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Influencing factors of biliary fistula after radical resection of hilar cholangiocarcinoma: a prospect cohort

European Journal of Medical Research volume 27, Article number: 214 (2022) Cite this article

Abstract

Background

Biliary fistula is a common but serious complication after radical resection of hilar cholangiocarcinoma. We aimed to evaluate the influencing factors of biliary fistula after radical resection, to provide insights to the clinical treatment of hilar cholangiocarcinoma.

Methods

Patients undergoing radical resection of hilar cholangiocarcinoma from January 1, 2015 to March 31, 2022 were selected. Patients’ personnel characteristics and laboratory test results of patients with and without biliary fistula were collected and compared. Logistic regression analyses were conducted to evaluate the associated risk factors of biliary fistula.

Results

160 patients undergoing radical resection of hilar cholangiocarcinoma were included, the incidence of postoperative biliary fistulas was 20.63%. There were significant differences in the age, preoperative cholangitis and number of biliary anastomosis between biliary fistula and no biliary fistula patients (all p < 0.05). There were significant differences in the gamma glutamyl transpeptidase (GGT) on the first day after surgery, Klebsiella pneumoniae between biliary fistula and no biliary fistula patients (all p < 0.05). Logistic regression analysis indicated that age ≥ 65 years (OR  2.035, 95%CI 1.131–3.007), preoperative cholangitis (OR 1.584, 95% CI 1.081–2.361), number of biliary anastomosis ≥ 2(OR 2.866, 95%CI 1.942–3.624), GGT on the first day after surgery ≥ 120 U/L (OR 1.823, 95%CI: 1.274–2.906), preoperative bile culture for Klebsiella pneumoniae (OR 3.181, 95%CI: 2.426–3.992) were the risk factors of postoperative biliary fistulas (all p < 0.05).

Conclusions

There are many independent risk factors for postoperative biliary fistula in patients undergoing radical resection of hilar cholangiocarcinoma. Clinical medical workers should take early interventions and treatment measures for these high-risk patients to reduce the occurrence of postoperative biliary fistula.

Introduction

Hilar cholangiocarcinoma is the most common malignant tumor of the biliary tract, which has the characteristics of special location, insidious onset, and complex structure [1, 2]. Diagnosis and treatment of hilar cholangiocarcinoma have always been one of the difficult problems in surgery. In recent years, the incidence of hilar cholangiocarcinoma has been on the rise [3, 4]. With the advancement of imaging and hepatobiliary surgery technology, the surgical resection rate and prognosis of the disease have been significantly improved. The concept of surgical treatment for the disease tends to expand the scope of resection and to achieve the effect of radical tumor resection [5]. Especially for the common Bismuth type IIIa, IIIb and IV, it is often necessary to combine left and right liver and caudate lobe resection to achieve negative resection margins and achieve the effect of radical tumor resection [6]. The invasion of surrounding tissues and organs requires combined vascular resection and reconstruction or pancreaticoduodenectomy [7]. Therefore, the safety and effect of resection of hilar cholangiocarcinoma have been the focus of surgeons.

In recent years, despite the continuous improvement of surgical skills and perioperative management, the incidence of biliary fistula radical resection of hilar cholangiocarcinoma can up to 39.16%, which is much higher than that of simple hepatectomy (4.04–16.85%) [8,9,10]. The occurrence of postoperative biliary fistula will lead to prolonged hospital stay, delayed adjuvant therapy, increased economic burden and perioperative mortality [11,12,13]. Some studies [14, 15] have pointed out that postoperative biliary fistula can also affect the long-term survival of patients. According to the definition and grading of postoperative biliary fistula by the International Study Group of Liver Surgery (ISGLS) [16], grade A biliary fistula has a short course (< 7 days) and hardly affects the postoperative management of patients, while biliary fistulas of grades B and C are closely related to the clinical situation, which usually means a protracted disease course or a change in treatment decisions. Therefore, early identification of grade B and C biliary fistulas and effective intervention are of great clinical significance to the progress of postoperative patients with hilar cholangiocarcinoma. Currently, the influencing factors of biliary fistula after radical resection of hilar cholangiocarcinoma remain unclear. Therefore, we prospectively analyzed the characteristics and laboratory test results of patients undergoing radical resection of hilar cholangiocarcinoma in our hospital, to analyze the risk factors of clinically relevant biliary fistula after radical resection of hilar cholangiocarcinoma, to provide reliable evidence to the clinical management and treatment of hilar cholangiocarcinoma.

