Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy

The American Journal of Surgery xxx (xxxx) xxx

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Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy Jiqiao Zhu, Xianliang Li, Han Li, Zixi Liu, Jun Ma, Jiantao Kou, Qiang He* Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

a r t i c l e i n f o

a b s t r a c t

Article history: Received 2 July 2019 Received in revised form 21 July 2019 Accepted 3 August 2019

Background: We aimed to compare the enhanced recovery after surgery pathway with the standard perioperative care protocol concerning complications, postoperative length of stay and 1-year survival rate. Methods: Using a beforeeafter cohort study design, data from patients with pancreatic head cancer, who consecutively underwent pancreaticoduodenectomy, were retrospectively collected. Results: Compared to the control group, patients with soft pancreas in the enhanced recovery after surgery group had a lower incidence of delayed gastric emptying (36.7% vs 13.3%, P ¼ 0.026) and respiratory complications (46.7% vs 20.0%, P ¼ 0.028), and shorter postoperative length of stay (All: 10.9 ± 3.4 d vs13.5 ± 3.8 d, P ¼ 0.002; Soft: 11.2 ± 3.8 d vs14.0 ± 4.5 d, P ¼ 0.001). The 1-year survival rates were similar between the groups. Conclusion: The enhanced recovery after surgery pathways can significantly reduce the incidence of certain surgical complications and decrease the postoperative length of stay. It does not affect 1-year survival. © 2019 Elsevier Inc. All rights reserved.

Keywords: Clinical pathways Pancreatic cancer Pancreaticoduodenectomy Postoperative complications Soft pancreatic texture

Introduction Pancreaticoduodenectomy (PD) remains the central treatment in patients with resectable cancer of the pancreatic head and other resectable periampullary cancers in spite of the emergence of various methods during the past several decades.1e3 Complications following PD have always been the surgeons' biggest concern, among which postoperative pancreatic fistula (POPF) and hence associated complications may be called the Achilles' heel of PD. Notably, the soft texture of the pancreas has been repeatedly presented to be a vital risk factor for POPF. Therefore, patients with soft pancreatic texture are reported to have higher complication rates.4,5 These complications severely affect patients’ functional improvement and overall health status, although postoperative morbidity and mortality rates have been reduced recently.6,7 Enhanced recovery after surgery (ERAS) pathways, also named fast-track or clinical pathway programs, are multidisciplinary management plans for patients following surgery.8 These protocols standardize a patient's course in hospital from admission until

* Corresponding author. Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, No.8 Gongtinan Road, Chaoyang District, Beijing, 100020, China. E-mail address: [email protected] (Q. He).

discharge. The ERAS pathways, which were first reported in colorectal surgery, have proven to reduce overall morbidity rates and shorten the length of hospital stay.9,10 There has been an increasing number of ERAS pathways implemented in PD since the guideline for perioperative care for PD was published.8 The benefit of implementing ERAS pathways on postoperative complications in PD, especially POPF, has not reached consensus.11e13 Moreover, the efficacy of the ERAS pathways in the group of patients with soft pancreatic texture has not been reported yet to the best of our knowledge. In the meantime, standard perioperative care for patients after PD has been challenged as a result of a lack of sufficient evidence. Recently, a modified ERAS pathway based on the guidelines for PD was initiated in patients with pancreatic head cancer at our department. The standard perioperative care protocol was replaced in these patients. The present beforeeafter cohort study compared the ERAS pathway to standard perioperative care protocol with respect to complications, postoperative length of stay and 1-year survival rate.

Materials and methods We prospectively applied the modified ERAS pathway in patients with pancreatic head cancer from December 2015, whereas

https://doi.org/10.1016/j.amjsurg.2019.08.002 0002-9610/© 2019 Elsevier Inc. All rights reserved.

Please cite this article as: Zhu J et al., Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy, The American Journal of Surgery, https://doi.org/10.1016/j.amjsurg.2019.08.002

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J. Zhu et al. / The American Journal of Surgery xxx (xxxx) xxx

the standard perioperative care protocol was used before. Data from patients, who consecutively underwent PD due to pancreatic head cancer between October 2014 and January 2017, were retrospectively collected. Written informed consent was obtained from these patients. The study was approved by the Institutional Review Board of Beijing Chaoyang Hospital (2015-9-12-34) in accordance with the 1964 Helsinki declaration and its later amendments.

