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T2、T3期胆囊癌行肝外胆管预防性切除的临床意义及生存预后研究
唐鹏, 朱恒昌, 李晨, 易建伟, 王恺
中国实用外科杂志 ›› 2025, Vol. 45 ›› Issue (12) : 1449-1455.
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T2、T3期胆囊癌行肝外胆管预防性切除的临床意义及生存预后研究
Clinical significance and prognostic impact of prophylactic extrahepatic bile duct resection in patients with T2 and T3 gallbladder cancer
目的 探讨T2、T3期胆囊癌（GBC）病人行肝外胆管（EHBD）预防性胆管切除（BDR）的临床意义及其对生存预后的影响。方法 回顾性分析2013年3月至2023年3月期间南昌大学第二附属医院肝胆胰外科收治并接受根治性手术的69例T2、T3期GBC病人的临床资料。依据是否行EHBD切除将病人分为BDR（+）组与BDR（-）组，对比两组的总体生存期（OS）与无病生存期（DFS），并采用Cox比例风险回归模型筛选危险因素，进一步进行亚组分析。组间比较应用t检验、卡方检验、Fisher精确检验和U检验，生存率采用Kaplan-Meier法绘制曲线，P<0.05为差异有统计学意义。结果 在总体样本中，BDR（+）组与BDR（-）组的中位OS（17.0个月 vs.13.0个月）和中位DFS（11.0个月 vs.10.0个月）差异均无统计学意义（P=0.282，P=0.760）。多因素分析提示阳性淋巴结个数≥2及T3期是影响OS的独立危险因素（P=0.022，P=0.003）。亚组分析结果显示，在阳性淋巴结个数≥2及阳性淋巴结比例≥0.2的病人中，BDR（+）组较BDR（-）组具有更好的预后（OS和DFS差异均有统计学意义，P<0.05）。此外，在伴有神经侵袭的病人中，BDR（+）组OS明显优于BDR（-）组（P=0.026），但DFS差异无统计学意义（P=0.187）。组间比较结果显示，BDR（+）组可清扫到更多阳性淋巴结，阳性淋巴结比例更高，且N分期更差（P<0.05），但术后并发症发生率与BDR（-）组相比差异无统计学意义（P=0.556）。结论 T2、T3期GBC病人行EHBD切除能够提高清扫阳性淋巴结的数量和比例。对于阳性淋巴结数量≥2或阳性淋巴结比例≥0.2的病人，EHBD切除可改善其生存预后。
Objective To investigate the clinical significance of prophylactic extrahepatic bile duct resection (EHBDR) in patients with T2 and T3 gallbladder cancer (GBC) and its impact on survival outcomes. Methods A retrospective analysis was performed on 69 patients with T2 and T3 GBC who underwent radical surgery at the Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, between March 2013 and March 2023. Patients were divided into the BDR (+) group and BDR (-) group according to whether EHBD resection was performed. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Risk factors were identified using the Cox proportional hazards regression model, and subgroup analyses were further conducted. Student’s t test, Chi-square test, Fisher’s exact test, and Mann-Whitney U test were applied for group comparisons. Survival curves were generated using the Kaplan-Meier method, with P<0.05 considered statistically significant. Results In the overall cohort, no significant differences were observed in median OS (17.0 months vs.13.0 months, P=0.282) or median DFS (11.0 months vs.10.0 months, P=0.760) between the BDR (+) and BDR (-) groups. Multivariate analysis indicated that ≥2 positive lymph nodes and T3 stage were independent risk factors for OS (P=0.022, P=0.003). Subgroup analysis revealed that in patients with ≥2 positive lymph nodes or a positive lymph node ratio ≥0.2, the BDR (+) group had significantly better OS and DFS than the BDR (-) group (both P<0.05). Furthermore, in patients with perineural invasion, OS was significantly longer in the BDR (+) group compared with the BDR (-) group (P=0.026), while no significant difference was observed in DFS (P=0.187). Group comparisons showed that the BDR (+) group yielded a greater number of positive lymph nodes, a higher positive lymph node ratio, and a worse N stage (P<0.05), while postoperative complication rates were similar between the two groups (P=0.556). Conclusion EHBD resection in T2 and T3 GBC increases the number and ratio of positive lymph nodes harvested. For patients with ≥2 positive lymph nodes or a positive lymph node ratio ≥0.2, EHBD resection may improve survival outcomes.