Methods

Ethics

In this study, all methods were performed in accordance with the relevant guidelines and regulations. This study was a prospective cohort design. This present study had been verified and approved by the ethical committee of The First Affiliated Hospital of Bengbu Medical College with approval number: 2021230. And written informed consents had been obtained from all the included patients.

Patients

We selected patients who underwent radical resection of hilar cholangiocarcinoma in our hospital from January 1, 2015 to March 31, 2022 as the research population. The inclusion criteria of patients were as follows: (1) the pathological results indicated the diagnosis of hilar cholangiocarcinoma; (2) patients received radical surgery including partial hepatectomy, extrahepatic bile duct resection, regional lymph node dissection and Roux-en-Y biliary anastomosis performed by the same group of surgeons; (3) the patients had complete clinical and pathological data; (4) patients agreed to participate in this study. The exclusion criteria of patients were as follows: (1) patients with incomplete data; (2) patients did not agree to participate in this study.

Patient management

After admission, the clinical diagnosis and treatment plan were determined by multidisciplinary discussion of hepatobiliary and pancreatic diseases. The patient's nutritional status was reassessed weekly and nutritional support regimens adjusted. For patients with preoperative infection, the operation should be performed after the infection has been effectively controlled (normal body temperature > 72 h, clinical symptoms are relieved, and the results of routine laboratory tests were in the normal range). Prophylactic antibiotic ceftriaxone sodium 2 g was routinely given 30 min before surgery.

All the included patients received the same surgical procedure, and the surgery was performed by the same group of surgeons. Preoperative laparoscopic exploration was performed to assess resectability in patients with peritoneal carcinomatosis. All patients underwent partial hepatectomy, extrahepatic bile duct resection, regional lymph node dissection, No. 9 and No. 16 lymph node biopsies, and Roux-en-Y cholangiojejunostomy. Anatomical hepatectomy was used during the operation. For the blood vessels of the preserved side liver, fine dissection and suspension protection were routinely performed during the operation. Before the end of the operation, the blood flow was routinely checked by intraoperative Doppler ultrasonography. During liver incision, the Pringle method was used to block the blood flow into the liver. The ultrasonic suction device combined with the fine clamp method was used to cut off the liver parenchyma. During the intraoperative assessment of the edge of the hepatic duct resection, additional duct resections were performed to achieve R0 resection. The pipe structures with a diameter of < 0.5 cm were clamped with titanium clips, and the pipe structures with a diameter of > 0.5 cm were clamped with titanium clamps. The oxidized cellulose was used to close the cut plane of the liver parenchyma. The bile duct and the jejunum bridge were sutured end-to-side with 5-0/6-0 PDS sutures for continuous cholangioenteric anastomosis. The liver section was carefully examined without active bleeding or biliary fistula.

Biochemical, bacterial smear and culture examinations were performed on the peritoneal drainage fluid on the 1st, 3rd, and 7th days after the operation, and blood biochemical examinations were performed at the same time. Follow-up monitoring was performed at least once a week until the peritoneal drainage tube was removed. Biochemical tests were performed immediately when bile-like fluid was observed to drain from the drain. For patients with postoperative biliary fistula, the formulation and change of treatment measures were ultimately decided by the multidisciplinary discussion of our medical teams according to the conditions of patient.

Observation indicator

The diagnostic criteria for biliary fistula were that after 3 days after operation, the total bilirubin (TBil) of peritoneal drainage fluid was > 3 times the serum level of the same period, or intervention or secondary surgery was required due to biliary peritonitis [16, 17]. According to the ISGLS definition [15], bile leakage was diagnosed and graded into A, B and C levels based on severity. The diagnostic criteria for cholangitis were systemic inflammation, cholestasis, and imaging evidence of at least one each. Systemic inflammatory manifestations including: (1) fever (body temperature > 38 °C) and/or chills; (2) laboratory support, including white blood cell (WBC) count < 4 × 109/L or > 10 × 109/L, C-reactive protein (CRP) > 10 mg/L [18].

We collected patients’ personnel characteristics including: gender, age, body mass index (BMI), hypertension, diabetes, Bismuth type, time of intraoperative liver ischemia based on the Pringle method, preoperative cholangitis, American Society of Anesthesiologists (ASA) score, number of biliary anastomosis, estimated blood loss during surgery, blood infusion during surgery, duration of surgery. Besides, we collected the laboratory test results before surgery and on the first day after surgery, including platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), gamma glutamyl transpeptidase (GGT), TBil, cholinesterase (ChE), international normalized ratio(INR). Additionally, we collected the preoperative bile culture results.

