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1. Perioperative management and anaesthetic considerations in pelvic exenterations using Delphi methodology: results from the PelvEx Collaborative

Author

Chok, AY, Oliver, A, Rasheed, S, Tan, EJ, Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bedford, M, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chang, GJ, Chew, MH, Chong, P, Christensen, HK, Clouston, H, Codd, M, Collins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, IR, Davies, M, Davies, RJ, Delaney, CP, de Wilt, JHW, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, George, V, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Hellawell, G, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Holmstrom, A, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, G, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mirnezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, Rasmussen, PC, Rausa, E, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Swartling, T, Sumrien, H, Sutton, PA, Swartking, T, Taylor, C, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, van Ramshorst, GH, van Zoggel, D, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warrier, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, Winter, DC, Tekkis, PP, Chok, AY, Oliver, A, Rasheed, S, Tan, EJ, Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bedford, M, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chang, GJ, Chew, MH, Chong, P, Christensen, HK, Clouston, H, Codd, M, Collins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, IR, Davies, M, Davies, RJ, Delaney, CP, de Wilt, JHW, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, George, V, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Hellawell, G, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Holmstrom, A, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, G, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mirnezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, Rasmussen, PC, Rausa, E, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Swartling, T, Sumrien, H, Sutton, PA, Swartking, T, Taylor, C, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, van Ramshorst, GH, van Zoggel, D, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warrier, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, Winter, DC, and Tekkis, PP

Abstract

BACKGROUND: The multidisciplinary perioperative and anaesthetic management of patients undergoing pelvic exenteration is essential for good surgical outcomes. No clear guidelines have been established, and there is wide variation in clinical practice internationally. This consensus statement consolidates clinical experience and best practice collectively, and systematically addresses key domains in the perioperative and anaesthetic management. METHODS: The modified Delphi methodology was used to achieve consensus from the PelvEx Collaborative. The process included one round of online questionnaire involving controlled feedback and structured participant response, two rounds of editing, and one round of web-based voting. It was held from December 2019 to February 2020. Consensus was defined as more than 80 per cent agreement, whereas less than 80 per cent agreement indicated low consensus. RESULTS: The final consensus document contained 47 voted statements, across six key domains of perioperative and anaesthetic management in pelvic exenteration, comprising preoperative assessment and preparation, anaesthetic considerations, perioperative management, anticipating possible massive haemorrhage, stress response and postoperative critical care, and pain management. Consensus recommendations were developed, based on consensus agreement achieved on 34 statements. CONCLUSION: The perioperative and anaesthetic management of patients undergoing pelvic exenteration is best accomplished by a dedicated multidisciplinary team with relevant domain expertise in the setting of a specialized tertiary unit. This consensus statement has addressed key domains within the framework of current perioperative and anaesthetic management among patients undergoing pelvic exenteration, with an international perspective, to guide clinical practice, and has outlined areas for future clinical research.

Published
2021

2. Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative

Author

Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chew, GJH, Chong, PC, Christensen, HK, Clouston, H, Codd, M, Coffins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, R, Davies, M, Davies, RJ, Delaney, CP, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, G, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kiran, RP, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mimezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, O'Connell, PR, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, van Ramshorst, GH, Rasheed, S, Rasmussen, PC, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Hellawell, G, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Sumrien, H, Sutton, PA, Swanking, T, Taylor, C, Tekkis, PP, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warner, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, de Wilt, JHW, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, van Zoggel, D, Winter, DC, Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chew, GJH, Chong, PC, Christensen, HK, Clouston, H, Codd, M, Coffins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, R, Davies, M, Davies, RJ, Delaney, CP, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, G, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kiran, RP, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mimezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, O'Connell, PR, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, van Ramshorst, GH, Rasheed, S, Rasmussen, PC, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Hellawell, G, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Sumrien, H, Sutton, PA, Swanking, T, Taylor, C, Tekkis, PP, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warner, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, de Wilt, JHW, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, van Zoggel, D, and Winter, DC

Abstract

AIM: At presentation, 15-20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection. METHOD: Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival. RESULTS: Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006). CONCLUSION: Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated.

