- Email: [email protected]
Measure of pancreas transection and postoperative pancreatic fistula
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Measure of pancreas transection and postoperative pancreatic fistula Shinichiro Takahashi, MD,* Naoto Gotohda, MD, Yuichiro Kato, MD, and Masaru Konishi, MD Department of Hepato-biliary Pancreatic Surgery, National Cancer Center Hospital East, Chiba, Japan
article info
abstract
Article history:
Background: In pancreaticoduodenectomy (PD), a standard protocol for pancreas transec-
Received 3 November 2015
tion has not been established although the method of pancreas transection might be
Received in revised form
involved in the occurrence of postoperative pancreatic fistula (POPF). This study aimed to
4 January 2016
compare whether pancreas transection by ultrasonically activated shears (UAS) or that by
Accepted 7 January 2016
scalpel contributed more to POPF development.
Available online 14 January 2016
Methods: A prospective database of 171 patients who underwent PD for periampullary tumor at National Cancer Center Hospital East between January 2010 and June 2013 was
Keywords:
reviewed. Among the 171 patients, 93 patients with soft pancreas were specifically
Pancreaticoduodenectomy
included in this study. Surgical results and background were compared between patients
Transection
with pancreas transection by UAS and scalpel to evaluate the effectiveness of UAS on
Pancreatic fistula
reducing POPF.
Scalpel
Results: Body mass index, main pancreatic duct diameter, or other clinicopathologic factors
Ultrasonically activated shears
that have been reported as predictive factors for POPF were not significantly different between the two groups. The incidence of all grades of POPF and that of grade B were significantly lower in the scalpel group (52%, 4%) than in the UAS group (74%, 42%). Postoperative complications grade III were also significantly fewer in the scalpel group. Conclusions: Scalpel transection was less associated with POPF than UAS transection in patients who underwent PD for soft pancreas. The method of pancreas transection plays an important role in the prevention of clinical POPF. ª 2016 Elsevier Inc. All rights reserved.
Introduction Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy (PD), which results in prolonged hospital stay [1,2], increased cost [2,3], and a higher mortality rate that ranges from 3% to 15% [4,5]. Preventing POPF is crucial to performing safe PD [6,7]. To reduce the occurrence of POPF, several measures have been used, such as various types of pancreaticoenteric anastomosis [8e10], prophylactic use of perioperative somatostatin [11,12], and
pancreatic duct stenting [13e15]. However, a standard procedure for minimizing the incidence of POPF has not been established. Minor pancreatic fistula, which originates from pancreatic duct branch or parenchyma at the pancreas cut surface, is thought to be a trigger that provokes major POPF, involves duct-to-mucosa anastomosis, and result in more than POPF grade B, in most types of pancreatico-digestive tract anastomoses [16e18]. Pancreatic fluid from a minor fistula at the pancreatic surface might sometimes cause consequent
* Corresponding author. Department of Hepato-biliary Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Tel.: þ81 471-33-1111; fax: þ81 471-31-4724. E-mail address: [email protected] (S. Takahashi). 0022-4804/$ e see front matter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2016.01.008
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disruption of the duct-to-mucosa anastomosis. Therefore, the method of pancreas transection, which affects the condition of the pancreas cut surface, is presumably associated with POPF. Ultrasonically activated shears (UAS) is a surgical instrument to cut and coagulate tissues simultaneously, using energy generated from ultrasonic vibration. Frictional heat created by UAS with the property of lower maximum and slower increase in tissue temperature is beneficial to stronger thermal coagulation and less heat injury than that by electrocautery. UAS has been used in general surgeries, including laparoscopic surgeries and open surgeries of lung, liver, and so forth. Currently, several studies have reported that pancreas transection by ultrasonically activated scalpel and shears might have an advantage over the other transection methods in preventing minor pancreatic fistula by sealing small branches of the pancreatic duct at the cut surface [17,19,20]. On the other hand, transection by ultrasonically activated devices might have a disadvantageous effect on regional wound healing because of coagulation necrosis or thermal artifact at the cut surface [21]. Then, it is obscure whether UAS pancreas transection decreases POPF through effect on transection surface in comparison with scalpel-transection, which has been one of the community standards. Therefore, we assessed correlations between POPF and patient and operative factors in patients who underwent PD for soft pancreas to test the hypothesis that pancreas transection by ultrasonically activated shears (UAS) reduced POPF compared with scalpel.
Materials and methods Patient population and data collection This study comprised an analysis of data registered prospectively from patients undergoing PD at National Cancer Center Hospital East between January 2010 and June 2013. During the study period, at least one of the experienced surgeons who had performed more than 100 PDs (S.T., M.K., N.G., or Y.K.) took part in each PD operation. Pancreatic texture was assessed intraoperatively by one of the aforementioned surgeons and recorded routinely. As described subsequently, the operative procedure and perioperative managementdexcept the method of pancreas transectiondwere standardized during the study period. The study was approved by the institutional review board of the National Cancer Center.
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superior mesenteric vein (SMV) was involved, PV/SMV resection was performed if reconstructible. For enteric reconstruction of the pancreatic stump, end-toside pancreaticojejunostomy was performed using the modified technique first described by Kakita et al. [22]. In brief, for the outer layer, two to four interrupted sutures penetrating the pancreatic parenchyma and picking up the seromuscular layer of the jejunum were placed using 30 nonabsorbable monofilament sutures with a straightened needle (Figs. 1A, 2A). Next, the pancreatic duct and fullthickness jejunal wall were fixed as the inner layer with eight to 14 interrupted stitches using 5-0 or 6-0 absorbable monofilament sutures (Figs. 1B, 2A). A 6-Fr short internal drainage tube was placed through the pancreatic duct (Figs. 1C, 2B). Then, approximation of the jejunal wall and the pancreatic stump was accomplished with ligation of the outer layer stitches to fully cover the cut surface of the pancreas (Figs. 1D, 2B). No autologous grafts, artificial grafts, or sealing agents were applied for coverage of the anastomosis. JacksonePratt type closed suction drains were placed near the pancreaticojejunal and choledochojejunal anastomoses.
Pancreas transection Transection by scalpel After ligation of the pancreas on the right side of the planned transection line, the pancreas was transected by scalpel. The supratransverse pancreatic artery and the other observed thin arteries, which ran laterally near the transection line were suture-ligated before transection. Hemostasis of every bleeding point at the pancreatic stump was performed by suture-ligation with 5-0 nonabsorbable monofilament sutures. No blood flow control of the remnant pancreas such as by intestinal clamp was applied during the aforementioned procedures (Fig. 3A).