(TEPJ), end-to-side hepaticojejunostomy (HJ), antecolic end-to-side gastrojejunostomy and Braun anastomosis. TEPJ included one inner layer of duct-to-mucosa anastomosis and one outer layer of parenchyma-to-jejunal seromuscular anastomosis using the parachute technique. HJ was reconstructed with one layer mucosa-tomucosa anastomosis. Both TEPJ and HJ were hand-sewn. One silicon drain was placed ventral to TEPJ and another dorsal to HJ.

Definitions

ERAS protocol and standard perioperative care protocol

The soft pancreas was evaluated by two experienced surgeons during the operation. Meanwhile, the pancreatic texture of the cut surface met the criteria of equal to or less than moderate fibrosis after hematoxylin and eosin staining assessed by an experienced pathologist who was blinded to the intraoperative evaluation.14 POPF was diagnosed and graded according to the International Study Group on Pancreatic Fistula (ISGPF) Definition.15 Delayed gastric emptying (DGE) was defined as needing maintenance of a nasogastric tube (NGT) for > 3 d, needing to reinsert the NGT for persistent vomiting after POD 3, or unable to tolerate a solid diet by POD 7 according to the International Study Group of Pancreatic Surgery's recommendation. Respiratory complications were defined as pneumonia and atelectasis. Inclusion criteria for patients were no distant metastases; patients with pancreatic head cancer; patients undergoing a standard PD; the follow-up period >1 year. Exclusion criteria were patients with carcinomas of the ampulla, the terminal portion of the common bile duct and the duodenum; total pancreatectomy; hepatopancreaticoduodenectomy.

The ERAS protocol was based on modified guidelines for perioperative care for PD8 while the standard perioperative care protocol was used before (Table 1). Both protocols were applied by the same group of surgeons.

Surgical technique Surgical procedures were performed by the same panel of surgeons. Inferior infracolic superior mesenteric artery-first approach16 and standard technique were both applied in all these patients. Superior mesenteric-portal vein resection was performed as previously reported when an invasion was detected.17 No pylorus-preserving PD was performed. Reconstruction was performed with the two-layer end-to-side pancreaticojejunostomy

Statistical analysis Data analyses were carried out by using SPSS 19.0 computer software (IBM Corp., Armonk, NY, USA). The Chi-square test or Fisher's exact test was used for categorical variables while the independent samples t-test or rank-sum test was employed for quantitative variables. A P value < 0.05 was considered statistically significant. Results There were a total of 133 patients enrolled in this study with 69 patients in the control group and 64 patients in the ERAS group. 30 patients were diagnosed with soft pancreas in each subgroup. Perioperative parameters were categorized into three types (preoperative, operative and postoperative parameters) and compared. Preoperative parameters The data of general patient characteristics, such as age, gender, pancreatic texture (soft), albumin (35 g/L), hemoglobin (120 g/ L), total bilirubin (300 mmol/l), preoperative biliary drainage, abdominal operation history, diabetes mellitus, smoking, heart

Table 1 Perioperative care protocol before and after introduction of ERAS.

Day of admission Pre-surgery education Artificial nutrition Pulmonary physiotherapy Day before surgery Bowel preparation Fasting Day of surgery Use of the elastic stockings Injection of antibiotics Use of warm air blower Total intravenous anesthesia Epidural analgesia Near-zero fluid balance After surgery Exercising Removal of urinary catheters Removal of nasogastric tubes Resumption of oral intake Removal of abdominal drains Use of epidural analgesia pump Use of pancreatic secretion inhibitor Use of nadroparin calcium

ERAS group

Control group

Yes Per os Yes

Yes Intervenous drop infusion Yes

No Intake of 6 h for solid food and 2 h for water

Yes Overnight fasting

Yes Yes Yes Yes Yes Yes

Yes Yes Yes Yes Yes Yes

On POD 1 On POD 2 On POD 3a After removal of nasogastric tubes On POD 4e5b When required No Yes

On POD 2-3 On POD 3-4 On POD 4-5 After removal of nasogastric tubes On POD 6-7 When required Yes Yes

ERAS, enhanced recovery after surgery; POD, postoperative day. a Fluids 200 ml/day with no apparent abnormal fluid drainage. b Fluids 100 ml/day and amylase <3 times the upper normal serum value with no apparent abnormal fluid drainage.

