H. M., Dudi-Venkata N. N., Liu J., Sammour T., Flamey N., Pattyn P., Chaoui A., Vansteenbrugge L., van den Broek N. E. J., Vanclooster P., de Gheldere C., Pletinckx P., Defoort B., Dewulf M., Slavchev M., Belev N., Atanasov B., Krastev P., Sokolov M., Maslyankov S., Gribnev P., Pavlov V., Ivanov T., Karamanliev M., Filipov E., Tonchev P., Aigner F., Mitteregger M., Allmer C., Seitinger G., Colucci N., Buchs N., Ris F., Toso C., Gialamas E., Vuagniaux A., Chautems R., Sauvain M. -O., Daester S., von Flue M., Guenin M. -O., Taha-Mehlitz S., Hess G. F., Martinek L., Skrovina M., Machackova M., Bencurik V., Uluk D., Pratschke J., Dittrich L. S., Guel-Klein S., Perez D., Grass J. -K., Melling N., Mueller S., Iversen L. H., Eriksen J. D., Baatrup G., Al-Najami I., Bjorsum-Meyer T., Teras J., Teras R. M., Monib F. A., Ahmed N. E. A. E., Alkady E., Ali A. K., Khedr G. A. E., Abdelaal A. S., Ashoush F. M. B., Ewedah M., Elshennawy E. M., Hussein M., Fernandez-Martinez D., Garcia-Florez L. J., Fernandez-Hevia M., Suarez-Sanchez A., Aretxabala I. D. H., Docampo I. L., Zabala J. G., Tejedor P., Morales Bernaldo de Quiros J. T., Quiroga I. B., Navarro-Sanchez A., Darias I. S., Fernandez C. L., de La Cruz Cuadrado C., Sanchez-Guillen L., Lopez-Rodriguez-Arias F., Soler-Silva A., Arroyo A., Bernal-Sprekelsen J. C., Gomez-Abril S. A., Gonzalvez P., Torres M. T., Sanchez T. R., Antona F. B., Lara J. E. S., Montero J. A. A., Mendoza-Moreno F., Diez-Alonso M., Matias-Garcia B., Quiroga-Valcarcel A., Colas-Ruiz E., Tasende-Presedo M. M., Fernandez-Hurtado I., Cifuentes-Rodenas J. A., Suarez M. C., Losada M., Hernandez M., Alonso A., Dieguez B., Serralta D., Quintana R. E. M., Lopez J. M. G., Pinto F. L., Nieto-Moreno E., Bonito A. C., Santacruz C. C., Marcos E. B., Septiem J. G., Calero-Lillo A., Alanez-Saavedra J., Munoz-Collado S., Lopez-Lara M., Martinez M. L., Herrero E. F., Borda F. J. G., Villar O. G., Escartin J., Blas J. L., Ferrer R., Egea J. G., Rodriguez-Infante A., Minguez-Ruiz G., Carreno-Villarreal G., Pire-Abaitua G., Dziakova J., Rodriguez C. S. -C., Aranda M. J. P., Huguet J. M. M., Borda-Arrizabalaga N., Enriquez-Navascues J. M., Echaniz G. E., Ansorena Y. S., Estaire-Gomez M., Martinez-Pinedo C., Barbero-Valenzuela A., Ruiz-Garcia P., Kraft M., Gomez-Jurado M. J., Pellino G., Espin-Basany E., Cotte E., Panel N., Goutard C. -A., de Angelis N., Lauka L., Shaikh S., Osborne L., Ramsay G., Nichita V. -I., Bhandari S., Sarmah P., Bethune R. M., Pringle H. C. M., Massey L., Fowler G. E., Hamid H. K. S., de Simone B. D., Kynaston J., Bradley N., Stienstra R. M., Gurjar S., Mukherjee T., Chandio A., Ahmed S., Singh B., Runau F., Chaudhri S., Siaw O., Sarveswaran J., Miu V., Ashmore D., Darwich H., Singh-Ranger D., Singh N., Shaban M., Gareb F., Petropolou T., Polydorou A., Dattani M., Afzal A., Bavikatte A., Sebastian B., Ward N., Mishra A., Manatakis D., Agalianos C., Tasis N., Antonopoulou M. -I., Karavokyros I., Charalabopoulos A., Schizas D., Baili E., Syllaios A., Karydakis L., Vailas M., Balalis D., Korkolis D., Plastiras A., Rompou A., Xenaki S., Xynos E., Chrysos E., Venianaki M., Christodoulidis G., Perivoliotis K., Tzovaras G., Baloyiannis I., Ho M. -F., Ng S. S., Mak T. W. -C., Futaba K., Santak G., Simlesa D., Cosic J., Zukanovic G., Kelly M. E., Larkin J. O., McCormick P. H., Mehigan B. J., Connelly T. M., Neary P., Ryan J., McCullough P., Al-Juaifari M. A., Hammoodi H., Abbood A. H., Calabro M., Muratore A., La Terra A., Farnesi F., Feo C. V., Fabbri N., Pesce A., Fazzin M., Roscio F., Clerici F., Lucchi A., Vittori L., Agostinelli L., Ripoli M. C., Sambucci D., Porta A., Sinibaldi G., Crescentini G., Larcinese A., Picone E., Persiani R., Biondi A., Pezzuto R., Lorenzon L., Rizzo G., Coco C., D'Agostino L., Spinelli A., Sacchi M. M., Carvello M., Foppa C., Maroli A., Palini G. M., Garulli G., Zanini N., Delrio P., Rega D., Carbone F., Aversano A., Pirozzolo G., Recordare A., D'Alimonte L., Vignotto C., Corbellini C., Sampietro G. M., Lorusso L., Manzo C. A., Ghignone F., Ugolini G., Montroni I., Pasini F., Ballabio M., Bisagni P., Armao F. T., Longhi M., Ghazouani O., Galleano R., Tamini N., Oldani M., Nespoli L., Picciariello A., Altomare D. F., Tomasicchio G., Lantone G., Catena F., Giuffrida M., Annicchiarico A., Perrone G., Grossi U., Santoro G. A., Zanus G., Iacomino A., Novello S., Passuello N., Zucchella M., Puca L., deGiuli M., Reddavid R., Scabini S., Aprile A., Soriero D., Fioravanti E., Rottoli M., Romano A., Tanzanu M., Belvedere A., Mariani N. M., Ceretti A. P., Opocher E., Gallo G., Sammarco G., de Paola G., Pucciarelli S., Marchegiani F., Spolverato G., Buzzi G., Di Saverio S., Meroni P., Parise C., Bottazzoli E. I., Lapolla P., Brachini G., Cirillo B., Mingoli A., Sica G., Siragusa L., Bellato V., Cerbo D., de Pasqual C. A., de Manzoni G., di Cosmo M. A., Alrayes B. M. H., Qandeel M. W. M., Hani M. B., Rabadi A., el Muhtaseb M. S., Abdeen B., Karmi F., Zilinskas J., Latkauskas T., Tamelis A., Pikuniene I., Slenfuktas V., Poskus T., Kryzauskas M., Jakubauskas M., Mikalauskas S., Jakubauskiene L., Hassan S. Y., Altrabulsi A., Abdulwahed E., Ghmagh R., Deeknah A., Alshareea E., Elhadi M., Abujamra S., Msherghi A. A., Tababa O. W. E., Majbar M. A., Souadka A., Benkabbou A., Mohsine R., Echiguer S., Moctezuma-Velazquez P., Salgado-Nesme N., Vergara-Fernandez O., Sainz-Hernandez J. C., Alvarez-Bautista F. E., Zakaria A. D., Zakaria Z., Wong M. P. K., Ismail R., Ibrahim A. F., Abdullah N. A. N., Julaihi R., Bhat S., O'Grady G., Bissett I., Lamme B., Musters G. D., Dinaux A. M., Grotenhuis B. A., Steller E. J., Aalbers A. G. J., Leeuwenburgh M. M., Rutten H. J. T., Burger J. W. A., Bloemen J. G., Ketelaers S. H. J., Waqar U., Chawla T., Rauf H., Rani P., Talsma A. K., Scheurink L., van Praagh J. B., Segelman J., Nygren J., Anderin K., Tiefenthal M., de Andres B., Beltran de Heredia J. P., Vazquez A., Gomez T., Golshani P., Kader R., Mohamed A., Westerterp M., Marinelli A., Niemer Q., Doornebosch P. G., Shapiro J., Vermaas M., de Graaf E. J. R., van Westreenen H. L., Zwakman M., van Dalsen A. D., Vles W. J., Nonner J., Toorenvliet B. R., Janssen P. T. J., Verdaasdonk E. G. G., Amelung F. J., Peeters K. C. M. J., Bahadoer R. R., Holman F. A., Heemskerk J., Vosbeek N., Leijtens J. W. A., Taverne S. B. M., Heijnen B. H. M., El-Massoudi Y., de Groot-Van Veen I., Hoff C., Jou-Valencia D., Consten E. C. J., Burghgraef T. A., Geitenbeek R., Hulshof L. G. W. L., Slooter G. D., Reudink M., Bouvy N. D., Wildeboer A. C. L., Verstappen S., Pennings A. J., van den Hengel B., Wijma A. G., de Haan J., de Nes L. C. F., Heesink V., Karsten T., Heidsma C. M., Koemans W. J., Dekker J. -W. T., van der Zijden C. J., Roos D., Demirkiran A., van der Burg S., Oosterling S. J., Hoogteijling T. J., Wiering B., Smeeing D. P. J., Havenga K., Lutfi H., Tsimogiannis K., Skoldberg F., Folkesson J., den Boer F., van Schaik T. G., van Gerven P., Sietses C., Hol J. C., Boerma E. -J. G., Creemers D. M. J., Schultz J. K., Frivold T., Riis R., Gregussen H., Busund S., Sjo O. H., Gaard M., Krohn N., Ersryd A. L., Leung E., Sultan H., Hajjaj B. N., Alhisi A. J., Khader A. A. E., Mendes A. F. D., Semiao M., Faria L. Q., Azevedo C., da Costa Devesa H. M., Martins S. F., Jarimba A. M. R., Marques S. M. R., Ferreira R. M., Oliveira A., Ferreira C., Pereira R., Surlin V. M., Graure G. M., Ramboiu S. P. S. D., Negoi I., Ciubotaru C., Stoica B., Tanase I., Negoita V. M., Florea S., Macau F., Vasile M., Stefanescu V., Dimofte G. -M., Lunca S., Roata C. -E., Musina A. -M., Garmanova T., Agapov M. N., Markaryan D. G., Eduard G., Yanishev A., Abelevich A., Bazaev A., Rodimov S. V., Filimonov V. B., Melnikov A. A., Suchkov I. A., Drozdov E. S., Kostromitskiy D. N., Sjostrom O., Matthiessen P., Baban B., Gadan S., Jadid K. D., Staffan M., Park J. M., Rydbeck D., Lydrup M. -L., Buchwald P., Jutesten H., Darlin L., Lindqvist E., Nilsson K., Larsson P. -A., Jangmalm S., Kosir J. A., Tomazic A., Grosek J., Bozic T. K., Zazo A., Zazo R., Fares H., Ayoub K., Niazi A., Mansour A., Abbas A., Tantoura M., Hamdan A., Hassan N., Hasan B., Saad A., Sebai A., Haddad A., Maghrebi H., Kacem M., Yalkin O., Samsa M. V., Atak I., Balci B., Haberal E., Dogan L., Gecim I. E., Akyol C., Koc M. A., Sivrikoz E., Piyadeoglu D., Avanagh D. O., Sokmen S., Bisgin T., Gunenc E., Guzel M., Leventoglu S., Yuksel O., Kozan R., Gobut H., Cengiz F., Erdinc K., Acar N. C., Kamer E., Ozgur I., Aydin O., Keskin M., Bulut M. T., Kulle C. B., Kara Y., Sibic O., Ozata I. H., Bugra D., Balik E., Cakir M., Alhardan A., Colak E., Aybar A. B. C., Sari A. C., Atici S. D., Kaya T., Dursun A., Calik B., Ozkan O. F., Ulgur H. S., Duzgun O., Monson J., George S., Woods K., Al-Eryani F., Albakry R., Coetzee E., Boutall A., Herman A., Warden C., Mugla N., Forgan T., Mia I., and Lambrechts A.
Abstract: Background: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2: 1). Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.
Published: 2023