胆囊癌 / 肝外胆管切除 / 阳性淋巴结 / 阳性淋巴结比例 / 生存预后
gallbladder cancer / extrahepatic bile duct resection / positive lymph nodes / proportion of positive lymph nodes / survival prognosis
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中华医学会外科学分会胆道外科学组, 中国医师协会外科医师分会胆道外科专业委员会. 胆囊癌诊断和治疗指南(2019版)[J]. 中华外科杂志, 2020, 58(4):243-251.DOI:10.3760/cma.j.cn112139-20200106-00014.
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Although radical re-resection for gallbladder cancer (GBC) has been advocated, the optimal extent of re-resection remains unknown. The current study aimed to assess the impact of common bile duct (CBD) resection on survival among patients undergoing surgery for GBC.Patients undergoing curative-intent surgery for GBC were identified using a multi-institutional cohort of patients. Multivariable Cox-proportional hazards regression was performed to identify risk factors for a poor overall survival (OS).Among the 449 patients identified, 26.9% underwent a concomitant CBD resection. The median number of lymph nodes harvested did not differ based on CBD resection (CBD, 4 [IQR: 2-9] vs. no CBD, 3 [IQR: 1-7], P = 0.108). While patients who underwent a CBD resection had a worse OS, after adjusting for potential confounders, CBD resection did not impact OS (HR = 1.40, 95%CI 0.87-2.27, P = 0.170). Rather, the presence of advanced disease (T3: HR = 3.11, 95%CI 1.22-7.96, P = 0.018; T4: HR = 7.24, 95%CI 1.70-30.85, P = 0.007) and the presence of disease at the surgical margin (HR = 2.58, 95%CI 1.26-5.31, P = 0.010) were predictive of a worse OS.CBD resection did not yield a higher lymph node count and was not associated with an improved survival. Routine CBD excision in the re-resection of GBC is unwarranted and should only be performed selectively. J. Surg. Oncol. 2016;114:176-180. © 2016 Wiley Periodicals, Inc.© 2016 Wiley Periodicals, Inc.
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The present study aimed to determine whether concomitant extrahepatic bile duct resection (EHBDR) improves the prognosis of patients with T2 gallbladder cancer (GBC).Between 2014 and 2018, 4947 patients with GBC were registered in the National Biliary Tract Cancer Registry in Japan. This included 3804 patients (76.9%) who underwent curative-intent surgical resection; 1609 of these patients had pT2 GBC with no distant metastasis. Of the 1609 patients with GBC, 520 underwent EHBDR and 1089 did not. We compared the patients' backgrounds and disease-specific survival rates between the groups.The frequency of lymph node metastasis was significantly higher in the EHBDR group than in the non-EHBDR group (38.2% vs. 20.7%, p < .001). In the entire cohort, however, there was no significant difference in disease-specific survival between the two groups (76% vs. 79%, p = .410). The EHBDR group had a significantly higher incidence of postoperative complications (Clavien-Dindo classification grade = 3) (32.4% vs. 11.7%, p < .001). When we focused on the survival of only T2N1 patients who underwent gallbladder bed resection, the prognosis was significantly improved for the EHBDR group (5-year survival rate: 64% vs. 54%, p = .017). The non-EHBDR group was subcategorized into two groups: D2 dissection and D1 dissection or sampling, and survival curves were compared between these subgroups. Although the EHBDR group tended to have a favorable prognosis compared to the D2 group, this difference was not significant (p = .167). However, the EHBDR group had a significantly greater prognosis than the D1 dissection or sampling group (5 year-survival rate: 64 vs. 49%, p = .027).The EHBDR may improve the prognosis of patients with T2 gall bladder cancer with lymph node metastases; however, its indication should be carefully determined because of the increased risk of postoperative complications.© 2023 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.