Statistical analysis

SPSS 22.0 statistical software was used for statistical analysis of data in this study. Quantitative data with normal distribution were described as mean ± standard deviation, and t-test was used for comparison. Quantitative data that were not normally distributed were expressed as medians (interquartile range) and compared using the rank sum test. The enumeration data were expressed as absolute numbers, and the comparison was performed by χ2 test, likelihood ratio test or Fisher's exact test according to the applicable conditions. Univariate and multivariate analyses of clinically relevant risk factors for biliary fistula were performed using logistic regression models. Combined with clinical application, variables with univariate analysis p < 0.05 were included in multivariate analysis. Receiver operating characteristic (ROC) curves were drawn and the diagnostic value of the model was analyzed by calculating the area under the curve (AUC). In this study, p < 0.05 was considered as a statistically significant difference between groups.

Results

The characteristics of included patients

A total of 160 patients undergoing radical resection of hilar cholangiocarcinoma were included, of whom 33 patients had postoperative grade B and C biliary fistulas, the incidence of postoperative biliary fistulas in patients undergoing radical resection of hilar cholangiocarcinoma was 20.63%. As shown in Table 1, there were significant differences in the age, preoperative cholangitis and number of biliary anastomosis between biliary fistula and no biliary fistula patients (all p < 0.05). There were no significant differences in the gender, BMI, hypertension, diabetes, Bismuth type, time of intraoperative liver ischemia, ASA score, estimated blood loss during surgery, blood infusion during surgery, duration of surgery between biliary fistula and no biliary fistula patients (all p > 0.05).

Table 1 The characteristics of included patients (n = 160)
Full size table

Laboratory test results

As shown in Table 2, there was significant difference in the GGT on the first day after surgery between biliary fistula and no biliary fistula patients (p = 0.025). There were no significant differences in the PLT, ALT, AST, AKP, TBil, ChE and INR before surgery and on the first day after surgery between biliary fistula and no biliary fistula patients (all p > 0.05).

Table 2 Comparison of laboratory test results before surgery and on the first day after surgery
Full size table

Preoperative bile culture results

As shown in Table 3, there was significant difference in the Klebsiella pneumoniae between biliary fistula and no biliary fistula patients (p = 0.015). There were no significant differences in the other pathogens of preoperative bile culture between biliary fistula and no biliary fistula patients (all p > 0.05).

Table 3 Comparison of preoperative bile culture results
Full size table

Logistic regression analysis

Variables with clinical significance in the univariate analysis were further included in the multivariate analysis. The variable assignments of multivariate logistic regression are shown in Table 4. As indicated in Table 5, logistic regression analysis showed that age ≥ 65 years (OR 2.035, 95% CI 1.131–3.007), preoperative cholangitis(OR 1.584, 95% CI 1.081–2.361), number of biliary anastomosis ≥ 2 (OR 2.866, 95% CI 1.942–3.624), GGT on the first day after surgery ≥ 120 U/L (OR 1.823, 95% CI 1.274–2.906), preoperative bile culture for Klebsiella pneumoniae (OR 3.181, 95% CI 2.426–3.992) were the risk factors of postoperative biliary fistulas in patients undergoing radical resection of hilar cholangiocarcinoma (all p < 0.05). The ROC curve is shown in Fig. 1. The ROC curve AUC = 0.836 in this prediction model (P = 0.008).

Table 4 The variable assignment of multivariate logistic regression
Full size table
Table 5 The logistic regression analysis on the risk factors of postoperative biliary fistulas in patients undergoing radical resection of hilar cholangiocarcinoma
Full size table
Fig. 1
figure 1

The ROC curve predicting the postoperative biliary fistulas in patients undergoing radical resection of hilar cholangiocarcinoma

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Discussion

Hilar cholangiocarcinoma is the main type of extrahepatic cholangiocarcinoma, accounting for 58% to 75% [19, 20]. Due to the special location of the disease and the characteristics of early invasion of blood vessels, nerves, lymphoid tissues and adjacent liver tissues, the operation for hilar cholangiocarcinoma is more difficult and complex [21, 22]. Patients with hilar cholangiocarcinoma usually require liver resection and extrahepatic bile duct resection to achieve radical cure. Previous studies [11, 23, 24] have found that the incidence of biliary fistula after such surgery is high, and biliary fistula has adverse effects on the short-term and long-term prognosis of patients. In this study, the incidence of biliary fistula after radical resection of hilar cholangiocarcinoma was 20.63%, which was lower than that reported in the previous literatures [12, 25, 26]. The reason may be that they have reported biliary fistulas with grades A, B, and C at the same time, and we only reported grade B, C cases of biliary fistula. Besides, we have found that age ≥ 65 years, preoperative cholangitis, number of biliary anastomosis ≥ 2, GGT on the first day after surgery ≥ 120 U/L, preoperative bile culture for Klebsiella pneumoniae are the risk factors of postoperative biliary fistulas in patients undergoing radical resection of hilar cholangiocarcinoma. Therefore, early identification, early diagnosis and early interventions of biliary fistula in high-risk patients have positive clinical significance.