Transection by UA shears The HARMONIC FOCUS curved shears and Ethicon G300 Gen 04 Ultracision Harmonic Scalpel Surgical Generator (Ethicon Endo-Surgery Inc, Cincinnati, OH) were used as the handpiece and generator. The power level was set at 3 (Fig. 3B). The pancreas was transected using the UA shears except for the main pancreatic duct (MPD). The MPD was cut by scalpel to avoid damaging the portion to be sutured. Hemostasis of bleeding at the pancreatic stump was performed by electrocautery or suture-ligation.
Operative procedure Selection of pancreas transection method Patients typically underwent subtotal stomach-preserving PD. Basically, a D2 lymphadenectomy, including the nodes along the common hepatic artery and superior mesenteric artery, and the regional lymph nodes around the pancreas and the hepatoduodenal ligament, was performed. Dissection of the para-aortic lymph nodes was not routinely performed. The operative procedure generally included resection of the nerve plexus around the superior mesenteric artery (half on the tumor side), the nerve plexus around the common hepatic artery, and the celiac plexus. When the portal vein (PV) or
Scalpel transection was adopted for all PDs between 2010/1/1 and 2010/9/30, whereas UAS transection was performed as the routine procedure between 2010/10/1 and 2012/6/30. After those periods, between 2012/7/1 and 2013/6/30, scalpel transection was always performed in the PDs, which the surgeon (S.T.) attended. UAS transection was always performed in the PDs, which one of the other surgeons (M.K., N.G., or Y.K.) attended, regardless of pancreas texture or the patient’s condition.
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Fig. 1 e Reconstructive procedure of end-to-side pancreaticoduodenectomy. (A) For the outer layer, two to four interrupted sutures penetrating the pancreatic parenchyma and picking up the seromuscular layer of the jejunum were placed. (B) The pancreatic duct and full-thickness jejunal wall were fixed as the inner layer with eight to 14 interrupted stitches. (C) A short internal drainage tube was placed through the pancreatic duct. (D) Approximation of the jejunal wall and the pancreatic cutend was executed with ligation of the outer layer stitches to fully cover the cut surface of the pancreas.
Perioperative management Amylase level of drainage fluid (D-Amy) and fluid culture were evaluated on postoperative day (POD) 1, 3, and 5. Drains were removed when the drainage fluid did not show high D-Amy or signs of infection after POD 4e6. In cases showing signs of infection in the drainage fluid, drain replacement was performed under fluorography on POD 7e10. Postoperative computed tomography was carried out occasionally when an inflammatory complication was suggested. In general, oral diet was restarted on POD 3. Octreotide was not used. POPF
was graded according to the International Study Group for Pancreatic Fistula criteria [23]. All postoperative complications including POPF were graded according to the ClavienDindo classification [24].
Definitions of POPF POPF was evaluated according to the International Study Group for Pancreatic Fistula criteria [23]: Grade A: transient fistula with no clinical effect, with amylase level of drainage fluid greater than three times the upper normal serum value
Fig. 2 e The modified Kakita method. (A) Duct-to-mucosa anastomosis with eight to 14 interrupted stitches with two to four interrupted penetrating sutures. (B) A short internal drainage tube was placed through the pancreatic duct.
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Fig. 3 e (A) Pancreas transection by scalpel. Hemostasis was performed by suture ligation. No blood flow control of the remnant pancreas was applied during transection or hemostasis. (B) Pancreas transection by ultrasonically activated shears. Only the main pancreatic duct was cut by scalpel so as to not damage the portion to be sutured.
(>375 IU/L) on or after POD 3; Grade B: required change in management (e.g., drain replacement because of infectious fluid or prolonged drain insertion, prolonged drain insertion because of high amylase level of drainage fluid more than 7 d even without infection, interventional drainage, antibiotics, partial or total parenteral nutrition); Grade C: major change in clinical management (clinical stability may be borderline and more aggressive intervention needed, e.g., intra-abdominal hemorrhage, sepsis, organ dysfunction).
frequently in the scalpel group than in the UAS group (P ¼ 0.04). Among the 93 PDs for soft pancreas, POPF grade A was observed in 34 (37%) cases, grade B in 29 (31%), and grade C in 0 cases. The incidence of postoperative complications grade III was 38% in the whole cohort. No 90-d mortality was observed. Incidentally, among 78 PDs for hard pancreas in the same period, POPF grade A and grade B were observed in two cases each (2.6%) and grade C in 0 cases.
Statistical analysis Statistical comparisons of data between patients whose pancreas was transected by UAS and those whose pancreas was transected by scalpel were performed using the chisquare test and independent t-test. In the analyses of risk factors for POPF, correlation between POPF grade B and each categorized factor was evaluated because POPF becomes clinically relevant only in cases of grade B. Then, multiple logistic regression analysis with the factors achieving statistical significance at P 0.05 was conducted to identify independent risk factors for POPF grade B. Statistical analysis was performed using SPSS version 17.0 software (SPSS, Inc, Chicago, IL).
Results From January 2010 to June 2013, 171 patients underwent PD. Among the 171 patients, 93 patients were revealed to have soft pancreas according to the prospectively registered patients’ records. Patient and operative factors according to the method of pancreas transection are summarized in Table 1. Age, primary tumor, body mass index (BMI), operative time, blood loss, MPD diameter, frequency of preoperative biliary drainage, and frequency of PV/SMV resection were not significantly different between the UAS group and the scalpel group. Patients with severe systemic disease (American Society of Anesthesiologists Physical Status 3) were seen more
Table 1 e Patient and operative factors according to the method of pancreas transection. Factor
Age, median, y Primary tumor Pancreatic cancer Bile duct cancer IPMN Ampullary cancer Other tumor BMI (kg/m2) Operative time (min) Intraoperative blood loss (mL) Main pancreatic duct diameter (mm) ASA PS 1 2 3 Preoperative biliary drainage PV/SMV resection
Surgical instrument used for pancreas transection
P
Ultrasonically activated scalpel
Scalpel
(n ¼ 66)
(n ¼ 27)
65 11
64 13
0.51
15 (23%) 23 (35%) 5 (8%) 10 (15%) 13 (19%) 22.2 3.2 370 77 839 748
8 (30%) 6 (22%) 6 (22%) 2 (7%) 5 (19%) 21.8 4.0 371 53 913 603
NS
0.63 0.78 0.69
2.4 1.8
2.9 1.7
0.44
23 42 1 34
8 15 4 9
(30%) (55%) (15%) (33%)
0.04 0.27
3 (11%)
0.35
(35%) (63%) (2%) (52%)
3 (5%)
ASA ¼ American Society of Anesthesiologists; IPMN ¼ intraductal papillary mucinous neoplasm; PS ¼ physical status.