3. Predicting mortality in patients with anastomotic leak after esophagectomy: development of a prediction model using data from the TENTACLE-Esophagus study.

Author: Ubels, S., Klarenbeek, B.R., Verstegen, M.H.P., Bouwense, S.A., Griffiths, E.A., Workum, F.T.W.E. van, Rosman, C., Hannink, G.J., Ubels, S., Klarenbeek, B.R., Verstegen, M.H.P., Bouwense, S.A., Griffiths, E.A., Workum, F.T.W.E. van, Rosman, C., and Hannink, G.J.
Abstract: Item does not contain fulltext, Anastomotic leak (AL) is a common but severe complication after esophagectomy, and over 10% of patients with AL suffer mortality. Different prognostic factors in patients with AL are known, but a tool to predict mortality after AL is lacking. This study aimed to develop a prediction model for postoperative mortality in patients with AL after esophagectomy. TENTACLE-Esophagus is an international retrospective cohort study, which included 1509 patients with AL after esophagectomy. The primary outcome was 90-day postoperative mortality. Previously identified prognostic factors for mortality were selected as predictors: patient-related (e.g. comorbidity, performance status) and leak-related predictors (e.g. leucocyte count, overall gastric conduit condition). The prediction model was developed using multivariable logistic regression and validated internally using bootstrapping. Among the 1509 patients with AL, 90-day mortality was 11.7%. Sixteen predictors were included in the prediction model. The model showed good performance after internal validation: the c-index was 0.79 (95% confidence interval 0.75-0.83). Predictions for mortality by the internally validated model aligned well with observed 90-day mortality rates. The prediction model was incorporated in an online tool for individual use and can be found at: https://www.tentaclestudy.com/prediction-model. The developed prediction model combines patient-related and leak-related factors to accurately predict postoperative mortality in patients with AL after esophagectomy. The model is useful for clinicians during counselling of patients and their families and may aid identification of high-risk patients at diagnosis of AL. In the future, the tool may guide clinical decision-making; however, external validation of the tool is warranted.
Published: 2023