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Gallbladder cancer (GBC) is the most common biliary malignancy and has the worst prognosis, but aggressive surgeries [., resection of the extrahepatic bile duct (EHBD), major hepatectomy and lymph node (LN) dissection] may improve long-term survival. GBC may be suspected preoperatively, identified intraoperatively, or discovered incidentally on histopathology.To present our data together with a discussion of the therapeutic strategies for GBC.We retrospectively investigated nineteen GBC patients who underwent surgical treatment.Nearly all symptomatic patients had poor outcomes, while suspicious or incidental GBCs at early stages showed excellent outcomes without the need for two-stage surgery. Lymph nodes around the cystic duct were reliable sentinel nodes in suspicious/incidental GBCs. Intentional LN dissection and EHBD resection prevented metastases or recurrence in early-stage GBCs but not in advanced GBCs with metastatic LNs or invasion of the nerve plexus. All patients with positive surgical margins (., the biliary cut surface) showed poor outcomes. Hepatectomies were performed in sixteen patients, nearly all of which were minor hepatectomies. Metastases were observed in the left-sided liver but not in the caudate lobe. We may need to reconsider the indications for major hepatectomy, minimizing its use except when it is required to accomplish negative bile duct margins. Only a few patients received neoadjuvant or adjuvant chemoradiation. There were significant differences in overall and disease-free survival between patients with stages ≤ IIB and ≥ IIIA disease. The median overall survival and disease-free survival were 1.66 and 0.79 years, respectively.Outcomes for GBC patients remain unacceptable, and improved therapeutic strategies, including neoadjuvant chemotherapy, optimal surgery and adjuvant chemotherapy, should be considered for patients with advanced GBCs.©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
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<b><i>Background:</i></b> Despite the increasing number of reports on the favorable outcomes of laparoscopic surgery for gallbladder cancer (GBC), there is no consensus regarding this surgical procedure. <b><i>Objective:</i></b> The study aimed to develop a consensus statement on the application of laparoscopic surgery for GBC based on expert opinions. <b><i>Methods:</i></b> A consensus meeting among experts was held on September 10, 2016, in Seoul, Korea. <b><i>Results:</i></b> Early concerns regarding port site/peritoneal metastasis after laparoscopic surgery have been abated by improved preoperative recognition of GBC and careful manipulation to avoid bile spillage. There is no evidence that laparoscopic surgery is associated with decreased survival compared with open surgery in patients with early-stage GBC if definitive resection during/after laparoscopic cholecystectomy is performed. Although experience with laparoscopic extended cholecystectomy for GBC has been limited to a few experts, the postoperative and survival outcomes were similar between laparoscopic and open surgeries. Laparoscopic reoperation for postoperatively diagnosed GBC is technically challenging, but its feasibility has been demonstrated by a few experts. <b><i>Conclusions:</i></b> Laparoscopic surgery for GBC is still in the early phase of the adoption curve, and more evidence is required to assess this procedure.
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Gallbladder cancer (GBC) is a rare malignancy with a dismal prognosis. Often identified incidentally after laparoscopic cholecystectomy for presumably benign biliary disease, reoperation with partial hepatic resection and periportal lymph node dissection (LND) is frequently performed. The impact of lymph node (LN) clearance for GBC remains unclear.The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed with GBC between 1988 and 2009. Survival was calculated using Kaplan-Meier method and compared using log-rank test. Multivariate analysis was performed to identify predictors of survival.A total of 11,815 patients diagnosed with GBC were identified. Cancer-directed surgery was performed in 8,436 (71.3%) patients. Optimal LN clearance (defined as ≥4 LNs) is associated with young age, advanced T-stage, no radiation therapy, and radical surgery (all <0.001). Greater LND improves survival for all stages (P<0.001). After adjusting for confounding factors, multivariable analysis of patients with node-negative disease demonstrated that early stage, greater LND, and radical surgery were strong independent predictors of survival.Extensive lymphadenectomy correlates with longer survival even in node negative patients. Extensive LND should be performed in patients with GBC as many patients in the USA are undertreated.
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Lymph node (LN) metastasis is an important prognostic factor in gallbladder cancer (GBCA). LN status has been adopted as a critical element of staging systems. However, the influence of total lymph node count (TLNC) remains unclear. We determined the optimal minimum TLNC and compared the prognostic significance of LN status indices in GBCA.We retrospectively reviewed medical records of 128 patients with T2 or greater GBCA who underwent LN dissection. We analyzed overall survival (OS) and relevance of the number of metastatic LNs, ratio of metastatic LNs to retrieved LNs (LNR), and TLNC in predicting OS.The median OS durations were 120, 35, and 18 months in T2, T3, and T4 GBCA. Five-year OS rates were 73%, 43%, and 0% in T2, T3, and T4 GBCA. LN status did not significantly impact OS in T2 or T4 GBCA. However, all LN indices were significantly correlated with OS in T3 GBCA. Furthermore, multivariate analysis revealed that a metastatic LN count of more than four and a TLNC of more than eight were independent prognostic factors of OS in T3 GBCA.TLNC and the number of positive LNs may be more important prognostic factors than LNR in T3 GBCA. Additionally, accurate staging may not be achieved in cases of T3 GBCA if the total number of retrieved LNs is less than eight. Thus, to ensure proper staging, we recommend that surgeons harvest more than eight LNs in patients with T3 GBCA.Copyright © 2015 Elsevier Ltd. All rights reserved.