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Table 2 e Postoperative pancreatic fistula and other morbidities after PD according to the method of pancreas transection. Factor
POPF All grades Grade A Grade B Grade C Amylase level of drainage fluid (IU/L) POD 1 POD 3 POD 5 Postoperative complication rate grade III* *
Surgical instrument used for pancreas transection
P
Ultrasonically activated scalpel
Scalpel
(n ¼ 66)
(n ¼ 27)
49 (74%) 21 (32%) 28 (42%) 0
14 (52%) 13 (48%) 1 (4%) 0
0.03 0.13 <0.01
25,943 2598 2402 31 (45%)
34,196 1912 1711 4 (15%)
0.64 0.52 0.51 <0.01
Graded by ClavieneDindo classification.
In comparing POPF between the UAS group and the scalpel group, the incidence of all grades of POPF and the incidence of POPF grade B were significantly higher in the UAS group (74%, 42%) than in the scalpel group (52%, 4%), whereas the incidence of POPF grade A did not differ significantly between the two groups (Table 2). In particular, the incidence of POPF grade B in the scalpel group was remarkably low in contrast to that in the UAS group (P < 0.01). In regard to postoperative complications, which affected clinical course (grade III), one each of POPF grade B, wound dehiscence, portal thrombus, and pancreatitis was observed in the scalpel group. In the UAS group, 28 POPF grade B, 2 intraabdominal abscess, and one each of afferent loop syndrome, cholangitis, bleeding from anastomotic ulcer were recognized as postoperative complications grade III. Owing to the low incidence of POPF grade B, postoperative complications grade III were significantly fewer in the scalpel group (15%) than in the UAS group (45%). In terms of the amylase level of drainage fluid, there was a tendency for the amylase level in the scalpel group to be higher than in the UAS group on POD 1, although statistical significance was not reached (Table 2; Fig. 4). Afterward, however, the fluid amylase level of the scalpel group declined sharply and reversed to a relatively lower amylase level than that of the UAS group on POD 3 and 5. To identify risk factors for POPF grade B, a possible correlation between POPF grade B and patient and operative factors were analyzed in all 93 patients with soft pancreas who underwent PD (Table 3). In the univariate analysis, BMI 25 kg/m2 (P < 0.01), MPD diameter 3 mm (P < 0.01), and pancreas transection by UAS (P < 0.01) were significantly correlated with POPF grade B. These three factors were entered into multivariate analysis with a multiple logistic regression model. BMI 25 kg/m2 (P ¼ 0.02), MPD diameter 3 mm (P < 0.01), and pancreas transection by UAS (P < 0.01) were all shown to be predictors for occurrence of POPF grade B.
Fig. 4 e Amylase level of drain fluid at 1, 3, and 5 d after surgery according to measure of pancreas transection. The amylase level in the scalpel group (34,196 IU/L) tends to be higher than that in the UAS group (25,943 IU/L) on POD 1 (not significant). On POD 3 and 5, however, the fluid amylase level of the scalpel group declined sharply and reversed to a relatively lower amylase level than that of the UAS group.
Discussion Although progress in pancreatic surgery has notably decreased morbidity after PD, POPF has not yet been fully overcome, sometimes leading to serious complications and even to treatment-related death [4,5,7]. The method of pancreas transection is considered one of the factors involved in the occurrence of POPF because the method of pancreas transection would influence the occurrence of minor pancreatic fistula, which originates from pancreatic duct branch or parenchyma at the pancreas cut surface [18]. Pancreatic juice escaping from a minor fistula at the transection surface would sometimes autodigest the pancreatic ductedigestive tract anastomosis and result in major POPF when pancreatic ductto-mucosa anastomosis is performed. Therefore, how the pancreas is transected is presumably significant in preventing POPF, especially in soft pancreas, which is frequently associated with POPF. To decrease the development of pancreatic fistula from the pancreas transection surface, various methods have been attempted for pancreas transection, such as use of the cavitron ultrasonic surgical aspirator [16,25], crush-clamping [26], and a sharp, hook-shaped ultrasonically activated scalpel [19] although pancreatic transection has also been conventionally performed using a surgical scalpel or electrocautery [18]. In terms of stump management in distal pancreatectomy, bipolar scissors [27] and bipolar radiofrequency [28] have also been evaluated. Although a low incidence of POPF incidence has been reported by applying the aforementioned methods, those results were seen only in small, one-arm, single-institutional studies. A standard procedure for pancreatic transection has not yet been established.
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Table 3 e Risk factors for POPF ‡ grade B (ISGPF classification) in pancreas with soft texture. Factor
POPF grade B ()
(þ)
U-analysis P
Gender Male 41 21 0.43 Female 23 8 Age 65 38 17 0.99 <65 26 12 BMI (kg/m2) 25 7 10 <0.01 <25 57 19 ASA PS 2 40 22 0.21 1 24 7 Operative time (h) 7 11 4 0.47 <7 53 25 Estimated blood loss (mL) 1000 15 8 0.67 <1000 49 21 Transfusion Yes 9 3 0.62 No 55 26 Preoperative biliary drainage Yes 29 14 0.78 No 35 15 Pancreatic adenocarcinoma Yes 18 8 0.96 No 46 21 MPD diameter (mm) >3 17 1 <0.01 3 47 28 Operative method PD 6 3 0.58 SSPPD 58 26 PV resection Yes 58 29 0.10 No 6 0 Method of pancreas transection UAS 38 28 <0.01 Scalpel 26 1
Multivariate analysis OR
95% CI
4.92
1.29e18.7
0.02
0.002
0.01e1.14
<0.01
2.30e166.43
<0.01
19.55
P
ASA ¼ American Society of Anesthesiologists; CI ¼ confidence interval; ISGPF ¼ International Study Group for Pancreatic Fistula; OR ¼ odds ratio, PS ¼ physical status, SSPPD ¼ subtotal stomachpreserving pancreaticoduodenectomy; U-analysis ¼ univariate analysis.
