胆囊肉瘤样癌16例临床诊治及预后分析

周雅淑; 马怡晖; 裴家鑫; 孟园园; 郭鹏; 梁曦月; 路太英

doi:10.12449/JCH240420

胆囊肉瘤样癌16例临床诊治及预后分析

DOI: 10.12449/JCH240420

a.
郑州大学第一附属医院肿瘤科，郑州 450052
b.
郑州大学第一附属医院病理科，郑州 450052

基金项目:

河南省医学科技攻关计划省部共建重点项目 (SBGJ202002068)

伦理学声明：本研究方案于2023年7月12日经由郑州大学第一附属医院科研和临床试验伦理委员会审批，批号：2023-KY-0607-001。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：周雅淑负责查阅文献，整理资料，撰写论文；裴家鑫、孟园园、郭鹏、梁曦月负责录入及整理数据，收集患者资料；马怡晖负责病理学分析，指导撰写文章；路太英负责提出选题，拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
路太英， fccluty@zzu.edu.cn （ORCID： 0000-0001-5690-8526）

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出版历程
- 收稿日期: 2023-07-19
- 录用日期: 2023-07-27
- 出版日期: 2024-04-25

Clinical diagnosis， treatment， and prognosis of gallbladder sarcomatoid carcinoma： An analysis of 16 cases

a.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University，Zhengzhou 450052，China
b.
Department of Pathology，The First Affiliated Hospital of Zhengzhou University，Zhengzhou 450052，China

Research funding:

Key Project of Henan Provincial Medical Science and Technology Research Plan (SBGJ202002068)

More Information

Corresponding author: LU Taiying， fccluty@zzu.edu.cn （ORCID： 0000-0001-5690-8526）

摘要

摘要: 目的分析胆囊肉瘤样癌（GBSC）的临床病理特征、诊疗方法及预后。方法回顾性分析2015年1月—2023年4月郑州大学第一附属医院收治的16例胆囊肉瘤样癌患者的临床资料，包括患者的一般资料、临床表现、影像学特点、病理学特点和治疗方式等，并进行随访。采用Kaplan-Meier法进行生存分析，并绘制生存曲线，Log-rank检验比较组间差异。结果 16例患者中男6例，女10例，年龄（62.9±8.4）岁。主要临床表现为右上腹痛13例（81.3%）、恶心5例（31.3%）、腹胀4例（25.0%）、纳差3例（18.8%）、乏力2例（12.5%）、发热2例（12.5%）、黄疸1例（6.3%），3例为无症状体检发现。其中81.3%（13/16）的患者初诊时处于疾病晚期（Ⅲ/Ⅳ期）。组织病理学表现：镜下观部分癌细胞呈梭形，核分裂像多见且异形性明显。免疫组化分析显示：Vimentin阳性表达率100%（16/16），AE1/AE3阳性表达率100%（16/16），CK8/18阳性表达率100%（16/16），81.3%（13/16）的患者Ki-67增殖指数高表达（≥50%），中位数为70%（范围：20%～90%）。16例患者均行手术治疗，根治性手术11例，姑息性手术5例，其中R0切除者9例，R1切除者2例，R2切除者5例，7例术后接受辅助治疗。16例患者均取得有效随访，随访0.5～26.0个月，中位随访时间11.0个月。至随访结束，2例患者存活，14例患者死亡，死亡原因均为肿瘤复发或转移，中位生存时间为10.0个月，术后1年、2年累积生存率分别为31.3%、8.3%。预后分析显示TNM分期（χ²=6.727，P=0.009）、手术方式（χ²=7.508，P=0.006）、切缘情况（χ²=7.934，P=0.005）、辅助治疗（χ²=4.608，P=0.032）与患者预后相关。结论胆囊肉瘤样癌的临床表现无特异性，确诊依赖免疫组化，大多数患者初诊时疾病处于晚期，总体预后较差，目前尚无针对性治疗方法，切缘阴性的根治性手术及辅助治疗可提高患者的生存率。
- 胆囊肿瘤 /
- 免疫组织化学 /
- 预后 /
- 治疗学
Abstract: Objective To investigate the clinicopathological features， diagnosis and treatment methods， and prognosis of gallbladder sarcomatoid carcinoma （GBSC）. Methods A retrospective analysis was performed for the clinical data of 16 patients with GBSC who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2015 to April 2023， including general information， clinical manifestations， imaging features， pathological features， and treatment modality， and follow-up was performed for all patients. The Kaplan-Meier method was used to perform the survival analysis and plot the survival curve， and the Log-rank test was used for comparison between groups. Results Among the 16 patients， there were 6 male patients and 10 female patients， with a mean age of 62.9±8.4 years. The main clinical manifestations were right upper abdominal pain in 13 patients （81.3%）， nausea in 5 patients （31.3%）， abdominal distension in 4 patients （25.0%）， poor appetite in 3 patients （18.8%）， weakness in 2 patients （12.5%）， fever in 2 patients （12.5%）， and jaundice in 1 patient （6.3%）， and 3 patients were asymptomatic and were found to have this disease by physical examination. Of all patients， 81.3% （13/16） were in the advanced stage （stage Ⅲ/Ⅳ） at the time of initial diagnosis. Histopathological examination showed that some cancer cells were spindle-shaped under the microscope， with marked nuclear division and noticeable heteromorphism. Immunohistochemistry showed a positive expression rate of 100% （16/16） for Vimentin， AE1/AE3， and CK8/18， and Ki-67 proliferation index was highly expressed in 81.3% （13/16） of the patients （≥50%）， with a median of 70% （range 20%‍ ‍—‍ ‍90%）. All 16 patients underwent surgical treatment， with radical surgery in 11 patients and palliative surgery in 5 patients， among whom 9 received R0 resection， 2 received R1 resection， and 5 received R2 resection， and 7 patients received adjuvant therapy after surgery. Effective follow-up was achieved for all 16 patients， with a follow-up time of 0.5‍ ‍—‍ ‍26.0 months and a median follow-up time of 11.0 months. By the end of follow-up， 2 patients survived and 14 patients died due to tumor recurrence or metastasis， with a median survival time of 10.0 months， and the 1- and 2-year cumulative survival rates after surgery were 31.3% and 8.3%， respectively. The prognostic analysis showed that TNM stage （χ²=6.727， P=0.009）， surgical approach （χ²=7.508， P=0.006）， margin condition （χ²=7.934， P=0.005）， and adjuvant therapy （χ²=4.608， P=0.032） were associated with the prognosis of patients. Conclusion The clinical manifestations of GBSC lack specificity， and a confirmed diagnosis relies on immunohistochemical analysis. Most patients are in the advanced disease at the time of initial diagnosis and tend to have a poor prognosis. There are currently no targeted therapies for this disease， and radical surgery with negative margins and adjuvant therapy can improve the survival rate of patients.
- Gallbladder Neoplasms /
- Immunohistochemistry /
- Prognosis /
- Therapeutics

