Skip to main content
Download PDF

Optimization of a laparoscopic procedure for advanced intrahepatic cholangiocarcinoma based on the concept of “waiting time”: a preliminary report

BMC Cancer volume 22, Article number: 1222 (2022) Cite this article

Abstract

Introduction

Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC.

Methods

Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared.

Results

The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009).

Conclusions

Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes.

Peer Review reports

Introduction

Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy. At diagnosis, ICC is often at an advanced stage and is accompanied by lymph node (LN) metastasis. In this case, hepatectomy is the only potential cure [1,2,3,4,5]. In contrast to hepatocellular carcinoma (HCC), the most common liver malignancy, there is controversy regarding the routine use of LN dissection (LND) in patients who receive open surgery or laparoscopic surgery. Many researchers believe that LND does not significantly improve overall survival (OS), but can lead to more accurate staging, reduce local recurrence, and provide information related to prognosis [6,7,8,9].

Several expert consensus statements recommend routine hepatoduodenal ligament dissection, especially for patients with advanced-stage ICC [4, 10,11,12,13]. Because it is relatively easy to perform dissection of the hepatoduodenal ligament LNs during traditional open surgery, most surgical procedures first remove the LNs and then perform liver resection. The low central venous pressure (LCVP) anesthesia technique allows the widespread use of laparoscopic surgery for LND in patients with ICC, because it provides more rapid recovery and it follows the same traditional process used during open surgery (“LND first”) [14,15,16,17]. However, patients with advanced-stage ICC often require resection of large liver volumes, such as integratedhemihepatectomy combined with ipsilateral caudate lobectomy and LND.

Patients with advanced-stage ICC have more affected LNs, and a laparoscopic approach for LND can be technically challenging because it requires much more time than an open approach to achieve fine 360° skeletalization of all vessels in the hepatic hilum. In this situation, the liver experiences a longer time of LND before hepatic parenchyma resection, which we define as the “waiting time” [10, 14, 18,19,20,21]. This inevitably leads to two major problems. First, when LND is performed before liver resection, it can lead to a long “waiting time”. In this case, a patient’s liver remains in a relatively ischemic or hypoxic state because of strict fluid restriction due to the prolonged LCVP before resection of hepatic parenchyma. This can cause microcirculation disorders and the accumulation of acidic substances, thus disrupting the condition of the hepatic surgical field and the ability to control LCVP [21,22,23,24,25,26,27,28,29]. Second, to perform liver resection as soon as possible, some surgeons may rush to complete the LND, which may reduce the quality of the procedure and potentially lead to incomplete or inadequate LND [10, 30,31,32,33].

Thus, to improve the condition of the hepatic surgical field and the quality of liver resection and laparoscopic LND, our center optimized the surgical procedure to reduce this “waiting time”. We modified the traditional laparoscopic procedure of LND followed by liver resection to a three-step sequential procedure that consists of pre-dissection of hepatic hilar vessels, liver resection, and then LND. This compared the quality of liver resection and LND, and the survival benefits of laparoscopic radical resection of advanced-stage ICC from the traditional procedure and our optimized procedure.

Methods

Patients

This prospective observational study examined patients who received laparoscopic radical liver resection for advanced-stage ICC by our optimized three-step procedure from January 2018 to March 2020. Data of patients who received traditional laparoscopic radical ICC surgery from January 2013 to December 2017 were retrospectively collected for comparison. This study was approved by the local Ethics Committee, and all procedures were performed in accordance with the 2013 Declaration of Helsinki. Written informed consent was provided by each patient.

The inclusion criteria were: (i) patient age of 18 to 80 years old; (ii) whole body PET-CT examination before the operation showing that the liver and duodenal ligament LNs had hyper-metabolism (suggesting LN metastasis) and no distant metastasis; (iii) pathological diagnosis of intrahepatic cholangiocarcinoma; (iv) receipt of laparoscopic radical left or right hemihepatectomy plus ipsilateral caudate lobectomy and hepatoduodenal ligament LND; and (v) valid and complete surgical video and perioperative data. The exclusion criteria were: (i) abdominal implant transfer or distant transfer (in which case only palliative surgery was indicated); (ii) co-occurrence of another malignant tumor; (iii) pathological results suggesting mixed hepatocellular-cholangiocarcinoma, hilar cholangiocarcinoma, or gallbladder cancer; and (iv) need for biliary anastomosis. All included patients were divided into an optimized group and a traditional group. All results are reported in line with the STROCSS guidelines [34].

Operation procedures

All operations were performed by experienced surgeons who specialized in hepatobiliary surgery and had extensive experience in laparoscopic techniques. All patients were anesthetized using endotracheal intubation with a controlled LCVP strategy that required fluid restriction [35]. In particular, strict fluid restriction was used from the night before surgery until liver parenchyma resection, and the reverse-Trendelenburg position was used. Thus, most patients had CVPs close to 5 cmH2O, and some were even lower than 5 cmH2O. When it was close to the time for hepatic parenchyma resection, a small amount of nitroglycerin was used to reduce the CVP to below 5 cmH2O if necessary.

With the patient in the French position, a 5-hole method was used to establish a pneumoperitoneum and maintain a pneumoperitoneum pressure of 12 mmHg. First, the abdominal and pelvic cavities were examined to determine if there were metastatic nodules. After confirming there was no metastatic transplantation, an ultrasonic scalpel (Harmonic Scalpel; Ethicon, Cincinnati, OH) was used to free the ligamentum teres hepatis, falciform ligament, coronary ligament, and triangular ligament of the liver, and the gallbladder was then removed.