Age is an important factor affecting the occurrence of biliary fistula after hilar cholangiocarcinoma. As the patient's age increases, the risk of biliary fistula after surgery is greatly increased, which may be related to the physiological characteristics of elderly patients and accompanying diseases [27]. The elderly have their special physiological and clinical characteristics. The solid organs of the elderly have different degrees of degenerative changes, the reserve function of each organ gradually declines, and the compensatory ability of some important organs also gradually declines; the immune function of the elderly declines, the ability to adapt to the internal and external environment, and the ability to resist diseases and tolerate surgery is significantly reduced [28,29,30]. Research statistics [31, 32] show that each elderly person suffers from changes in more than 1.6 organs on average, such as cardiovascular disease accounting for 50–60%. Surgery can exacerbate these preoperative comorbidities, and the presence of these preoperative comorbidities often complicates surgical treatment and increases the risk of serious postoperative complications [33]. Therefore, it is very important to pay attention to the influence of age on serious postoperative complications of hilar cholangiocarcinoma, and adequate preoperative evaluation and preoperative preparation should be done when formulating surgical treatment plans for elderly patients with hilar cholangiocarcinoma.

In this study, preoperative cholangitis and positive Klebsiella pneumoniae in preoperative bile culture may be associated with the occurrence of postoperative clinically relevant biliary fistulas. Inflammation caused by biliary tract infection can lead to bile duct wall edema and the formation of small abscesses, hinder the healing of postoperative bile duct stumps and lead to the occurrence of hepatic section or anastomotic biliary leakage [25, 34]. Previous studies [35, 36] have shown that the clinical isolation rate and drug resistance rate of Klebsiella pneumoniae are increasing year by year, and it has become one of the main pathogens of biliary tract infection. The choice of preventive antibiotics in our center is mainly cephalosporins, and ESBL can make bacteria resistant to most β-lactam antibiotics including cephalosporins. Bacterial virulence factors may also contribute to the development of biliary fistulas. Preoperative biliary drainage is not only the need to monitor the etiology to guide the choice of antibiotics, but also an irreplaceable means of treating acute cholangitis.

The number of biliary–enteric anastomosis was associated with the risk of postoperative biliary leakage through the biliary–enteric anastomosis. Hemihepatic resection and tri-regional resection are the most commonly used surgical methods for hilar cholangiocarcinoma. The advantages are that it is easy to obtain R0 resection, there is no large hepatic pedicle branch in the liver section, the number of bile duct openings is relatively small, and the cholangiojejunostomy is relatively simple. The disadvantage is that they are all large-scale liver resections and require high liver reserve function, so preoperative preparations such as biliary drainage are often required before surgery [37,38,39]. Simple perihepatectomy and other surgical procedures often have more than 3 bile duct openings, and biliary–enteric anastomosis is more difficult [40, 41]. The advantage is that they are limited liver resections, have low requirements for liver reserve function, and do not require long preoperative preparations [42]. Several studies [43,44,45] have demonstrated the safety and efficacy of extensive liver resection. Therefore, under the premise of the condition, a reasonable selection of large-scale liver resection can effectively reduce the number of anastomosis and the difficulty of biliary–enteric anastomosis, thereby reducing the risk of postoperative biliary fistula in patients with hilar cholangiocarcinoma.

GGT is a plasma membrane-bound glycoprotein widely distributed in mammalian tissues, and is a key enzyme in the γ-glutamyl cycle [46]. And in body fluids, the enzyme activity in serum mainly comes from the hepatobiliary system [47]. Clinical data [48] show that GGT will increase in patients with hepatocellular carcinoma, and it is positively correlated with the size and extent of cancer cells. After tumor resection, GGT can be reduced to normal, and it will increase again when it recurs. Dynamic observation of GGT may predict the curative effect and prognosis of hepatocellular carcinoma [49]. This study has found that the occurrence of postoperative clinically relevant biliary fistula is positively correlated with GGT on postoperative day 1. Previous study [50] has reported the clinical value of GGT in predicting postoperative biliary fistula in patients with hepatic hydatid disease. However, the specific mechanism of the relationship between GGT and postoperative biliary fistula has not yet been fully elucidated, which needs further investigations.

