Top

Journal of Gastrointestinal Surgery

Published in:

01-03-2021 | Pancreaticojejunostomy | Original Article

Impact of Neoadjuvant Systemic Therapy on Pancreatic Fistula Rates Following Pancreatectomy: a Population-Based Propensity-Matched Analysis

Authors: Fadi S. Dahdaleh, Samer A. Naffouje, Mark H. Hanna, George I. Salti

Published in: Journal of Gastrointestinal Surgery | Issue 3/2021

Abstract

Introduction

Postoperative pancreatic fistula (POPF) drives morbidity and mortality following pancreatectomy. Use of neoadjuvant chemotherapy (NAC) has recently increased in the treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC). This study examined the effect of NAC on POPF rates and postoperative outcomes in PDAC.

Methods

The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) Targeted Pancreatectomy dataset was queried to identify PDAC patients who underwent curative-intent pancreatectomies. Propensity score matching was used to stratify patients by receipt of NAC. Postoperative outcomes were compared and logistic regression applied to identify POPF predictors.

Results

Six thousand eight hundred sixty-three patients met the inclusion criteria; of those, 1908 (27.8%) received NAC and 4955 (72.2%) did not (NNAC). Two thousand sixty-two patients were matched 1:1 from each group. NAC patients had significantly lower POPF rates (9.0% vs. 14.5%; P < 0.001); the majority were categorized as grade A (5.1% vs. 9.5%). Overall 30-day morbidity was lower with NAC (40.4% vs. 49.5%; P < 0.001). Specifically, pneumonia (2.3% vs. 4.1%), organ space infections (7.9% vs. 13.2%), sepsis (5.2% vs. 8.0%), and delayed gastric emptying (10.1% vs. 14.8%) occurred less frequently in the NAC group. Postoperative mortality and unplanned reoperations were similar. On multivariate analysis, receipt of NAC was an independent predictor of decreased POPF rates (HR, 0.73 [0.56–0.94]; P = 0.016). Other factors included gland texture, duct size, male gender, and lower BMI.

Conclusions

In this propensity-matched, population-based cohort study of PDAC patients, NAC was associated with lower POPF rates and overall major complications. Those findings suggest a modest protective effect of NAC from POPF.

Available only for authorised users

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi:https://doi.org/10.3322/caac.21551.CrossRefPubMed

Sirri E, Castro FA, Kieschke J, Jansen L, Emrich K, Gondos A et al. Recent Trends in Survival of Patients With Pancreatic Cancer in Germany and the United States. Pancreas. 2016;45(6):908–14. doi:https://doi.org/10.1097/MPA.0000000000000588.CrossRefPubMed

Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21. doi:https://doi.org/10.1158/0008-5472.CAN-14-0155.CrossRefPubMed

Allen PJ, Kuk D, Castillo CF, Basturk O, Wolfgang CL, Cameron JL et al. Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma. Ann Surg. 2017;265(1):185–91. doi:https://doi.org/10.1097/SLA.0000000000001763.CrossRefPubMed

Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395–406. doi:https://doi.org/10.1056/NEJMoa1809775.CrossRefPubMed

Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–24. doi:https://doi.org/10.1016/S0140-6736(16)32409-6.CrossRefPubMed

Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304(10):1073–81. doi:https://doi.org/10.1001/jama.2010.1275.CrossRefPubMed

Altman AM, Wirth K, Marmor S, Lou E, Chang K, Hui JYC et al. Completion of Adjuvant Chemotherapy After Upfront Surgical Resection for Pancreatic Cancer Is Uncommon Yet Associated With Improved Survival. Ann Surg Oncol. 2019. doi:https://doi.org/10.1245/s10434-019-07602-6.

Mackay TM, Smits FJ, Roos D, Bonsing BA, Bosscha K, Busch OR et al. The risk of not receiving adjuvant chemotherapy after resection of pancreatic ductal adenocarcinoma: a nationwide analysis. HPB (Oxford). 2019. doi:https://doi.org/10.1016/j.hpb.2019.06.019.

10.