Patients in the traditional group received hepatoduodenal LND before resection of the liver (integrated left hemihepatectomy or right hemihepatectomy combined with ipsilateral caudate lobectomy). The sequence of procedures in the traditional group was: (i) LND (fine 360° skeletalization of all vessels in the hepatic hilum); (ii) ligation and cutting off the target side blood vessels and bile duct; and (iii) resection of target-side hepatic parenchyma. The sequence of procedures in the optimized group was: (i) pre-dissection of hepatic hilar vessels (simply freeing, ligating, and severing the target side vessels and bile duct for subsequent ligation and disconnection); (ii) resection of target-side hepatic parenchyma; and (iii) hepatoduodenal ligament LND (fine 360° skeletalization of the remaining vessels within the porta hepatis). All other procedures in the two groups were the same. The LND included station 12 (hepatoduodenal), station 8 (common hepatic artery), and station 13 (posterior to pancreas). For left-sided tumors, station 7 (left gastric artery) and station 1 (right esophageal crus) were also removed [36].

Outcome measurements

Quality of liver resection

The condition of the hepatic surgical field was evaluated using a bleeding score and the surgeon’s satisfaction score [25, 37]. The bleeding score was 1 (minor bleeding, no aspiration required), 2 (minor bleeding, aspiration required), 3 (minor bleeding, frequent aspiration required), 4 (moderate bleeding, no visibility without aspiration), or 5 (severe bleeding, frequent aspiration required, very hard to perform surgery). The surgeon satisfaction score was 1 (bad), 2 (moderate), 3 (good), or 4 (excellent).

The total operation time, “waiting time”, liver resection time, LND time, total blood loss, blood loss during liver resection, and rate of transfusion and conversion were used to assess the quality of liver resection. All of these times were recorded by review of the operation video.

The “waiting time” was defined as the time from observation of the trocar puncture to liver parenchyma resection. The “waiting time” of the optimized group was the time needed to establish a laparoscopic tunnel plus the time needed for pre-dissection of the hepatic hilar vessels (simple separation and disconnection of the target side vessels and bile duct). The “waiting time” of traditional group was the time needed for establishment of laparoscopic tunnel, plus the time needed for fine 360° skeletalization of the hilar blood vessels, plus the time needed to sever the target side blood vessels and bile ducts.

Quality of LND

LND was evaluated using the pathological reports of LNs that were harvested from around the hepatoduodenal ligament. The number of harvested LNs, number of positive LNs, positive rate of LNs, and rate of adequate LND were used to assess the quality of LND. As described by the eighth edition of the American Joint Committee on Cancer (AJCC) guidelines for ICC, dissection was described as adequate when at least 6 nodes were harvested [10].

Other outcomes

Arterial blood gas analysis was used to measure lactate levels before anesthesia (preoperative lactate), immediately before liver resection (pre-resection lactate), immediately after removal of liver lesions (post-resection lactate), and before patient discharge from the postanesthesia care unit (postoperative lactate). The State Trait Anxiety Inventory (STAI) scale, which is routinely used in our center, was used to characterize the mental stress of the chief surgeon after the operation. The STAI measures stress using 6 items: 3 positive items (“I feel calm,” “I feel content,” and “I feel relaxed”) and 3 negative items (“I feel tense,” “I feel upset,” and “I feel worried”). Each item was self-rated on a 4-point scale, so the total score ranged from 6 (very low stress) to 24 (very high stress) [32]. Higher scores indicate higher stress. Postoperative outcomes, including recovery indicators and morbidities, were also recorded. The Clavein-Dindo classification was used to classify morbidities [38]. Bile leakage was diagnosed, classified, and treated as proposed by the International Study Group for Liver Surgery [39, 40]. The recovery indicators were postoperative length of stay (PLOS), time to resume out-of-bed activities, time for recovery of bowel movements, and time for recovery of oral intake of a semi-liquid diet.

Follow up

Each patient received adjuvant chemotherapy and routine postoperative monitoring (liver function tests; routine blood examinations; serum CEA and CA19-9; and CT or MRI scans) every 3 months. Disease-free survival (DFS) and overall survival (OS) were calculated as the times from the operation to recurrence.

Statistical analysis

All data were analyzed using SPSS version 26.0 (IBM Corporation, Armonk, NY). Propensity score (PS) matching (1:2) was performed using R software version 4.1.0 (“Matchit package”). Continuous variables were analyzed using Student’s t-test or the Mann–Whitney U test, as appropriate. Categorical variables were analyzed using Pearson’s χ 2 statistic or Fisher’s exact test. DFS and OS was analyzed using the Kaplan–Meier method and compared using the log-rank test. Logistic regression analysis was used to identify factors associated with morbidities, and Cox regression analysis was used to identify factors associated with DFS and OS. A P value below 0.05 was considered significant.

Results

Baseline characteristic

Before PS matching, 42 patients were in the optimized group and 127 patients were in the traditional group (Fig.  1).After 1:2 PS matching, there were 42 patients in the optimized group and 84 in the traditional group. There were also 24 males (57%) and 18 females (43%) in the optimized group and similar percentages (59.5% and 40.5%) in the traditional group (Table 1). Analysis of age, BMI, ASA score, comorbidities, serological indexes, tumor location, number of tumors, T stage, preoperative suspicious LN metastasis, and vascular invasion indicated no significant differences after matching (Table 1).

Fig. 1
figure 1

Identification of eligible patients and establishment of traditional and optimized groups by 1:2 propensity score matching. Abbreviations: ICC, intrahepatic cholangiocarcinoma; PSM, propensity score matching; BMI, body mass index; ASA, American Society of Anesthesiologists; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; T.Bil, total bilirubin

Full size image
Table 1 Baseline characteristics
Full size table

Intraoperative outcomes

Twenty-eight patients in the optimized group received left hemihepatectomy and 14 received right hemihepatectomy; 56 patients in the traditional group received left hepatectomy and 28 received right hepatectomy. These differences were not significant (Table 2). Nine patients in the optimized group and 11 patients in the traditional group received vascular reconstruction (P = 0.752).