4. Practice variation in anastomotic leak after esophagectomy: Unravelling differences in failure to rescue.

Author: Ubels, S., Matthée, E.P.C., Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S., Berge Henegouwen, M.I. van, Daams, F., Dekker, J.W.T., Det, M.J. van, Esser, S. van, Griffiths, E.A., Haveman, J.W., Nieuwenhuijzen, G., Siersema, P.D., Wijnhoven, B., Hannink, G.J., Workum, F.T.W.E. van, Rosman, C., Heisterkamp, J., Polat, F., Schouten, J.A., Singh, P., Ubels, S., Matthée, E.P.C., Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S., Berge Henegouwen, M.I. van, Daams, F., Dekker, J.W.T., Det, M.J. van, Esser, S. van, Griffiths, E.A., Haveman, J.W., Nieuwenhuijzen, G., Siersema, P.D., Wijnhoven, B., Hannink, G.J., Workum, F.T.W.E. van, Rosman, C., Heisterkamp, J., Polat, F., Schouten, J.A., and Singh, P.
Abstract: Item does not contain fulltext, INTRODUCTION: Failure to rescue (FTR) is an important outcome measure after esophagectomy and reflects mortality after postoperative complications. Differences in FTR have been associated with hospital resection volume. However, insight into how centers manage complications and achieve their outcomes is lacking. Anastomotic leak (AL) is a main contributor to FTR. This study aimed to assess differences in FTR after AL between centers, and to identify factors that explain these differences. METHODS: TENTACLE - Esophagus is a multicenter, retrospective cohort study, which included 1509 patients with AL after esophagectomy. Differences in FTR were assessed between low-volume (<20 resections), middle-volume (20-60 resections) and high-volume centers (≥60 resections). Mediation analysis was performed using logistic regression, including possible mediators for FTR: case-mix, hospital resources, leak severity and treatment. RESULTS: FTR after AL was 11.7%. After adjustment for confounders, FTR was lower in high-volume vs. low-volume (OR 0.44, 95%CI 0.2-0.8), but not versus middle-volume centers (OR 0.67, 95%CI 0.5-1.0). After mediation analysis, differences in FTR were found to be explained by lower leak severity, lower secondary ICU readmission rate and higher availability of therapeutic modalities in high-volume centers. No statistically significant direct effect of hospital volume was found: high-volume vs. low-volume 0.86 (95%CI 0.4-1.7), high-volume vs. middle-volume OR 0.86 (95%CI 0.5-1.4). CONCLUSION: Lower FTR in high-volume compared with low-volume centers was explained by lower leak severity, less secondary ICU readmissions and higher availability of therapeutic modalities. To reduce FTR after AL, future studies should investigate effective strategies to reduce leak severity and prevent secondary ICU readmission.
Published: 2023

5. Alignment in the Hospital-Physician Relationship: A Qualitative Multiple Case Study of Medical Specialist Enterprises in the Netherlands.

Author: Ubels, S., Raaij, E.M. van, Ubels, S., and Raaij, E.M. van
Abstract: Item does not contain fulltext, BACKGROUND: Policy-makers and hospital boards throughout the world have implemented different measures to create and sustain effective hospital-physician relationships. The 'integrated funding' policy reform in the Netherlands was aimed at increasing hospital-physician alignment and led to the unforeseen formation of medical specialist enterprises (MSEs): a fiscal entity representing all self-employed physicians in a hospital. It is unknown how hospitals and MSEs perceive their alignment and how they govern the relationship. This study explores the hospital-MSE relationship, and how governance styles influence perceived alignment in this relationship. METHODS: A multiple case study of five non-academic hospitals in the Netherlands was performed. Data was derived from two sources: (1) analysis of hospital-MSE contracts and (2) semi-structured interviews with hospital and MSE board members. Contracts were analysed using a predefined contract analysis template. Interview recordings were transcribed and subsequently coded using the sensitizing concepts approach. RESULTS: Contracts, relational characteristics, governance styles and perceived alignment differed substantially between cases. Two out of five contracts were prevention contracts, one was a mixed type, and two were promotion contracts. However, in all cases the contract played no role in the relationship. The use of incentives varied widely between the hospitals; most incentives were financial penalties. The governance style varied between contractual for two hospitals, mixed for one hospital and predominantly relational for two hospitals. Development of a shared business strategy was identified as an important driver of relational governance, which was perceived to boost alignment. CONCLUSION: Large variation was observed regarding relational characteristics, governance and perceived alignment. MSE formation was perceived to have contributed to hospital-physician alignment by uniting physicians, boosting physi
Published: 2023

6. Treatment of anastomotic leak after oesophagectomy for oesophageal cancer: large, collaborative, observational TENTACLE cohort study.

Author: Ubels, S., Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S., Berge Henegouwen, M.I. van, Daams, F., Det, M.J. van, Griffiths, E.A., Haveman, J.W., Heisterkamp, J., Nieuwenhuijzen, G., Polat, F., Schouten, J.A., Siersema, P.D., Singh, P., Wijnhoven, B., Hannink, G.J., Workum, F.T.W.E. van, Rosman, C., Ubels, S., Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S., Berge Henegouwen, M.I. van, Daams, F., Det, M.J. van, Griffiths, E.A., Haveman, J.W., Heisterkamp, J., Nieuwenhuijzen, G., Polat, F., Schouten, J.A., Siersema, P.D., Singh, P., Wijnhoven, B., Hannink, G.J., Workum, F.T.W.E. van, and Rosman, C.
Abstract: Contains fulltext : 294540.pdf (Publisher’s version ) (Open Access), BACKGROUND: Anastomotic leak is a severe complication after oesophagectomy. Anastomotic leak has diverse clinical manifestations and the optimal treatment strategy is unknown. The aim of this study was to assess the efficacy of treatment strategies for different manifestations of anastomotic leak after oesophagectomy. METHODS: A retrospective cohort study was performed in 71 centres worldwide and included patients with anastomotic leak after oesophagectomy (2011-2019). Different primary treatment strategies were compared for three different anastomotic leak manifestations: interventional versus supportive-only treatment for local manifestations (that is no intrathoracic collections; well perfused conduit); drainage and defect closure versus drainage only for intrathoracic manifestations; and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis. The primary outcome was 90-day mortality. Propensity score matching was performed to adjust for confounders. RESULTS: Of 1508 patients with anastomotic leak, 28.2 per cent (425 patients) had local manifestations, 36.3 per cent (548 patients) had intrathoracic manifestations, 9.6 per cent (145 patients) had conduit ischaemia/necrosis, 17.5 per cent (264 patients) were allocated after multiple imputation, and 8.4 per cent (126 patients) were excluded. After propensity score matching, no statistically significant differences in 90-day mortality were found regarding interventional versus supportive-only treatment for local manifestations (risk difference 3.2 per cent, 95 per cent c.i. -1.8 to 8.2 per cent), drainage and defect closure versus drainage only for intrathoracic manifestations (risk difference 5.8 per cent, 95 per cent c.i. -1.2 to 12.8 per cent), and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis (risk difference 0.1 per cent, 95 per cent c.i. -21.4 to 1.6 per cent). In general, less morbidity was found after less extensive primary tre
Published: 2023

7. Performance of a consensus-based algorithm for diagnosing anastomotic leak after minimally invasive esophagectomy for esophageal cancer.

Author: Lemmens, Jobbe, Klarenbeek, B., Verstegen, M.H.P., Workum, F.T.W.E. van, Hannink, G.J., Ubels, S., Rosman, C., Lemmens, Jobbe, Klarenbeek, B., Verstegen, M.H.P., Workum, F.T.W.E. van, Hannink, G.J., Ubels, S., and Rosman, C.
Abstract: Item does not contain fulltext, Anastomotic leak (AL) is a common and severe complication after esophagectomy. This study aimed to assess the performance of a consensus-based algorithm for diagnosing AL after minimally invasive esophagectomy. This study used data of the ICAN trial, a multicenter randomized clinical trial comparing cervical and intrathoracic anastomosis, in which a predefined diagnostic algorithm was used to guide diagnosing AL. The algorithm identified patients suspected of AL based on clinical signs, blood C-reactive protein (cut-off value 200 mg/L), and/or drain amylase (cut-off value 200 IU/L). Suspicion of AL prompted evaluation with contrast swallow computed tomography and/or endoscopy to confirm AL. Primary outcome measure was algorithm performance in terms of sensitivity, specificity, and positive and negative predictive values (PPV, NPV), respectively. AL was defined according to the definition of the Esophagectomy Complications Consensus Group. 245 patients were included, and 125 (51%) patients were suspected of AL. The algorithm had a sensitivity of 62% (95% confidence interval [CI]: 46-75), a specificity of 97% (95% CI: 89-100), and a PPV and NPV of 94% (95% CI: 79-99) and 77% (95% CI: 66-86), respectively, on initial assessment. Repeated assessment in 19 patients with persisting suspicion of AL despite negative or inconclusive initial assessment had a sensitivity of 100% (95% CI: 77-100). The algorithm showed poor performance because the low sensitivity indicates the inability of the algorithm to confirm AL on initial assessment. Repeated assessment using the algorithm was needed to confirm remaining leaks.
Published: 2023

8. Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients.