There are many limitations in this study worth considering. Firstly, as a single-center prospective study with a small sample, this study has a small sample size and may have certain selection and regional biases. Secondly, the surgical methods and perioperative management of hilar cholangiocarcinoma are still controversial in many aspects, and the differences in the diagnosis and treatment strategies of different centers will limit the development of multi-center retrospective studies. Besides, we have no further more data about the patients' comorbidities, which may influence anastomotic leakage. Therefore, it is necessary to draw more reliable conclusions by designing prospective studies in the future. Thirdly, this study failed to identify the source of the biliary fistula. Although the author's center routinely places peritoneal drainage tubes on the liver section and around the anastomosis, it is difficult to accurately determine the source of biliary fistula by detecting ascites because the drainage areas are not independent of each other. Fourthly, we did not perform microbiological analysis of the bile of all patients and preoperative drug resistances of the Klebsiella; those results can be useful for clinical drug use and management. Finally, no further stratified analysis of grade B and C biliary fistulas was performed in this study. Since there is no unified standard for the indications and timing of secondary surgery for postoperative biliary fistula, differences between different centers will undoubtedly affect the comparability of biliary fistula grading.

Conclusions

In summary, this present study has found that the incidence of biliary fistula after radical resection of hilar cholangiocarcinoma is 20.63%. For patients with age ≥ 65 years, preoperative cholangitis, number of biliary anastomosis ≥ 2, GGT on the first day after surgery ≥ 120 U/L, preoperative bile culture for Klebsiella pneumoniae, there may have higher risk of postoperative biliary fistulas. Clinical medical workers should take early preventions and treatment strategies for these high-risk factors to reduce the occurrence of postoperative biliary fistula and improve the prognosis of patients.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

ISGLS:

International Study Group of Liver Surgery

WBC:

White blood cell

CRP:

C-reactive protein

BMI:

Body mass index

ASA:

American Society of Anesthesiologists

PLT:

Platelet count

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AKP:

Alkaline phosphatase

GGT:

Gamma glutamyl transpeptidase

TBil:

Total bilirubin

ChE:

Cholinesterase

INR:

International normalized ratio

ROC:

Receiver operating characteristic

AUC:

Area under the curve

References

  1. Laughlin BS, Petersen MM, Yu NY, Anderson JD, Rule WG, Borad MJ, Aqel BA, Sonbol MB, Mathur AK, Moss AA, et al. Clinical outcomes for hilar and extrahepatic cholangiocarcinoma with adjuvant, definitive, or liver transplant-based neoadjuvant chemoradiotherapy strategies: a single-center experience. J Gastrointest Oncol. 2022;13(1):288–97.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ma D, Wang W, Wang J, Zhang T, Jiang Z, Du G, Yang J, Zhang X, Qin G, Jin B. Laparoscopic versus open surgery for hilar cholangiocarcinoma: a retrospective cohort study on short-term and long-term outcomes. Surg Endosc. 2022;36(6):3721–31.

    Article  PubMed  Google Scholar 

  3. Wang SY, Jiang N, Zeng JP, Yu SQ, Xiao Y, Jin S. Characteristic of perineural invasion in hilar cholangiocarcinoma based on whole-mount histologic large sections of liver. Front Oncol. 2022;12: 855615.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tee MC, Brahmbhatt RD, Franko J. Robotic resection of type I hilar cholangiocarcinoma with intrapancreatic bile duct dissection. Ann Surg Oncol. 2022;29(2):964–9.

    Article  PubMed  Google Scholar 

  5. Song J, Lei X, Lin H, Dai H, Liu X, Jiang Y, Hu F, Li Y, Fan H, Zhang L, et al. Predictive model for the intraoperative unresectability of hilar cholangiocarcinoma: reducing futile surgical exploration. PLoS ONE. 2022;17(4): e0258522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Liu ZP, Zhang QY, Chen WY, Huang YY, Zhang YQ, Gong Y, Jiang Y, Bai J, Chen ZY, Dai HS. Evaluation of four lymph node classifications for the prediction of survival in hilar cholangiocarcinoma. J Gastrointest Surg. 2022;26(5):1030–40.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu ZP, Chen WY, Zhang YQ, Jiang Y, Bai J, Pan Y, Zhong SY, Zhong YP, Chen ZY, Dai HS. Postoperative morbidity adversely impacts oncological prognosis after curative resection for hilar cholangiocarcinoma. World J Gastroenterol. 2022;28(9):948–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Martin AN, Narayanan S, Turrentine FE, Bauer TW, Adams RB, Stukenborg GJ, Zaydfudim VM. Clinical factors and postoperative impact of bile leak after liver resection. J Gastrointest Surg. 2018;22(4):661–7.