Table 2 Intraoperative and pathological outcomes
Full size table

Quality of liver resection

The optimized group had a significantly lower surgical bleeding score (1.98 ± 1.16 vs. 2.37 ± 1.06, P = 0.038) and a significantly higher surgeon satisfaction score (3.10 ± 0.96 vs. 2.52 ± 0.89, P = 0.001; Table 2). Relative to the traditional group, the optimized group also had significantly less blood loss during hepatectomy (190 mL [IQR: 139–290] vs. 295 mL [IQR: 176–480], P < 0.001), significantly less total blood loss (200 mL [IQR: 150–300] vs. 295 mL [IQR: 176.25–480], P = 0.016), a lower rate of rate transfusion (14.3% vs. 33.3%, P = 0.023), and a marginally lower conversion rate (0% vs. 8.3%, P = 0.054). No patients in the optimized group converted to open surgery. However, 7 patients in the traditional group (8.33%) converted to an open approach due to severe bleeding of the hepatic surgical field during liver resection.

The optimized group had a shorter total operation time (222 min [IQR: 177–297] vs. 280 min [IQR: 250–355), P < 0.001), shorter “waiting time” (29 min [IQR: 27–32] vs. 112 min [IQR: 105–119], P < 0.001), shorter liver resection time (119 min [IQR: 79–179] vs. 160 min [IQR: 128.5–230], P = 0.001), and a shorter LND time (65 min [IQR: 70–85] vs. 92 min [IQR: 85–99], P < 0.001).

The difference of the preoperative lactate level in the optimized and traditional groups was not statistically significant (P = 0.723), but the optimized group had a lower pre-resection lactate level (P < 0.001), a lower post-resection lactate level (P < 0.001), and a lower postoperative lactate level (P < 0.001; Table 2). Pearson correlation analysis showed there were positive correlations of “waiting time” with pre-resection lactate, post-resection lactate, postoperative lactate, total blood loss, and blood loss during liver resection (all P < 0.001, Fig. 2). However, the two groups had no significant difference in oncological outcomes (Table 2).

Fig. 2
figure 2

Pearson correlation matrix showing the relationship of “waiting time” with lactate level and blood loss. ***, P < 0.001; **, P < 0.01

Full size image

Quality of LND

The optimized group and traditional group had similar LN positivity (92.9% vs. 90.5%, P = 0.113; Table 3). However, the optimized group had significantly more harvested LNs (12.0 [IQR: 10.0–13.0] vs. 8.0 [IQR: 7.0–9.5], P < 0.001) and more positive LNs (8.0 [IQR: 8.0–10.0] vs. 5.0 [IQR: 5.0–6.0], P < 0.001). Thirty-seven patients (88.1%) in the optimized group achieved adequate LND (6 or more harvested LNs) and 65 patients (77.4%) in the traditional group achieved adequate LND (P = 0.149). We also analyzed LN metastasis and adequate LND for each T stage of patients with N1 status (Table 3). The optimized group had more harvested LNs (12.0 [IQR: 10.5–13.5] vs. 8.0 [IQR: 7.0–10.0], P < 0.001) and more positive LNs (9.0 [IQR: 8.0–10.0] vs. 5.5 [IQR: 5.0–6.0], P < 0.001), but the two groups were similar in the rate of adequate LND (89.7% vs. 77.6%, P = 0.111).

Table 3 The quality evaluation of lymph node dissection
Full size table

Postoperative recovery outcomes

The optimized group had a shorter PLOS (11.33 ± 2.54 vs. 13.49 ± 3.85, P < 0.001), bowel recovery time (2.38 ± 0.58 vs. 2.90 ± 0.79, P < 0.001), time before resumption of oral-intake (1.93 ± 0.71 vs. 2.63 ± 0.67, P < 0.001), and off-bed activity time (2.29 ± 0.71 vs. 2.83 ± 0.92, P = 0.001, Table 4). The optimized group also had a lower incidence rate of total morbidities (14.3% vs. 36.9%, P = 0.009), although the groups had no significant differences in specific complications except delirium, which was more common in the traditional group (13.1% vs. 2.4%, P = 0.046). Multivariate logistic regression analysis showed that the optimized group had a reduced incidence of overall morbidities (OR: 0.332 [95%CI: 0.123–0.891], P = 0.029, Table 5).

Table 4 Postoperative outcome
Full size table
Table 5 The logistic analysis of morbidity
Full size table

Survival outcome

Analysis of DFS showed that the optimized group had a better outcome (9.00 months [IQR: 8.12–9.88] vs. 7.00 months [IQR: 6.05–8.00], P = 0.018, Fig. 3A). The results were similar for patients with stage N1 (P = 0.019, Fig. 3B). Patients in the two groups who had stage N0 had no significant difference in DFS (P = 0.590, Fig. 3C). The optimized group also had a significantly longer OS (15.0 months [IQR: 11.39–18.62] vs. 13.00 months [IQR: 10.87–15.14], P = 0.046, Fig. 3D–F).