Published
2020

3. Predicting outcomes of pelvic exenteration using machine learning

Author

Dudurych, I, Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bedford, M, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chang, GJ, Chew, MH, Chok, AK, Chong, P, Christensen, HK, Clouston, H, Codd, M, Collins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, IR, Davies, M, Davies, RJ, Delaney, CP, de Wilt, JHW, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, George, V, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, GV, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kiran, RP, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mirnezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, Oliver, A, O'Connell, PR, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, Rasheed, S, Rasmussen, PC, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Shellawell, G, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Swartling, T, Sumrien, H, Sutton, PA, Swartking, T, Tan, EJ, Taylor, C, Tekkis, PP, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, van Ramshorst, GH, van Zoggel, D, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warrier, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, Winter, DC, Dudurych, I, Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bedford, M, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chang, GJ, Chew, MH, Chok, AK, Chong, P, Christensen, HK, Clouston, H, Codd, M, Collins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, IR, Davies, M, Davies, RJ, Delaney, CP, de Wilt, JHW, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, George, V, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, GV, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kiran, RP, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mirnezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, Oliver, A, O'Connell, PR, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, Rasheed, S, Rasmussen, PC, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Shellawell, G, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Swartling, T, Sumrien, H, Sutton, PA, Swartking, T, Tan, EJ, Taylor, C, Tekkis, PP, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, van Ramshorst, GH, van Zoggel, D, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warrier, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, and Winter, DC

Abstract

AIM: We aim to compare machine learning with neural network performance in predicting R0 resection (R0), length of stay > 14 days (LOS), major complication rates at 30 days postoperatively (COMP) and survival greater than 1 year (SURV) for patients having pelvic exenteration for locally advanced and recurrent rectal cancer. METHOD: A deep learning computer was built and the programming environment was established. The PelvEx Collaborative database was used which contains anonymized data on patients who underwent pelvic exenteration for locally advanced or locally recurrent colorectal cancer between 2004 and 2014. Logistic regression, a support vector machine and an artificial neural network (ANN) were trained. Twenty per cent of the data were used as a test set for calculating prediction accuracy for R0, LOS, COMP and SURV. Model performance was measured by plotting receiver operating characteristic (ROC) curves and calculating the area under the ROC curve (AUROC). RESULTS: Machine learning models and ANNs were trained on 1147 cases. The AUROC for all outcome predictions ranged from 0.608 to 0.793 indicating modest to moderate predictive ability. The models performed best at predicting LOS > 14 days with an AUROC of 0.793 using preoperative and operative data. Visualized logistic regression model weights indicate a varying impact of variables on the outcome in question. CONCLUSION: This paper highlights the potential for predictive modelling of large international databases. Current data allow moderate predictive ability of both complex ANNs and more classic methods.