Please cite this article as: Zhu J et al., Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy, The American Journal of Surgery, https://doi.org/10.1016/j.amjsurg.2019.08.002

J. Zhu et al. / The American Journal of Surgery xxx (xxxx) xxx

diseases, respiratory diseases, American Society of Anesthesiologists grade, body mass index (28 kg/m2) were similar between the two groups (P > 0.05; see Table 2).

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1-Year survival rate The 1-year survival rates were similar between the two groups (All: 67.2% vs 65.2%, P > 0.05; Soft: 63.3% vs 60%, P > 0.05; see Table 4).

Operative parameters Comparison of operative parameters including operative time, blood loss (>400 ml), blood transfusion, surgical technique (arteryfirst approach), vein resection, R0 resection, Lymph nodes recovered, Lymph nodes positive and tumor differentiation (poor) did not reach significance between the two groups (P > 0.05; see Table 3).

Postoperative parameters The patients were evaluated during hospitalization and a follow-up period of more than one year. No perioperative death or readmission (within 30 days) was detected. Postoperative length of stay was shorter in patients of the ERAS group than those of the control group (All:10.9 ± 3.4 d vs13.5 ± 3.8 d, P ¼ 0.002; Soft:11.2 ± 3.8 d vs14.0 ± 4.5 d, P ¼ 0.001). When surgical complications were compared, POPF Grade B and Grade C, bile leak, surgical site infection, and hemorrhage were similar between the two groups (P > 0.05). However, we observed higher incidence of DGE (36.7% vs 13.3%, P ¼ 0.026) and respiratory complications (46.7% vs 20.0%, P ¼ 0.028) in patients with soft pancreas of the control group (see Table 4).

Discussion In this study, we found the ERAS pathway could significantly reduce the incidence of DGE and pulmonary complications, and decrease the postoperative length of stay. It did not affect 1-year survival. Currently, PD is still considered a high-risk and complicated surgery worldwide. From the earliest days of pancreatic surgery to the most recent clinical series, POPF is known to dominate causes of morbidity after PD as it is associated with higher rates of hemorrhage,18,19 abdominal infection20,21 and DGE.22,23 These complications are the main reasons for the prolonged length of stay. The soft pancreatic texture is regarded as an important predictor for POPF.4,5 Mahvi et al. analyzed a subset of patients discharged within 5 days from surgery and found hard pancreatic texture instead of soft pancreatic texture was a predictor of early discharge.24 Therefore, patients with or without soft pancreas may have totally different outcomes. Apart from the surgeon's factor and the patient's factor, it is vital for surgeons to develop new perioperative care strategies aiming at reducing complications in these patients. Growing evidence has suggested that ERAS pathways can reduce the incidence of postoperative complications, accelerate recovery for patients and reduce hospitalization costs in colorectal surgery.9,10 In patients

Table 2 General patient characteristics. Characteristics

ERAS group (n ¼ 64)

Control group (n ¼ 69)

P

Age (years) Gender (male) Pancreatic texture (soft) Albumin (35 g/L) Hemoglobin (120 g/L) Total bilirubin (300 mmol/l) Preoperative biliary drainage Abdominal operation history Diabetes mellitus Smoking Heart diseases Respiratory diseases ASA grade 1 2 3 Body mass index (28 kg/m2)

64.3 ± 7.9 27 30 40 46 12 7 9 13 28 10 18

64.1 ± 11.5 32 30 45 53 16 8 7 18 30 9 16

0.935 0.627 0.694 0.744 0.514 0.530 0.905 0.488 0.431 0.975 0.671 0.514 0.822

17 34 13 44

21 33 15 42

0.342

ERAS, enhanced recovery after surgery; ASA, American Society of Anesthesiologists.

Table 3 Operative data of the two groups. Characteristics

Operative time (h) Blood loss (>400 ml) Blood transfusion Surgical technique (AFA) Vein resection R0 resection Lymph nodes recovered Lymph nodes positive Tumor differentiation (poor)

ERAS group

Control group

All (n ¼ 64)

Soft (n ¼ 30)

All (n ¼ 69)

Soft (n ¼ 30)

6.9 ± 2.3 20 11 37 24 59 26.4 ± 5.8 11.0 ± 3.6 14

7.3 ± 2.6 11 5 17 11 25 25.9 ± 5.3 11.8 ± 2.8 6

7.0 ± 2.2 17 9 33 21 61 26.1 ± 5.6 11.1 ± 3.4 18

7.1 ± 2.0 9 4 13 9 26 26.0 ± 5.2 12.0 ± 3.0 8

P1

P2

0.731 0.395 0.504 0.249 0.390 0.463 0.524 0.702 0.570

0.076 0.584 1.000 0.302 0.584 1.000 0.698 0.435 0.542

ERAS, enhanced recovery after surgery; P1, comparison of ‘All’ column; P2, comparison of ‘Soft’ column; AFA, artery-first approach.

Please cite this article as: Zhu J et al., Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy, The American Journal of Surgery, https://doi.org/10.1016/j.amjsurg.2019.08.002

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J. Zhu et al. / The American Journal of Surgery xxx (xxxx) xxx

Table 4 Postoperative data of the two groups. Characteristics

Parenteral fluid therapy (ml) POD 1 POD 2 POD 3 Blood transfusion POPF Grade B Grade C Bile leak Surgical site infection Delayed gastric emptying Hemorrhage Respiratory complications Postoperative length of stay 1-year survival

ERAS group

Control group

P1

P2

3091 ± 783 2589 ± 435 1738 ± 362 12

0.928 0.683 0.580 0.485

0.847 0.883 0.895 0.288

10 1 0 7 11 5 14 14.0 ± 4.5 18

0.094 0.932 0.395 0.203 0.073 0.463 0.056 0.002 0.810

0.067 1.000 e 0.166 0.026 0.742 0.028 0.001 0.791

All (n ¼ 64)

Soft (n ¼ 30)

All (n ¼ 69)

Soft (n ¼ 30)

3086 ± 724 2696 ± 473 1810 ± 666 16

3127 ± 652 2573 ± 393 1759 ± 792 7

3074 ± 772 2662 ± 475 1755 ± 466 21

7 3 1 7 8 5 12 10.9 ± 3.4 43

4 2 0 3 4 3 6 11.2 ± 3.8 19

15 2 1 13 17 8 23 13.5 ± 4.0 45

ERAS, enhanced recovery after surgery; POD, postoperative day; POPF, postoperative pancreatic fistula; P1, comparison of ‘All’ column; P2, comparison of ‘Soft’ column.