    Article  PubMed  Google Scholar 

  9. Ito A, Ebata T, Yokoyama Y, Igami T, Mizuno T, Yamaguchi J, Onoe S, Nagino M. Ethanol ablation for refractory bile leakage after complex hepatectomy. Br J Surg. 2018;105(8):1036–43.

    Article  CAS  PubMed  Google Scholar 

  10. Braunwarth E, Primavesi F, Gobel G, Cardini B, Oberhuber R, Margreiter C, Maglione M, Schneeberger S, Ofner D, Stattner S. Is bile leakage after hepatic resection associated with impaired long-term survival? Eur J Surg Oncol. 2019;45(6):1077–83.

    Article  PubMed  Google Scholar 

  11. Liu F, Hu HJ, Ma WJ, Wang JK, Ran CD, Regmi P, Li FY. Is radical resection of hilar cholangiocarcinoma plus partial resection of pancreatic head justified for advanced hilar cholangiocarcinoma? ANZ J Surg. 2020;90(9):1666–70.

    Article  PubMed  Google Scholar 

  12. Xu J, Xiong YF, Huang XJ, Yang FC, Li JD, Liu JH, Zhao WX, Qin RY, Yin XM, Zheng SG, et al. A multicenter clinical analysis of short-term efficacy of laparoscopic radical resection of hilar cholangiocarcinoma. Zhonghua Wai Ke Za Zhi. 2020;58(10):758–64.

    CAS  PubMed  Google Scholar 

  13. Wu WG, Gu J, Dong P, Lu JH, Li ML, Wu XS, Yang JH, Zhang L, Ding QC, Weng H, et al. Duct-to-duct biliary reconstruction after radical resection of bismuth IIIa hilar cholangiocarcinoma. World J Gastroenterol. 2013;19(15):2441–4.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Spetzler VN, Schepers M, Pinnschmidt HO, Fischer L, Nashan B, Li J. The incidence and severity of post-hepatectomy bile leaks is affected by surgical indications, preoperative chemotherapy, and surgical procedures. Hepatobiliary Surg Nutr. 2019;8(2):101–10.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, et al. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the international study group of liver surgery. Surgery. 2011;149(5):680–8.

    Article  PubMed  Google Scholar 

  16. Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, et al. The 2016 update of the international study group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161(3):584–91.

    Article  PubMed  Google Scholar 

  17. Xiaoyuan C, Liang M, Shiquan S. Analysis of risk factors for clinically relevant biliary fistula after radical resection of hilar cholangiocarcinoma. Chin J Pract Surg. 2020;40(4):6–9.

    Google Scholar 

  18. Yudong Q. Difficulties and implementation points of nutritional therapy in the perioperative period of liver resection. J Appl Surg. 2018;38(3):270–3.

    Google Scholar 

  19. Doherty B, Nambudiri VE, Palmer WC. Update on the Diagnosis and Treatment of Cholangiocarcinoma. Curr Gastroenterol Rep. 2017;19(1):2.

    Article  PubMed  Google Scholar 

  20. Shin SP, Koh DH. Clinical Impact of Sarcopenia on Cholangiocarcinoma. Life (Basel). 2022;12(6):815.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Uemura S, Maeda H, Hanazaki K. Unexpected gastrointestinal bleeding from the ileocolic artery penetrating the duodenum after hilar cholangiocarcinoma surgery. Clin Case Rep. 2022;10(4): e05764.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yu Z, Liu Q, Liao H, Shi J, Zhou Z, Yan Y, Xu J, He C, Mao K, Zhang J, et al. Prognostic nomogram for predicting cancer-specific survival in patients with resected hilar cholangiocarcinoma: a large cohort study. J Gastrointest Oncol. 2022;13(2):833–46.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mohammed M, Kobayashi K, Jawed M. Biliary-pleural fistula following portal vein embolization for perihilar cholangiocarcinoma. Case Rep Gastroenterol. 2017;11(2):277–83.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chen HM, Fu ZH, Deng DF, Huang JZ, Zhang X, Xu ZQ, Wang YD. The safety and efficacy of combined hepatic artery resection in treatment of hilar cholangiocarcinoma: a meta-analysis. Zhonghua Yi Xue Za Zhi. 2021;101(4):286–92.