Published
2020

4. Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative

Author

Kelly, M. E., Aalbers, A. G. J., Abdul Aziz, N., Abecasis, N., Abraham‐Nordling, M., Akiyoshi, T., Alberda, W., Albert, M., Andric, M., Angenete, E., Antoniou, A., Auer, R., Austin, K. K., Aziz, O., Baker, R. P., Bali, M., Baseckas, G., Bebington, B., Bednarski, B. K., Beets, G. L., Berg, P. L., Beynon, J., Biondo, S., Boyle, K., Bordeianou, L., Bremers, A. B., Brunner, M., Buchwald, P., Bui, A., Burgess, A., Burger, J. W. A., Burling, D., Burns, E., Campain, N., Carvalhal, S., Castro, L., Caycedo‐Marulanda, A., Chan, K. K. L., Chang, G. J., Chew, M. H., Chong, P. C., Christensen, H. K., Clouston, H., Codd, M., Collins, D., Colquhoun, A. J., Corr, A., Coscia, M., Coyne, P. E., Creavin, B., Croner, R. S., Damjanovic, L., Daniels, I. R., Davies, M., Davies, R. J., Delaney, C. P., Denost, Q., Deutsch, C., Dietz, D., Domingo, S., Dozois, E. J., Duff, M., Eglinton, T., Enrique‐Navascues, J. M., Espin‐Basany, E., Evans, M. D., Fearnhead, N. S., Flatmark, K., Fleming, F., Frizelle, F. A., Gallego, M. A., Garcia‐Granero, E., Garcia‐Sabrido, J. L., Gentilini, L., George, M. L., Ghouti, L., Giner, F., Ginther, N., Glynn, R., Golda, T., Griffiths, B., Harris, D. A., Hagemans, J. A. W., Hanchanale, V., Harji, D. P., Helewa, R. M., Heriot, A. G., Hochman, D., Hohenberger, W., Holm, T., Hompes, R., Jenkins, J. T., Kaffenberger, S., Kandaswamy, G. V., Kapur, S., Kanemitsu, Y., Kelley, S. R., Keller, D. S., Khan, M. S., Kiran, R. P., Kim, H., Kim, H. J., Koh, C. E., Kok, N. F. M., Kokelaar, R., Kontovounisios, C., Kristensen, H. Ø., Kroon, H. M., Kusters, M., Lago, V., Larsen, S. G., Larson, D. W., Law, W. L., Laurberg, S., Lee, P. J., Limbert, M., Lydrup, M. L., Lyons, A., Lynch, A. C., Mantyh, C., Mathis, K. L., Margues, C. F. S., Martling, A., Meijerink, W. J. H. J., Merkel, S., Mehta, A. M., McArthur, D. R., McDermott, F. D., McGrath, J. S., Malde, S., Mirnezami, A., Monson, J. R. T., Morton, J. R., Mullaney, T. G., Negoi, I., Neto, J. W. M., Nguyen, B., Nielsen, M. B., Nieuwenhuijzen, G. A. P., Nilsson, P. J., O’Connell, P. R., O’Dwyer, S. T., Palmer, G., Pappou, E., Park, J., Patsouras, D., Pellino, G., Peterson, A. C., Poggioli, G., Proud, D., Quinn, M., Quyn, A., Radwan, R. W., van Ramshorst, G. H., Rasheed, S., Rasmussen, P. C., Regenbogen, S. E., Renehan, A., Rocha, R., Rochester, M., Rohila, J., Rothbarth, J., Rottoli, M., Roxburgh, C., Rutten, H. J. T., Ryan, É. J., Safar, B., Sagar, P. M., Sahai, A., Saklani, A., Sammour, T., Sayyed, R., Schizas, A. M. P., Schwarzkopf, E., Scripcariu, V., Selvasekar, C., Shaikh, I., Hellawell, G., Shida, D., Simpson, A., Smart, N. J., Smart, P., Smith, J. J., Solbakken, A. M., Solomon, M. J., Sørensen, M. M., Steele, S. R., Steffens, D., Stitzenberg, K., Stocchi, L., Stylianides, N. A., Sumrien, H., Sutton, P. A., Swartking, T., Taylor, C., Tekkis, P. P., Teras, J., Thurairaja, R., Toh, E. L., Tsarkov, P., Tsukada, Y., Tsukamoto, S., Tuech, J. J., Turner, W. H., Tuynman, J. B., Vasquez‐Jimenez, W., Verhoef, C., Vizzielli, G., Voogt, E. L. K., Uehara, K., Wakeman, C., Warrier, S., Wasmuth, H. H., Weber, K., Weiser, M. R., Wheeler, J. M. D., Wild, J., Wilson, M., de Wilt, J. H. W., Wolthuis, A., Yano, H., Yip, B., Yip, J., Yoo, R. N., van Zoggel, D., Winter, D. C., Kelly, M. E., Aalbers, A. G. J., Abdul Aziz, N., Abecasis, N., Abraham‐nordling, M., Akiyoshi, T., Alberda, W., Albert, M., Andric, M., Angenete, E., Antoniou, A., Auer, R., Austin, K. K., Aziz, O., Baker, R. P., Bali, M., Baseckas, G., Bebington, B., Bednarski, B. K., Beets, G. L., Berg, P. L., Beynon, J., Biondo, S., Boyle, K., Bordeianou, L., Bremers, A. B., Brunner, M., Buchwald, P., Bui, A., Burgess, A., Burger, J. W. A., Burling, D., Burns, E., Campain, N., Carvalhal, S., Castro, L., Caycedo‐marulanda, A., Chan, K. K. L., Chang, G. J., Chew, M. H., Chong, P. C., Christensen, H. K., Clouston, H., Codd, M., Collins, D., Colquhoun, A. J., Corr, A., Coscia, M., Coyne, P. E., Creavin, B., Croner, R. S., Damjanovic, L., Daniels, I. R., Davies, M., Davies, R. J., Delaney, C. P., Denost, Q., Deutsch, C., Dietz, D., Domingo, S., Dozois, E. J., Duff, M., Eglinton, T., Enrique‐navascues, J. M., Espin‐basany, E., Evans, M. D., Fearnhead, N. S., Flatmark, K., Fleming, F., Frizelle, F. A., Gallego, M. A., Garcia‐granero, E., Garcia‐sabrido, J. L., Gentilini, L., George, M. L., Ghouti, L., Giner, F., Ginther, N., Glynn, R., Golda, T., Griffiths, B., Harris, D. A., Hagemans, J. A. W., Hanchanale, V., Harji, D. P., Helewa, R. M., Heriot, A. G., Hochman, D., Hohenberger, W., Holm, T., Hompes, R., Jenkins, J. T., Kaffenberger, S., Kandaswamy, G. V., Kapur, S., Kanemitsu, Y., Kelley, S. R., Keller, D. S., Khan, M. S., Kiran, R. P., Kim, H., Kim, H. J., Koh, C. E., Kok, N. F. M., Kokelaar, R., Kontovounisios, C., Kristensen, H. Ø., Kroon, H. M., Kusters, M., Lago, V., Larsen, S. G., Larson, D. W., Law, W. L., Laurberg, S., Lee, P. J., Limbert, M., Lydrup, M. L., Lyons, A., Lynch, A. C., Mantyh, C., Mathis, K. L., Margues, C. F. S., Martling, A., Meijerink, W. J. H. J., Merkel, S., Mehta, A. M., Mcarthur, D. R., Mcdermott, F. D., Mcgrath, J. S., Malde, S., Mirnezami, A., Monson, J. R. T., Morton, J. R., Mullaney, T. G., Negoi, I., Neto, J. W. M., Nguyen, B., Nielsen, M. B., Nieuwenhuijzen, G. A. P., Nilsson, P. J., O’Connell, P. R., O’Dwyer, S. T., Palmer, G., Pappou, E., Park, J., Patsouras, D., Pellino, G., Peterson, A. C., Poggioli, G., Proud, D., Quinn, M., Quyn, A., Radwan, R. W., van Ramshorst, G. H., Rasheed, S., Rasmussen, P. C., Regenbogen, S. E., Renehan, A., Rocha, R., Rochester, M., Rohila, J., Rothbarth, J., Rottoli, M., Roxburgh, C., Rutten, H. J. T., Ryan, É. J., Safar, B., Sagar, P. M., Sahai, A., Saklani, A., Sammour, T., Sayyed, R., Schizas, A. M. P., Schwarzkopf, E., Scripcariu, V., Selvasekar, C., Shaikh, I., Hellawell, G., Shida, D., Simpson, A., Smart, N. J., Smart, P., Smith, J. J., Solbakken, A. M., Solomon, M. J., Sørensen, M. M., Steele, S. R., Steffens, D., Stitzenberg, K., Stocchi, L., Stylianides, N. A., Sumrien, H., Sutton, P. A., Swartking, T., Taylor, C., Tekkis, P. P., Teras, J., Thurairaja, R., Toh, E. L., Tsarkov, P., Tsukada, Y., Tsukamoto, S., Tuech, J. J., Turner, W. H., Tuynman, J. B., Vasquez‐jimenez, W., Verhoef, C., Vizzielli, G., Voogt, E. L. K., Uehara, K., Wakeman, C., Warrier, S., Wasmuth, H. H., Weber, K., Weiser, M. R., Wheeler, J. M. D., Wild, J., Wilson, M., de Wilt, J. H. W., Wolthuis, A., Yano, H., Yip, B., Yip, J., Yoo, R. N., van Zoggel, D., Winter, D. C., Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chew, GJH, Chong, PC, Christensen, HK, Clouston, H, Codd, M, Coffins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, R, Davies, M, Davies, RJ, Delaney, CP, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, GV, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kiran, RP, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mimezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, O'Connell, PR, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, van Ramshorst, GH, Rasheed, S, Rasmussen, PC, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Hellawell, G, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Sumrien, H, Sutton, PA, Swanking, T, Taylor, C, Tekkis, PP, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warner, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, de Wilt, JHW, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, van Zoggel, D, Winter, DC, Surgery, CCA - Cancer Treatment and quality of life, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Male, medicine.medical_specialty, Adolescent, Colorectal cancer, survival outcomes, medicine.medical_treatment, surgical outcome, surgical outcomes, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Interquartile range, medicine, Humans, liver metastasi, Rectal cancer, Retrospective Studies, Pelvic exenteration, business.industry, Rectal Neoplasms, Mortality rate, Liver Neoplasms, Gastroenterology, Postoperative complication, Perioperative, medicine.disease, Surgery, Pelvic Exenteration, liver metastasis, Treatment Outcome, 030220 oncology & carcinogenesis, international collaboration, Resection margin, 030211 gastroenterology & hepatology, Hepatectomy, Neoplasm Recurrence, Local, business
Abstract