undergoing PD, Aviles et al. reported the ERAS guidelines were feasible and safely implemented with no change in morbidity and mortality rates,11 while Dai et al. found ERAS pathway could reduce the incidence of POPF and DGE.12 Therefore, the benefit of ERAS pathways for these patients is not certain. Basically, our modified ERAS pathway contains the removal of all kinds of tubes and enhanced mobilization in an early period, and no bowel preparation and decreased time of fasting before surgery. With clinical research development, routine abdominal drain placement has become debatable. A meta-analysis indicated the routine use of abdominal drains may result in a higher risk for major complications.25 However, the main function of drainage is the prevention of fluid collections and the detection of POPF which could actually be seen in a clinical setting varying from 0% to 42.5%.26 Further studies suggest removing drains early may be an alternative to reduce the incidence of complications.27 Our study also demonstrated this measure could lower the POPF rate of patients from the ERAS group, although the comparison between the two groups failed to reach significance. Recently, routine nasogastric tube insertion is controversial. Researches show that the nasogastric tube can lead to increased pulmonary complications and prolonged nausea and vomiting.28,29 On the contrary, Kaya B used a nasogastric tube as a stent in risky hepaticojejunostomies to prevent bile leak.30 A double-lumen gastrojejunostomy tube could improve the average length of stay.31 Due to its function and the complicated reconstruction, insertion of a nasogastric tube is preferred at our center. However, we started to reduce the intubation time to speed the patient's recovery. Moreover, enhanced mobilization in the early postoperative period was reported to be safe and feasible in abdominal surgery as it could reduce the patient's pain and increase the patient's comfort.32 Hence, we observed a decrease in pulmonary complications in the ERAS group but no increase in the incidence of anastomotic leakage. Traditionally, mechanical bowel preparation is done before surgery. Koller et al. found mechanical bowel preparation might be associated with higher morbidity for elective colorectal surgery.33 Meanwhile, the reduced time of fasting before surgery can decrease insulin resistance and may promote postoperative muscle strength and earlier gut function recovery.34 Taken together, no bowel preparation before surgery, enhanced oral intake and early mobilization following surgery may protect the gastrointestinal mucosal barrier and promote the recovery of gastrointestinal motility.35 We found patients with soft pancreas of the ERAS group had a lower incidence of DGE. What's more, the development of

POPF is remarkably demonstrated to be associated with DGE among reported postoperative factors.22,23 The relatively low POPF rate in patients with soft pancreas of the ERAS group might contribute to the decreased DGE rate. Finally, as a result of the lower incidence of postoperative complications, postoperative length of stay was significantly shortened in the ERAS group. And the 1-year survival rate was found not to be affected by the ERAS pathway. It is notable that these improvements in outcomes were demonstrated with protocol implementation. The ERAS pathway significantly relieved physiological stress and accelerated patients' recovery. The main limitation of this study is that it represents the experience of a single center with a before-after design. Future studies, preferably randomized controlled trials in multicenter, are needed to further validate our initial report. Acknowledgment None. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.amjsurg.2019.08.002. Disclosure statement The authors have no conflicts of interest to declare. Funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References 1. Ansari D, Gustafsson A, Andersson R. Update on the management of pancreatic cancer: surgery is not enough. World J Gastroenterol. 2015;21:3157e3165. https://doi.org/10.3748/wjg.v21.i11.3157. 2. Abrams RA. Evolving concepts regarding the use of radiotherapy in the adjuvant management of periampullary pancreatic adenocarcinoma. Cancer J. 2012;18:624e632. https://doi.org/10.1097/PPO.0b013e3182758c84. 3. Smeenk HG, van Eijck CH, Hop WC, et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg. 2007;246: 734e740. https://doi.org/10.1097/SLA.0b013e318156eef3. 4. Okabayashi T, Kobayashi M, Nishimori I, Sugimoto T, Onishi S, Hanazaki K. Risk

Please cite this article as: Zhu J et al., Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy, The American Journal of Surgery, https://doi.org/10.1016/j.amjsurg.2019.08.002

