Drain and nasogastric tube use following pancreatoduodenectomy: a narrative review

Introduction

By 2030, it is predicted that pancreatic ductal adenocarcinoma (PDAC) will be a leading cause of cancer-related death in the developed world (1). Prognosis is extremely poor with five-year survival being around 9% (1). For fit patients with early disease affecting the head of the pancreas, curative-intent pancreatoduodenectomy (PD) is recommended. This operation remains high-risk and is associated with considerable morbidity. Whilst patients traditionally left theatre with at least one intraperitoneal drain and a nasogastric (NG) tube in situ, some authors advise against this and practice is highly variable. This review aims to consolidate the findings of notable recent studies which have reported on these controversial topics. We present the following article in accordance with the Narrative Review reporting checklist (available at https://apc.amegroups.com/article/view/10.21037/apc-21-18/rc).

Methods

A comprehensive online search of the PubMed database was carried out on 1^st May 2021 (Table 1). One search was conducted using the terms [“drain” AND “pancreatoduodenectomy”] and an additional search was carried out using the terms [“nasogastric tube” AND “pancreatoduodenectomy”]. Articles from May 2011 through to May 2021 were included. Included were clinical studies, systematic reviews (SR), and meta-analyses (MA) reporting on intraperitoneal drain and NG tube use and their impact on PD outcomes. The following criteria were used: (I) English language; (II) human studies; (III) studies with at least 100 PDs; (IV) in terms of risk factors/associations, only statistically significant results were considered (P<0.05). Where available, exact figures have been provided for direct comparison. Otherwise, odds ratio (OR), relative risk (RR), or mean/median difference (MD) has been provided.

Results

Drains

Surgical drains have been used in abdominal operations since the nineteenth century; they serve multiple purposes (2). Firstly, since drain contents can be inspected, measured and sent for laboratory analysis, they facilitate the diagnosis and monitoring of anastomotic leakage and postoperative bleeding. This is especially important following PD since the early diagnosis of postoperative pancreatic fistula (POPF) and post-pancreatectomy haemorrhage (PPH) can improve outcomes (3). Drains can also help prevent fluid accumulation and reduce the incidence of intra-abdominal abscesses (2). However, as an indwelling foreign body, they are an infection risk. Furthermore, the presence of a drain, and the resulting adjacent inflammation, may contribute to postoperative bleeding and has the potential to disrupt an anastomosis (4). Finally, drains can limit patient mobilisation which is associated with further morbidity such as pulmonary embolism and atelectasis (2). Whilst it is difficult to quantify these associations, drains should only be used when there is a clear indication. Recent authors have challenged their routine use in PD (2,4,5).

Drain placement

In a recent MA, Wang et al. [one randomized controlled trial (RCT), four non-randomised comparative studies, n=1,728, 45.3% in the drain group] concluded that prophylactic drainage correlated with decreased perioperative mortality (OR 2.32, P=0.02) (6). However, this also correlated with increased overall morbidity (OR 0.62, P<0.01), major morbidity (OR 0.75, P=0.01) and readmission (OR 0.77, P=0.04) (6). Rates of POPF (including biochemical leak), intra-abdominal abscess, PPH, bile leak, delayed gastric emptying (DGE) and re-intervention, including radiologic-guided drainage, were unaffected (6). Three studies used the International Study Group of Pancreatic Fistula (ISGPF) definition of POPF and the remaining two used their own definitions. Due to the small number of studies available for analysis, the authors could not safely recommend or advise against drain use and suggested that future RCTs should compare routine versus selective drainage (6). Results from this MA are compared to other similar studies in Table 2. In another recent MA, Hüttner et al. (three RCTs, n=711, 50.5% in the drain group) found routine drainage did not affect rates of perioperative mortality, overall morbidity, re-operation, intra-abdominal abscess or surgical site infection (SSI) (7). POPF was more common in the drain group (15.9% vs. 7.1%, P=0.03) but this was not significant when biochemical leaks (formerly grade A POPF) were excluded (11.5% vs. 9.5%, P=0.67) (7). The authors concluded that the current evidence does not support routine drainage and advised that future research should focus on the identification of the sub-set of patients in whom a drain would be beneficial (7). As in the Wang et al. MA, only a limited number of studies were included.