Author: Greijdanus, N.G., Wienholts, K., Ubels, S., Talboom, K., Hannink, G.J., Wolthuis, A., Lacy, F.B. de, Lefevre, J.H., Solomon, M., Frasson, M., Rotholtz, N., Denost, Q., Perez, R.O., Konishi, T., Panis, Y., Rutegård, M., Hompes, R., Rosman, C., Workum, F.T.W.E. van, Tanis, P.J., Wilt, J.H.W. de, Greijdanus, N.G., Wienholts, K., Ubels, S., Talboom, K., Hannink, G.J., Wolthuis, A., Lacy, F.B. de, Lefevre, J.H., Solomon, M., Frasson, M., Rotholtz, N., Denost, Q., Perez, R.O., Konishi, T., Panis, Y., Rutegård, M., Hompes, R., Rosman, C., Workum, F.T.W.E. van, Tanis, P.J., and Wilt, J.H.W. de
Abstract: Contains fulltext : 300157.pdf (Publisher’s version ) (Open Access), BACKGROUND: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. METHODS: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1). RESULTS: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). CONCLUSION: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.
Published: 2023

9. Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage

Author: Greijdanus, N.G., Wienholts, K., Ubels, S., Talboom, K., Hannink, G.J., Wolthuis, A., Rosman, C., Tanis, P.J., Wilt, J.H.W. de, Greijdanus, N.G., Wienholts, K., Ubels, S., Talboom, K., Hannink, G.J., Wolthuis, A., Rosman, C., Tanis, P.J., and Wilt, J.H.W. de
Abstract: Contains fulltext : 298934.pdf (Publisher’s version ) (Open Access)
Published: 2023

10. Optimising diagnostics to discriminate complicated from uncomplicated appendicitis: a prospective cohort study protocol

Author: Bom, Wouter J., Scheijmans, Jochem C.G., Ubels, S., Geloven, Anna A.W. van, Gans, Sarah L., Tytgat, Kristien M.A.J., Dijkgraaf, Marcel G.W., Boermeester, Marja A., Bom, Wouter J., Scheijmans, Jochem C.G., Ubels, S., Geloven, Anna A.W. van, Gans, Sarah L., Tytgat, Kristien M.A.J., Dijkgraaf, Marcel G.W., and Boermeester, Marja A.
Abstract: Contains fulltext : 249107.pdf (Publisher’s version ) (Open Access)
Published: 2022

11. Severity of oEsophageal Anastomotic Leak in patients after oesophagectomy: the SEAL score

Author: Ubels, S., Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S., Berge Henegouwen, M.I. van, Daams, F., Det, M.J. van, Griffiths, E.A., Haveman, J.W., Heisterkamp, J., Koshy, R., Nieuwenhuijzen, G., Polat, Fatih, Siersema, P.D., Singh, P., Wijnhoven, B., Hannink, G.J., Workum, F.T.W.E. van, Rosman, C., Ubels, S., Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S., Berge Henegouwen, M.I. van, Daams, F., Det, M.J. van, Griffiths, E.A., Haveman, J.W., Heisterkamp, J., Koshy, R., Nieuwenhuijzen, G., Polat, Fatih, Siersema, P.D., Singh, P., Wijnhoven, B., Hannink, G.J., Workum, F.T.W.E. van, and Rosman, C.
Abstract: Contains fulltext : 282376.pdf (Publisher’s version ) (Open Access), BACKGROUND: Anastomotic leak (AL) is a common but severe complication after oesophagectomy. It is unknown how to determine the severity of AL objectively at diagnosis. Determining leak severity may guide treatment decisions and improve future research. This study aimed to identify leak-related prognostic factors for mortality, and to develop a Severity of oEsophageal Anastomotic Leak (SEAL) score. METHODS: This international, retrospective cohort study in 71 centres worldwide included patients with AL after oesophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. Leak-related prognostic factors were identified after adjusting for confounders and were included in multivariable logistic regression to develop the SEAL score. Four classes of leak severity (mild, moderate, severe, and critical) were defined based on the risk of 90-day mortality, and the score was validated internally. RESULTS: Some 1509 patients with AL were included and the 90-day mortality rate was 11.7 per cent. Twelve leak-related prognostic factors were included in the SEAL score. The score showed good calibration and discrimination (c-index 0.77, 95 per cent c.i. 0.73 to 0.81). Higher classes of leak severity graded by the SEAL score were associated with a significant increase in duration of ICU stay, healing time, Comprehensive Complication Index score, and Esophagectomy Complications Consensus Group classification. CONCLUSION: The SEAL score grades leak severity into four classes by combining 12 leak-related predictors and can be used to the assess severity of AL after oesophagectomy.
Published: 2022

12. Treatment of anastomotic leak after esophagectomy: insights of an international case vignette survey and expert discussions

Author: Ubels, S., Lubbers, Merel, Verstegen, M.H.P., Bouwense, S.A., Daele, E. van, Ferri, L., Gisbertz, S.S., Griffiths, E.A., Grimminger, P., Hanna, G., Hubka, M., Law, S., Low, D., Luyer, M., Merritt, R.E., Morse, C., Mueller, C.L., Nieuwenhuijzen, G.A., Nilsson, M., Reynolds, J.V., Ribeiro, U., Rosati, R., Shen, Y., Wijnhoven, B.P., Klarenbeek, B.R., Workum, F.T.W.E. van, Rosman, C., Ubels, S., Lubbers, Merel, Verstegen, M.H.P., Bouwense, S.A., Daele, E. van, Ferri, L., Gisbertz, S.S., Griffiths, E.A., Grimminger, P., Hanna, G., Hubka, M., Law, S., Low, D., Luyer, M., Merritt, R.E., Morse, C., Mueller, C.L., Nieuwenhuijzen, G.A., Nilsson, M., Reynolds, J.V., Ribeiro, U., Rosati, R., Shen, Y., Wijnhoven, B.P., Klarenbeek, B.R., Workum, F.T.W.E. van, and Rosman, C.
Abstract: Item does not contain fulltext, Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy.
Published: 2022

13. International expert opinion on optimal treatment of anastomotic leakage after rectal cancer resection: a case-vignette study