J. Zhu et al. / The American Journal of Surgery xxx (xxxx) xxx

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

factors, predictors and prevention of pancreatic fistula formation after pancreatoduodenectomy. J Hepatobiliary Pancreat Surg. 2007;14:557e563. https:// doi.org/10.1007/s00534-007-1242-5. Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer Jr CM. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013;216:1e14. https://doi.org/10.1016/j. jamcollsurg.2012.09.002. Marandola M, Cilli T, Alessandri F, et al. Perioperative management in patients undergoing pancreatic surgery: the anesthesiologist's point of view. Transplant Proc. 2008;40:1195e1199. https://doi.org/10.1016/j.transproceed.2008.03.114. Salvia R, Malleo G, Butturini G, et al. Perioperative management of patients undergoing pancreatic resection: implementation of a care plan in a tertiarycare center. J Surg Oncol. 2013;107:51e57. https://doi.org/10.1002/jso.23285. Lassen K, Coolsen MM, Slim K, et al. Guidelines for perioperative care for pancreaticoduodenectomy: enhanced recovery after surgery (ERAS®) society recommendations. Clin Nutr. 2012;31(6):817e830. https://doi.org/10.1016/j. clnu.2012.08.011. Bagnall NM, Malietzis G, Kennedy RH, Athanasiou T, Faiz O, Darzi A. A systematic review of enhanced recovery care after colorectal surgery in elderly patients. Colorectal Dis. 2014;16(12):947e956. https://doi.org/10.1111/ codi.12718. Greco M, Capretti G, Beretta L, Gemma M, Pecorelli N, Braga M. Enhanced recovery program in colorectal surgery: a meta-analysis of randomized controlled trials. World J Surg. 2014;38(6):1531e1541. https://doi.org/10.1007/ s00268-013-2416-8. Aviles C, Hockenberry M, Vrochides D, et al. Perioperative care implementation: evidence-based practice for patients with pancreaticoduodenectomy using the enhanced recovery after surgery guidelines. Clin J Oncol Nurs. 2017;21(4):466e472. https://doi.org/10.1188/17.CJON.466-472. Dai J, Jiang Y, Fu D. Reducing postoperative complications and improving clinical outcome: enhanced recovery after surgery in pancreaticoduodenectomy - a retrospective cohort study. Int J Surg. 2017;39: 176e181. https://doi.org/10.1016/j.ijsu.2017.01.089. Bai X, Zhang X, Lu F, et al. The implementation of an enhanced recovery after surgery (ERAS) program following pancreatic surgery in an academic medical center of China. Pancreatology. 2016;16(4):665e670. https://doi.org/10.1016/j. pan.2016.03.018. Wellner UF, Kayser G, Lapshyn H, et al. A simple scoring system based on clinical factors related to pancreatic texture predicts postoperative pancreatic fistula preoperatively. HPB (Oxford). 2010;12:696e702. https://doi.org/10. 1111/j.1477-2574.2010.00239.x. Bassi C, Dervenis C, Butturini G, et al. International Study Group on Pancreatic Fistula Definition. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138:8e13. https://doi.org/10.1016/j. surg.2005.05.001. Zhu J, Han D, Li X, et al. Inferior infracolic 'superior mesenteric artery first' approach with a No-touch isolation surgical technique in patients with a borderline resectable cancer of the pancreatic head. Ann Surg Oncol. 2016;23(Suppl 5):976e980. https://doi.org/10.1245/s10434-016-5542-3. Zhu J, Li X, Kou J, et al. Proposed Chaoyang vascular classification for superior mesenteric-portal vein invasion, resection, and reconstruction in patients with pancreatic head cancer during pancreaticoduodenectomy - a retrospective cohort study. Int J Surg. 2018;53:292e297. https://doi.org/10.1016/j.ijsu.2018. 04.011. Wang WG, Fu L, Babu SR, Wang L, Liang CP, Tian BL. Incidence of and risk factors and reinterventions for post-pancreatoduodenectomy hemorrhage: retrospective analysis. Dig Surg. 2018;35(1):19e27. https://doi.org/10.1159/ 000460263. Gao F, Li J, Quan S, et al. Risk factors and treatment for hemorrhage after pancreaticoduodenectomy: a case series of 423 patients. BioMed Res Int. 2016;2016, 2815693. https://doi.org/10.1155/2016/2815693.