In a retrospective, multi-centre study, Zaghal et al. (n=6,858, 87.4% in the drain group) found routine drainage correlated with reduced perioperative mortality (1.7% vs. 2.9%, P=0.003) but higher rates of overall morbidity (49.5% vs. 41.2%, P=0.0008), DGE (18.1% vs. 13.7%, P=0.004), and POPF (19.4% vs. 9.9%, P<0.0001), and longer length of stay (3.1% vs. 1.6% >10 days, P=0.02) (4). This study employed a non-randomised design and only considered follow-up to 30-days postoperatively. In a similar retrospective, multi-centre study, Addison et al. (n=7,583, 87.9% in the drain group) reached contrasting conclusions. Drainage was associated with reduced risk of major morbidity (RR 0.73, P<0.0001), overall morbidity (RR 0.79, P<0.0001), and intra-abdominal collection (RR 0.72, P<0.0001) (8). Routine drainage did not affect incidence of clinically relevant (CR) POPF and, in those who had a drain placed, length of drainage was independently associated with major morbidity (HR 3.06, P<0.0001), overall morbidity (HR 2.48, P<0.0001) and intra-abdominal collection (HR 1.47, P<0.0001) (8). As such, the authors advise prophylactic drain placement and suggest early removal should be considered. Since this study was also retrospective and did not consider key confounding variables, the authors argue a prospective RCT with strict protocol adherence is required.

Finally, a more recent MA by Liu et al. (five RCTs and ten retrospective studies, n=16,648) also showed that routine drainage correlated with reduced perioperative mortality (OR 0.62, P<0.01) but overall morbidity rates were unaffected (9). Routine drainage was associated with increased incidence of CR-POPF (OR 1.98, P=0.002) but did not affect rates of bile leak, DGE, PPH, intra-abdominal abscess, SSI, reoperation, or unplanned readmission (9). As in the Wang et al. MA, definitions of POPF were not consistent between the included studies. This MA contained mostly non-randomised studies, important confounding variables were not considered (e.g., pancreatic texture, main pancreatic duct diameter etc.), and the use of drains was not standardised. Due to the heterogeneity of the included studies, the authors could not arrive at clinically relevant conclusions.

Drain fluid amylase

A key advantage of drain placement is that drain fluid can be inspected, measured and send for laboratory analysis. A high drain fluid amylase (DFA) may indicate POPF which is associated with prolonged length of stay, delayed adjuvant therapy, poor quality of life, and mortality (10). Conversely, a normal DFA is reassuring and suggests drain removal is appropriate. The timing of fluid analysis, as well as the threshold for diagnosing POPF, remain a source of debate. The International Study Group of Pancreatic Surgery (ISGPS) suggest POPF should be diagnosed when DFA is greater than three times the upper normal serum value, starting from postoperative day (POD) three (11). Whilst numerous studies have demonstrated that DFA is useful for the early diagnosis of POPF, the addition of drain fluid lipase has not been shown to improve sensitivity or specificity (12).

Following a MA, Yang et al. (eight prospective and two retrospective studies, n=2,886) concluded that DFA on POD one may be more useful than DFA on POD three as a criterion for the early identification of POPF and suggested a threshold value of 1,300 IU (13). The pooled sensitivity and specificity of DFA on POD one was 81% and 87%, respectively (13). Figures of 56% and 79% were obtained for POD three DFA (13). However, this analysis also included biochemical leaks. The authors argue that DFA should be performed on POD one since this can assist with the early diagnosis of POPF and facilitate early drain removal. Most of the included studies were single centre, the sample size in each was relatively small and most did not consider important operation and drain factors. Hence, the authors argue a large, multi-centre study is required to validate their conclusions. Results from this MA and other similar studies are displayed in Table 3. In a retrospective, single centre study, Hasselgren et al. (n=170) also investigated the usefulness of POD one DFA. A DFA three times the upper limit of the serum reference range was used as the threshold. Patients with a raised DFA had a higher major morbidity rate but this was not significant (14). Two patients who developed a CR-POPF did not have a raised DFA on POD one, whereas 29 did (2.0% vs. 45%) (14). The authors concluded that raised DFA on POD one correlates with CR-POPF but did not suggest how this should affect management and argue a prospective, randomised trial is required to validate their findings (14).