Aim: At presentation, 15–20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection. Method: Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival. Results: Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006). Conclusion: Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated.

Published
2020
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5. Changing outcomes following pelvic exenteration for locally advanced and recurrent rectal cancer

Author

Kelly, M. E., Aalbers, A. G. J., Aziz, N. Abdul, Abraham-Nordling, M., Alberda, W., Antoniou, A., Austin, K. K., Baker, R., Bali, M., Baseckas, G., Bednarski, B. K., Beets, G. L., Berg, P. L., Beynon, J., Biondo, S., Bordeianou, L., Brunner, M., Buchwald, P., Burger, J. W. A., Burling, D., Campain, N., Chan, K. K. L., Chang, G., Chew, M. H., Chong, P. C., Christensen, H. K., Codd, M., Colquhoun, A. J., Corr, A., Coscia, M., Coyne, P. E., Creavin, B., Damjanovic, L., Daniels, I. R., Davies, M., Davies, R. J., de Wilt, J. H. W., Denost, Q., Deutsch, C., Dietz, D., Dozois, E. J., Duff, M., Eglinton, T., Evans, M., Evans, M. D., Fearnhead, N. S., Frizelle, F. A., Garcia-Granero, E., Garcia-Sabrido, J. L., Gentilini, L., George, M. L., Glynn, R., Golda, T., Griffiths, B., Hagemans, J. A. W., Harji, D. P., Harris, D. A., Heriot, A. A. G., Hohenberger, W., Holm, T., Jenkins, J. T., Kanemitsu, Y., Kapur, S., Keller, D. S., Kelley, S. R., Kim, H., Koh, C. E., Kok, N. F. M., Kokelaar, R., Kontovounisios, C., Kusters, M., Larson, D. W., Laurberg, S., Law, W. L., Lee, P., Lydrup, M. L., Lynch, A. C., Martling, A., Mathis, K. L., Meijerink, W. J. H. J., Mentha, A. M., Merkel, S., McDermott, F. D., McGrath, J. S., Mihailo, A., Mirnezami, A., Morton, J. R., Mullaney, T. G., Nielsen, M. B., Nieuwenhuijzen, G. A. P., Nilsson, P. J., O'Connell, P. R., Palmer, G., Patsouras, D., Pellino, G., Poggioli, G., Quinn, M., Quyn, A., Radwan, R. W., Rasheed, S., Rasmussen, P. C., Rocha, R., Rothbarth, J., Roxburgh, C., Rutten, H. J. T., Ryan, E., Sagar, P. M., Sammour, T., Schizas, A. M. P., Schwarzkopf, E., Scripcariu, V, Shaikh, I, Shida, D., Simpson, A., Smart, N. J., Smith, J., Solomon, M. J., Sorensen, M. M., Steele, S. R., Steffens, D., Stocchi, L., Stylianides, N. A., Taylor, C., Tekkis, P. P., Tsukamoto, S., Turner, W. H., Tuynman, J. B., van Ramshorst, Gabriëlle, van Zoggel, D., Vasquez-Jimenez, W., Verhoef, C., Verstegen, M., Wakeman, C., Warrier, S., Wasmuth, H. H., Weiser, M. R., Wheeler, J. M. D., Wild, J., Winter, D. C., Yip, J., Kelly, M. E., Aalbers, A. G. J., Aziz, N. Abdul, Abraham‐Nordling, M., Alberda, W., Antoniou, A., Austin, K. K., Baker, R., Bali, M., Baseckas, G., Bednarski, B. K., Beets, G. L., Berg, P. L., Beynon, J., Biondo, S., Bordeianou, L., Brunner, M., Buchwald, P., Burger, J. W. A., Burling, D., Campain, N., Chan, K. K. L., Chang, G., Chew, M. H., Chong, P. C., Christensen, H. K., Codd, M., Colquhoun, A. J., Corr, A., Coscia, M., Coyne, P. E., Creavin, B., Damjanovic, L., Daniels, I. R., Davies, M., Davies, R. J., Wilt, J. H. W., Denost, Q., Deutsch, C., Dietz, D., Dozois, E. J., Duff, M., Eglinton, T., Evans, M., Evans, M.D., Fearnhead, N. S., Frizelle, F. A., Garcia‐Granero, E., Garcia‐Sabrido, J. L., Gentilini, L., George, M. L., Glynn, R., Golda, T., Griffiths, B., Hagemans, J. A.W., Harji, D. P., Harris, D. A., Heriot, A. A. G., Hohenberger, W., Holm, T., Jenkins, J. T., Kanemitsu, Y., Kapur, S., Keller, D. S., Kelley, S. R., Kim, H., Koh, C. E., Kok, N. F. M., Kokelaar, R., Kontovounisios, C., Kusters, M., Larson, D. W., Laurberg, S., Law, W. L., Lee, P., Lydrup, M. L., Lynch, A. C., Martling, A., Mathis, K. L., Meijerink, W. J. H. J., Mentha, A. M., Merkel, S., McDermott, F. D., McGrath, J. S., Mihailo, A., Mirnezami, A., Morton, J. R., Mullaney, T. G., Nielsen, M. B., Nieuwenhuijzen, G. A. P., Nilsson, P. J., O'Connell, P. R., Palmer, G., Patsouras, D., Pellino, G., Poggioli, G., Quinn, M., Quyn, A., Radwan, R. W., Rasheed, S., Rasmussen, P. C., Rocha, R., Rothbarth, J., Roxburgh, C., Rutten, H. J. T., Ryan, É., Sagar, P. M., Sammour, T., Schizas, A. M. P., Schwarzkopf, E., Scripcariu, V., Shaikh, I., Shida, D., Simpson, A., Smart, N. J., Smith, J., Solomon, M. J., Sørensen, M.M., Steele, S. R., Steffens, D., Stocchi, L., Stylianides, N. A., Taylor, C., Tekkis, P. P., Tsukamoto, S., Turner, W. H., Tuynman, J. B., Ramshorst, G. H., Zoggel, D., Vasquez‐Jimenez, W., Verhoef, C., Verstegen, M., Wakeman, C., Warrier, S., Wasmuth, H. H., Weiser, M. R., Wheeler, J. M. D., Wild, J., Winter, D. C., Yip, J., Kelly, Me, Aalbers, Agj, Aziz, Na, Abraham-Nordling, M, Alberda, W, Antoniou, A, Austin, Kk, Baker, R, Bali, M, Baseckas, G, Bednarski, Bk, Beets, Gl, Berg, Pl, Beynon, J, Biondo, S, Bordeianou, L, Brunner, M, Buchwald, P, Burger, Jwa, Burling, D, Campain, N, Chan, Kkl, Chang, G, Chew, Mh, Chong, Pc, Christensen, Hk, Codd, M, Colquhoun, Aj, Corr, A, Coscia, M, Coyne, Pe, Creavin, B, Damjanovic, L, Daniels, Ir, Davies, M, Davies, Rj, de Wilt, Jhw, Denost, Q, Deutsch, C, Dietz, D, Dozois, Ej, Duff, M, Eglinton, T, Evans, M, Evans, Md, Fearnhead, N, Frizelle, Fa, Garcia-Granero, E, Garcia-Sabrido, Jl, Gentilini, L, George, Ml, Glynn, R, Golda, T, Griffiths, B, Hagemans, Jaw, Harji, Dp, Harris, Da, Heriot, Aag, Hohenberger, W, Holm, T, Jenkins, Jt, Kanemitsu, Y, Kapur, S, Keller, D, Kelley, Sr, Kim, H, Koh, Ce, Kok, Nfm, Kokelaar, R, Kontovounisios, C, Kusters, M, Larson, Dw, Laurberg, S, Law, Wl, Lee, P, Lydrup, Ml, Lynch, Ac, Martling, A, Mathis, Kl, Meijerink, Wjhj, Mentha, Am, Merkel, S, Mcdermott, Fd, Mcgrath, J, Mihailo, A, Mirnezami, A, Morton, Jr, Mullaney, Tg, Nielsen, Mb, Nieuwenhuijzen, Gap, Nilsson, Pj, O'Connell, Pr, Palmer, G, Patsouras, D, Pellino, G, Poggioli, G, Quinn, M, Quyn, A, Radwan, Rw, Rasheed, S, Rasmussen, Pc, Rocha, R, Rothbarth, J, Roxburgh, C, Rutten, Hjt, Ryan, E, Sagar, Pm, Sammour, T, Schizas, Amp, Schwarzkopf, E, Scripcariu, V, Shaikh, I, Shida, D, Simpson, A, Smart, Nj, Smith, J, Solomon, Mj, Sorensen, Mm, Steele, Sr, Steffens, D, Stocchi, L, Stylianides, Na, Taylor, C, Tekkis, Pp, Tsukamoto, S, Turner, Wh, Tuynman, Jb, van Ramshorst, Gh, van Zoggel, D, Vasquez-Jimenez, W, Verhoef, C, Verstegen, M, Wakeman, C, Warrier, S, Wasmuth, Hh, Weiser, Mr, Wheeler, Jmd, Wild, J, Winter, Dc, and Yip, J