5

20. Zhang JF, Zhu HY, Sun YW, et al. Pseudomonas aeruginosa infection after pancreatoduodenectomy: risk factors and clinic impacts. Surg Infect (Larchmt). 2015;16(6):769e774. https://doi.org/10.1089/sur.2015.041. 21. Shinkawa H, Takemura S, Uenishi T, et al. Nutritional risk index as an independent predictive factor for the development of surgical site infection after pancreaticoduodenectomy. Surg Today. 2013;43(3):276e283. https://doi.org/ 10.1007/s00595-012-0350-2. 22. Robinson JR, Marincola P, Shelton J, Merchant NB, Idrees K, Parikh AA. Perioperative risk factors for delayed gastric emptying after a pancreaticoduodenectomy. HPB (Oxford). 2015;17(6):495e501. https://doi.org/10. 1111/hpb.12385. 23. Qu H, Sun GR, Zhou SQ, He QS. Clinical risk factors of delayed gastric emptying in patients after pancreaticoduodenectomy: a systematic review and metaanalysis. Eur J Surg Oncol. 2013;39(3):213e223. https://doi.org/10.1016/j.ejso. 2012.12.010. 24. Mahvi DA, Pak LM, Bose SK, Urman RD, Gold JS, Whang EE. Fast-track pancreaticoduodenectomy: factors associated with early discharge. World J Surg. 2019;43(5):1332e1341. https://doi.org/10.1007/s00268-019-04916-0. 25. van der Wilt AA, Coolsen MM, de Hingh IH, et al. To drain or not to drain: a cumulative meta-analysis of the use of routine abdominal drains after pancreatic resection. HPB (Oxford). 2013;15(5):337e344. https://doi.org/10. 1111/j.1477-2574.2012.00609.x. 26. Pedrazzoli S. Pancreatoduodenectomy (PD) and postoperative pancreatic fistula (POPF): a systematic review and analysis of the POPF-related mortality rate in 60,739 patients retrieved from the English literature published between 1990 and 2015. Medicine (Baltimore). 2017;96(19), e6858. https://doi.org/10. 1097/MD.0000000000006858. 27. Bassi C, Molinari E, Malleo G, et al. Early versus late drain removal after standard pancreatic resections: results of a prospective randomized trial. Ann Surg. 2010;252(2):207e214. https://doi.org/10.1097/SLA.0b013e3181e61e88. 28. Park JS, Kim JY, Kim JK, Yoon DS. Should gastric decompression be a routine procedure in patients who undergo pylorus-preserving pancreatoduodenectomy? World J Surg. 2016;40(11):2766e2770. https://doi.org/ 10.1007/s00268-016-3604-0. 29. Chaudhary A, Barreto SG, Talole SD, Singh A, Perwaiz A, Singh T. Early discharge after pancreatoduodenectomy: what helps and what prevents? Pancreas. 2015;44(2):273e278. https://doi.org/10.1097/MPA.0000000000000254. 30. Kaya B, Ozcabi Y, Tasdelen I, Onur E, Memisoglu K. Nasogastric tube placement into the hepaticojejunostomy anastomosis in pancreaticoduodenectomy: a simple surgical technique for prevention of bile leak. Korean J Hepatobiliary Pancreat Surg. 2016;20(2):89e92. https://doi.org/10.14701/kjhbps.2016.20.2. 89. 31. Mack LA, Kaklamanos IG, Livingstone AS, Levi JU, Robinson C, et al. Gastric decompression and enteral feeding through a double-lumen gastrojejunostomy tube improves outcomes after pancreaticoduodenectomy. Ann Surg. 2004;240(5):845e851. https://doi.org/10.1097/01.sla.0000143299. 72623.73. 32. Ni CY, Wang ZH, Huang ZP, et al. Early enforced mobilization after liver resection: a prospective randomized controlled trial. Int J Surg. 2018;54(Pt A): 254e258. https://doi.org/10.1016/j.ijsu.2018.04.060. 33. Koller SE, Bauer KW, Egleston BL, et al. Comparative effectiveness and risks of bowel preparation before elective colorectal surgery. Ann Surg. 2018;267(4): 734e742. https://doi.org/10.1097/SLA.0000000000002159. 34. Singh BN, Dahiya D, Bagaria D, et al. Effects of preoperative carbohydrates drinks on immediate postoperative outcome after day care laparoscopic cholecystectomy. Surg Endosc. 2015;29(11):3267e3272. https://doi.org/10.1007/ s00464-015-4071-7. 35. Ji HB, Zhu WT, Wei Q, Wang XX, Wang HB, Chen QP. Impact of enhanced recovery after surgery programs on pancreatic surgery: a meta-analysis. World J Gastroenterol. 2018;24(15):1666e1678. https://doi.org/10.3748/wjg.v24.i15. 1666.

Please cite this article as: Zhu J et al., Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy, The American Journal of Surgery, https://doi.org/10.1016/j.amjsurg.2019.08.002