In a recent SR, Davidson et al. investigated the diagnostic accuracy of DFA on or after POD two for the diagnosis of CR-POPF (two prospective and three retrospective studies, n=868). Threshold amylase values and the timing of analysis was highly variable between the studies. Sensitivities ranged from 72–100%, and specificities from 73–99% (15). Post-test probability for POPF ranged from 35.9–94.5% for a positive DFA, and from 0–5.5% for a negative DFA (15). The authors acknowledged that not all grade B POPF are secondary to pancreatic leaks and this may have affected diagnostic accuracy calculations. Secondly, three of the included studies did not pre-specify the DFA threshold. Finally, the sample sizes were small and MA could not be performed due to the high degree of heterogeneity between the included studies. The authors concluded that there is no clear evidence which suggests DFA should be used for diagnosing CR-POPF and that the optimal cut-off for DFA is also unclear (15).They advised further diagnostic test accuracy studies with pre-specified DFA thresholds with appropriate follow-up and clearly defined reference standards.

In a single centre, prospective study by Vutukuru et al. (n=110), DFA was performed on POD three and this was repeated on POD five in patients who met the criteria for POPF (as per the ISGPS definition). Forty-four patients (40%) developed POPF (16). Of these, 36 (82%) had a normalised DFA on POD five, and eight (18%) had a persistently raised DFA. No patients in the former group developed CR-POPF, but six (75%) in the latter did (P<0.0001) (16). The authors concluded that DFA performed on POD five is more clinically relevant than DFA performed on POD three (16). Whilst only a small, single centre study, these results highlight that patients with a raised DFA on POD three are likely to have a normalising DFA by POD five and are unlikely to develop CR-POPF. Hence, the authors argue DFA should be repeated on POD five if it is raised on POD three (16).

In a retrospective series of all pancreatic resections, Lee et al. (n=117) evaluated the clinical applicability of DFA to obtain appropriate baseline values. DFA on PODs one, three and five were all significantly higher in patients who developed CR-POPF. In contrast to the findings of Vutukuru et al., POD three DFA was the only significant predictor of CR-POPF following multivariate analysis (P<0.001) (10). A cut-off value of 1,004 IU had the highest sensitivity (92%) and specificity (82%) for diagnosing POPF (10). This study also included distal pancreatectomies, where the risk of CR-POPF is higher, and so the findings should be interpreted with caution. Although the authors argue that if POD three DFA <1,004 IU it is safe to remove a drain, these findings require validation by prospective, multi-institutional studies.

Drain removal

Enhanced recovery after surgery (ERAS) protocols advise on minimising drain use and early removal where possible (17). The optimal timing for drain removal, as well as the criteria for this, remain a source of debate (Table 4). Some authors have suggested that drain removal can be considered as early as POD one. For example, in a single centre, prospective evaluation, ven Fong et al. (n=495) found POD one DFA of >611 IU was an accurate predictor of POPF (sensitivity 93%, sensitivity 79%) and concluded that a DFA <600 IU resulted in a <1% risk of POPF, and that drains should be removed on POD one in this subgroup (18). Others have suggested optimum outcomes are achieved if the drain is removed on or before POD three. In a multi-centre retrospective study, Zorbas et al. (n=1,066) found this was associated with reduced major morbidity (OR 2.03, P<0.001), POPF (OR 6.76, P<0.001), overall morbidity (OR 2.13, P<0.001) and organ space infection (OR 2.46, P=0.001) (19). Mortality rates were unaffected (19). Those with POD one DFA ≥5,000 IU were excluded. In another large, retrospective study, Beane et al. (n=2,698) matched patients with a POD one DFA of <5,000 IU who underwent drain removal by (and including) POD three (n=580) to patients whose drain was removed after POD three. The former had reduced overall morbidity (35.3% vs. 52.3%, P<0.05), POPF (0.9% vs. 7.9%, P<0.05), and length of stay (6 vs. 8 days, P<0.05) (20). The authors concluded that clinical outcomes were best when POD one DFA was <5,000 IU and drains were removed on or before POD three (20). It is worth noting that just 21.5% of the included patients had a POD one DFA recorded. However, this was associated with shorter time to drain removal (P<0.01). In a single centre RCT, Dai et al. randomly assigned patients to either early drain removal (POD three) or standard removal (POD five), providing DFA was <5,000 IU on PODs one and three, and daily drain output was <300 mL. The former had reduced major morbidity (OR 0.31, P=0.039), and POPF rates was similar (21). This study also included distal pancreatectomy cases. The authors concluded that a further multicentre study with a larger sample size which only considers PD would be desirable to obtain higher powered results (21).

