Introduction

Pancreatoduodenectomy (PD) applied as a standard surgical approach for both benign and malignant tumors of the pancreatic head and periampullary carcinoma has benefitted most patients. In the last two decades, the popularization of PD certainly profits from not the improvement of surgical techniques and instruments but the perioperative management significantly reducing the mortality rate after PD. Furthermore, several large medical records have nearly reached a zero mortality rate1,2. However, many patients must endure the complications after operation, which include pancreatic fistula, delayed gastric emptying,postoperative pancreatic fistula (POPF)-related hemorrhage,intra-abdominal and pleural effusions, wound infection,bacteremia, and septic shock. Although the incidence of postoperative complications showed a downward trend, the desired result is still difficult to achieve3,4. POPF is considered as the most common and threatening complication, which can cause potential secondary infection,long-term hospitalization, and serious economic burden5.Numerous relevant literatures have reported that the occurrence of POPF is not only related to the patients’ own features such as higher body mass index (BMI), soft texture of the pancreas, small pancreatic duct diameter, and high blood loss6-8, but is also influenced by the anastomosis method in pancreatojejunostomy (PJ)9-11. Thus, the most urgent issue in improving postoperative condition is the development of a safer and more effective anastomotic method.

Currently, various anastomotic techniques and differences still exist in PJ. Blumgart anastomosis (BA) using a U-suture technique has attracted great attention and has been proved to be a common and effective technique12-14. On the basis of the limitation of complex operation procedures in the conventional BA (c-BA), many surgical specialists simplified the procedures and achieved satisfactory results5,15,16. In our study, to improve the original method, we made a further change by using firm ligation of a supporting tube and the main pancreatic duct to replace the pancreatic duct-tojejunum mucosa anastomosis of the c-BA.

In this study, we attentively present the m-BA in detail.Furthermore, we made a synthetic comparison of the m-BA and c-BA to analyze the advantages of the m-BA in improving the surgical procedure and postoperative complications.

（2）能够将一些似是而非的因素加以区分，并利用关联函数计算方法，在临界阈值上加以界定，避免了因为一些微小区别而产生的判断误区。

Patients and methods

Patient selection

Between October 2011 and October 2015, 147 consecutive patients who underwent PD using BA in the Department of Hepatobiliary Surgery at Tianjin Medical University Cancer Institute and Hospital were enrolled in this study. According to the type of PJ, 50 patients underwent the modified BA (m-BA; the modified group) and the remaining 97 patients underwent the conventional BA (c-BA; the conventional group) in this retrospective study. No invasion of the superior mesenteric vessels, and distant and portal vein metastases were found in all the patients. The two patient cohorts were compared, and the evaluated variables were operation time, the incidence rate of POPF, postoperative hospital stay (POHS), and other perioperative complications.

当细白的蟹肉与Bin311在舌尖上不期而遇，便开始成就一场味蕾的盛宴：霞多丽清新而爽口的果香，弥漫着桃子与梨皮的气息，化解了蟹膏的浓腻，唇齿留香；冷凉产区溯源地的葡萄提供了脆爽而持久的酸度，不仅解腻而且还提升了蟹的鲜美；经由橡木桶的“画龙点睛”而呈现出燧石的复杂度与乳脂般质地的酒体，更是与蟹的甜美交相呼应并将其所有的鲜味唤醒，令人愉悦。一眨眼的功夫，佐以干白，几屉蟹便已全部食得干净，回味无穷。

Surgical technique

All the 147 patients underwent the standard PD performed by experienced chief physicians. The patients in the m-BA group underwent operation by our principal researcher, and in the other group, the operation was performed by two experienced surgeons in our department. The primary lesions were either distal common bile duct or periampullary carcinomas without vascular invasion. The surgical procedure of the c-BA was similar to the classic technique reported previously12-14. Between the modified group or conventional group, no substantial differences in gastrointestinal anastomosis and cholangiojejunostomy were found, except for pancreaticojejunostomy. Two drainage tubes were respectively placed at the underside of the pancreaticojejunostomy and cholangiojejunostomy by routine.