Author: Talboom, K., Greijdanus, N.G., Workum, F.T.W.E. van, Ubels, S., Rosman, C., Hompes, R., Wilt, J.H.W. de, Tanis, P.J., Talboom, K., Greijdanus, N.G., Workum, F.T.W.E. van, Ubels, S., Rosman, C., Hompes, R., Wilt, J.H.W. de, and Tanis, P.J.
Abstract: Item does not contain fulltext, PURPOSE: Little is known about the optimal treatment of anastomotic leakage after low anterior resection (LAR) for rectal cancer and whether treatment strategy depends on leakage features and patient characteristics. The objective of this study was to determine which treatment principles are used by expert colorectal surgeons worldwide. METHODS: In this international case-vignette study, participants completed a survey on their preferred treatment for 11 clinical cases with varying leakage features and two patient scenarios depending on surgical risk (a total of 22 cases). RESULTS: In total, 42 of 64 invited surgeons completed the survey from 18 countries worldwide. The majority worked at a university training hospital (62%) and had more than 15 years of experience performing LAR for rectal cancer (52%). Early leaks in septic patients were preferably treated by major salvage surgery, to some extent depending on the patient scenario. In early leaks in non-septic patients, drainage and faecal diversion were the cornerstones of the proposed treatment. Endoscopic vacuum therapy was more often proposed than percutaneous drainage. A minority proposed anastomotic reconstruction, more often for larger defects. Treatment of late leaks ranged from watchful waiting, drainage, or transanal repair to major (non-)restorative salvage surgery, with minimal influence of the degree of symptoms on the proposed strategy. Leaks of the blind loop and rectovaginal fistulae showed high variability in the proposed treatment strategy. CONCLUSION: This TENTACLE-Rectum case-vignette study demonstrates tailored treatment strategies depending on the clinical type of leak and patient characteristics, with variable degrees of consensus and knowledge gaps which should be addressed in future studies.
Published: 2022

14. 10: INTRATHORACIC VERSUS CERVICAL ANASTOMOSIS AFTER MINIMALLY INVASIVE OESOPHAGECTOMY FOR OESOPHAGEAL CANCER: A RANDOMISED CONTROLLED TRIAL

Author: Van Workum, F, primary, Verstegen, M, additional, Klarenbeek, B, additional, Bouwense, S, additional, Van Berge Henegouwen, M, additional, Daams, F, additional, Gisbertz, S, additional, Hannink, G, additional, Haveman, J W, additional, Heisterkamp, J, additional, Jansen, W, additional, Kouwenhoven, E, additional, Van Lanschot, J, additional, Nieuwenhuijzen, G, additional, Van Der Peet, D, additional, Polat, F, additional, Ubels, S, additional, Wijnhoven, B, additional, Rovers, M, additional, and Rosman, C, additional
Published: 2022
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15. 39: TREATMENT OF ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY (TENTACLE—ESOPHAGUS) STUDY: EFFICACY OF DIFFERENT INITIAL TREATMENT STRATEGIES FOR ANASTOMOTIC LEAKAGE

Author: Ubels, S, primary, Verstegen, M, additional, Bouwense, S, additional, Hannink, G, additional, Siersema, P, additional, Klarenbeek, B, additional, Van Workum, F, additional, and Rosman, C, additional
Published: 2022
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16. 124: DETERMINING SEVERITY OF ESOPHAGEAL ANASTOMOTIC LEAK IN PATIENTS AFTER ESOPHAGECTOMY: DEVELOPMENT OF THE SEAL SCORE

Author: Ubels, S, primary, Verstegen, M, additional, Bouwense, S, additional, Hannink, G, additional, Siersema, P, additional, Klarenbeek, B, additional, Van Workum, F, additional, and Rosman, C, additional
Published: 2022
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17. Commentary: endoscopic vacuum therapy for anastomotic leakage after esophagectomy and total gastrectomy: obstacles to finding true evidence

Author: Ubels, S., Verstegen, M.H.P., Bouwense, S.A., Klarenbeek, B.R., Workum, F.T.W.E. van, Rosman, C., Ubels, S., Verstegen, M.H.P., Bouwense, S.A., Klarenbeek, B.R., Workum, F.T.W.E. van, and Rosman, C.
Abstract: Contains fulltext : 238989.pdf (Publisher’s version ) (Open Access)
Published: 2021

18. Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer: A Randomized Clinical Trial

Author: Workum, F.T.W.E. van, Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S.A.W., Berge Henegouwen, M.I. van, Daams, F., Gisbertz, S.S., Hannink, G.J., Haveman, J.W., Heisterkamp, J., Jansen, Walther, Kouwenhoven, E.A., Lanschot, J.Jan B. van, Nieuwenhuijzen, G.A., Peet, D.L. van der, Polat, F., Ubels, S., Wijnhoven, B.P., Rovers, M.M., Rosman, C., Workum, F.T.W.E. van, Verstegen, M.H.P., Klarenbeek, B.R., Bouwense, S.A.W., Berge Henegouwen, M.I. van, Daams, F., Gisbertz, S.S., Hannink, G.J., Haveman, J.W., Heisterkamp, J., Jansen, Walther, Kouwenhoven, E.A., Lanschot, J.Jan B. van, Nieuwenhuijzen, G.A., Peet, D.L. van der, Polat, F., Ubels, S., Wijnhoven, B.P., Rovers, M.M., and Rosman, C.
Abstract: Item does not contain fulltext, BACKGROUND: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE. OBJECTIVE: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. INTERVENTION: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. MAIN OUTCOMES AND MEASURES: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. RESULTS: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI,
Published: 2021

19. 388 TREATMENT OF ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY (TENTACLE—ESOPHAGUS) STUDY: FACTORS ASSOCIATED WITH ANASTOMOTIC LEAKAGE SEVERITY

Author: Ubels, S, primary, Verstegen, M, additional, Bouwense, S, additional, Hannink, G, additional, Siersema, P, additional, Klarenbeek, B, additional, van Workum, F, additional, and Rosman, C, additional
Published: 2020
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20. 380 TREATMENT OF ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY (TENTACLE—ESOPHAGUS) STUDY: OUTCOME OF VARIOUS LEAKAGE TREATMENTS

Author: Van Workum, F, primary, Verstegen, M, additional, Ubels, S, additional, Hannink, G, additional, Klarenbeek, B, additional, Rosman, C, additional, and Bouwense, S, additional
Published: 2020
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21. Pancreatoduodenectomy should be avoided when para-aortic lymph node metastases are found during surgical exploration for suspected pancreatic ductal adenocarcinoma

Author: Pranger, B., primary, Tseng, D., additional, Ubels, S., additional, Patijn, G., additional, Borel Rinkes, I.H., additional, Offerhaus, J.H., additional, Nieuwenhuis, V., additional, de Jong, K.P., additional, Klaase, J.M., additional, Molenaar, I.Q., additional, Erdmann, J., additional, and de Meijer, V., additional
Published: 2018
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22. Understanding abstract geo-information workflows and converting them to executable workflows using Semantic Web technologies

Author: Ubels, S., Lemmens, R.L.G. (Thesis Advisor), Ubels, S., and Lemmens, R.L.G. (Thesis Advisor)
Published: 2018

23. 10: INTRATHORACIC VERSUS CERVICAL ANASTOMOSIS AFTER MINIMALLY INVASIVE OESOPHAGECTOMY FOR OESOPHAGEAL CANCER: A RANDOMISED CONTROLLED TRIAL.