Other authors have suggested that serum C-reactive protein (CRP) level should be considered prior to drain removal. In a single centre, prospective study, Iwasaki et al. (n=300) concluded that drain removal on POD three was safe provided DFA was <350 IU and CRP was <140 mg/L (22). Fifty-percent of the patients included met these criteria (22). In another single centre, prospective trial, Taniguchi et al. (n=198) found a soft pancreas intra-operatively (OR 6.3, P<0.001), positive drain fluid culture on POD one (OR 2.7, P=0.026), and CRP ≥130 mg/L on POD four (OR 3.6, P=0.019) were all independent predictors of CR-POPF (P<0.05) (23). The authors concluded that drain removal on POD four can be considered in the absence of these factors. Ninety-two percent of patients in the validation cohort met these criteria in whom incidence of CR-POPF was 5.6% (23).

Nasogastric tube

Traditionally, PD patients would leave theatre with a NG tube in place. This was thought to reduce rates of patient discomfort, wound dehiscence, anastomotic leakage, and respiratory morbidity (24). However, there is no strong evidence to support this and some authors argue this could be detrimental. Although mainly based on the findings of colorectal studies, there is evidence to suggest that patients who undergo abdominal surgery should not routinely have a NG tube placed (25). A MA from 1995 by Cheatham et al. (26 studies, n=3,964) suggested elective laparotomy patients managed with selective (rather than routine) NG tube placement had reduced rates of atelectasis (RR 0.46, 0.001) and pneumonia (RR 0.49, P<0.0001) (26). The authors concluded that, although these patients may be more likely to develop abdominal distention or vomiting, this is not associated with additional morbidity or increased length of stay (26). A SR from 2005 by Nelson et al. (28 studies, n=4,194) found routine NG tube placement was associated with increased interval to first flatus (MD 0.5 days, P<0.001) and increased incidence of respiratory morbidity (RR 1.35, P=0.07), although the latter was not quite significant (27). The authors concluded that selective NG placement in high-risk patients is more appropriate (27). These findings have been validated by a more recent MA from 2011 (seven studies, n=1,416) (28).

Specific to pancreatic resection, there is no strong evidence to suggest that routine gastric decompression is indicated. In a single centre prospective trial, Kunstman et al. (n=250) studied the outcomes of two consecutive series, the first routinely had a NG tube placed intraoperatively which was maintained until clinically indicated. The second did not routinely have a tube placed and only received a NG tube if they required prolonged endotracheal intubation or if they developed a clinical indication for a tube. The latter tolerated a liquid (3.7 vs. 7.4 days, P<0.001) and solid diet (MD 4.9 vs. 9.2 days, P<0.001) sooner, had lower rates of DGE (8.0% vs. 18.4%, P=0.02) and shorter length of stay (6 vs. 7 days, P<0.001) (29). No difference was observed in terms of respiratory morbidity (29). Other recent studies have reached similar conclusions (24,30,31). Following a recent MA, Gao et al. (six studies, n=940), also concluded that routine gastric decompression did not improve clinical outcomes (32). Routine decompression was associated with higher incidence of DGE (OR 5.45, P<0.001), longer length of stay (MD 5.4 days, P=0.04) and higher perioperative mortality (OR 1.53, P=0.03) (32). Rates of overall morbidity, major morbidity, NG tube reinsertion and POPF were all unaffected. Whilst all six included studies employed a non-randomised design, the results failed to show any benefit of routine gastric decompression. The authors argue a well-designed RCT is indicated (32).