    CAS  PubMed  Google Scholar 

  25. Tsema I, Slobodianyk V, Rahushyn D, Myrhorodskiy D, Yurkiv O, Dinets A. Non-operative management of bronchobiliary fistula due to proximal migration of biliary stent in a patient with unresectable Klatskin tumor. Clin Med Insights Case Rep. 2021;14:11795476211043068.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Shim DJ, Gwon DI, Han K, Kim Y, Ko GY, Shin JH, Ko HK, Kim JH, Kim JW, Yoon HK, et al. Percutaneous metallic stent placement for palliative management of malignant biliary hilar obstruction. Korean J Radiol. 2018;19(4):597–605.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zhang GW, Lin JH, Qian JP, Zhou J. Analyzing risk factors for early postoperative bile leakage based on Clavien classification in bile duct stones. Int J Surg. 2014;12(8):757–61.

    Article  PubMed  Google Scholar 

  28. Li SQ, Liang LJ, Peng BG, Lu MD, Lai JM, Li DM. Bile leakage after hepatectomy for hepatolithiasis: risk factors and management. Surgery. 2007;141(3):340–5.

    Article  PubMed  Google Scholar 

  29. Lee J, Song O, Park HM, Lee SY, Kim CH, Kim HR. Postoperative bile leakage caused by intrahepatic duct injury during right hemicolectomy: A case report. Medicine (Baltimore). 2021;100(46): e27877.

    Article  Google Scholar 

  30. Miyagi S, Kawagishi N, Kashiwadate T, Fujio A, Tokodai K, Hara Y, Nakanishi C, Kamei T, Ohuchi N, Satomi S. Relationship between bile duct reconstruction and complications in living donor liver transplantation. Transplant Proc. 2016;48(4):1166–9.

    Article  CAS  PubMed  Google Scholar 

  31. Wenming W. Analysis of risk factors for acute liver failure after partial hepatectomy in patients with liver cirrhosis and liver cancer. J Hepatobiliary Surg. 2020;28(1):5–9.

    Google Scholar 

  32. Ting W, Yan W, Liwei L. Influence of the burden of underlying diseases on the severity and prognosis of drug-induced liver injury. Liver. 2022;27(1):23–7.

    Google Scholar 

  33. Giuliante F, Ardito F, Vellone M, Nuzzo G. Liver resections for hilar cholangiocarcinoma. Eur Rev Med Pharmacol Sci. 2010;14(4):368–70.

    CAS  PubMed  Google Scholar 

  34. Mansour JC, Aloia TA, Crane CH, Heimbach JK, Nagino M, Vauthey JN. Hilar cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17(8):691–9.

    Article  PubMed Central  Google Scholar 

  35. Li J, Zhou MH, Ma WJ, Li FY, Deng YL. Extended lymphadenectomy in hilar cholangiocarcinoma: what it will bring? World J Gastroenterol. 2020;26(24):3318–25.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Chen Y, Xu Y, Zhang Y. Current status of laparoscopic radical hilar cholangiocarcinoma in Mainland China. Biosci Trends. 2020;14(3):168–73.

    Article  PubMed  Google Scholar 

  37. Sapisochin G, Ivanics T, Subramanian V, Doyle M, Heimbach JK, Hong JC. Multidisciplinary treatment for hilar and intrahepatic cholangiocarcinoma: a review of the general principles. Int J Surg. 2020;82S:77–81.

    Article  PubMed  Google Scholar 

  38. Aloia TA. Precision hilar cholangiocarcinoma surgery. Ann Surg Oncol. 2018;25(5):1103–4.

    Article  PubMed  Google Scholar 

  39. Chou S, Chang ZY, Zhao GD, Song DD, Zhang X, Hu MG, Liu R. Robotic hilar cholangiocarcinoma radical resection compared with laparotomy in prognosis. Zhonghua Wai Ke Za Zhi. 2020;58(3):230–4.

    CAS  PubMed  Google Scholar 

  40. Hu HJ, Wu ZR, Jin YW, Ma WJ, Yang Q, Wang JK, Liu F, Li FY. Minimally invasive surgery for hilar cholangiocarcinoma: state of art and future perspectives. ANZ J Surg. 2019;89(5):476–80.