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罗艺, 刘东明, 李广涛, 等. T3期胆囊癌淋巴结清扫范围对预后影响分析[J]. 中国实用外科杂志, 2022, 42(7):794-799.DOI:10.19538/j.cjps.issn1005-2208.2022.07.19.
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The authors' objective was to evaluate the effectiveness of radical surgery with lymph node dissection for gallbladder carcinoma. Long-term results were analyzed in 40 patients in a 5-year study. The authors divided the 40 cases into two groups: 20 without positive nodes and 20 with positive nodes. In the group without positive nodes, one patient who underwent R1 resection died of a recurrence at 1 year 7 months. Seventeen of the 19 patients treated with R0 resection survived more than 5 years. The 5-year survival rate was 85% (17/20). In the group with positive nodes, 9 of the 13 patients treated with R0 resection survived more than 5 years, whereas the seven patients treated with R1 or R2 resection died within 5 years. The 5-year survival rate was 45% (9/20). Patients treated by R0 resection showed a 5-year survival rate of 69% (9/13). Thus we documented the favorable long-term results of radical surgery. R0 resection is a prerequisite for long-term survival. The results justify radical surgery with lymph node dissection.
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The aim of this study was to determine the clinical significance of extrahepatic bile duct (EHBD) resection during surgery for advanced gallbladder cancer.Among 110 patients with pT2 or higher grade gallbladder cancer, 58 patients without microscopic invasion to the EHBD were reviewed. Prognostic factors of the 58 patients were evaluated by multivariate analysis. The impact of EHBD resection on survival was assessed in relation to two prognostic determinants: (i) lymph node metastasis: positive (n = 23) and negative (n = 35); (ii) perineural invasion: positive (n = 25) and negative (n = 33).Hepatic metastasis and perineural invasion were found to be independently significant prognostic factors. (i) No survival benefit of additional EHBD resection could be confirmed in each group of patients with or without nodal metastasis. (ii) In 25 patients with perineural invasion, 14 patients who underwent EHBD resection showed better survival as compared to the 11 patients who did not undergo EHBD resection (5-year survival rate, 46% vs. 0%, P = 0.009). In the remaining 33 patients without perineural invasion, the additional EHBD resection did not yield significant improvement of survival (P = 0.28).Resection of EHBD may offer prognostic advantage when perineural invasion exists, even in the absence of biliary infiltration.(c) 2006 Wiley-Liss, Inc.
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Gallbladder cancer has historically been considered an incurable malignancy; although, extended resection has been associated with cure in selected patients. However, the optimal extent of resection is unknown. The objective of this study was to analyze the impact of the extent of resection for gallbladder adenocarcinoma on disease-specific survival (DSS) and perioperative morbidity. Analysis of a prospective hepatobiliary surgery database identified patients undergoing surgical resection for gallbladder adenocarcinoma from 1990 to 2002. Clinicopathologic factors including extent of resection were analyzed for their association with DSS and perioperative morbidity. Long-term outcome was evaluable in 104 patients. With median follow-up of 58 months for survivors, the actuarial 5-year DSS was 42%. Thirty-six patients (35%) underwent major hepatectomy, but in 15 this was not mandatory to clear all disease. Sixty-eight patients (65%) underwent common bile duct (CBD) excision, but 32 were performed empirically. Twenty-one patients (20%) underwent en bloc resection of adjacent organs other than the liver. The performance of a major hepatectomy or a CBD excision was not associated with other clinicopathologic variables or long-term survival. Resection of adjacent organs were associated with advanced T stage but not with survival. T stage, N stage, histologic differentiation, and CBD involvement were independently associated with survival. Major hepatectomy and CBD excision were significantly associated with perioperative morbidity. We conclude that tumor biology and stage, rather than extent of resection, predict outcome after resection for gallbladder cancer. Major hepatic resections, including major hepatectomy and CBD excision, are appropriate when necessary to clear disease but are not mandatory in all cases.