Author: Workum, F Van, Verstegen, M, Klarenbeek, B, Bouwense, S, Henegouwen, M Van Berge, Daams, F, Gisbertz, S, Hannink, G, Haveman, J W, Heisterkamp, J, Jansen, W, Kouwenhoven, E, Lanschot, J Van, Nieuwenhuijzen, G, Peet, D Van Der, Polat, F, Ubels, S, Wijnhoven, B, Rovers, M, and Rosman, C
Subjects: RANDOMIZED controlled trials, ESOPHAGEAL cancer, LARYNGEAL nerve palsy, RECURRENT laryngeal nerve, ESOPHAGECTOMY
Abstract: Background and aim Transthoracic minimally invasive oesophagectomy (MIO) is increasingly performed as part of curative multimodality treatment. There is no robust evidence on the preferred location of the anastomosis after transthoracic MIO. The aim of this study was to compare an intrathoracic with a cervical anastomosis in a randomised controlled trial. Methods An open multicentre randomised controlled superiority trial was performed. Patients with mid to distal oesophageal or gastro-oesophageal junction cancer planned for curative resection were included. Patients were randomly assigned (1:1) to transthoracic MIO with intrathoracic or cervical anastomosis. The primary endpoint was anastomotic leakage requiring endoscopic, radiologic or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality and quality of life. The ICAN trial is registered in the Dutch trial register under number NTR4333. Results Two hundred and sixty-two patients were randomised and 245 were eligible for analysis. Anastomotic leakage necessitating re-intervention occurred in 15 of 122 (12.3%) patients with intrathoracic anastomosis and in 39 of 123 (31.7%) patients with cervical anastomosis (risk difference − 19.4%, 95% CI -29.5%—-9.3%). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference − 21.9%, 95% CI -32.1%—-11.6%). ICU length of stay, mortality rates and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with less severe complications, lower incidence of recurrent laryngeal nerve palsy and better quality of life in three subdomains. Conclusion Intrathoracic anastomosis is the preferred technique for patients treated with transthoracic MIO for mid to distal oesophageal or gastro-oesophageal junction cancer. [ABSTRACT FROM AUTHOR]
Published: 2022
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24. Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients.

Author: Greijdanus NG, Wienholts K, Ubels S, Talboom K, Hannink G, Wolthuis A, de Lacy FB, Lefevre JH, Solomon M, Frasson M, Rotholtz N, Denost Q, Perez RO, Konishi T, Panis Y, Rutegård M, Hompes R, Rosman C, van Workum F, Tanis PJ, and de Wilt JHW
Subjects: Humans, Cohort Studies, Anastomosis, Surgical methods, Rectum surgery, Retrospective Studies, Anastomotic Leak etiology, Anastomotic Leak surgery, Rectal Neoplasms surgery, Rectal Neoplasms complications
Abstract: Background: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied., Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1)., Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days)., Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)
Published: 2023
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25. Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort.

Author: Greijdanus NG, Wienholts K, Ubels S, Talboom K, Hannink G, Wolthuis A, de Lacy FB, Lefevre JH, Solomon M, Frasson M, Rotholtz N, Denost Q, Perez RO, Konishi T, Panis Y, Rutegård M, Hompes R, Rosman C, van Workum F, Tanis PJ, and de Wilt JHW
Subjects: Humans, Rectum surgery, Retrospective Studies, Anastomosis, Surgical methods, Risk Factors, Anastomotic Leak etiology, Anastomotic Leak surgery, Rectal Neoplasms surgery
Abstract: Objective: To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL)., Background: AL after RC resection often results in a permanent stoma., Methods: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated., Results: This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76)., Conclusions: The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Published: 2023
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26. Performance of a consensus-based algorithm for diagnosing anastomotic leak after minimally invasive esophagectomy for esophageal cancer.

Author: Lemmens J, Klarenbeek B, Verstegen M, van Workum F, Hannink G, Ubels S, and Rosman C
Subjects: Humans, Esophagectomy adverse effects, Esophagectomy methods, Consensus, Retrospective Studies, Anastomosis, Surgical adverse effects, Anastomosis, Surgical methods, Anastomotic Leak diagnosis, Anastomotic Leak etiology, Anastomotic Leak surgery, Esophageal Neoplasms complications
Abstract: Anastomotic leak (AL) is a common and severe complication after esophagectomy. This study aimed to assess the performance of a consensus-based algorithm for diagnosing AL after minimally invasive esophagectomy. This study used data of the ICAN trial, a multicenter randomized clinical trial comparing cervical and intrathoracic anastomosis, in which a predefined diagnostic algorithm was used to guide diagnosing AL. The algorithm identified patients suspected of AL based on clinical signs, blood C-reactive protein (cut-off value 200 mg/L), and/or drain amylase (cut-off value 200 IU/L). Suspicion of AL prompted evaluation with contrast swallow computed tomography and/or endoscopy to confirm AL. Primary outcome measure was algorithm performance in terms of sensitivity, specificity, and positive and negative predictive values (PPV, NPV), respectively. AL was defined according to the definition of the Esophagectomy Complications Consensus Group. 245 patients were included, and 125 (51%) patients were suspected of AL. The algorithm had a sensitivity of 62% (95% confidence interval [CI]: 46-75), a specificity of 97% (95% CI: 89-100), and a PPV and NPV of 94% (95% CI: 79-99) and 77% (95% CI: 66-86), respectively, on initial assessment. Repeated assessment in 19 patients with persisting suspicion of AL despite negative or inconclusive initial assessment had a sensitivity of 100% (95% CI: 77-100). The algorithm showed poor performance because the low sensitivity indicates the inability of the algorithm to confirm AL on initial assessment. Repeated assessment using the algorithm was needed to confirm remaining leaks., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Published: 2023
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27. Erratum to "Practice variation in anastomotic leak after esophagectomy: Unravelling differences in failure to rescue" [Eur J Surg Oncol 49 (5) (May 2023) 974-982].

Author: Ubels S, Matthée E, Verstegen M, Klarenbeek B, Bouwense S, van Berge Henegouwen MI, Daams F, Dekker JWT, van Det MJ, van Esser S, Griffiths EA, Haveman JW, Nieuwenhuijzen G, Siersema PD, Wijnhoven B, Hannink G, van Workum F, and Rosman C
Published: 2023
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28. Treatment of anastomotic leak after oesophagectomy for oesophageal cancer: large, collaborative, observational TENTACLE cohort study.

Author: Ubels S, Verstegen MHP, Klarenbeek BR, Bouwense S, van Berge Henegouwen MI, Daams F, van Det MJ, Griffiths EA, Haveman JW, Heisterkamp J, Nieuwenhuijzen G, Polat F, Schouten J, Siersema PD, Singh P, Wijnhoven B, Hannink G, van Workum F, and Rosman C
Subjects: Humans, Anastomosis, Surgical adverse effects, Cohort Studies, Esophagectomy adverse effects, Ischemia surgery, Necrosis complications, Necrosis surgery, Retrospective Studies, Anastomotic Leak etiology, Anastomotic Leak surgery, Esophageal Neoplasms surgery, Esophageal Neoplasms complications
Abstract: Background: Anastomotic leak is a severe complication after oesophagectomy. Anastomotic leak has diverse clinical manifestations and the optimal treatment strategy is unknown. The aim of this study was to assess the efficacy of treatment strategies for different manifestations of anastomotic leak after oesophagectomy., Methods: A retrospective cohort study was performed in 71 centres worldwide and included patients with anastomotic leak after oesophagectomy (2011-2019). Different primary treatment strategies were compared for three different anastomotic leak manifestations: interventional versus supportive-only treatment for local manifestations (that is no intrathoracic collections; well perfused conduit); drainage and defect closure versus drainage only for intrathoracic manifestations; and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis. The primary outcome was 90-day mortality. Propensity score matching was performed to adjust for confounders., Results: Of 1508 patients with anastomotic leak, 28.2 per cent (425 patients) had local manifestations, 36.3 per cent (548 patients) had intrathoracic manifestations, 9.6 per cent (145 patients) had conduit ischaemia/necrosis, 17.5 per cent (264 patients) were allocated after multiple imputation, and 8.4 per cent (126 patients) were excluded. After propensity score matching, no statistically significant differences in 90-day mortality were found regarding interventional versus supportive-only treatment for local manifestations (risk difference 3.2 per cent, 95 per cent c.i. -1.8 to 8.2 per cent), drainage and defect closure versus drainage only for intrathoracic manifestations (risk difference 5.8 per cent, 95 per cent c.i. -1.2 to 12.8 per cent), and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis (risk difference 0.1 per cent, 95 per cent c.i. -21.4 to 1.6 per cent). In general, less morbidity was found after less extensive primary treatment strategies., Conclusion: Less extensive primary treatment of anastomotic leak was associated with less morbidity. A less extensive primary treatment approach may potentially be considered for anastomotic leak. Future studies are needed to confirm current findings and guide optimal treatment of anastomotic leak after oesophagectomy., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)
Published: 2023
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29. Predicting mortality in patients with anastomotic leak after esophagectomy: development of a prediction model using data from the TENTACLE-Esophagus study.