Fig. 3
figure 3

Disease-free survival of all patients in the optimized and traditional groups (A), the subgroup with positive lymph nodes (N1) (B), and the subgroup with negative lymph nodes (N0) (C). Overall survival of all patients in the optimized and traditional groups (D), the subgroup with positive lymph nodes (N1) (E), and the subgroup with negative lymph nodes (N0) (F)

Full size image

Cox regression analysis confirmed the optimized three-step procedure provided a better DFS (OR: 0.627 [95%CI: 0.407–0.967], P = 0.035, Table 6) and marginally better OS (OR: 0.625 [95%CI: 0.408–1.043], P = 0.074, Table 6). Notably, the imaging results from the initial postoperative monitoring also showed there was a tendency for a greater prevalence of signs of lymphadenectasis around the hepatoduodenal ligament in the traditional group than in the optimized group (25.0% vs. 11.9%, P = 0.066).

Table 6 The cox analysis of DFS
Full size table

Discussion

Many studies advocated the use of laparoscopy for surgical treatment of ICC because this technique is minimally invasive, allows abdominal exploration, improves early recovery, and provides a non-inferior oncological survival benefit [19, 36, 41,42,43,44,45,46]. However, this procedure can be technically difficult, complicated, require a long operation time, and is less developed, especially for patients with advanced-stage ICC [10, 19, 36, 41,42,43,44,45,46]. To the best of our knowledge, this study is the first to propose an optimization of the laparoscopy procedure for advanced ICC, which was designed to improve the quality of liver resection and LND, increase the duration of DFS, shorten the operation time, and improve postoperative recovery. In contrast to many previous studies of this topic, we adopted a rigorous study design. First, all enrolled patients had advanced ICC with high probabilities of preoperative LN metastasis and all patients received regional LND. This reduced the outcome bias caused by the incomplete or lack of LND of some patients, as reported in previous studies [7, 16, 45]. Second, we used PS matching to compare the two groups, and accurately determined the blood loss, the times needed for liver resection and LND, and the quality of liver resection and LND. Our comprehensive and detailed examination of these procedures from multiple angles helped to reduce selection bias and improve the reliability of the results. Finally, this study was the first to consider the variable of “waiting-time” during the process of liver resection.

Unlike treatments for HCC, treatments for ICC require hepatoduodenal ligament LND. This procedure can be time-consuming when using a laparoscopic approach, and increases the “waiting time” during LCVP, possibly having an adverse effect on the quality of subsequent liver resection. We found a positive correlation between “waiting time” and blood loss (Fig. 2), a result not reported in previous studies. This correlation may be due to the accumulation of acidic products and local vasodilators in the liver caused by long-term LCVP. During relative hypoxia, production of catecholamines, and the massive accumulation of lactic acid, 5-HT, adenosine, and bradykinin substances can occur. This can lead to microvascular expansion, vascular reactivity, and decreased contractility, and result a decreased quality of liver resection and increased bleeding [47,48,49]. The higher lactate levels in our traditional group before and after liver resection reflected this difference. Many studies reported that a laparoscopic approach can reduce blood loss compared with open surgery. The blood loss in our traditional group was similar to that reported in some studies, but lower than that from open surgery in other studies [10, 18, 20, 44, 50,51,52,53,54]. The present study is the first to report that optimizing the laparoscopic procedure can reduce blood loss and improve the condition of the hepatic surgical field. A dry surgical field in the liver provides better visualization of the intrahepatic vessels, and therefore reduces bleeding and conversion caused by accidental injury to these intrahepatic vessels [47,48,49]. When the surgical field is in a better condition, this reduces the rate of transfusion and conversion, and the time needed for hepatectomy, leading to a shorter operation time and improved intraoperative outcomes [20, 46, 51,52,53,54].

Surgeons increasingly prefer routine regional LND, and the AJCC recommends harvesting more than 6 LNs [12]. However, there is limited understanding of quality of LND using a laparoscopic approach [4, 36, 50, 55]. We unexpectedly found that optimizing the surgical procedure improved the quality of laparoscopic LND and increased the number of harvested LNs (10.0 vs. 8.0, P < 0.001). Furthermore, the rate of adequate LND in this study reached 88.1% (optimized procedure) and 77.4% (traditional procedure), higher than the 20 to 43% reported in previous research [55]. A recent multi-center study of ICC by Brustia et al. showed that laparoscopic surgery was non-inferior to open surgery in terms of OS and DFS, and led to similar numbers of harvested LNs (2.23 ± 0.78 vs. 2.42 ± 1.25), but their corresponding rates of performed LND was only 17.9% (laparoscopic) and 21.3% (open) [44]. Another multi-center study showed that laparoscopic surgery led to a greater number of harvested LNs (5 [IQR: 4–7] vs. 3 [IQR: 2–6]) and a higher rate of adequate LND (43% vs. 35%), but these differences were not statistically significant and may have been biased by the different numbers of patients who received LND [10].

Compared with previous studies, we harvested more LNs and had a higher rate of adequate LND. We can suggest several reasons for these results. First, we only included patients with advanced-stage ICC, all of whom received LND because of preoperative suspicious LNs. Second, our center is the largest hepato-biliary-pancreatic center in Southeast China, and has extensive experience in laparoscopic liver resection and LND [56, 57]. Third, at a technical level, removal of the lesion improves the visual field when there is no occlusion by LNs. In the traditional procedure, one of the arms of the assistant’s forceps must be used to help expose the hepatic duodenal ligament area from occlusion by the liver. This procedure is unnecessary when using the optimized procedure, and this allows experienced surgeons at each side (a “bilateral two chief surgeons approach”) for exposing the hilar blood vessels and performing the LND [57]. Fourth, the main task (liver resection) in the optimized group was completed before the LND, and there was almost no psychological pressure on the surgical team due to the “waiting time”. A more relaxed mental state is conducive to more refined operations during surgery [58,59,60], and the lower STAI in the optimized group reflects this benefit. Moreover, the presence of more positive LNs in the optimized group may be because this group had more harvested LNs; the two groups had no significant difference in the percentages of positive LNs.