Use of an ultrasonically activated device is one of the new transection methods expected to reduce the incidence of POPF. The blade of a UA device vibrates longitudinally at 55,000 times per second. These vibrations generate heat energy, which enable tissue to be cut and coagulated simultaneously. Vessels and ducts up to 5 mm in diameter are expected to be sealed by UA shears. Pancreas transection by UA shears has been initiated in expectation of good hemostasis and sealing of the pancreatic duct branches at the transection surface. Takao et al. [17] reported no POPF after 39 pancreatogastrostomies and two pancreaticojejunostomies when the UA scalpel was used in pancreatic transection although the diameter of the MPD was less than 2 mm in 29%
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of the 41 study patients. Takao et al. assumed that the stumps of the small pancreatic ducts on the transection surface might have been sealed by the UA scalpel, consequently preventing the development of a pancreatic fistula from the transection surface. Considering other advantages such as good hemostasis and availability for endoscopic surgery, UA device transection is considered to be a promising method for pancreatic transection. In the present study, we evaluated the effectiveness of UAS by comparing the occurrence of POPFs among UAS transections and scalpel transections in patients with soft pancreatic texture. The incidence of all-grade POPF and that of grade B were significantly higher in the UAS group (74%, 42%) than in the scalpel group (52%, 4%). Although we hypothesized that pancreas transection by UAS reduced POPF compared with scalpel, our study does not support the hypothesis. On the contrary, the results indicated that UAS transection was more associated with POPF than scalpel transection. Several possible explanations could account for the fact that UAS transection was more associated with POPF than scalpel transection. Ultrasonically activated scalpel produces high blade temperatures and can damage adjacent tissues or organs [29e31]. In an experimental study with swine, histologic examination revealed that UAS dissection caused serious injuries to various structures [32]. A recent study compared pancreatic injury responses according to method of pancreatic transection either with UAS, electrocautery, or surgical scalpel in a rat model [21]. The study showed that resection with a surgical scalpel induced less tissue injury than with UAS or electrocautery. The depth of coagulation necrosis or acinar cell necrosis when the pancreas was transected by UAS or electrocautery was deeper than when the pancreas was transected by a surgical scalpel. Moreover, in laparoscopic gastrectomy, collateral thermal damage to the pancreas by ultrasonic instruments during lymph node dissection was reported [33,34]. The amylase concentrations of the drainage fluid on POD 1 and 3 were significantly higher in laparoscopic gastrectomy using UAS than those in open gastrectomy using electric cautery. There was also a tendency that clinically relevant pancreatic fistula was more frequent in laparoscopic gastrectomy using UAS than that in open gastrectomy using electric cautery [34]. Considering the aforementioned results, pancreas injury to some depth by UAS might directly induce POPF grade B by means of worsening minor fistula. Curiously, the amylase level of the drainage fluid in the scalpel group was higher than that of the UAS group on POD 1; however, the amylase level declined sharply and reversed to a relatively lower amylase level than that of the UAS group on POD 3 and 5. A high fluid amylase level on POD 1 in both the UAS and scalpel groups may indicate that minor fistula at the transection surface frequently occurs after any method used for pancreas transection in patients who undergo PD for soft pancreas. However, the fluid amylase level decreased greatly on POD 3 and 5 in patients who did not suffer clinical POPF. Accordingly, prevention of major POPF might partly depend on wound healing at the pancreatico-digestive tract anastomoses, which attributes to immediate recovery from minor pancreatic fistula originating from pancreatic duct branch or parenchyma at the pancreas cut surface. It is possible that tissue injury caused by UAS has a negative influence on normal
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wound healing, which involves complicated interactions of various cells and cytokines [35], and might increase the rate of clinical POPF by disruption of the duct-to-mucosa anastomosis through persistence of minor pancreatic fistula. In the present era of innovation, various medical devices have been applied for pancreas transection to gain good hemostasis and produce a robust seal on small pancreatic duct branches at the transection surface. However, the results of the present study indicate that simple scalpel pancreas transection was superior to pancreas transection by UAS in reducing the incidence of clinical POPF, which sometimes causes serious complications and incurs a large financial cost. Avoiding tissue damage must be kept in mind during future development of a medical device suitable for transection in soft pancreas. The main limitation of the present study is that it was a nonrandomized study in a single-center setting. The study took into account the issue of surgeons’ experience or differences in skill. All surgeons in the present study were experienced. They devoted time to mastering each method, and then, they selected favorable methods to be applied for the next period. Interestingly, one of the surgeons who participated in the present study experienced clear improvement in the incidence of POPF by returning to scalpel transection from UAS transection. However, it cannot be excluded that part of the better outcome in the scalpel group was because of an increase in experience or differences in each surgeon’s skill. A minutely designed, randomized, multicenter study is greatly desired to confirm the present results. In summary, scalpel transection was less associated with POPF than UAS transection in patients who underwent PD for soft pancreas. How the pancreas is transected plays a role just as important as the method of anastomosis in reducing the incidence of POPF. Rapid wound healing at the pancreas cut surface might be crucial for safe pancreatico-digestive tract anastomoses.
[11]
Acknowledgment
[12]
This work was supported by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development, AMED (15Ack0106154h0001) and the National Cancer Center Research and Development Fund (25-B-8). Authors’ contributions: S.T. had full access to all the data and takes responsibility for data integrity and accuracy of the data analyses. All the authors contributed to the study concept and design and did the acquisition of data. S.T. did the drafting of the article. N.G., Y.K., and M.K. did the critical revision of the article.
Disclosure
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[13]
[14]
[15]
The authors declare no conflict of interest. [16]
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[27] Kawai M, Tani M, Yamaue H. Transection using bipolar scissors reduces pancreatic fistula after distal pancreatectomy. J Hepatobiliary Pancreat Surg 2008;15:366. [28] Pai M, Spalding D, Jiao L, Habib N. Use of bipolar radiofrequency in parenchymal transection of the liver, pancreas and kidney. Dig Surg 2012;29:43. [29] Kim FJ, Chammas MF Jr, Gewehr E, et al. Temperature safety profile of laparoscopic devices: Harmonic ACE (ACE), Ligasure V (LV), and plasma trisector (PT). Surg Endosc 2008; 22:1464. [30] Sankaranarayanan G, Resapu RR, Jones DB, et al. Common uses and cited complications of energy in surgery. Surg Endosc 2013;27:3056. [31] Emam TA, Cuschieri A. How safe is high-power ultrasonic dissection? Ann Surg 2003;237:186. [32] Clements RH, Palepu R. In vivo comparison of the coagulation capability of SonoSurg and Harmonic Ace on 4 mm and 5 mm arteries. Surg Endosc 2007;21:2203. [33] Obama K, Okabe H, Hosogi H, et al. Feasibility of laparoscopic gastrectomy with radical lymph node dissection for gastric cancer: from a viewpoint of pancreas-related complications. Surgery 2011;149:15. [34] Fujita T, Ohta M, Ozaki Y, et al. Collateral thermal damage to the pancreas by ultrasonic instruments during lymph node dissection in laparoscopic gastrectomy. Asian J Endosc Surg 2015;8:281. [35] Thompson SK, Chang EY, Jobe BA. Clinical review: healing in gastrointestinal anastomoses, part I. Microsurgery 2006; 26:131.