Discussion

The use of prophylactic intraperitoneal drainage following PD is a complex issue and one that remains controversial. Drains can assist with the early diagnosis of anastomotic leakage and postoperative bleeding, and may reduce the incidence of intra-abdominal collections. However, they are an infection risk, are uncomfortable for patients and can hinder mobility in the early postoperative period. Some authors have suggested that drains may contribute towards postoperative bleeding or disrupt newly formed anastomoses in rare circumstances. Concerning routine versus selective drainage, three of the five included studies concluded that prophylactic drainage correlated with reduced perioperative mortality whilst two did not observe this. This is likely as early diagnosis of anastomotic leakage or postoperative bleeding results in timely intervention; however, this is assumed. Since the included studies were mostly non-randomised, this effect may be explained by surgeons electing not to place drains in low-risk patients. Two of the three included MA looked at five or fewer studies and the remaining MA considered data from mostly retrospective, non-randomised studies. The two large, multicentre studies included were retrospective and neither considered important confounding variables (e.g., patient comorbidities) or complications occurring after 30 days. A prospective, randomised study would potentially allow the identification of the sub-set of low-risk patients in whom a drain may not be necessary and the sub-set of high-risk patients in whom a drain would be beneficial.

Whether prophylactic drainage is a cause of additional morbidity or merely an association is unknown. Two of the five included studies suggest routine drainage is associated with increased overall morbidity whereas two did not observe this. One suggested this resulted in decreased overall morbidity. A prospective, randomised study would shed light on this. Whether prophylactic drainage is associated with CR-POPF is also controversial. Two of five included studies observed this effect whereas three found no association. Crucially, none of the included studies found prophylactic drainage decreased the incidence of CR-POPF.

None of the included studies suggested that patients who did not receive a drain had a higher rate of radiologic-guided drainage or unplanned return to theatre. Hence, one might argue that on-demand drainage should be performed in those who develop a collection. We would argue against this as one of the key benefits of prophylactic drainage is the early diagnosis of anastomotic failure and PPH. Prophylactic drainage requires no additional procedure and is of minimal detriment to the patient, particularly if the drain is removed in a timely manner. Whilst this likely results in a proportion of patients who receive an unnecessary drain, this seems a reasonable approach.

Whilst most authors advise prophylactic drain placement, the timing of, and conditions for, drain removal is another complex issue. Whilst DFA is a useful tool for diagnosing POPF, drain fluid lipase is unlikely to be of any additional benefit. Although DFA is both sensitive and specific, when it should be performed, and what the cut-off for diagnosing POPF should be, remain debated. The Yang et al. MA included mostly prospective studies but these were of small sample size. The authors suggested POD one DFA was more clinically relevant than POD three DFA and suggested a cut-off value of 1,300 IU for diagnosing POPF. However, this included biochemical leaks. The SR by Davidson et al. contained mostly small, retrospective studies. Due to the high degree of heterogeneity between the included studies, the authors could not confidently suggest when DFA should be performed or what the threshold for diagnosing POPF should be. The other topical studies mentioned are all retrospective and single centre. They all arrive at contrasting conclusions. Further diagnostic test accuracy studies with pre-specified DFA thresholds and clearly defined reference standards are required as practice is not currently evidence-based.

Whilst most authors support early drain removal and argue this improves outcomes, what constitutes “early” drain removal remains debated. Some authors have suggested it is reasonable to remove drains on POD one providing certain criteria are met, whereas others might not consider this until POD four. Most of the large studies performed suggest drain removal on or before POD three is reasonable providing POD one DFA is <5,000 IU. However, these studies are all retrospective in nature. The prospective studies which have been carried out are all single centre and have small sample sizes. Threshold values for DFA anywhere between 600–5,000 IU have been suggested. Whereas most criteria for drain removal involve DFA only, some authors have suggested that threshold values for CRP and drain output should also be used. A further, multi-centre, prospective, randomised trial comparing outcomes of patients who have their drains removed on PODs one, three or five (providing they met pre-specified criteria) would address this.

PD patients would traditionally leave theatre with a NG tube in situ. These are uncomfortable and may affect patient mobilisation. The recent literature suggests routine NG tube placement is not beneficial to patients who undergo elective laparotomy (all types of resection) or PD. Whilst patients without a tube may be more likely to experience abdominal distention or vomiting, this doesn’t corelate with additional morbidity and so they should only be used when clinically indicated. This results in reduced time to patients achieving adequate oral diet and reduced length of stay. Although most of the included studies employed a non-randomised design, none suggested that routine gastric decompression was of benefit. A well-designed, multi-centre RCT would validate these findings.