    Article  PubMed  Google Scholar 

  41. Mizuno T, Ebata T, Nagino M. Advanced hilar cholangiocarcinoma: an aggressive surgical approach for the treatment of advanced hilar cholangiocarcinoma: Perioperative management, extended procedures, and multidisciplinary approaches. Surg Oncol. 2020;33:201–6.

    Article  PubMed  Google Scholar 

  42. Machado MA, Mattos BV, Lobo Filho MM, Makdissi F. Robotic resection of hilar cholangiocarcinoma. Ann Surg Oncol. 2020;27(11):4166–70.

    Article  PubMed  Google Scholar 

  43. Wu W, Cheng Q, Chen J, Chen D, Feng X, Wu J. Left-side vs. right-side hepatectomy for hilar cholangiocarcinoma: a meta-analysis. World J Surg Oncol. 2021;19(1):107.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Cipriani F, Ratti F, Fiorentini G, Reineke R, Aldrighetti L. Systematic review of perioperative and oncologic outcomes of minimally-invasive surgery for hilar cholangiocarcinoma. Updates Surg. 2021;73(2):359–77.

    Article  PubMed  Google Scholar 

  45. Dondossola D, Ghidini M, Grossi F, Rossi G, Foschi D. Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma. World J Gastroenterol. 2020;26(25):3542–61.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ndrepepa G, Colleran R, Kastrati A. Gamma-glutamyl transferase and the risk of atherosclerosis and coronary heart disease. Clin Chim Acta. 2018;476:130–8.

    Article  CAS  PubMed  Google Scholar 

  47. Fu HY, Zhao RQ, Bai GL, Yin CL, Yin RK, Li HH, Shi WN, Liu YL, Cheng LJ, Jia XY, et al. Value of serum gamma-glutamyl transpeptidase combined with direct bilirubin in the diagnosis of biliary atresia in infants. Zhongguo Dang Dai Er Ke Za Zhi. 2019;21(12):1198–202.

    PubMed  Google Scholar 

  48. Fanchuang K, Haoqiang C, Limin J. Clinical application of combined detection of multiple tumor markers in the diagnosis of liver cancer. Chin Lab Diagn. 2004;8(3):255–6.

    Google Scholar 

  49. Haifeng G, Qiujian Z, Jing W. The role of serum alpha-fetoprotein, α-L-fucosidase, 5’-nucleotidase and γ-glutamyl transpeptidase in the early diagnosis of hepatocellular carcinoma application. Cancer Res Clin. 2016;16(8):5–7.

    Google Scholar 

  50. Kilic M, Yoldas O, Koc M, Keskek M, Karakose N, Ertan T, Gocmen E, Tez M. Can biliary-cyst communication be predicted before surgery for hepatic hydatid disease: does size matter? Am J Surg. 2008;196(5):732–5.

    Article  PubMed  Google Scholar 

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Acknowledgements

None.

Funding

This study was funded by Anhui Provincial Natural Science Foundation (2008085MH256) and the sixth batch of "special support plan" leading talent projects in Anhui Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. Dengyong Zhang and Feiyu Qi contributed equally to this work and share first authorship

Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, No. 287, Changhuai Road, Zhihuai Street, Longzihu District, Bengbu, 233000, Anhui Province, China

    Dengyong Zhang, Feiyu Qi, Wanliang Sun, Guanru Zhao, Dongdong Wang, Shuo Zhou, Zhong Liu & Zheng Lu

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  1. Dengyong Zhang
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  2. Feiyu Qi
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  6. Shuo Zhou
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  7. Zhong Liu
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  8. Zheng Lu
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Contributions

ZL designed research; DYZ, FYQ, WLS, GRZ, DDW, SZ, ZL, ZL conducted research; DYZ, FYQ, ZL analyzed data; DYZ, FYQ wrote the first draft of manuscript; DYZ had primary responsibility for final content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zheng Lu.

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Ethics approval and consent to participate

In this study, all methods were performed in accordance with the relevant guidelines and regulations. This present study had been verified and approved by the ethical committee of The First Affiliated Hospital of Bengbu Medical College with approval number: 2021230. And written informed consents had been obtained from all the included patients.

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Zhang, D., Qi, F., Sun, W. et al. Influencing factors of biliary fistula after radical resection of hilar cholangiocarcinoma: a prospect cohort. Eur J Med Res 27, 214 (2022). https://doi.org/10.1186/s40001-022-00851-4

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European Journal of Medical Research

ISSN: 2047-783X

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