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Lymph node (LN) status is one of the strongest prognostic factors after gallbladder cancer (GBC) resection. The adequate extension of LN dissection and the stratification of the prognosis in N+ patients have been debated. The present study aims to clarify these issues.A total of 112 consecutive patients who underwent operations for GBC with LN dissection were analyzed. Twenty-five patients (22.3%) had D1 dissection (hepatic pedicle), and 87 (77.7%) had D2 dissection (hepatic pedicle, celiac and retro-pancreatic area). The LN ratio (LNR) was computed as follows: number of metastatic LNs/number of retrieved LNs.The median number of retrieved LNs was 7 (1-35). Fifty-nine patients (52.7%) had LN metastases (22 N2). D2 dissection allowed the retrieval of more LNs (8 vs. 3, p = 0.0007), with similar short-term outcomes. Common bile duct (CBD) resection (n = 41) did not increase the number of retrieved LNs. In five patients, D2 dissection identified skip LN metastases that otherwise would have been missed. LN metastases negatively impacted survival (5-years survival 57.2% if N0 vs. 12.4% if N+, p < 0.0001), but N1 and N2 patients had similar survival rates. The number of LN+ (1-3 vs. ≥4) did not impact prognosis. An LNR = 0.15 stratified the prognosis of N+ patients: 5-years survival 32.7% if LNR ≤ 0.15 vs. 10.3% if LNR > 0.15 (multivariate analysis p = 0.007).A D2 LN dissection is recommended in all patients, because it allows for better staging. CBD resection does not improve LN dissection. An LNR = 0.15, not the site of metastatic LNs, stratified the prognoses of N+ patients.
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Radical cholecystectomy is recommended for T2 gallbladder cancer. However, it is unclear whether hepatic resection is essential for peritoneal-side gallbladder cancer.From January 2000 to December 2011, we identified T2 gallbladder cancer patients who had undergone curative intent surgery. A peritoneal-side tumor was defined when the epicenter of the tumor was located within the free peritoneal-side gallbladder mucosa. Hepatic-side gallbladder cancer was defined when the epicenter of the tumor was located within the gallbladder bed or neck.A total of 157 patients with T2 gallbladder cancer were included; 33 peritoneal-side and 124 hepatic-side tumors. In total, 122 patients underwent hepatic resection, whereas the remaining 35 patients did not. After a median follow-up period of 40 (range 5-170) months, the survival of the peritoneal-side group was better than that of the hepatic-side group (p = 0.002). In a multivariate analysis, tumor location, lymph node metastasis, hepatic resection, lymphatic invasion, and perineural invasion were significant prognostic factors (p = 0.045, p < 0.001, p = 0.003, p = 0.046, and p = 0.027, respectively). For the peritoneal-side group, there was no recurrence or death after cholecystectomy without hepatic resection. However, hepatic resection was an important factor associated with overall survival in patients with hepatic-side gallbladder cancer (p = 0.007).In T2 gallbladder cancer patients, hepatic resection is recommended when there is tumor invasion of the gallbladder bed or neck. However, it is not always necessary in selected patients with peritoneal-side gallbladder cancer.
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This retrospective study was designed to appraise the surgical procedures for pT2 gallbladder (GB) carcinomas. Twenty patients with pT2 GB carcinomas underwent surgical resection. Hepatectomy of segments 4b and 5 was performed in 19 patients, and an extended right hepatic lobectomy was performed in 1. The extrahepatic bile duct was preserved in 8 patients in whom the disease was limited to the GB fundus and/or body. Regional lymphadenectomy was performed in 18 patients. A separate radical second operation was performed in 8 patients after cholecystectomy. Final pathological staging was stage IB in 15 patients, IIB in 4, and IV in 1. Overall 5-year survival rate in those 20 patients was 77% without operative deaths. The 5-year survival rate in 5 patients with nodal metastasis and in 8 patients without extrahepatic biliary resection was 80% and 100%, respectively. A separate radical second operation in 8 patients yielded 75% survival after 5 years. Perineural invasion as a prognostic determinant was closely associated with tumor extending to the neck or the cystic duct. Partial hepatectomy, usually with extrahepatic biliary resection and regional lymphadenectomy, was appropriate as a standard radical operation for pT2 GB carcinoma, but preservation of extrahepatic bile duct is advocated for disease limited to the GB fundus and/or body. Radical second operation enhanced the chance for cure in patients with pT2 GB carcinoma.
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李斌. 周围神经侵犯对胆囊癌外科治疗的不利影响和对策[J]. 中国实用外科杂志, 2025, 45(2):168-173.DOI:10.19538/j.cjps.issn1005-2208.2025.02.08.
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