This review has limitations. It is a narrative review rather than a formal systematic review so not all the available evidence has been considered. We have attempted to include the most relevant recent studies as outlined in the method section. This article has not aimed to answer a specific research question but aims to provide the reader with a broad overview of the recent evidence on several important topics. We have not considered different types or sizes of drain, or the site of drain placement (we have assumed that most surgeons aim to place a drain adjacent to the pancreatic anastomosis and may elect to place an additional drain next to the hepato-jejunostomy). We have also not considered different sizes of NG tubes.

Conclusions

Prophylactic intraperitoneal drain placement following PD correlates with reduced perioperative mortality and increased overall morbidity. This is mostly based on the findings of retrospective, non-randomised studies. Some authors have argued routine drainage in low-risk patients is unnecessary but this is controversial. Early drain removal should be considered in those with a normal DFA and a low drain output. However, the exact criteria and timing for this remains debated. A randomised trial would address these issues. Routine NG tube placement does not improve outcomes so this should be performed selectively.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://apc.amegroups.com/article/view/10.21037/apc-21-18/rc

Peer Review File: Available at https://apc.amegroups.com/article/view/10.21037/apc-21-18/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apc.amegroups.com/article/view/10.21037/apc-21-18/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol 2019;10:10-27. [Crossref] [PubMed]
2. Wang Q, Jiang YJ, Li J, et al. Is routine drainage necessary after pancreaticoduodenectomy? World J Gastroenterol 2014;20:8110-8. [Crossref] [PubMed]
3. Smits FJ, Molenaar IQ, Besselink MG, et al. Early recognition of clinically relevant postoperative pancreatic fistula: a systematic review. HPB (Oxford) 2020;22:1-11. [Crossref] [PubMed]
4. Zaghal A, Tamim H, Habib S, et al. Drain or No Drain Following Pancreaticoduodenectomy: The Unsolved Dilemma. Scand J Surg 2020;109:228-37. [Crossref] [PubMed]
5. Van Buren G 2nd, Bloomston M, Hughes SJ, et al. A randomized prospective multicenter trial of pancreaticoduodenectomy with and without routine intraperitoneal drainage. Ann Surg 2014;259:605-12. [Crossref] [PubMed]
6. Wang YC, Szatmary P, Zhu JQ, et al. Prophylactic intra-peritoneal drain placement following pancreaticoduodenectomy: a systematic review and meta-analysis. World J Gastroenterol 2015;21:2510-21. [Crossref] [PubMed]
7. Hüttner FJ, Probst P, Knebel P, et al. Meta-analysis of prophylactic abdominal drainage in pancreatic surgery. Br J Surg 2017;104:660-8. [Crossref] [PubMed]
8. Addison P, Nauka PC, Fatakhova K, et al. Impact of Drain Placement and Duration on Outcomes After Pancreaticoduodenectomy: A National Surgical Quality Improvement Program Analysis. J Surg Res 2019;243:100-7. [Crossref] [PubMed]
9. Liu X, Chen K, Chu X, et al. Prophylactic Intra-Peritoneal Drainage After Pancreatic Resection: An Updated Meta-Analysis. Front Oncol 2021;11:658829. [Crossref] [PubMed]
10. Lee SR, Kim HO, Shin JH. Significance of drain fluid amylase check on day 3 after pancreatectomy. ANZ J Surg 2019;89:497-502. [Crossref] [PubMed]
11. Pulvirenti A, Ramera M, Bassi C. Modifications in the International Study Group for Pancreatic Surgery (ISGPS) definition of postoperative pancreatic fistula. Transl Gastroenterol Hepatol 2017;2:107. [Crossref] [PubMed]
12. Müssle B, Oehme F, Schade S, et al. Drain Amylase or Lipase for the Detection of POPF-Adding Evidence to an Ongoing Discussion. J Clin Med 2019;9:7. [Crossref] [PubMed]