Modified Blumgart anastomosis

The vital sign and drainage of each tube were carefully monitored postoperatively. Prophylactic antibiotics,including second- or third-generation cephalosporin, was routinely administered, but postoperative administration of octreotide was not conventional. On the first postoperative day, bacterial examination, including aerobic and anaerobic bacterial cultures, of drainage fluid was routinely performed.At 3, 5, and 7 days, the amylase levels were measured. Blood culture, routine blood test, and abdominal ultrasonography were immediately performed if the patient had a fever. POPF was diagnosed and graded in accordance with the International Study Group on Pancreatic Fistula (ISGPF)classification 201617. Biochemical fistula POPF was defined as“measurable fluid output on or after postoperative day 3,with an amylase content higher than 3 times the upper normal serum level, ” which has no impact on the normal postoperative pathway and POHS. Clinically significant POPF are of grades B and C. Grade B POPF requires a change in the management of the expected postoperative pathway.Whenever reoperation is needed or organ failure occurs, the fistula shifts to a grade C POPF.

Postoperative management and assessment of POPF

Figure 1 The operation sketch map of the modified Blumgart anastomosis. (A) The MPD was freed adequately up to 1–1.5 cm and then a short anesthetic extension tube was inserted in the MPD through the opening cut in advance. (B) A 5–0 polypropylene suture that transverse sutured the pancreatic parenchyma was entwined 2–4 laps on the overlapping parts of the internal stent and the MPD, then fasten it. (C-E) The establishment of the U-sutures.

Figure 2 The operation pictures. (A) The mobilization of the main pancreatic duct (MPD). (B) The supporting tube was inserted in MPD from the side wall opening. (C) To make the internal stent and the MPD fully fixed, a 5–0 polypropylene suture that transverse sutured the pancreatic transaction was entwined 2–4 laps on the overlapping parts of the internal stent and the MPD, then fasten it.

(1) Mobilization of the main pancreatic duct (MPD):mutilation of the pancreatic parenchyma was performed with an electrotome. Small bleeding spots and small branches of pancreatic ducts according to its thickness were managed with electrical coagulation or ligated with 5-0 monofilament stitches. The MPD was freed carefully with a clamp technique, and its length was adequately up to 1–1.5 cm. (2)Placement and fixation of the MPD supporting tube: a small opening was cut with ophthalmic forceps on the side wall of the exposed MPD, and then a short anesthetic extension tube was inserted in the MPD in advance from the opening, acting as the internal stent, which used to drain the pancreatic fluid to the intestinal tract through a small opening in the jejunum(Figure 1A). To fully fix the internal stent and MPD, a 5-0 polypropylene suture that transverse sutured the pancreatic parenchyma was entwined for 2–4 rounds on the overlapping parts of the internal stent and MPD, and then fastened(Figure 1B and 2). (3) Establishment of U-sutures: five or six double-armed 3-0 polypropylene sutures were pierced through the pancreatic stump from front to back, nearly 1 cm lateral to the previous sutures, and then reverted through the posterior part of the pancreatic stump after the seromuscular layer of the jejunum was bitten (Figure 1C).The sutures should be clear of the MPD to avoid unnecessary damage. U-sutures were placed without tightening on the surface of the pancreas and held with rubber shod clamps separately. (4) Tightening of the U-sutures: One needle of the double-armed 3-0 polypropylene sutures was longitudinally sutured through the seromuscular layer of the jejunum(Figure 1D). The previous U-sutures were tightened gently and knotted in case of laceration of the pancreas. Here, we used the ventral wall of the jejunum to cover the pancreatic stump (Figure 1E).

Data collection and outcome measures

The clinical related data collected and analyzed included age,sex, preoperative serum albumin, BMI, and preoperative biliary drainage. The following factors associated with POPF due to the operation were also recorded attentively:pancreatic texture, diameter of the MPD, pathological diagnosis, operation time, blood loss volume, and perioperative blood transfusion. The main end points were the incidence rate of clinically significant POPF according to the ISGPF definition and the duration of POHS. The secondary end point included some postoperative complications (delayed gastric emptying, POPF-related hemorrhage, intra-abdominal and pleural effusions, wound infection, bacteremia, septic shock, and in-hospital mortality) and readmission within 30 days after discharge.

Statistical analysis

In addition, we analyzed the factors that influenced the incidence of POPF. In the univariate analysis, BMI, and MPD diameter were associated with POPF. Furthermore, the multivariate analysis revealed that only BMI was a significant factor. However, the influences of preoperative biliary drainage, pancreatic texture, anastomosis method (m-BA),operation time, intraoperative blood loss, perioperative blood transfusion, and pathological diagnosis of POPF were not significant. The correlation between BMI and POPF is still controversial. Del Chiaro et al.23 mentioned that obesity increased not only the risk of POPF but also the difficulty of operation and blood loss, but some literatures considered that no necessary correlation existed between BMI and POPF24,25. Our study shows that BMI was associated with POPF both in the univariate anal multivariate analyses.Moreover, our study also found a significant correlation between pancreatic duct diameter and POPF in the univariate analysis, while that in the multivariate analysis was not significant. This may be related to the routine use of a