Author: Ubels S, Klarenbeek B, Verstegen M, Bouwense S, Griffiths EA, van Workum F, Rosman C, and Hannink G
Subjects: Humans, Esophagectomy adverse effects, Retrospective Studies, Risk Factors, Esophagus surgery, Anastomosis, Surgical adverse effects, Anastomotic Leak surgery, Esophageal Neoplasms complications
Abstract: Anastomotic leak (AL) is a common but severe complication after esophagectomy, and over 10% of patients with AL suffer mortality. Different prognostic factors in patients with AL are known, but a tool to predict mortality after AL is lacking. This study aimed to develop a prediction model for postoperative mortality in patients with AL after esophagectomy. TENTACLE-Esophagus is an international retrospective cohort study, which included 1509 patients with AL after esophagectomy. The primary outcome was 90-day postoperative mortality. Previously identified prognostic factors for mortality were selected as predictors: patient-related (e.g. comorbidity, performance status) and leak-related predictors (e.g. leucocyte count, overall gastric conduit condition). The prediction model was developed using multivariable logistic regression and validated internally using bootstrapping. Among the 1509 patients with AL, 90-day mortality was 11.7%. Sixteen predictors were included in the prediction model. The model showed good performance after internal validation: the c-index was 0.79 (95% confidence interval 0.75-0.83). Predictions for mortality by the internally validated model aligned well with observed 90-day mortality rates. The prediction model was incorporated in an online tool for individual use and can be found at: https://www.tentaclestudy.com/prediction-model. The developed prediction model combines patient-related and leak-related factors to accurately predict postoperative mortality in patients with AL after esophagectomy. The model is useful for clinicians during counselling of patients and their families and may aid identification of high-risk patients at diagnosis of AL. In the future, the tool may guide clinical decision-making; however, external validation of the tool is warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2023
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30. Alignment in the Hospital-Physician Relationship: A Qualitative Multiple Case Study of Medical Specialist Enterprises in the Netherlands.

Author: Ubels S and van Raaij EM
Subjects: Humans, Netherlands, Contracts, Social Behavior, Hospitals, Physicians
Abstract: Background: Policy-makers and hospital boards throughout the world have implemented different measures to create and sustain effective hospital-physician relationships. The 'integrated funding' policy reform in the Netherlands was aimed at increasing hospital-physician alignment and led to the unforeseen formation of medical specialist enterprises (MSEs): a fiscal entity representing all self-employed physicians in a hospital. It is unknown how hospitals and MSEs perceive their alignment and how they govern the relationship. This study explores the hospital-MSE relationship, and how governance styles influence perceived alignment in this relationship., Methods: A multiple case study of five non-academic hospitals in the Netherlands was performed. Data was derived from two sources: (1) analysis of hospital-MSE contracts and (2) semi-structured interviews with hospital and MSE board members. Contracts were analysed using a predefined contract analysis template. Interview recordings were transcribed and subsequently coded using the sensitizing concepts approach., Results: Contracts, relational characteristics, governance styles and perceived alignment differed substantially between cases. Two out of five contracts were prevention contracts, one was a mixed type, and two were promotion contracts. However, in all cases the contract played no role in the relationship. The use of incentives varied widely between the hospitals; most incentives were financial penalties. The governance style varied between contractual for two hospitals, mixed for one hospital and predominantly relational for two hospitals. Development of a shared business strategy was identified as an important driver of relational governance, which was perceived to boost alignment., Conclusion: Large variation was observed regarding relational characteristics, governance and perceived alignment. MSE formation was perceived to have contributed to hospital-physician alignment by uniting physicians, boosting physicians' managerial responsibilities, increasing financial alignment and developing shared business strategies. Relational governance was found to promote intensive collaboration between hospital and MSE, and thus may improve alignment in the hospital-physician relationship., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)
Published: 2023
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31. Treatment of anastomotic leak after esophagectomy: insights of an international case vignette survey and expert discussions.

Author: Ubels S, Lubbers M, Verstegen MHP, Bouwense SAW, van Daele E, Ferri L, Gisbertz SS, Griffiths EA, Grimminger P, Hanna G, Hubka M, Law S, Low D, Luyer M, Merritt RE, Morse C, Mueller CL, Nieuwenhuijzen GAP, Nilsson M, Reynolds JV, Ribeiro U, Rosati R, Shen Y, Wijnhoven BPL, Klarenbeek BR, van Workum F, and Rosman C
Subjects: Humans, Anastomotic Leak etiology, Anastomotic Leak surgery, Retrospective Studies, Anastomosis, Surgical adverse effects, Anastomosis, Surgical methods, Surveys and Questionnaires, Esophagectomy methods, Esophageal Neoplasms
Abstract: Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)
Published: 2022
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32. International expert opinion on optimal treatment of anastomotic leakage after rectal cancer resection: a case-vignette study.

Author: Talboom K, Greijdanus NG, van Workum F, Ubels S, Rosman C, Hompes R, de Wilt JHW, and Tanis PJ
Subjects: Anastomosis, Surgical adverse effects, Anastomotic Leak etiology, Anastomotic Leak surgery, Humans, Retrospective Studies, Rectal Neoplasms etiology, Rectal Neoplasms surgery, Rectum surgery
Abstract: Purpose: Little is known about the optimal treatment of anastomotic leakage after low anterior resection (LAR) for rectal cancer and whether treatment strategy depends on leakage features and patient characteristics. The objective of this study was to determine which treatment principles are used by expert colorectal surgeons worldwide., Methods: In this international case-vignette study, participants completed a survey on their preferred treatment for 11 clinical cases with varying leakage features and two patient scenarios depending on surgical risk (a total of 22 cases)., Results: In total, 42 of 64 invited surgeons completed the survey from 18 countries worldwide. The majority worked at a university training hospital (62%) and had more than 15 years of experience performing LAR for rectal cancer (52%). Early leaks in septic patients were preferably treated by major salvage surgery, to some extent depending on the patient scenario. In early leaks in non-septic patients, drainage and faecal diversion were the cornerstones of the proposed treatment. Endoscopic vacuum therapy was more often proposed than percutaneous drainage. A minority proposed anastomotic reconstruction, more often for larger defects. Treatment of late leaks ranged from watchful waiting, drainage, or transanal repair to major (non-)restorative salvage surgery, with minimal influence of the degree of symptoms on the proposed strategy. Leaks of the blind loop and rectovaginal fistulae showed high variability in the proposed treatment strategy., Conclusion: This TENTACLE-Rectum case-vignette study demonstrates tailored treatment strategies depending on the clinical type of leak and patient characteristics, with variable degrees of consensus and knowledge gaps which should be addressed in future studies., (© 2022. The Author(s).)
Published: 2022
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33. Severity of oEsophageal Anastomotic Leak in patients after oesophagectomy: the SEAL score.