Available online at www.sciencedirect.com
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Measure of pancreas transection and postoperative pancreatic fistula Shinichiro Takahashi, MD,* Naoto Gotohda, MD, Yuichiro Kato, MD, and Masaru Konishi, MD Department of Hepato-biliary Pancreatic Surgery, National Cancer Center Hospital East, Chiba, Japan
article info
abstract
Article history:
Background: In pancreaticoduodenectomy (PD), a standard protocol for pancreas transec-
Received 3 November 2015
tion has not been established although the method of pancreas transection might be
Received in revised form
involved in the occurrence of postoperative pancreatic fistula (POPF). This study aimed to
4 January 2016
compare whether pancreas transection by ultrasonically activated shears (UAS) or that by
Accepted 7 January 2016
scalpel contributed more to POPF development.
Available online 14 January 2016
Methods: A prospective database of 171 patients who underwent PD for periampullary tumor at National Cancer Center Hospital East between January 2010 and June 2013 was
Keywords:
reviewed. Among the 171 patients, 93 patients with soft pancreas were specifically
Pancreaticoduodenectomy
included in this study. Surgical results and background were compared between patients
Transection
with pancreas transection by UAS and scalpel to evaluate the effectiveness of UAS on
Pancreatic fistula
reducing POPF.
Scalpel
Results: Body mass index, main pancreatic duct diameter, or other clinicopathologic factors
Ultrasonically activated shears
that have been reported as predictive factors for POPF were not significantly different between the two groups. The incidence of all grades of POPF and that of grade B were significantly lower in the scalpel group (52%, 4%) than in the UAS group (74%, 42%). Postoperative complications grade III were also significantly fewer in the scalpel group. Conclusions: Scalpel transection was less associated with POPF than UAS transection in patients who underwent PD for soft pancreas. The method of pancreas transection plays an important role in the prevention of clinical POPF. ª 2016 Elsevier Inc. All rights reserved.
Introduction Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy (PD), which results in prolonged hospital stay [1,2], increased cost [2,3], and a higher mortality rate that ranges from 3% to 15% [4,5]. Preventing POPF is crucial to performing safe PD [6,7]. To reduce the occurrence of POPF, several measures have been used, such as various types of pancreaticoenteric anastomosis [8e10], prophylactic use of perioperative somatostatin [11,12], and
pancreatic duct stenting [13e15]. However, a standard procedure for minimizing the incidence of POPF has not been established. Minor pancreatic fistula, which originates from pancreatic duct branch or parenchyma at the pancreas cut surface, is thought to be a trigger that provokes major POPF, involves duct-to-mucosa anastomosis, and result in more than POPF grade B, in most types of pancreatico-digestive tract anastomoses [16e18]. Pancreatic fluid from a minor fistula at the pancreatic surface might sometimes cause consequent
* Corresponding author. Department of Hepato-biliary Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Tel.: þ81 471-33-1111; fax: þ81 471-31-4724. E-mail address: [email protected] (S. Takahashi). 0022-4804/$ e see front matter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2016.01.008
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disruption of the duct-to-mucosa anastomosis. Therefore, the method of pancreas transection, which affects the condition of the pancreas cut surface, is presumably associated with POPF. Ultrasonically activated shears (UAS) is a surgical instrument to cut and coagulate tissues simultaneously, using energy generated from ultrasonic vibration. Frictional heat created by UAS with the property of lower maximum and slower increase in tissue temperature is beneficial to stronger thermal coagulation and less heat injury than that by electrocautery. UAS has been used in general surgeries, including laparoscopic surgeries and open surgeries of lung, liver, and so forth. Currently, several studies have reported that pancreas transection by ultrasonically activated scalpel and shears might have an advantage over the other transection methods in preventing minor pancreatic fistula by sealing small branches of the pancreatic duct at the cut surface [17,19,20]. On the other hand, transection by ultrasonically activated devices might have a disadvantageous effect on regional wound healing because of coagulation necrosis or thermal artifact at the cut surface [21]. Then, it is obscure whether UAS pancreas transection decreases POPF through effect on transection surface in comparison with scalpel-transection, which has been one of the community standards. Therefore, we assessed correlations between POPF and patient and operative factors in patients who underwent PD for soft pancreas to test the hypothesis that pancreas transection by ultrasonically activated shears (UAS) reduced POPF compared with scalpel.
Materials and methods Patient population and data collection This study comprised an analysis of data registered prospectively from patients undergoing PD at National Cancer Center Hospital East between January 2010 and June 2013. During the study period, at least one of the experienced surgeons who had performed more than 100 PDs (S.T., M.K., N.G., or Y.K.) took part in each PD operation. Pancreatic texture was assessed intraoperatively by one of the aforementioned surgeons and recorded routinely. As described subsequently, the operative procedure and perioperative managementdexcept the method of pancreas transectiondwere standardized during the study period. The study was approved by the institutional review board of the National Cancer Center.
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superior mesenteric vein (SMV) was involved, PV/SMV resection was performed if reconstructible. For enteric reconstruction of the pancreatic stump, end-toside pancreaticojejunostomy was performed using the modified technique first described by Kakita et al. [22]. In brief, for the outer layer, two to four interrupted sutures penetrating the pancreatic parenchyma and picking up the seromuscular layer of the jejunum were placed using 30 nonabsorbable monofilament sutures with a straightened needle (Figs. 1A, 2A). Next, the pancreatic duct and fullthickness jejunal wall were fixed as the inner layer with eight to 14 interrupted stitches using 5-0 or 6-0 absorbable monofilament sutures (Figs. 1B, 2A). A 6-Fr short internal drainage tube was placed through the pancreatic duct (Figs. 1C, 2B). Then, approximation of the jejunal wall and the pancreatic stump was accomplished with ligation of the outer layer stitches to fully cover the cut surface of the pancreas (Figs. 1D, 2B). No autologous grafts, artificial grafts, or sealing agents were applied for coverage of the anastomosis. JacksonePratt type closed suction drains were placed near the pancreaticojejunal and choledochojejunal anastomoses.