Results

Patient demographic

BA has been applied in PD since 2010 in our department.We noticed that during BA, duct-to-mucosa anastomosis was quite difficult to successfully perform in a relatively narrow space, especially when confronting a relatively small pancreatic duct. More seriously, the tightening of the suture may cause tearing of the fragile pancreatic duct, which increases the possibility of POPF. Lastly, a discontinuous pinhole of the MPD may become a potential outflow channel that increases the risk of pancreatic leakage when the pancreatic duct pressure increased. On the basis of the abovementioned considerations, we modified the original method of duct-to-mucosa anastomosis. The advantages of the m-BA are mainly as follows: (1) we first freed the main pancreatic duct and then placed the supporting tube in to support and fully secure the MPD, which had adequate operation space;(2) the m-BA simplified the process of duct-to-mucosa anastomosis and shortened the time while also avoiding tearing of the MPD to minimize a potential POPF; (3) owing to a certain free length of the MPD into the jejunum, the supporting tube will flow directly into the jejunum in spite of a small amount of pancreatic leakage.

切片时长的大小对预测结果有很大的影响.本次实验进行了两轮,预测结果均为单节点对间的链路状态,第一轮实验验证切片时长获取方法的合理性,设定不同的切片时长T1、T2、T3与式(1)计算所得的最优时长TR进行对比,这四种时长分别为180s、240s、480s和320s.第二轮实验则与文献[21]中切片效果作对比,TS1、TS2、TS3均为该文献中使用的切片时长,分别为300s、600s和1800s,实验结果如图10、11所示.

Postoperative complications

POPF is one of the most challenging complications that are closely related to perioperative death in PD. Even in centers with high volume of pancreatic surgical cases, absolute safety is difficult to achieve. To reduce the occurrence of POPF,many domestic and foreign experts have performed numerous anastomotic and gastrointestinal reconstruction techniques18-20. In recent years, BA, which uses the jejunum as a buffer pad to prevent pancreatic laceration when knotting the sutures, has gradually stood out and has beenaccepted increasingly by more medical centers13. To further simplify the rigmarole of BA, Oda et al.16 tightened U-sutures after duct-to-mucosa anastomosis without knotting them and then took two needles, respectively passing them through the seromuscular antimesenteric edge of the jejunum and bringing the jejunum to cover the front of the pancreatic cut edge to finish knotting, which was defined as the one-step Blumgart method. Fujii et al,5 on the basis of the method of Oda et al,16 attempted to further reduce the U-sutures to 1 to 3 sutures, making it a safe and simple method.

Risk factors for POPF

The risk factors for POPF are shown in Table 3. The univariate analysis revealed that BMI (≥25 kg/m2; P = 0.009)and MPD diameter (＜3 mm; P = 0.019) were associated with POPF. However, the multivariate analysis revealed that only BMI (≥25 kg/m2; P = 0.046) was an independent risk factor for clinically significant POPF. We particularly wanted to confirm that the anastomosis methods were not related to the occurrence of pancreatic leakage (P ＞ 0.05). However, as described earlier, the time in the m-BA group was much shorter than that in the c-BA group, with a significant difference (P ＜ 0.001).

Discussion

The postoperative complications in the two groups are shown in Table 2. POPF occurred in 6 patients in the m-BA group, among whom were 6 (12.0%) and 0 with ISGPF grade B and C POPF. In the c-BA group, 10 patients had a pancreatic fistula, and 10 (10.3%) and 0 had ISGPF grade B and C POPF, respectively. No significant difference in the incidence of clinically relevant POPF was found between the two groups (P ＞ 0.05). In addition, the incidence rates of other postoperative complications, including delayed gastric emptying, POPF-related hemorrhage, intra-abdominal and pleural effusions, wound infection, bacteremia, and septic shock, were essentially similar between the two groups (P ＞0.05). No in-hospital death occurred in the m-BA group,while one patient died of infection caused by POPF in the c-BA group. The POHS durations in the m-BA and c-BA groups were 23 ± 8 and 22 ± 10 days, respectively, showing no significant difference (P ＞ 0.05).