Interestingly, our observations indicated that some surgeons in the traditional group were eager to complete the LND first. As a result, the quality of some LNDs was unsatisfactory. Some surgeons who had more patience may spend a long time in carefully performing LND and achieve high-quality results. However, this could lead to an excessive “waiting time”, so that the subsequent condition of the hepatic surgical field was unsatisfactory, often with large blood loss and the need for an extremely long operation time. In other words, using the traditional procedure does not allow both high-quality LND and a short “waiting time”. The optimization procedure described here resolves this dilemma. A more encouraging result is our finding of longer median DFS and OS in the optimized group. This may be because of the improved quality of LND and the earlier discharge and receipt of chemotherapy [61]. Subgroup analysis and Cox regression analysis confirmed these findings (Fig. 3, Table 6). Among patients with stage N0, our two groups had no significant difference in DFS and OS, consistent with previous studies [4, 13].

Patients in our optimized group also had a lower incidence of total morbidities and a faster postoperative recovery, possibly because of the shorter operation time and lower blood lactate levels. Previous studies reported that an excessive operation time increased the risk of intraoperative blood loss, lactic acid level, and various perioperative adverse events [27]. Optimizing the surgical procedure and shortening the operation time can also reduce the frequency of adverse events [62]. Our regression analysis confirmed that optimizing the surgical procedure reduced total morbidities. The incidence rates of complications in our two groups were similar to those reported in previous studies, indicating that the optimized three-step procedure described here is safe and feasible [41, 44,45,46]. Importantly, the optimized procedure described here is also low-cost, easy to develop, and provides good clinical value.

This study had some limitations. First, this was an observational study. Although selection bias cannot be completely prevented, we used PS matching to minimize this bias. Second, this study was performed at a single center in China, and therefore requires confirmation by studies at other centers. Third, given the small sample size, further follow-up of survival times is required in the future.

Conclusions

Based on the concept of “waiting time”, we developed a three-step optimized laparoscopic procedure for advanced ICC to improve the quality of liver resection and LND, to prolong DFS and OS, and to provide better intraoperative and postoperative outcomes. Our results indicated the three-step laparoscopic procedure described here is feasible and effective, and should be considered for patients with advanced ICC.

Availability of data and materials

All data generated during this study are shown in the figures and tables. The datasets generated during the current study are not publicly available, but are available from the corresponding author on reasonable request.

References

  1. Khan SA, Davidson BR, Goldin RD, Heaton N, Karani J, Pereira SP, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61:1657–69.

    Article  CAS  PubMed  Google Scholar 

  2. Njei B. Changing pattern of epidemiology in intrahepatic cholangiocarcinoma. Hepatology. 2014;60:1107–8.

    Article  PubMed  Google Scholar 

  3. Bagante F, Spolverato G, Weiss M, Alexandrescu S, Marques HP, Aldrighetti L, et al. Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging System. J Gastrointest Surg. 2018;22:52–9.

    Article  PubMed  Google Scholar 

  4. de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29:3140–5.

    Article  PubMed  Google Scholar 

  5. Amini N, Ejaz A, Spolverato G, Maithel SK, Kim Y, Pawlik TM. Management of lymph nodes during resection of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: a systematic review. J Gastrointest Surg. 2014;18:2136–48.

    Article  PubMed  Google Scholar 

  6. Vitale A, Moustafa M, Spolverato G, Gani F, Cillo U, Pawlik TM. Defining the possible therapeutic benefit of lymphadenectomy among patients undergoing hepatic resection for intrahepatic cholangiocarcinoma. J Surg Oncol. 2016;113:685–91.

    Article  PubMed  Google Scholar 

  7. Uchiyama K, Yamamoto M, Yamaue H, Ariizumi S, Aoki T, Kokudo N, et al. Impact of nodal involvement on surgical outcomes of intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci. 2011;18:443–52.

    Article  PubMed  Google Scholar 

  8. Kim DH, Choi DW, Choi SH, Heo JS, Kow AW. Is there a role for systematic hepatic pedicle lymphadenectomy in intrahepatic cholangiocarcinoma? A review of 17 years of experience in a tertiary institution. Surgery. 2015;157:666–75.

    Article  PubMed  Google Scholar 

  9. Yoh T, Cauchy F, Le Roy B, Seo S, Taura K, Hobeika C, et al. Prognostic value of lymphadenectomy for long-term outcomes in node-negative intrahepatic cholangiocarcinoma: a multicenter study. Surgery. 2019;166:975–82.

    Article  PubMed  Google Scholar 

  10. Hobeika C, Cauchy F, Fuks D, Barbier L, Fabre JM, Boleslawski E, et al. Laparoscopic versus open resection of intrahepatic cholangiocarcinoma: nationwide analysis. Br J Surg. 2021;108:419–26.

    Article  CAS  PubMed  Google Scholar 

  11. Lee AJ, Chun YS. Intrahepatic cholangiocarcinoma: the AJCC/UICC 8th edition updates. Chin Clin Oncol. 2018;7:52.

    Article  PubMed  Google Scholar 

  12. Spolverato G, Bagante F, Weiss M, Alexandrescu S, Marques HP, Aldrighetti L, et al. Comparative performances of the 7th and the 8th editions of the American Joint Committee on Cancer staging systems for intrahepatic cholangiocarcinoma. J Surg Oncol. 2017;115:696–703.

    Article  PubMed  Google Scholar 

  13. Zhang XF, Xue F, Dong DH, Weiss M, Popescu I, Marques HP, et al. Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis. Ann Surg. 2021;274:e1187–95.