Pancreas transection Transection by scalpel After ligation of the pancreas on the right side of the planned transection line, the pancreas was transected by scalpel. The supratransverse pancreatic artery and the other observed thin arteries, which ran laterally near the transection line were suture-ligated before transection. Hemostasis of every bleeding point at the pancreatic stump was performed by suture-ligation with 5-0 nonabsorbable monofilament sutures. No blood flow control of the remnant pancreas such as by intestinal clamp was applied during the aforementioned procedures (Fig. 3A).
Transection by UA shears The HARMONIC FOCUS curved shears and Ethicon G300 Gen 04 Ultracision Harmonic Scalpel Surgical Generator (Ethicon Endo-Surgery Inc, Cincinnati, OH) were used as the handpiece and generator. The power level was set at 3 (Fig. 3B). The pancreas was transected using the UA shears except for the main pancreatic duct (MPD). The MPD was cut by scalpel to avoid damaging the portion to be sutured. Hemostasis of bleeding at the pancreatic stump was performed by electrocautery or suture-ligation.
Operative procedure Selection of pancreas transection method Patients typically underwent subtotal stomach-preserving PD. Basically, a D2 lymphadenectomy, including the nodes along the common hepatic artery and superior mesenteric artery, and the regional lymph nodes around the pancreas and the hepatoduodenal ligament, was performed. Dissection of the para-aortic lymph nodes was not routinely performed. The operative procedure generally included resection of the nerve plexus around the superior mesenteric artery (half on the tumor side), the nerve plexus around the common hepatic artery, and the celiac plexus. When the portal vein (PV) or
Scalpel transection was adopted for all PDs between 2010/1/1 and 2010/9/30, whereas UAS transection was performed as the routine procedure between 2010/10/1 and 2012/6/30. After those periods, between 2012/7/1 and 2013/6/30, scalpel transection was always performed in the PDs, which the surgeon (S.T.) attended. UAS transection was always performed in the PDs, which one of the other surgeons (M.K., N.G., or Y.K.) attended, regardless of pancreas texture or the patient’s condition.
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Fig. 1 e Reconstructive procedure of end-to-side pancreaticoduodenectomy. (A) For the outer layer, two to four interrupted sutures penetrating the pancreatic parenchyma and picking up the seromuscular layer of the jejunum were placed. (B) The pancreatic duct and full-thickness jejunal wall were fixed as the inner layer with eight to 14 interrupted stitches. (C) A short internal drainage tube was placed through the pancreatic duct. (D) Approximation of the jejunal wall and the pancreatic cutend was executed with ligation of the outer layer stitches to fully cover the cut surface of the pancreas.
Perioperative management Amylase level of drainage fluid (D-Amy) and fluid culture were evaluated on postoperative day (POD) 1, 3, and 5. Drains were removed when the drainage fluid did not show high D-Amy or signs of infection after POD 4e6. In cases showing signs of infection in the drainage fluid, drain replacement was performed under fluorography on POD 7e10. Postoperative computed tomography was carried out occasionally when an inflammatory complication was suggested. In general, oral diet was restarted on POD 3. Octreotide was not used. POPF
was graded according to the International Study Group for Pancreatic Fistula criteria [23]. All postoperative complications including POPF were graded according to the ClavienDindo classification [24].
Definitions of POPF POPF was evaluated according to the International Study Group for Pancreatic Fistula criteria [23]: Grade A: transient fistula with no clinical effect, with amylase level of drainage fluid greater than three times the upper normal serum value
Fig. 2 e The modified Kakita method. (A) Duct-to-mucosa anastomosis with eight to 14 interrupted stitches with two to four interrupted penetrating sutures. (B) A short internal drainage tube was placed through the pancreatic duct.
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Fig. 3 e (A) Pancreas transection by scalpel. Hemostasis was performed by suture ligation. No blood flow control of the remnant pancreas was applied during transection or hemostasis. (B) Pancreas transection by ultrasonically activated shears. Only the main pancreatic duct was cut by scalpel so as to not damage the portion to be sutured.
(>375 IU/L) on or after POD 3; Grade B: required change in management (e.g., drain replacement because of infectious fluid or prolonged drain insertion, prolonged drain insertion because of high amylase level of drainage fluid more than 7 d even without infection, interventional drainage, antibiotics, partial or total parenteral nutrition); Grade C: major change in clinical management (clinical stability may be borderline and more aggressive intervention needed, e.g., intra-abdominal hemorrhage, sepsis, organ dysfunction).
frequently in the scalpel group than in the UAS group (P ¼ 0.04). Among the 93 PDs for soft pancreas, POPF grade A was observed in 34 (37%) cases, grade B in 29 (31%), and grade C in 0 cases. The incidence of postoperative complications grade III was 38% in the whole cohort. No 90-d mortality was observed. Incidentally, among 78 PDs for hard pancreas in the same period, POPF grade A and grade B were observed in two cases each (2.6%) and grade C in 0 cases.
Statistical analysis Statistical comparisons of data between patients whose pancreas was transected by UAS and those whose pancreas was transected by scalpel were performed using the chisquare test and independent t-test. In the analyses of risk factors for POPF, correlation between POPF grade B and each categorized factor was evaluated because POPF becomes clinically relevant only in cases of grade B. Then, multiple logistic regression analysis with the factors achieving statistical significance at P 0.05 was conducted to identify independent risk factors for POPF grade B. Statistical analysis was performed using SPSS version 17.0 software (SPSS, Inc, Chicago, IL).