将该养殖场病死的5头猪解剖后，发现病变器官主要在呼吸道系统，鼻粘膜、喉头黏膜、气管黏膜、支气管黏膜高度充血肿胀，在黏膜表面附着粘稠状的液体。将心包和胸腔打开后，可发现内部具有大量纤维素性浆液；纵隔淋巴结、支气管淋巴结肿大出血；所有病死猪肺脏存在不同程度的病变，大多发生在尖叶、心叶、中间叶、隔叶的背部和基底部，病变部位呈现紫红色，质地坚硬，向内凹陷，病灶周围的肺脏组织呈现苍白色，气肿明显，病变部位和健康部位界限明显[1]。所有病死猪肺间质增宽，出现炎症变化；脾脏轻微肿大，胃肠黏膜充血出血，并呈现卡他性炎症病变，其中十二指肠充血更为明显。

Table 1 Demographic, characteristics and operational indexes of the patients

PC: pancreatic cancer; DBC: distal bile duct cancer; DC: duodenal carcinoma; AC: ampullary carcinoma; MPD: main pancreatic duct; BA:Blumgart anastomosis.

Characteristics Conventional group (n=97) Modified group (n=50) P Age, years 0.068＜65 57 (58.8%) 37 (74.0%)≥65 40 (41.2%) 13 (26.0%)Gender (male/female) 58/39 30/20 0.981 BMI (kg/m2)＜25 64 (66.0%) 34 (68.0%) 0.806≥25 33 (34.0%) 16 (32.0%)ALB (g/L)＜40 44 (45.6%) 23 (46.0%) 0.941≥40 53 (54.4%) 27 (54.0%)Preoperative biliary drainage 17 (17.5%) 21 (42.9%) 0.001 Disease PC 36 (37.1%) 14 (28.0%) 0.601 DBC 15 (15.5%) 12 (24.0%)DC 15 (15.5%) 10 (20.0%)AC 12 (12.4%) 6 (12.0%)Others 19 (19.6%) 8 (16%)Operation Pancreaticojejunostomy anastomosis time, min (mean±SD) 32±4 11±1 ＜0.001 Surgical time (min) 0.276＜300 55 (56.7%) 33 (66.0%)≥300 42 (43.3%) 17 (34.0%)Blood loss (mL)0.941＜400 72 (74.2%) 37 (74.0%)≥400 25 (25.8%) 13 (26.0%)Blood transfusion, yes 68 (70.1%) 20 (40.0%) ＜0.001 Pancreatic texture Hard 58 (59.8%) 25 (50.0%) 0.257 Soft 39 (40.2%) 25 (50.0%)MPD (mm)＜3 12 (12.4%) 16 (32.0%) 0.004≥3 85 (87.6%) 34 (68.0%)

Table 2 Pancreatic fistula and perioperative complications of pancreatoduodenectomy patients

POPF: postoperative pancreatic fistula; POHS: postoperative hospital stay

Conventional group (n=97) Modified group (n=50) P Pancreatic fistula (ISGPF) 0.682 None 87 (89.7%) 44 (88.0%)B 9 (9.3%) 6 (12.0%)C 1 (1.0%) 0 Delayed gastric emptying 7 (7.2%) 4 (8.0%) 0.864 POPF related hemorrhage 0 0 NA Intra-abdominal effusion 19 (19.6%) 6 (12.0%) 0.246 Pleural effusion 10 (10.3%) 2 (4%) 0.186 Bacteremia 4 (4.1%) 1 (2.0%) 0.501 Wound infection 1 (1.0%) 0 0.471 Septic shock 1 (1.0%) 1 (2.0%) 0.631 Readmission 1 (1.0%) 0 0.471 In-hospital mortality 1 (1.0%) 0 0.471 POHS 22±10 23±8 0.289

The patient’s demographic characteristics are shown in Table 1. No significant differences in the main variables,namely age, sex ratio, BMI, preoperative serum albumin level, pancreatic texture, pathological diagnosis, operation time, blood loss volume, and perioperative blood transfusion,were found. Our statistical results demonstrate that a MPD of＜3 mm accounted for a larger proportion in the m-BA group than in the c-BA group (32.0% vs 12.0%, P = 0.004).Moreover, most people in the m-BA group received preoperative biliary drainage (17.5% vs 44.0%, P ＜ 0.001).The duct-to-mucosa anastomosis time in the m-BA group was 11 ± 1 min, which was apparently shorter than that in the c-BA group (32 ± 4 min, P ＜ 0.001). Operation time showed no significant difference between the two groups(P ＞ 0.05), which may be due to the time of duct-to-mucosa anastomosis being just a part of the entire operation time.