    Article  PubMed  Google Scholar 

  14. Takahashi M, Wakabayashi G, Nitta H, Takeda D, Hasegawa Y, Takahara T, et al. Pure laparoscopic right hepatectomy by anterior approach with hanging maneuver for large intrahepatic cholangiocarcinoma. Surg Endosc. 2013;27:4732–3.

    Article  PubMed  Google Scholar 

  15. Fiorentini G, Ratti F, Cipriani F, Catena M, Paganelli M, Aldrighetti L. Challenges and Technical Innovations for an Effective Laparoscopic Lymphadenectomy in Liver Malignancies. J Laparoendosc Adv Surg Tech A. 2019;29:72–5.

    Article  PubMed  Google Scholar 

  16. Ratti F, Fiorentini G, Cipriani F, Paganelli M, Catena M, Aldrighetti L. Perioperative and Long-Term Outcomes of Laparoscopic Versus Open Lymphadenectomy for Biliary Tumors: A Propensity-Score-Based, Case-Matched Analysis. Ann Surg Oncol. 2019;26:564–75.

    Article  PubMed  Google Scholar 

  17. Abu Hilal M, Badran A, Di Fabio F, Pearce NW. Pure laparoscopic en bloc left hemihepatectomy and caudate lobe resection in patients with intrahepatic cholangiocarcinoma. J Laparoendosc Adv Surg Tech A. 2011;21:845–9.

    Article  PubMed  Google Scholar 

  18. Ratti F, Cipriani F, Ariotti R, Gagliano A, Paganelli M, Catena M, et al. Safety and feasibility of laparoscopic liver resection with associated lymphadenectomy for intrahepatic cholangiocarcinoma: a propensity score-based case-matched analysis from a single institution. Surg Endosc. 2016;30:1999–2010.

    Article  PubMed  Google Scholar 

  19. Uy BJ, Han HS, Yoon YS, Cho JY. Laparoscopic liver resection for intrahepatic cholangiocarcinoma. J Laparoendosc Adv Surg Tech A. 2015;25:272–7.

    Article  PubMed  Google Scholar 

  20. Wei F, Lu C, Cai L, Yu H, Liang X, Cai X. Can laparoscopic liver resection provide a favorable option for patients with large or multiple intrahepatic cholangiocarcinomas? Surg Endosc. 2017;31:3646–55.

    Article  PubMed  Google Scholar 

  21. Fagenson AM, Pitt HA, Lau KN. Perioperative Blood Transfusions or Operative Time: Which Drives Post-Hepatectomy Outcomes? Am Surg. 2022;88(7):1644–52.

  22. Cheng ES, Hallet J, Hanna SS, Law CH, Coburn NG, Tarshis J, et al. Is central venous pressure still relevant in the contemporary era of liver resection? J Surg Res. 2016;200:139–46.

    Article  PubMed  Google Scholar 

  23. McNally SJ, Revie EJ, Massie LJ, McKeown DW, Parks RW, Garden OJ, et al. Factors in perioperative care that determine blood loss in liver surgery. HPB (Oxford). 2012;14:236–41.

    Article  PubMed  Google Scholar 

  24. Pulitano C, Arru M, Bellio L, Rossini S, Ferla G, Aldrighetti L. A risk score for predicting perioperative blood transfusion in liver surgery. Br J Surg. 2007;94:860–5.

    Article  CAS  PubMed  Google Scholar 

  25. Yu L, Sun H, Jin H, Tan H. The effect of low central venous pressure on hepatic surgical field bleeding and serum lactate in patients undergoing partial hepatectomy: a prospective randomized controlled trial. BMC Surg. 2020;20:25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Pietsch UC, Herrmann ML, Uhlmann D, Busch T, Hokema F, Kaisers UX, et al. Blood lactate and pyruvate levels in the perioperative period of liver resection with Pringle maneuver. Clin Hemorheol Microcirc. 2010;44:269–81.

    Article  CAS  PubMed  Google Scholar 

  27. Lemke M, Karanicolas PJ, Habashi R, Behman R, Coburn NG, Hanna SS, et al. Elevated Lactate is Independently Associated with Adverse Outcomes Following Hepatectomy. World J Surg. 2017;41:3180–8.

    Article  PubMed  Google Scholar 

  28. Davies SJ, Vistisen ST, Jian Z, Hatib F, Scheeren TWL. Ability of an Arterial Waveform Analysis-Derived Hypotension Prediction Index to Predict Future Hypotensive Events in Surgical Patients. Anesth Analg. 2020;130:352–9.

    Article  PubMed  Google Scholar 

  29. Jegatheeswaran S, Siriwardena AK. Experimental and clinical evidence for modification of hepatic ischaemia-reperfusion injury by N-acetylcysteine during major liver surgery. HPB (Oxford). 2011;13:71–8.

    Article  PubMed  Google Scholar 

  30. Poolton JM, Wilson MR, Malhotra N, Ngo K, Masters RS. A comparison of evaluation, time pressure, and multitasking as stressors of psychomotor operative performance. Surgery. 2011;149:776–82.

    Article  PubMed  Google Scholar 

  31. Whelehan DF, Connelly TM, Burke JR, Doherty EM, Ridgway PF. Self-reported surgeon health behaviours: a multicentre, cross-sectional exploration into the modifiable factors that impact surgical performance with the association of surgeons in training. Ann Med Surg (Lond). 2021;65:102299.

    Article  PubMed  Google Scholar 

  32. Wheelock A, Suliman A, Wharton R, Babu ED, Hull L, Vincent C, et al. The Impact of Operating Room Distractions on Stress, Workload, and Teamwork. Ann Surg. 2015;261:1079–84.