Results From January 2010 to June 2013, 171 patients underwent PD. Among the 171 patients, 93 patients were revealed to have soft pancreas according to the prospectively registered patients’ records. Patient and operative factors according to the method of pancreas transection are summarized in Table 1. Age, primary tumor, body mass index (BMI), operative time, blood loss, MPD diameter, frequency of preoperative biliary drainage, and frequency of PV/SMV resection were not significantly different between the UAS group and the scalpel group. Patients with severe systemic disease (American Society of Anesthesiologists Physical Status 3) were seen more
Table 1 e Patient and operative factors according to the method of pancreas transection. Factor
Age, median, y Primary tumor Pancreatic cancer Bile duct cancer IPMN Ampullary cancer Other tumor BMI (kg/m2) Operative time (min) Intraoperative blood loss (mL) Main pancreatic duct diameter (mm) ASA PS 1 2 3 Preoperative biliary drainage PV/SMV resection
Surgical instrument used for pancreas transection
P
Ultrasonically activated scalpel
Scalpel
(n ¼ 66)
(n ¼ 27)
65 11
64 13
0.51
15 (23%) 23 (35%) 5 (8%) 10 (15%) 13 (19%) 22.2 3.2 370 77 839 748
8 (30%) 6 (22%) 6 (22%) 2 (7%) 5 (19%) 21.8 4.0 371 53 913 603
NS
0.63 0.78 0.69
2.4 1.8
2.9 1.7
0.44
23 42 1 34
8 15 4 9
(30%) (55%) (15%) (33%)
0.04 0.27
3 (11%)
0.35
(35%) (63%) (2%) (52%)
3 (5%)
ASA ¼ American Society of Anesthesiologists; IPMN ¼ intraductal papillary mucinous neoplasm; PS ¼ physical status.
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Table 2 e Postoperative pancreatic fistula and other morbidities after PD according to the method of pancreas transection. Factor
POPF All grades Grade A Grade B Grade C Amylase level of drainage fluid (IU/L) POD 1 POD 3 POD 5 Postoperative complication rate grade III* *
Surgical instrument used for pancreas transection
P
Ultrasonically activated scalpel
Scalpel
(n ¼ 66)
(n ¼ 27)
49 (74%) 21 (32%) 28 (42%) 0
14 (52%) 13 (48%) 1 (4%) 0
0.03 0.13 <0.01
25,943 2598 2402 31 (45%)
34,196 1912 1711 4 (15%)
0.64 0.52 0.51 <0.01
Graded by ClavieneDindo classification.
In comparing POPF between the UAS group and the scalpel group, the incidence of all grades of POPF and the incidence of POPF grade B were significantly higher in the UAS group (74%, 42%) than in the scalpel group (52%, 4%), whereas the incidence of POPF grade A did not differ significantly between the two groups (Table 2). In particular, the incidence of POPF grade B in the scalpel group was remarkably low in contrast to that in the UAS group (P < 0.01). In regard to postoperative complications, which affected clinical course (grade III), one each of POPF grade B, wound dehiscence, portal thrombus, and pancreatitis was observed in the scalpel group. In the UAS group, 28 POPF grade B, 2 intraabdominal abscess, and one each of afferent loop syndrome, cholangitis, bleeding from anastomotic ulcer were recognized as postoperative complications grade III. Owing to the low incidence of POPF grade B, postoperative complications grade III were significantly fewer in the scalpel group (15%) than in the UAS group (45%). In terms of the amylase level of drainage fluid, there was a tendency for the amylase level in the scalpel group to be higher than in the UAS group on POD 1, although statistical significance was not reached (Table 2; Fig. 4). Afterward, however, the fluid amylase level of the scalpel group declined sharply and reversed to a relatively lower amylase level than that of the UAS group on POD 3 and 5. To identify risk factors for POPF grade B, a possible correlation between POPF grade B and patient and operative factors were analyzed in all 93 patients with soft pancreas who underwent PD (Table 3). In the univariate analysis, BMI 25 kg/m2 (P < 0.01), MPD diameter 3 mm (P < 0.01), and pancreas transection by UAS (P < 0.01) were significantly correlated with POPF grade B. These three factors were entered into multivariate analysis with a multiple logistic regression model. BMI 25 kg/m2 (P ¼ 0.02), MPD diameter 3 mm (P < 0.01), and pancreas transection by UAS (P < 0.01) were all shown to be predictors for occurrence of POPF grade B.
Fig. 4 e Amylase level of drain fluid at 1, 3, and 5 d after surgery according to measure of pancreas transection. The amylase level in the scalpel group (34,196 IU/L) tends to be higher than that in the UAS group (25,943 IU/L) on POD 1 (not significant). On POD 3 and 5, however, the fluid amylase level of the scalpel group declined sharply and reversed to a relatively lower amylase level than that of the UAS group.
Discussion Although progress in pancreatic surgery has notably decreased morbidity after PD, POPF has not yet been fully overcome, sometimes leading to serious complications and even to treatment-related death [4,5,7]. The method of pancreas transection is considered one of the factors involved in the occurrence of POPF because the method of pancreas transection would influence the occurrence of minor pancreatic fistula, which originates from pancreatic duct branch or parenchyma at the pancreas cut surface [18]. Pancreatic juice escaping from a minor fistula at the transection surface would sometimes autodigest the pancreatic ductedigestive tract anastomosis and result in major POPF when pancreatic ductto-mucosa anastomosis is performed. Therefore, how the pancreas is transected is presumably significant in preventing POPF, especially in soft pancreas, which is frequently associated with POPF. To decrease the development of pancreatic fistula from the pancreas transection surface, various methods have been attempted for pancreas transection, such as use of the cavitron ultrasonic surgical aspirator [16,25], crush-clamping [26], and a sharp, hook-shaped ultrasonically activated scalpel [19] although pancreatic transection has also been conventionally performed using a surgical scalpel or electrocautery [18]. In terms of stump management in distal pancreatectomy, bipolar scissors [27] and bipolar radiofrequency [28] have also been evaluated. Although a low incidence of POPF incidence has been reported by applying the aforementioned methods, those results were seen only in small, one-arm, single-institutional studies. A standard procedure for pancreatic transection has not yet been established.
