Risk factors of pancreatic fistula after distal pancreas resections: an observational retrospective study

Abstract

BACKGROUND: The main complication of surgical pancreas interventions is the pancreatic fistula (PF) — abnormal secretion of pancreatic secretions into the abdominal cavity, which can lead to more severe complications. At the same time, some predictors of PF remain poorly understood.

AIM: To investigate the risk factors for the development of PF after distal pancreatic resection.

MATERIALS AND METHODS: The study included 40 patients who underwent distal resection. The influence of various clinical parameters on the development of PF after surgery was evaluated. Methods of mathematical modeling and correlation analysis were used. Mathematical modeling was carried out using the Random forest machine learning algorithm, and the indicator of the relative importance of the “importance” parameters was evaluated.

RESULTS: According to the Random forest model, on day 1 after surgery, the most significant predictors of the development of PF were: the volume of neoplasm, age and stage of the oncological process, for which “importance” was 53.2, 13.7 and 12.5 (AUC ROC=62%); on day 3–5, “importance” was 61.7, 11.5 and 5.2 (AUC ROC=79%). An increase in the concentration of pancreatic amylase in blood plasma for 2–3 and 3–5 days correlated with its increase in the drainage discharge for 5-7 days after the intervention (r=0.48 and 0.76; p <0.05). A correlation was found between the level of amylase in the drainage discharge on 3–5 days after the intervention and the level of leukocytes according to the general blood test (r=0.62, p <0.05).

CONCLUSION: An increase in plasma amylase levels is the main risk factor for the development of PF. An increase in the concentration of amylase in the drainage discharge can be considered as a potential risk factor for the development of pancreatic fistulas with clinical manifestations in the following days. The stage of the oncological process, the size of the neoplasm and the age of the patient are also risk factors.

Keywords

precision oncology / distal pancreatic resection / postoperative pancreatic fistula / mathematical modelling / machine learning

References

[1] Akhtanin EA, Kriger AG. Causes and prevention of pancreatic fistulas after pancreas resection. Pirogov Russian Journal of Surgery. 2014;(5):7983. (In Russ).

[2] Ахтанин Е.А., Кригер А.Г. Причины возникновения и профилактика панкреатических свищей после резекционных операций на поджелудочной железе // Хирургия. Журнал им. Н.И. Пирогова. 2014. № 5. С. 79–83. EDN: QIUFRM

[3] Kubyshkin VA, Vishnevskii VA. Pancreatic cancer. Moscow: Medpraktika; 2003. 375 p. (In Russ).

[4] Кубышкин В.А., Вишневский В.А. Рак поджелудочной железы. Москва: Медпрактика, 2003. 375 с.

[5] McEvoy SH, Lavelle LP, Hoare SM, et al. Pancreaticoduodenectomy: expected post-operative anatomy and complications. Br J Radiol. 2014;87:1–8. doi: 10.1259/bjr.20140050

[6] McEvoy S.H., Lavelle L.P., Hoare S.M., et al. Pancreaticoduodenectomy: expected post-operative anatomy and complications // Br J Radiol. 2014. Vol. 87. P. 1–8. doi: 10.1259/bjr.20140050

[7] Bassi C, Marchegiani G, Dervenis C, et al. International Study Group on Pancreatic Surgery (ISGPS). The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017;161(3):584–591. doi: 10.1016/j.surg.2016.11.014

[8] Bassi C., Marchegiani G., Dervenis C., et al. International Study Group on Pancreatic Surgery (ISGPS). The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After// Surgery. 2017. Vol. 161, N. 3. P. 584–591. doi: 10.1016/j.surg.2016.11.014

[9] Lowy AM, Lee JE, Pisters PW, et al. Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. Ann Surg. 1997;226:632–641. doi: 10.1097/00000658-199711000-00008

[10] Lowy A.M., Lee J.E., Pisters P.W., et al. Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease // Ann Surg. 1997. Vol. 226. P. 632–641. doi: 10.1097/00000658-199711000-00008

[11] Kabanov MY, Sementsov KV, Yakovleva DM, Alekseev VV. The problem of development pancreatic fistula in patients undergoing pancreaticoduodenal resection. Bulletin of Pirogov National Medical & Surgical Center. 2017;12(2):112-116. EDN: YTQHHV

[12] Кабанов М.Ю., Семенцов К.В., Яковлева Д.М., Алексеев В.В. Состояние проблемы развития панкреатической фистулы у пациентов, перенесших панкреатодуоденальную резекцию // Вестник Национального медико-хирургического Центра им. Н.И. Пирогова. 2017. Т. 12, № 2. С. 112–116 EDN: YTQHHV

[13] Peng YP, Zhu XL, Yin LD, et al. Risk factors of postoperative pancreatic fistula in patients after distal pancreatectomy: a systematic review and meta-analysis. Sci Rep. 2017;7(1):185. doi: 10.1038/s41598-017-00311-8

[14] Peng Y.P., Zhu X.L., Yin L.D., et al. Risk factors of postoperative pancreatic fistula in patients after distal pancreatectomy: a systematic review and meta-analysis // Sci Rep. 2017. Vol. 7, N. 1. P. 185. doi: 10.1038/s41598-017-00311-8

[15] Voskanyan SEH, Korotko GF. Morphofunctional organization of the pancreas and acute postoperative pancreatitis (experimental and clinical aspects). Moscow: Litterra; 2017. 523 p. (In Russ). EDN: ZGLFUH

[16] Восканян С.Э., Коротько Г.Ф. Морфофункциональная организация поджелудочной железы и острый послеоперационный панкреатит (экспериментальные и клинические аспекты). Москва: Литтерра, 2017. 523 с. EDN: ZGLFUH