This study was conducted to compare the m-BA with the c-BA for the first time . We analyzed and compared operation time, the incidence rate of clinically relevant POPF,and the POHS of the two groups. For the operation time, the mean time in the m-BA group was shorter than that in the c-BA group; however, the smaller time gap between the two groups was masked by the lengthy operation procedure. The incidence of clinical relevant POPF was similar between the two groups (12% vs 10.3%), which was consistent with previous reports21,22. There were no significant differences in POHS duration and other complications of the two groups.In summary, the m-BA, as a convenient method for duct-tomucosa anastomosis, did not increase the risk of pancreatic leakage and related complications.

All statistical analyses were performed using SPSS version 23.0 (IBM, USA). Continuous variables were expressed as mean ± SD and compared using the Student's t-test. The Chi-square test and Fisher exact test were applied to the categorical variables. The factors associated with POPF were evaluated in the univariate and multivariate analyses by using the Chi-square test and logistic regression analysis,respectively. A P-value of ＜0.05 was considered statistically significant.

supporting tube in MPD26. In conclusion, patient characteristics play an important role in POPF.

在大数据时代城乡规划学走向计量化的过程中，个人方面也面临着相应的挑战，即隐私保护。具体表现为：大数据时代城乡规划计量中涉及海量的数据，使大量的个人信息被采集，从而对个人隐私安全状况产生了潜在威胁。在此期间，个人隐私保护工作将会面临较大的工作压力，无形之中使城乡规划学走向计量化的过程中面临着相应的挑战，即能否满足个人隐私保护方面的实际要求，确保城乡规划计量工作落实的有效性。

Table 3 Risk factors of POPF

Factors n POPF rate (%)Univariate Multivariate χ2 P HR 95% CI P Sex 0.052 0.820 Male 10 62.5 Female 6 37.5 Age (year)0.461 0.497＜65 9 56.3≥65 7 43.8 BMI (kg/m2)6.873 0.009＜25 6 37.5≥25 10 62.5 3.682 1.235-10.979 0.019 ALB (g/L) 0.024 0.876＜40 7 43.8≥40 9 56.2 Preoperative biliary drainage (yes)0.455 no 13 81.3 0.558 yes 3 18.7 Pancreatic texture 0.266 0.755 Hard 10 62.5 Soft 6 37.5 MPD (mm)3.965 0.046＜3 6 37.5 2.664 0.848-8.371 0.094≥3 10 62.5 Anastomosis method 0.097 0.755 Conventional 10 62.5 Modified 6 37.5 Surgical time (min)0.590 0.442＜300 11 68.8≥300 5 31.2 Blood loss (mL)1.271 0.260＜400 10 62.5≥400 6 37.5 Perioperative blood transfusion 1.712 0.191 No 4 25.0 Yes 12 75.0 Pathological diagnosis 24.258 0.760 PC 5 31.3 DBC 3 18.8 DC 6 37.6 AC 1 6.3 Others 1 6.3

The m-BA has no distinct advantage over c-BA in reducing the rate of pancreatic fistula. Many factors affect pancreatic fistula, one of which is anastomotic mode. In addition, c-BA

has significantly reduced the incidence of pancreatic fistula12-14,which is difficult to surpass. Patient characteristics also play an important role in POPF. The m-BA is equal to the c-BA in terms of the incidence rate of pancreatic fistula, but it is simple, reliable, and suitable for any type of pancreatic fistula. Moreover, it requires a short learning period and has been applied to robotic pancreaticoduodenectomy safely and feasibly. Compared with the multicentral randomized controlled study, the evidence from our prospective (to some extent) but not randomized study might not be adequately sufficient. However, the safety and effectiveness of the m-BA is apparent and irreplaceable. Our study has limitations that need further improvement, including the small number of study cases. A single-center randomized controlled study is probably best to further confirm our conclusion.

As we mentioned earlier, the m-BA using firm ligation of the supporting tube and MPD to replace the pancreatic ductto-mucosa anastomosis is a simple, safe, and reliable operation method without sacrifice of surgical quality. In conclusion, the m-BA has a relatively high clinical value to reduce the duct-to-mucosa anastomosis time with no increased risk of POPF.

Conflict of interest statement

No potential conflicts of interest are disclosed.

知识服务是一种针对特定问题的决策支持活动，需要就用户关心的相关领域和复杂问题，全面、系统、准确地分析相关领域的历史与现状、问题与原因，并由此提供解决之道，而这些工作仅靠信息检索、内容组织、数据挖掘，难以很好地实现，人工智能等关键技术的应用将会为知识服务的快速发展提供有力的技术支持。知识管理工具能够帮助机构对复杂问题做出正确的决策在人工智能等关键技术取得广泛应用的背景下，将获得行业的高度重视，并获得广阔的应用前景。

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