    Article  PubMed  Google Scholar 

  33. Platte K, Alleblas CCJ, Inthout J, Nieboer TE. Measuring fatigue and stress in laparoscopic surgery: validity and reliability of the star-track test. Minim Invasive Ther Allied Technol. 2019;28:57–64.

    Article  PubMed  Google Scholar 

  34. Agha R, Abdall-Razak A, Crossley E, Dowlut N, Iosifidis C, Mathew G, et al. STROCSS 2019 Guideline: Strengthening the reporting of cohort studies in surgery. Int J Surg. 2019;72:156–65.

    Article  PubMed  Google Scholar 

  35. Mungroop TH, Geerts BF, Veelo DP, Pawlik TM, Bonnet A, Lesurtel M, et al. Fluid and pain management in liver surgery (MILESTONE): a worldwide study among surgeons and anesthesiologists. Surgery. 2019;165:337–44.

    Article  PubMed  Google Scholar 

  36. Weber SM, Ribero D, O’Reilly EM, Kokudo N, Miyazaki M, Pawlik TM. Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17:669–80.

    Article  PubMed  Google Scholar 

  37. Das A, Chhaule S, Bhattacharya S, Basunia SR, Mitra T, Halder PS, et al. Controlled hypotension in day care functional endoscopic sinus surgery: a comparison between esmolol and dexmedetomidine: a prospective, double-blind, and randomized study. Saudi J Anaesth. 2016;10:276–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.

    Article  PubMed  Google Scholar 

  39. Brooke-Smith M, Figueras J, Ullah S, Rees M, Vauthey JN, Hugh TJ, et al. Prospective evaluation of the International Study Group for Liver Surgery definition of bile leak after a liver resection and the role of routine operative drainage: an international multicentre study. HPB (Oxford). 2015;17:46–51.

    Article  PubMed  Google Scholar 

  40. Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, 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;149:680–8.

    Article  PubMed  Google Scholar 

  41. Yamamoto M, Kobayashi T, Oshita A, Abe T, Kohashi T, Onoe T, et al. Laparoscopic versus open limited liver resection for hepatocellular carcinoma with liver cirrhosis: a propensity score matching study with the Hiroshima Surgical study group of Clinical Oncology (HiSCO). Surg Endosc. 2020;34:5055–61.

    Article  PubMed  Google Scholar 

  42. Tranchart H, O’Rourke N, Van Dam R, Gaillard M, Lainas P, Sugioka A, et al. Bleeding control during laparoscopic liver resection: a review of literature. J Hepatobiliary Pancreat Sci. 2015;22:371–8.

    Article  PubMed  Google Scholar 

  43. Waisberg DR, Pinheiro RS, Nacif LS, Rocha-Santos V, Martino RB, Arantes RM, et al. Resection for intrahepatic cholangiocellular cancer: new advances. Transl Gastroenterol Hepatol. 2018;3:60.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Brustia R, Laurent A, Goumard C, et al. Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: Report of an international multicenter cohort study with propensity score matching. Surgery. 2022;171(5):1290–302.

  45. Wu J, Han J, Zhang Y, Liang L, Zhao J, Han F, et al. Safety and feasibility of laparoscopic versus open liver resection with associated lymphadenectomy for intrahepatic cholangiocarcinoma. Biosci Trends. 2020;14:376–83.

    Article  PubMed  Google Scholar 

  46. Ratti F, Rawashdeh A, Cipriani F, Primrose J, Fiorentini G, Abu Hilal M, et al. Intrahepatic cholangiocarcinoma as the new field of implementation of laparoscopic liver resection programs. A comparative propensity score-based analysis of open and laparoscopic liver resections. Surg Endosc. 2021;35:1851–62.

    Article  PubMed  Google Scholar 

  47. Zhang ZS, Chen W, Li T, Liu LM. Organ-specific changes in vascular reactivity and roles of inducible nitric oxide synthase and endothelin-1 in a rabbit endotoxic shock model. J Trauma Acute Care Surg. 2018;85:725–33.

    Article  CAS  PubMed  Google Scholar 

  48. Liu LM, Dubick MA. Hemorrhagic shock-induced vascular hyporeactivity in the rat: relationship to gene expression of nitric oxide synthase, endothelin-1, and select cytokines in corresponding organs. J Surg Res. 2005;125:128–36.

    Article  CAS  PubMed  Google Scholar 

  49. Saidi RF, Kenari SK. Liver ischemia/reperfusion injury: an overview. J Invest Surg. 2014;27:366–79.

    Article  PubMed  Google Scholar 

  50. Zhang XF, Chakedis J, Bagante F, Chen Q, Beal EW, Lv Y, et al. Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma. Br J Surg. 2018;105:857–66.

    Article  PubMed  Google Scholar 

  51. Kang SH, Choi Y, Lee W, Ahn S, Cho JY, Yoon YS, et al. Laparoscopic liver resection versus open liver resection for intrahepatic cholangiocarcinoma: 3-year outcomes of a cohort study with propensity score matching. Surg Oncol. 2020;33:63–9.

    Article  PubMed  Google Scholar 

  52. Kinoshita M, Kanazawa A, Takemura S, Tanaka S, Kodai S, Shinkawa H, et al. Indications for laparoscopic liver resection of mass-forming intrahepatic cholangiocarcinoma. Asian J Endosc Surg. 2020;13:46–58.

    Article  PubMed  Google Scholar 

  53. Lee W, Park JH, Kim JY, Kwag SJ, Park T, Jeong SH, et al. Comparison of perioperative and oncologic outcomes between open and laparoscopic liver resection for intrahepatic cholangiocarcinoma. Surg Endosc. 2016;30:4835–40.