[17] Kleeff J, Diener MK, Z’graggen K, et al. Distal pancreatectomy: risk factors for surgical failure in 302 consecutive cases. Ann Surg. 2007;245(4):573–582. doi: 10.1097/01.sla.0000251438.43135

[18] Kleeff J., Diener M.K., Z’graggen K., et al. Distal pancreatectomy: risk factors for surgical failure in 302 consecutive cases // Ann Surg. 2007. Vol. 245, N. 4. P. 573–582. doi: 10.1097/01.sla.0000251438.43135

[19] Wang X, Tan CL, Zhang H, Chen YH, et al. Short-term outcomes and risk factors for pancreatic fistula after pancreatic enucleation: A single-center experience of 142 patients. J Surg Oncol. 2018;117(2):182–190. doi: 10.1002/jso.24804

[20] Wang X., Tan C.L., Zhang H., Chen Y.H., et al. Short-term outcomes and risk factors for pancreatic fistula after pancreatic enucleation: A single-center experience of 142 patients // J Surg Oncol. 2018. Vol. 117, N. 2. P. 182–190. doi: 10.1002/jso.24804

[21] Breiman L. Arcing Classifiers. Annals of Statistics. 1998;26:801–849.

[22] Breiman L. Arcing Classifiers // Annals of Statistics. 1998. N. 26. P. 801–849.

[23] Breiman L. Random Forests. Machine Learning. 2001;45(1):5–32. doi: 10.1023/A:1010933404324

[24] Breiman L. Random Forests // Machine Learning. 2001. Vol. 45, N. 1. P. 5–32. doi: 10.1023/A:1010933404324

[25] Geurts P, Ernst D, Wehenkel L. Extremely randomized trees. Machine Learning, 2006;63(1):3–42. doi: 10.1007/s10994-006-6226-1

[26] Geurts P., Ernst. D., Wehenkel L. Extremely randomized trees // Machine Learning, 2006. Vol. 63, N. 1. P. 3–42. doi: 10.1007/s10994-006-6226-1

[27] Hastie T, Tibshirani R, Friedman J. The Elements of Statistical Learning. Cham: Springer; 2009. 745 p.

[28] Hastie T., Tibshirani R., Friedman J. The elements of statistical learning. Cham: Springer, 2009. 745 p.

[29] Kohavi R. A Study of cross-validation and bootstrap for accuracy estimation and model selection. In: Appears in the International Joint Conference AI. 1995;14(2):1137–1145.

[30] Kohavi R. A Study of cross-validation and bootstrap for accuracy estimation and model selection. In: Appears in the International Joint Conference AI. 1995. Vol. 14, N. 2. P. 1137–1145.

[31] Callery MP, Pratt WB, Kent TS, et al. A Prospectively Validated Clinical Risk Score Accurately Predicts Pancreatic Fistula after Pancreatoduodenectomy. J Am Colleg Surgeons. 2013;216(1):1–14. doi: 10.1016/j.jamcollsurg.2012.09.002

[32] Callery M.P., Pratt W.B., Kent T.S., et al. A Prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy // J Am Colleg Surgeons. 2013. Vol. 216, N. 1. P. 1–14. doi: 10.1016/j.jamcollsurg.2012.09.002

[33] Miller BC, Christein JD, Behrman SW, et al. A multi-institutional external validation of the fistula risk score for pancreatoduodenectomy. J Gastrointest Surg. 2014;18(1):172–179. doi: 10.1007/s11605-013-2337-8

[34] Miller B.C., Christein J.D., Behrman S.W., et al. A multi-institutional external validation of the fistula risk score for pancreatoduodenectomy // J Gastrointest Surg. 2014. Vol. 18, N. 1. P. 172–179. doi: 10.1007/s11605-013-2337-8

[35] Khatkov IE, Domrachev SA, Tsvirkun VV, et al Prediction of postpancreatoduodenectomy pancreatic fistula with the use of computer tomography. Medical Visualization. 2019;23(1):19–27. doi: 10.24835/1607-0763-2019-1-19-27

[36] Хатьков И.Е., Домрачев С.А., Цвиркун В.В. с соавт. Прогнозирование панкреатической фистулы после панкреатодуоденальной резекции с помощью компьютерной томографии // Медицинская визуализация. 2019. Т. 23, № 1. С. 19-27. doi: 10.24835/1607-0763-2019-1-19-27

[37] Callery MP, Pratt WB, Vollmer CM. Prevention and management of pancreatic fistula. J Gastroint Surg. 2009;13(1):163–173. doi: 10.1007/s11605-008-0534-7

[38] Callery M.P, Pratt W.B., Vollmer C.M. Prevention and management of pancreatic fistula // J Gastroint Surg. 2009. Vol. 13, N. 1. P. 163–173. doi: 10.1007/s11605-008-0534-7

[39] Zarzavadjian Le Bian A, Fuks D, Montali F, et al. Predicting the severity of pancreatic fistula after pancreaticoduodenectomy: overweight and blood loss as independent risk factors: Retrospective analysis of 277 patients. Surgical Infections. 2019;20(6):486–491. doi: 10.1089/sur.2019.027

[40] Zarzavadjian Le Bian A., Fuks D., Montali F., et al. Predicting the severity of pancreatic fistula after pancreaticoduodenectomy: overweight and blood loss as independent risk factors: Retrospective analysis of 277 patients // Surgical Infections. 2019. Vol. 20, N. 6. P. 486–491. doi: 10.1089/sur.2019.027

[41] Vallance AE, Young AL, Macutkiewicz C, et al. Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review. HPB (Oxford). 2015;17:1040–1048. doi: 10.1111/hpb.12503

[42] Vallance A.E., Young A.L., Macutkiewicz C., et al. Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review // HPB (Oxford). 2015. N. 17. P. 1040–1048. doi: 10.1111/hpb.12503

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