13. Yang J, Huang Q, Wang C. Postoperative drain amylase predicts pancreatic fistula in pancreatic surgery: A systematic review and meta-analysis. Int J Surg 2015;22:38-45. [Crossref] [PubMed]
14. Hasselgren K, Benjaminsson-Nyberg P, Halldestam I, et al. The prognostic value of drain amylase on post operative day 1 after Whipple procedure. HPB (Oxford) 2016;18:e400. [Crossref]
15. Davidson TB, Yaghoobi M, Davidson BR, et al. Amylase in drain fluid for the diagnosis of pancreatic leak in post-pancreatic resection. Cochrane Database Syst Rev 2017;4:CD012009. [Crossref] [PubMed]
16. Vutukuru VR, Gavini SK. Drain fluid amylase in defining clinically relevant postoperative pancreatic fistula following pancreaticoduodenectomy: Day 5 is better than day 3. Int Surg J 2017;4:4058-61. [Crossref]
17. Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A Review. JAMA Surg 2017;152:292-8. [Crossref] [PubMed]
18. Ven Fong Z, Correa-Gallego C, Ferrone CR, et al. Early drain removal - the middle ground between the drain versus no drain debate in patients undergoing pancreaticoduodenectomy: A prospective validation study. Ann Surg 2015;262:378-83. [Crossref] [PubMed]
19. Zorbas KA, Daly JM, Esnaola N, et al. Early drain removal improves outcomes after whipple procedure. HPB (Oxford) 2018;20:S269-70. [Crossref]
20. Beane JD, House MG, Ceppa EP, et al. Variation in Drain Management After Pancreatoduodenectomy: Early Versus Delayed Removal. Ann Surg 2019;269:718-24. [Crossref] [PubMed]
21. Dai M, Liu Q, Xing C, et al. Early drain removal after major pancreatectomy reduces postoperative complications: A single-center, randomized, controlled trial. J Pancreatol 2020;3:93-100. [Crossref]
22. Iwasaki T, Nara S, Kishi Y, et al. Proposal of a Clinically Useful Criterion for Early Drain Removal After Pancreaticoduodenectomy. J Gastrointest Surg 2021;25:737-46. [Crossref] [PubMed]
23. Taniguchi K, Matsuyama R, Yabushita Y, et al. Prophylactic drain management after pancreaticoduodenectomy without focusing on the drain fluid amylase level: A prospective validation study regarding criteria for early drain removal that do not include the drain fluid amylase level. J Hepatobiliary Pancreat Sci 2020;27:950-61. [Crossref] [PubMed]
24. Fisher WE, Hodges SE, Cruz G, et al. Routine nasogastric suction may be unnecessary after a pancreatic resection. HPB (Oxford) 2011;13:792-6. [Crossref] [PubMed]
25. Xu X, Zheng C, Zhao Y, et al. Enhanced recovery after surgery for pancreaticoduodenectomy: Review of current evidence and trends. Int J Surg 2018;50:79-86. [Crossref] [PubMed]
26. Cheatham ML, Chapman WC, Key SP, et al. A meta-analysis of selective versus routine nasogastric decompression after elective laparotomy. Ann Surg 1995;221:469-76; discussion 476-8. [Crossref] [PubMed]
27. Nelson R, Tse B, Edwards S. Systematic review of prophylactic nasogastric decompression after abdominal operations. Br J Surg 2005;92:673-80. [Crossref] [PubMed]
28. Rao W, Zhang X, Zhang J, et al. The role of nasogastric tube in decompression after elective colon and rectum surgery: a meta-analysis. Int J Colorectal Dis 2011;26:423-9. [Crossref] [PubMed]
29. Kunstman JW, Klemen ND, Fonseca AL, et al. Nasogastric drainage may be unnecessary after pancreaticoduodenectomy: a comparison of routine vs selective decompression. J Am Coll Surg 2013;217:481-8. [Crossref] [PubMed]
30. Roland CL, Mansour JC, Schwarz RE. Routine nasogastric decompression is unnecessary after pancreatic resections. Arch Surg 2012;147:287-9. [Crossref] [PubMed]
31. Bergeat D, Merdrignac A, Robin F, et al. Nasogastric Decompression vs No Decompression After Pancreaticoduodenectomy: The Randomized Clinical IPOD Trial. JAMA Surg 2020;155:e202291. [Crossref] [PubMed]
32. Gao J, Liu X, Wang H, et al. Efficacy of gastric decompression after pancreatic surgery: a systematic review and meta-analysis. BMC Gastroenterol 2020;20:126. [Crossref] [PubMed]