    Article  PubMed  Google Scholar 

  54. Zhu Y, Song J, Xu X, Tan Y, Yang J. Safety and feasibility of laparoscopic liver resection for patients with large or multiple intrahepatic cholangiocarcinomas: a propensity score based case-matched analysis from a single institute. Medicine (Baltimore). 2019;98:e18307.

    Article  PubMed  Google Scholar 

  55. Lauterio A, De Carlis R, Centonze L, Buscemi V, Incarbone N, Vella I, et al. Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma. Cancers (Basel). 2021;13:3657.

    Article  CAS  PubMed  Google Scholar 

  56. Liao C, Wang D, Huang L, Bai Y, Yan M, Zhou S, et al. A new strategy of laparoscopic anatomical hemihepatectomy guided by the middle hepatic vein combined with transhepatic duct lithotomy for complex hemihepatolithiasis: a propensity score matching study. Surgery. 2021;170:18–29.

    Article  PubMed  Google Scholar 

  57. Chen S, Huang L, Qiu FN, Zhou SQ, Yan ML, Bai YN, et al. Total laparoscopic partial hepatectomy versus open partial hepatectomy for primary left-sided hepatolithiasis: a propensity, long-term follow-up analysis at a single center. Surgery. 2018;163:714–20.

    Article  PubMed  Google Scholar 

  58. Arora S, Sevdalis N, Nestel D, Woloshynowych M, Darzi A, Kneebone R. The impact of stress on surgical performance: a systematic review of the literature. Surgery. 2010;147:318–30, 30 e1-6.

    Article  PubMed  Google Scholar 

  59. Grantcharov PD, Boillat T, Elkabany S, Wac K, Rivas H. Acute mental stress and surgical performance. BJS Open. 2019;3:119–25.

    Article  CAS  PubMed  Google Scholar 

  60. Chrouser KL, Xu J, Hallbeck S, Weinger MB, Partin MR. The influence of stress responses on surgical performance and outcomes: Literature review and the development of the surgical stress effects (SSE) framework. Am J Surg. 2018;216:573–84.

    Article  PubMed  Google Scholar 

  61. Croome KP, Farnell MB, Que FG, Reid-Lombardo KM, Truty MJ, Nagorney DM, et al. Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches? Ann Surg. 2014;260:633–8; discussion 8-40.

    Article  PubMed  Google Scholar 

  62. Chacon E, Eman P, Dugan A, Davenport D, Marti F, Ancheta A, et al. Effect of operative duration on infectious complications and mortality following hepatectomy. HPB (Oxford). 2019;21:1727–33.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

None

Provenance and peer review

Not commissioned, externally peer-reviewed.

Funding

This work was supported by the Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare (No.2021(60), to Shi Chen), the Fujian Youth Talent Support Program (No.2018(05), to Shi Chen) and the Youth Scientific Research Project of Fujian Provincial Health Commission (No. 2020QNA005, to Dan-Feng Wang). This work was sponsored by key Clinical Specialty Discipline Construction Program of Fujian, P.R.C.

Author information

Author notes

  1. Cheng-Yu Liao, Dan-Feng Wang and Bin-Hua Jiang contributed equally to this work and should be considered first coauthors.

Authors and Affiliations

  1. Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China

    Cheng-Yu Liao, Dan-Feng Wang, Bin-Hua Jiang, Long Huang, Tian-Sheng Lin, Fu-Nan Qiu, Song-Qiang Zhou, Yao-Dong Wang, Xiao-Chun Zheng, Yi-Feng Tian & Shi Chen

  2. Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, 350001, China

    Cheng-Yu Liao, Bin-Hua Jiang, Long Huang, Tian-Sheng Lin, Fu-Nan Qiu, Song-Qiang Zhou, Yao-Dong Wang, Yi-Feng Tian & Shi Chen

  3. Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou, 350001, China

    Dan-Feng Wang & Xiao-Chun Zheng

  4. Fujian Emergency Medical Center, Fujian Emergency Medical Center, Fujian Provincial Key Laboratory of Emergency Medicine, Fujian Provincial Key Laboratory of Critical Medicine, Fujian Provincial Coconstructed Laboratory of “Belt and Road”, Fuzhou, China

    Xiao-Chun Zheng

Authors
  1. Cheng-Yu Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan-Feng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin-Hua Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Long Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tian-Sheng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fu-Nan Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Song-Qiang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yao-Dong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiao-Chun Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yi-Feng Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Shi Chen, Yi-Feng Tian and Xiao-Chun Zheng had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analyses. Concept and design: Shi Chen, Cheng-Yu Liao and Yi-Feng Tian. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Cheng-Yu Liao and Dan-Feng Wang. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Bin-Hua Jiang and Cheng-Yu Liao. Administrative, technical, or material support: All authors. Study supervision: Shi Chen. The author(s) read and approved the final manuscript.

Corresponding authors

Correspondence to Xiao-Chun Zheng, Yi-Feng Tian or Shi Chen.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee, and all procedures were performed in accordance with the 2013 Declaration of Helsinki. Written informed consent was provided by each patient.

Consent for publication

Not applicable.

Competing interests

None reported.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

All the authors above meet the criteria for authorship in the Consensus Statement on Journal Authorship cited later in these instructions. All the authors have not published, posted, or submitted any related papers from the same study.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liao, CY., Wang, DF., Jiang, BH. et al. Optimization of a laparoscopic procedure for advanced intrahepatic cholangiocarcinoma based on the concept of “waiting time”: a preliminary report. BMC Cancer 22, 1222 (2022). https://doi.org/10.1186/s12885-022-10323-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12885-022-10323-x

Keywords

BMC Cancer

ISSN: 1471-2407

Contact us