Author: Ubels S, Verstegen M, Klarenbeek B, Bouwense S, van Berge Henegouwen M, Daams F, van Det MJ, Griffiths EA, Haveman JW, Heisterkamp J, Koshy R, Nieuwenhuijzen G, Polat F, Siersema PD, Singh P, Wijnhoven B, Hannink G, van Workum F, and Rosman C
Subjects: Anastomosis, Surgical adverse effects, Anastomotic Leak diagnosis, Anastomotic Leak etiology, Anastomotic Leak surgery, Humans, Logistic Models, Retrospective Studies, Esophageal Neoplasms complications, Esophageal Neoplasms surgery, Esophagectomy adverse effects
Abstract: Background: Anastomotic leak (AL) is a common but severe complication after oesophagectomy. It is unknown how to determine the severity of AL objectively at diagnosis. Determining leak severity may guide treatment decisions and improve future research. This study aimed to identify leak-related prognostic factors for mortality, and to develop a Severity of oEsophageal Anastomotic Leak (SEAL) score., Methods: This international, retrospective cohort study in 71 centres worldwide included patients with AL after oesophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. Leak-related prognostic factors were identified after adjusting for confounders and were included in multivariable logistic regression to develop the SEAL score. Four classes of leak severity (mild, moderate, severe, and critical) were defined based on the risk of 90-day mortality, and the score was validated internally., Results: Some 1509 patients with AL were included and the 90-day mortality rate was 11.7 per cent. Twelve leak-related prognostic factors were included in the SEAL score. The score showed good calibration and discrimination (c-index 0.77, 95 per cent c.i. 0.73 to 0.81). Higher classes of leak severity graded by the SEAL score were associated with a significant increase in duration of ICU stay, healing time, Comprehensive Complication Index score, and Esophagectomy Complications Consensus Group classification., Conclusion: The SEAL score grades leak severity into four classes by combining 12 leak-related predictors and can be used to the assess severity of AL after oesophagectomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)
Published: 2022
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34. Optimising diagnostics to discriminate complicated from uncomplicated appendicitis: a prospective cohort study protocol.

Author: Bom WJ, Scheijmans JCG, Ubels S, van Geloven AAW, Gans SL, Tytgat KMAJ, van Rossem CC, Koens L, Stoker J, Bemelman WA, Dijkgraaf MGW, and Boermeester MA
Subjects: Acute Disease, Adult, Cohort Studies, Humans, Observational Studies as Topic, Predictive Value of Tests, Prospective Studies, Appendicitis complications, Appendicitis diagnosis, Appendicitis surgery
Abstract: Introduction: Growing evidence is showing that complicated and uncomplicated appendicitis are two different entities that may be treated differently. A correct diagnosis of the type of appendicitis is therefore essential. The Scoring system of Appendicitis Severity (SAS) combines clinical, laboratory and imaging findings. The SAS rules out complicated appendicitis in 95% (negative predictive value, NPV) and detects 95% (sensitivity) of patients with complicated appendicitis in adults suspected of acute appendicitis. However, this scoring system has not yet been validated externally. In this study, we aim to provide a prospective external validation of the SAS in a new cohort of patients with clinical suspicion of appendicitis. We will optimise the score when necessary., Methods and Analysis: The SAS will be validated in 795 consecutive adult patients diagnosed with acute appendicitis confirmed by imaging. Data will be collected prospectively in multiple centres. The predicted diagnosis based on the SAS score will be compared with the combined surgical and histological diagnosis. Diagnostic accuracy for ruling out complicated appendicitis will be calculated. If the SAS does not reach a sensitivity and NPV of 95% in its present form, the score will be optimised. After optimisation, a second external validation will be performed in a new group of 328 patients. Furthermore, the diagnostic accuracy of the clinical perspective of the treating physician for differentiation between uncomplicated and complicated appendicitis and the patient's preferences for different treatment options will be assessed., Ethics and Dissemination: Ethical approval was granted by the Amsterdam UMC Medical Ethics Committee (reference W19_416 # 19.483). Because of the observational nature of this study, the study does not fall under the scope of the Medical Research Involving Human Subjects Act. Results will be presented in peer-reviewed journals. This protocol is submitted for publication before analysis of the results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2022
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35. Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer: A Randomized Clinical Trial.

Author: van Workum F, Verstegen MHP, Klarenbeek BR, Bouwense SAW, van Berge Henegouwen MI, Daams F, Gisbertz SS, Hannink G, Haveman JW, Heisterkamp J, Jansen W, Kouwenhoven EA, van Lanschot JJB, Nieuwenhuijzen GAP, van der Peet DL, Polat F, Ubels S, Wijnhoven BPL, Rovers MM, and Rosman C
Subjects: Aged, Anastomosis, Surgical, Carcinoma mortality, Carcinoma pathology, Esophageal Neoplasms mortality, Esophageal Neoplasms pathology, Esophagectomy methods, Esophagogastric Junction, Female, Humans, Length of Stay, Male, Middle Aged, Minimally Invasive Surgical Procedures, Netherlands, Quality of Life, Treatment Outcome, Anastomotic Leak epidemiology, Carcinoma surgery, Esophageal Neoplasms surgery, Esophagectomy adverse effects
Abstract: Background: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE., Objective: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial., Design, Setting, and Participants: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020., Intervention: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis., Main Outcomes and Measures: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life., Results: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7])., Conclusions and Relevance: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer., Trial Registration: Trialregister.nl Identifier: NL4183 (NTR4333).
Published: 2021
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36. Commentary: endoscopic vacuum therapy for anastomotic leakage after esophagectomy and total gastrectomy: obstacles to finding true evidence.

Author: Ubels S, Verstegen M, Bouwense S, Klarenbeek B, van Workum F, and Rosman C
Subjects: Esophagectomy adverse effects, Esophagoscopy, Gastrectomy adverse effects, Humans, Anastomotic Leak etiology, Anastomotic Leak surgery, Negative-Pressure Wound Therapy
Published: 2021
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37. How to Approach Para-Aortic Lymph Node Metastases During Exploration for Suspected Periampullary Carcinoma: Resection or Bypass?

Author: Pranger BK, Tseng DSJ, Ubels S, van Santvoort HC, Nieuwenhuijs VB, de Jong KP, Patijn G, Molenaar IQ, Erdmann JI, and de Meijer VE
Subjects: Aged, Cohort Studies, Female, Humans, Lymphatic Metastasis, Male, Middle Aged, Retrospective Studies, Carcinoma, Lymph Nodes surgery
Abstract: Background: Intraoperative para-aortic lymph node (PALN) sampling during surgical exploration in patients with suspected pancreatic head cancer remains controversial., Objective: The aim of this study was to assess the value of routine PALN sampling and the consequences of different treatment strategies on overall patient survival., Methods: A retrospective, multicenter cohort study was performed in patients who underwent surgical exploration for suspected pancreatic head cancer. In cohort A, the treatment strategy was to avoid pancreatoduodenectomy and to perform a double bypass procedure when PALN metastases were found during exploration. In cohort B, routinely harvested PALNs were not examined intraoperatively and pancreatoduodenectomy was performed regardless. PALNs were examined with the final resection specimen. Clinicopathological data, survival data and complication data were compared between study groups., Results: Median overall survival for patients with PALN metastases who underwent a double bypass procedure was 7.0 months (95% confidence interval [CI] 5.5-8.5), versus 11 months (95% CI 8.8-13) in the pancreatoduodenectomy group (p = 0.049). Patients with PALN metastases who underwent pancreatoduodenectomy had significantly increased postoperative morbidity compared with patients who underwent a double bypass procedure (p < 0.001). In multivariable analysis, severe comorbidity (ASA grade 2 or higher) was an independent predictor for decreased survival in patients with PALN involvement (hazard ratio 3.607, 95% CI 1.678-7.751; p = 0.001)., Conclusion: In patients with PALN metastases, pancreatoduodenectomy was associated with significant survival benefit compared with a double bypass procedure, but with increased risk of complications. It is important to weigh the advantages of resection versus bypass against factors such as comorbidities and clinical performance when positive intraoperative PALNs are found.
Published: 2020
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