Del Chiaro M, Soreide K. Trials and tribulations of neoadjuvant therapy in pancreatic cancer. Br J Surg. 2018;105(11):1387–9. doi:https://doi.org/10.1002/bjs.11003.CrossRefPubMed

11.

Michelakos T, Pergolini I, Castillo CF, Honselmann KC, Cai L, Deshpande V et al. Predictors of Resectability and Survival in Patients With Borderline and Locally Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment With FOLFIRINOX. Ann Surg. 2019;269(4):733–40. doi:https://doi.org/10.1097/SLA.0000000000002600.CrossRefPubMed

12.

Hackert T, Sachsenmaier M, Hinz U, Schneider L, Michalski CW, Springfeld C et al. Locally Advanced Pancreatic Cancer: Neoadjuvant Therapy With Folfirinox Results in Resectability in 60% of the Patients. Ann Surg. 2016;264(3):457–63. doi:https://doi.org/10.1097/SLA.0000000000001850.CrossRefPubMed

13.

Versteijne E, van Eijck CH, Punt CJ, Suker M, Zwinderman AH, Dohmen MA et al. Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial. Trials. 2016;17(1):127. doi:https://doi.org/10.1186/s13063-016-1262-z.CrossRefPubMedPubMedCentral

14.

Cullen JJ, Sarr MG, Ilstrup DM. Pancreatic anastomotic leak after pancreaticoduodenectomy: incidence, significance, and management. Am J Surg. 1994;168(4):295–8. doi:https://doi.org/10.1016/s0002-9610(05)80151-5.CrossRefPubMed

15.

Schmidt CM, Choi J, Powell ES, Yiannoutsos CT, Zyromski NJ, Nakeeb A et al. Pancreatic fistula following pancreaticoduodenectomy: clinical predictors and patient outcomes. HPB Surg. 2009;2009:404520. doi:https://doi.org/10.1155/2009/404520.CrossRefPubMedPubMedCentral

16.

Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017;161(3):584–91. doi:https://doi.org/10.1016/j.surg.2016.11.014.CrossRefPubMed

17.

Fuks D, Piessen G, Huet E, Tavernier M, Zerbib P, Michot F et al. Life-threatening postoperative pancreatic fistula (grade C) after pancreaticoduodenectomy: incidence, prognosis, and risk factors. Am J Surg. 2009;197(6):702–9. doi:https://doi.org/10.1016/j.amjsurg.2008.03.004.CrossRefPubMed

18.

McMillan MT, Vollmer CM, Jr., Asbun HJ, Ball CG, Bassi C, Beane JD et al. The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy. J Gastrointest Surg. 2016;20(2):262–76. doi:https://doi.org/10.1007/s11605-015-2884-2.CrossRefPubMed

19.

Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P et al. NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery. 2011;149(3):311–20. doi:https://doi.org/10.1016/j.surg.2010.07.048.CrossRefPubMed

20.

Rose JB, Rocha FG, Alseidi A, Biehl T, Moonka R, Ryan JA et al. Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol. 2014;21(5):1530–7. doi:https://doi.org/10.1245/s10434-014-3486-z.CrossRefPubMed

21.

Takahashi H, Ogawa H, Ohigashi H, Gotoh K, Yamada T, Ohue M et al. Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma. Surgery. 2011;150(3):547–56. doi:https://doi.org/10.1016/j.surg.2011.03.001.CrossRefPubMed

22.

NSQIP PUF User Guide 2017. In: American College of Surgeons: National Surgical Quality Improvement Program. 2018. https://www.facs.org/quality-programs/acs-nsqip/participant-use.

23.

File ANPUD. 2017 Pancreatectomy PUF https://www.facs.org/-/media/files/quality-programs/nsqip/pt_nsqip_puf_userguide_2017.ashx. Accessed 11/13/2019 2019.

24.

Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM, Jr. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013;216(1):1–14. doi:https://doi.org/10.1016/j.jamcollsurg.2012.09.002.CrossRefPubMed

25.