Subjects
Male, Blood transfusion, Colorectal cancer, medicine.medical_treatment, Surgical Flaps, COLORECTAL-CANCER, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Postoperative Complications, Retrospective Studie, Medicine and Health Sciences, Mortality rate, General Medicine, Middle Aged, Treatment Outcome, medicine.anatomical_structure, HOSPITAL VOLUME, SURVIVAL, Original Article, Female, Life Sciences & Biomedicine, Human, medicine.medical_specialty, lcsh:Surgery, Rectum, Subgroup analysis, SDG 3 - Good Health and Well-being, medicine, Humans, Blood Transfusion, Retrospective Studies, Aged, Science & Technology, Pelvic exenteration, Rectal Neoplasms, business.industry, MORTALITY, PelvEx Collaborative, Retrospective cohort study, Original Articles, lcsh:RD1-811, Length of Stay, medicine.disease, SURGEON VOLUME, Pelvic Exenteration, Surgery, Surgical Flap, Postoperative Complication, Neoplasm Recurrence, Local, business, Complication
Abstract

Contains fulltext : 215764.pdf (Publisher’s version ) (Open Access) Background: Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is technically challenging but increasingly performed in specialist centres. The aim of this study was to compare outcomes of exenteration over time. Methods: This was a multicentre retrospective study of patients who underwent exenteration for LARC and LRRC between 2004 and 2015. Surgical outcomes, including rate of bone resection, flap reconstruction, margin status and transfusion rates, were examined. Outcomes between higher- and lower-volume centres were also evaluated. Results: Some 2472 patients underwent pelvic exenteration for LARC and LRRC across 26 institutions. For LARC, rates of bone resection or flap reconstruction increased from 2004 to 2015, from 3.5 to 12.8 per cent, and from 12.0 to 29.4 per cent respectively. Fewer units of intraoperative blood were transfused over this interval (median 4 to 2 units; P = 0.040). Subgroup analysis showed that bone resection and flap reconstruction rates increased in lower- and higher-volume centres. R0 resection rates significantly increased in low-volume centres but not in high-volume centres over time (low-volume: from 62.5 to 80.0 per cent, P = 0.001; high-volume: from 83.5 to 88.4 per cent, P = 0.660). For LRRC, no significant trends over time were observed for bone resection or flap reconstruction rates. The median number of units of intraoperative blood transfused decreased from 5 to 2.5 units (P < 0.001). R0 resection rates did not increase in either low-volume (from 51.7 to 60.4 per cent; P = 0.610) or higher-volume (from 48.6 to 65.5 per cent; P = 0.100) centres. No significant differences in length of hospital stay, 30-day complication, reintervention or mortality rates were observed over time. Conclusion: Radical resection, bone resection and flap reconstruction rates were performed more frequently over time, while transfusion requirements decreased.

Published
2019

6. First-in-human phase 1 dose-escalation study of CAN04, a first-in-class interleukin-1 receptor accessory protein (IL1RAP) antibody in patients with solid tumours.

Author

Robbrecht D, Jungels C, Sorensen MM, Spanggaard I, Eskens F, Fretland SØ, Guren TK, Aftimos P, Liberg D, Svedman C, Thorsson L, Steeghs N, and Awada A

Subjects
Antibodies, Monoclonal adverse effects, Dose-Response Relationship, Drug, Humans, Interleukin-1 Receptor Accessory Protein therapeutic use, Maximum Tolerated Dose, Antineoplastic Agents, Neoplasms pathology
Abstract

Background: Interleukin-1 (IL-1) signalling is involved in various protumoural processes including proliferation, immune evasion, metastasis and chemoresistance. CAN04 is a first-in-class monoclonal antibody that binds IL-1 receptor accessory protein (IL1RAP), required for IL-1 signalling. In this first-in-human phase 1 study, we assessed safety, recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of CAN04 monotherapy., Methods: Patients with advanced solid tumours known to express IL1RAP and refractory to standard treatments were enrolled in a dose-escalation study with 5 dose levels (1.0-10.0 mg/kg) of weekly CAN04., Results: Twenty-two patients were enrolled. Most common adverse events were infusion-related reactions (41%), fatigue (32%), constipation (27%), diarrhoea (27%), decreased appetite (23%), nausea (23%) and vomiting (23%). One dose limiting toxicity was reported. No maximum tolerated dose was identified. Pharmacokinetics analyses indicate higher exposures and slower elimination with increasing doses. Decreases in serum IL-6 and CRP were observed in most patients. Twenty-one patients were evaluable for response, 43% had stable disease per immune-related response criteria with no partial/complete responses., Conclusions: The IL1RAP targeting antibody CAN04 can be safely administered to patients up to 10.0 mg/kg weekly, which was defined as the RP2D. Serum biomarkers supported target engagement and IL-1 pathway inhibition., Clinical Trial Registration: NCT03267316., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2022
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7. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer: outcome and results of KRAS mutational analysis in plasma.