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图 1 GBSC患者的CT图像

注： a，CT平扫示不规则软组织密度突向腔内，边界欠清；b，增强扫描后呈明显强化（箭头提示病灶）。

Figure 1. CT image of a patient with gallbladder sarcomatoid carcinoma

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图 2 GBSC组织病理学特点及免疫组化

注： a，部分癌细胞呈梭形，细胞异型性明显（HE，×200）；b，Vimentin阳性表达于肿瘤细胞膜和细胞质，呈棕褐色颗粒（EnVision，×200）；c，AE1/AE3阳性表达于肿瘤细胞膜和细胞质，呈棕黄色颗粒（EnVision，×200）；d，CK8/18阳性表达于肿瘤细胞膜和细胞质，呈棕黄色颗粒（EnVision，×200）。

Figure 2. Histopathological features and immunohistochemistry of gallbladder sarcomatoid carcinoma

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图 3 术后辅助治疗对Ⅲ/Ⅳ期GBSC患者预后的影响

Figure 3. Effect of postoperative adjuvant therapy on the prognosis of patients with stage Ⅲ/Ⅳ gallbladder sarcomatoid carcinoma

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图 4 术后辅助治疗对Ⅰ~Ⅳ期GBSC患者预后的影响

Figure 4. Effect of postoperative adjuvant therapy on the prognosis of patients with stage Ⅰ~Ⅳ gallbladder sarcomatoid carcinoma

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表 1 16例GBSC患者的治疗方式及预后

Table 1. Treatment and prognosis of 16 patients with gallbladder sarcomatoid carcinoma

序号	性别/年龄（岁）	TNM分期	手术方式	切缘	辅助治疗	生存时间（月）
1	女/44	Ⅳa	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R0	化疗+免疫	11.0
2	女/59	Ⅰ‍a	胆囊切除	R0	化疗	18.0
3	男/70	Ⅲb	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R0	无	12.0
4	男/68	Ⅱa	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R0	化疗	26.0
5	女/69	Ⅳa	胆囊姑息性切除术	R2	无	4.0
6	女/68	Ⅲb	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R0	化疗+免疫	17.0
7	男/68	Ⅳb	胆囊切除+胆囊床部分肝组织楔形切除+部分十二指肠切除+结肠部分切除+胃肠吻合术	R1	化疗	12.0
8	女/57	Ⅳa	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R0	化疗+免疫	20.0
9	女/64	Ⅱb	胆囊切除	R0	无	20.0
10	男/56	Ⅲb	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R0	无	6.0
11	男/70	Ⅳa	胆囊姑息性切除术+肝门部淋巴结活检	R2	无	7.0
12	女/63	Ⅲb	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R0	化疗+靶向	4.0
13	女/65	Ⅲb	胆囊姑息性切除	R2	无	0.5
14	女/50	Ⅳb	胆囊切除+胆囊床部分肝组织楔形切除+肝十二指肠韧带淋巴结清扫	R1	无	1.0
15	男/58	Ⅲa	剖腹探查+小网膜穿刺活检术	R2	无	10.0
16	女/77	Ⅳb	剖腹探查+胆囊造瘘+胆囊活检术+大网膜穿刺活检	R2	无	2.0
注：至随访结束例2和例4患者仍存活。

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表 2 16例GBSC患者预后分析

Table 2. Prognosis analysis of 16 patients with gallbladder sarcomatoid carcinoma

因素	例数	1年累积生存率（%）	χ²值	P值
性别			0.174	0.677
男	6	16.7
女	10	40.0
年龄			0.082	0.775
<65岁	8	25.0
≥65岁	8	37.5
肿瘤大小			1.411	0.235
<5 cm	11	27.3
≥5 cm	5	40.0
TNM分期			6.727	0.009
Ⅰ/Ⅱ期	3	100
Ⅲ/Ⅳ期	13	15.4
手术方式
根治性	11	63.6	7.508	0.006
姑息性	5	0
切缘
R0	9	55.6	7.934	0.005
R1/R2	7	0
辅助治疗
有	7	57.1	4.608	0.032
无	9	11.1

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