Marchegiani G, Andrianello S, Nessi C, Sandini M, Maggino L, Malleo G et al. Neoadjuvant Therapy Versus Upfront Resection for Pancreatic Cancer: The Actual Spectrum and Clinical Burden of Postoperative Complications. Ann Surg Oncol. 2018;25(3):626–37. doi:https://doi.org/10.1245/s10434-017-6281-9.CrossRefPubMed

26.

Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–7. doi:https://doi.org/10.1097/SLA.0000000000000867.CrossRefPubMed

27.

Hank T, Sandini M, Ferrone CR, Rodrigues C, Weniger M, Qadan M et al. Association Between Pancreatic Fistula and Long-term Survival in the Era of Neoadjuvant Chemotherapy. JAMA Surg. 2019. doi:https://doi.org/10.1001/jamasurg.2019.2272.

28.

Kalimuthu SN, Serra S, Dhani N, Chetty R. The spectrum of histopathological changes encountered in pancreatectomy specimens after neoadjuvant chemoradiation, including subtle and less-well-recognised changes. J Clin Pathol. 2016;69(6):463–71. doi:https://doi.org/10.1136/jclinpath-2016-203604.CrossRefPubMed

29.

Mungroop TH, van Rijssen LB, van Klaveren D, Smits FJ, van Woerden V, Linnemann RJ et al. Alternative Fistula Risk Score for Pancreatoduodenectomy (a-FRS): Design and International External Validation. Ann Surg. 2019;269(5):937–43. doi:https://doi.org/10.1097/SLA.0000000000002620.CrossRefPubMed

30.

Shamali A, De’Ath HD, Jaber B, Abuawad M, Barbaro S, Hamaday Z et al. Elderly patients have similar short term outcomes and five-year survival compared to younger patients after pancreaticoduodenectomy. Int J Surg. 2017;45:138–43. doi:https://doi.org/10.1016/j.ijsu.2017.07.106.CrossRefPubMed

31.

Conzo G, Gambardella C, Tartaglia E, Sciascia V, Mauriello C, Napolitano S et al. Pancreatic fistula following pancreatoduodenectomy. Evaluation of different surgical approaches in the management of pancreatic stump. Literature review. Int J Surg. 2015;21 Suppl 1:S4–9. doi:https://doi.org/10.1016/j.ijsu.2015.04.088.CrossRefPubMed

32.

Kantor O, Talamonti MS, Pitt HA, Vollmer CM, Riall TS, Hall BL et al. Using the NSQIP Pancreatic Demonstration Project to Derive a Modified Fistula Risk Score for Preoperative Risk Stratification in Patients Undergoing Pancreaticoduodenectomy. J Am Coll Surg. 2017;224(5):816–25. doi:https://doi.org/10.1016/j.jamcollsurg.2017.01.054.CrossRefPubMed

Title: Impact of Neoadjuvant Systemic Therapy on Pancreatic Fistula Rates Following Pancreatectomy: a Population-Based Propensity-Matched Analysis
Authors: Fadi S. Dahdaleh
Samer A. Naffouje
Mark H. Hanna
George I. Salti
Publication date: 01-03-2021
Publisher: Springer US
Keywords: Pancreaticojejunostomy
Pancreatectomy
Published in: Journal of Gastrointestinal Surgery / Issue 3/2021
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-020-04581-y

2024 ASCO Annual Meeting

Springer Medicine

Impact of Neoadjuvant Systemic Therapy on Pancreatic Fistula Rates Following Pancreatectomy: a Population-Based Propensity-Matched Analysis

Abstract

Introduction

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2021

Surgical Duct-to-Duct Reconstruction: an Alternative Approach to Late Biliary Anastomotic Stricture After Deceased Donor Liver Transplantation

Assessment of Cancer Center Variation in Textbook Oncologic Outcomes Following Colectomy for Adenocarcinoma

Benchmarking Performance in Pancreatic Surgery: a Systematic Review of Published Quality Metrics

Internal Hernia After Laparoscopic Gastric Bypass Without Preventive Closure of Mesenteric Defects: a Single Institution’s Experience

Effect of Primary Tumor Location on Postmetastasectomy Survival in Patients with Colorectal Cancer Liver Metastasis

Massive Acute Gastric Dilatation in a Patient with Anorexia Nervosa