Author

Spindler KL, Sorensen MM, Pallisgaard N, Andersen RF, Havelund BM, Ploen J, Lassen U, and Jakobsen AK

Subjects
Adenocarcinoma genetics, Adenocarcinoma pathology, Aged, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Disease Progression, Drug Resistance, Neoplasm, Female, Humans, Irinotecan, Male, Middle Aged, Mutation, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), Sirolimus administration & dosage, Sirolimus analogs & derivatives, Treatment Outcome, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms drug therapy, Proto-Oncogene Proteins genetics, ras Proteins genetics
Abstract

Background: Patients with chemotherapy refractory metastatic colorectal cancer and KRAS mutations have no effective treatment option. The present study evaluated the efficacy of temsirolimus in chemotherapy refractory mCRC with KRAS mutations. Furthermore, we wanted to investigate if resistance to temsirolimus could be reversed by the addition of irinotecan. Finally, we analyzed pre-treatment blood samples for KRAS mutations to investigate the association between quantitative measures of KRAS mutated alleles and clinical outcome., Material and Methods: Patients received weekly temsirolimus 25 mg until progression. Thereafter patients were treated with combination therapy comprising biweekly irinotecan 180 mg/m(2) and weekly temsirolimus. A polymerase chain reaction method was used to quantify the KRAS mutated alleles in plasma (pKRAS)., Results: Sixty-four patients were included. Treatment was well tolerated. Thirty-eight percent achieved stable disease on monotherapy and 63% on combination therapy. Four and eight patients had a minimal response, respectively. Median overall survival was 160 days. Median time to progression was 45 and 84 days, respectively. The concordance between KRAS status in tumor and plasma was 82%. All patients with tumor reduction had low levels of pKRAS. Patients with high pKRAS had a 77% risk of early progression on monotherapy compared to 43% in patients with lower levels. Multivariate survival analysis confirmed that pKRAS was a strong prognostic factor., Conclusion: Temsirolimus has limited efficacy in chemotherapy resistant KRAS mutant disease, but plasma KRAS quantification is a strong predictor of outcome.

Published
2013
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8. Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane.

Author

Aamann MD, Sorensen MM, Hvitby C, Berquist BR, Muftuoglu M, Tian J, de Souza-Pinto NC, Scheibye-Knudsen M, Wilson DM 3rd, Stevnsner T, and Bohr VA

Subjects
Cell Line, DNA Helicases analysis, DNA Helicases deficiency, DNA Repair Enzymes analysis, DNA Repair Enzymes deficiency, Guanine analogs & derivatives, Guanine analysis, Humans, Mitochondrial Membranes chemistry, Oxidative Stress, Poly-ADP-Ribose Binding Proteins, Uracil analogs & derivatives, Uracil analysis, DNA Helicases physiology, DNA Repair, DNA Repair Enzymes physiology, DNA, Mitochondrial, Mitochondrial Membranes physiology
Abstract

Cockayne syndrome (CS) is a human premature aging disorder associated with severe developmental deficiencies and neurodegeneration, and phenotypically it resembles some mitochondrial DNA (mtDNA) diseases. Most patients belong to complementation group B, and the CS group B (CSB) protein plays a role in genomic maintenance and transcriptome regulation. By immunocytochemistry, mitochondrial fractionation, and Western blotting, we demonstrate that CSB localizes to mitochondria in different types of cells, with increased mitochondrial distribution following menadione-induced oxidative stress. Moreover, our results suggest that CSB plays a significant role in mitochondrial base excision repair (BER) regulation. In particular, we find reduced 8-oxo-guanine, uracil, and 5-hydroxy-uracil BER incision activities in CSB-deficient cells compared to wild-type cells. This deficiency correlates with deficient association of the BER activities with the mitochondrial inner membrane, suggesting that CSB may participate in the anchoring of the DNA repair complex. Increased mutation frequency in mtDNA of CSB-deficient cells demonstrates functional significance of the presence of CSB in the mitochondria. The results in total suggest that CSB plays a direct role in mitochondrial BER by helping recruit, stabilize, and/or retain BER proteins in repair complexes associated with the inner mitochondrial membrane, perhaps providing a novel basis for understanding the complex phenotype of this debilitating disorder.

Published
2010
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