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Table 3 e Risk factors for POPF ‡ grade B (ISGPF classification) in pancreas with soft texture. Factor
POPF grade B ()
(þ)
U-analysis P
Gender Male 41 21 0.43 Female 23 8 Age 65 38 17 0.99 <65 26 12 BMI (kg/m2) 25 7 10 <0.01 <25 57 19 ASA PS 2 40 22 0.21 1 24 7 Operative time (h) 7 11 4 0.47 <7 53 25 Estimated blood loss (mL) 1000 15 8 0.67 <1000 49 21 Transfusion Yes 9 3 0.62 No 55 26 Preoperative biliary drainage Yes 29 14 0.78 No 35 15 Pancreatic adenocarcinoma Yes 18 8 0.96 No 46 21 MPD diameter (mm) >3 17 1 <0.01 3 47 28 Operative method PD 6 3 0.58 SSPPD 58 26 PV resection Yes 58 29 0.10 No 6 0 Method of pancreas transection UAS 38 28 <0.01 Scalpel 26 1
Multivariate analysis OR
95% CI
4.92
1.29e18.7
0.02
0.002
0.01e1.14
<0.01
2.30e166.43
<0.01
19.55
P
ASA ¼ American Society of Anesthesiologists; CI ¼ confidence interval; ISGPF ¼ International Study Group for Pancreatic Fistula; OR ¼ odds ratio, PS ¼ physical status, SSPPD ¼ subtotal stomachpreserving pancreaticoduodenectomy; U-analysis ¼ univariate analysis.
Use of an ultrasonically activated device is one of the new transection methods expected to reduce the incidence of POPF. The blade of a UA device vibrates longitudinally at 55,000 times per second. These vibrations generate heat energy, which enable tissue to be cut and coagulated simultaneously. Vessels and ducts up to 5 mm in diameter are expected to be sealed by UA shears. Pancreas transection by UA shears has been initiated in expectation of good hemostasis and sealing of the pancreatic duct branches at the transection surface. Takao et al. [17] reported no POPF after 39 pancreatogastrostomies and two pancreaticojejunostomies when the UA scalpel was used in pancreatic transection although the diameter of the MPD was less than 2 mm in 29%
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of the 41 study patients. Takao et al. assumed that the stumps of the small pancreatic ducts on the transection surface might have been sealed by the UA scalpel, consequently preventing the development of a pancreatic fistula from the transection surface. Considering other advantages such as good hemostasis and availability for endoscopic surgery, UA device transection is considered to be a promising method for pancreatic transection. In the present study, we evaluated the effectiveness of UAS by comparing the occurrence of POPFs among UAS transections and scalpel transections in patients with soft pancreatic texture. The incidence of all-grade POPF and that of grade B were significantly higher in the UAS group (74%, 42%) than in the scalpel group (52%, 4%). Although we hypothesized that pancreas transection by UAS reduced POPF compared with scalpel, our study does not support the hypothesis. On the contrary, the results indicated that UAS transection was more associated with POPF than scalpel transection. Several possible explanations could account for the fact that UAS transection was more associated with POPF than scalpel transection. Ultrasonically activated scalpel produces high blade temperatures and can damage adjacent tissues or organs [29e31]. In an experimental study with swine, histologic examination revealed that UAS dissection caused serious injuries to various structures [32]. A recent study compared pancreatic injury responses according to method of pancreatic transection either with UAS, electrocautery, or surgical scalpel in a rat model [21]. The study showed that resection with a surgical scalpel induced less tissue injury than with UAS or electrocautery. The depth of coagulation necrosis or acinar cell necrosis when the pancreas was transected by UAS or electrocautery was deeper than when the pancreas was transected by a surgical scalpel. Moreover, in laparoscopic gastrectomy, collateral thermal damage to the pancreas by ultrasonic instruments during lymph node dissection was reported [33,34]. The amylase concentrations of the drainage fluid on POD 1 and 3 were significantly higher in laparoscopic gastrectomy using UAS than those in open gastrectomy using electric cautery. There was also a tendency that clinically relevant pancreatic fistula was more frequent in laparoscopic gastrectomy using UAS than that in open gastrectomy using electric cautery [34]. Considering the aforementioned results, pancreas injury to some depth by UAS might directly induce POPF grade B by means of worsening minor fistula. Curiously, the amylase level of the drainage fluid in the scalpel group was higher than that of the UAS group on POD 1; however, the amylase level declined sharply and reversed to a relatively lower amylase level than that of the UAS group on POD 3 and 5. A high fluid amylase level on POD 1 in both the UAS and scalpel groups may indicate that minor fistula at the transection surface frequently occurs after any method used for pancreas transection in patients who undergo PD for soft pancreas. However, the fluid amylase level decreased greatly on POD 3 and 5 in patients who did not suffer clinical POPF. Accordingly, prevention of major POPF might partly depend on wound healing at the pancreatico-digestive tract anastomoses, which attributes to immediate recovery from minor pancreatic fistula originating from pancreatic duct branch or parenchyma at the pancreas cut surface. It is possible that tissue injury caused by UAS has a negative influence on normal
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wound healing, which involves complicated interactions of various cells and cytokines [35], and might increase the rate of clinical POPF by disruption of the duct-to-mucosa anastomosis through persistence of minor pancreatic fistula. In the present era of innovation, various medical devices have been applied for pancreas transection to gain good hemostasis and produce a robust seal on small pancreatic duct branches at the transection surface. However, the results of the present study indicate that simple scalpel pancreas transection was superior to pancreas transection by UAS in reducing the incidence of clinical POPF, which sometimes causes serious complications and incurs a large financial cost. Avoiding tissue damage must be kept in mind during future development of a medical device suitable for transection in soft pancreas. The main limitation of the present study is that it was a nonrandomized study in a single-center setting. The study took into account the issue of surgeons’ experience or differences in skill. All surgeons in the present study were experienced. They devoted time to mastering each method, and then, they selected favorable methods to be applied for the next period. Interestingly, one of the surgeons who participated in the present study experienced clear improvement in the incidence of POPF by returning to scalpel transection from UAS transection. However, it cannot be excluded that part of the better outcome in the scalpel group was because of an increase in experience or differences in each surgeon’s skill. A minutely designed, randomized, multicenter study is greatly desired to confirm the present results. In summary, scalpel transection was less associated with POPF than UAS transection in patients who underwent PD for soft pancreas. How the pancreas is transected plays a role just as important as the method of anastomosis in reducing the incidence of POPF. Rapid wound healing at the pancreas cut surface might be crucial for safe pancreatico-digestive tract anastomoses.
[11]
Acknowledgment
[12]
This work was supported by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development, AMED (15Ack0106154h0001) and the National Cancer Center Research and Development Fund (25-B-8). Authors’ contributions: S.T. had full access to all the data and takes responsibility for data integrity and accuracy of the data analyses. All the authors contributed to the study concept and design and did the acquisition of data. S.T. did the drafting of the article. N.G., Y.K., and M.K. did the critical revision of the article.
Disclosure
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[13]
[14]
[15]
The authors declare no conflict of interest. [16]
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