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Article(id=1211268820677825145, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211268819788632695, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.01.08, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1584633600000, receivedDateStr=2020-03-20, revisedDate=1596902400000, revisedDateStr=2020-08-09, acceptedDate=null, acceptedDateStr=null, onlineDate=1766718591136, onlineDateStr=2025-12-26, pubDate=1611763200000, pubDateStr=2021-01-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766718591136, onlineIssueDateStr=2025-12-26, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766718591136, creator=13701087609, updateTime=1766718591136, updator=13701087609, issue=Issue{id=1211268819788632695, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='1', pageStart='1', pageEnd='100', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766718590924, creator=13701087609, updateTime=1766718828068, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1211269814484594852, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211268819788632695, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1211269814484594853, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211268819788632695, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=42, endPage=48, ext={EN=ArticleExt(id=1211268820975620733, articleId=1211268820677825145, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Clinical features of 30 cases of primary appendiceal mucinous adenocarcinoma, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To analyze the clinical features of primary appendiceal mucinous adenocarcinoma (AMAC), and investigate the diagnosis and treatment principles of the disease. Methods Thirty cases of primary AMAC from October 2011 to September 2019 in Daping Hospital of the Army Medical University were retrospectively analyzed, including demography, imaging, hematology, pathology and treatment method. Results The main clinical features of the 30 cases were right lower abdominal pain. Of whom 12 cases were diagnosed as acute or chronic appendicitis before operation, and 8 cases were as combined with ovarian space occupying. Preoperative routine abdominal B ultrasonography combined with other imaging examinations (including abdominal CT, MRI and PET/CT) obviously improved the diagnostic accuracy (68.2%) than that with B ultrasonography alone(25.0%, P=0.049). Carcinoembryonic antigen (CEA) and carbohydrate antigens (CA199, CA125 and CA242) were the most common tumor markers, which had the highest diagnostic value for AMAC. Intestinal obstruction occured in four patients undergoing stage Ⅱ extended surgery, while in only three patients without undergoing stage Ⅱ extended surgery (Fisher's exact test, P=0.181). The mean survival time of patients with R0 resection was (57.5±9.5) months and the median survival time was 59.0 months. The mean survival time of patients without R0 resection was (29.8±4.1) months and the median survival time was 33.0 months (χ2=1.255, P=0.263). Conclusions Appendiceal B ultrasound combined with abdominal enhanced MRI, CT or PET/CT can significantly improve the diagnostic rate of appendiceal mucinous adenocarcinoma. The monitoring of CEA, CA199, CA125, CA242 is helpful for the preoperative diagnosis of appendiceal mucinous adenocarcinoma.

, correspAuthors=Yan Feng, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 分析原发性阑尾黏液腺癌的临床特点，探讨该病的诊断方式及治疗原则。方法 选取陆军军医大学大坪医院2011年10月—2019年9月收治的30例原发性阑尾黏液腺癌患者，回顾分析其人口学、影像学、血液学、病理学特征及治疗方式等临床资料。结果 30例患者的主要临床表现为右下腹疼痛，术前诊断为急、慢性阑尾炎者12例，合并卵巢占位者8例。术前行常规阑尾B超并联合多项影像学(腹部CT、MRI、PET/CT)检查的诊断率(68.2%)明显高于单纯B超检查(25.0%)，差异有统计学意义(P=0.049)。肿瘤标志物中以癌胚抗原(CEA)、糖类抗原199(CA199)、糖类抗原125(CA125)、糖类抗原242(CA242)升高最为常见，对阑尾黏液腺癌的诊断价值最高。二次扩大手术肠梗阻发生4例，而未行二次手术者肠梗阻发生3例(Fisher's确切概率法，P=0.181)。手术R0切除患者平均生存期为(57.5±9.5)个月，中位生存期59.0个月，未R0切除患者平均生存期为(29.8±4.1)个月，中位生存期33.0个月(χ2=1.255，P=0.263)。结论 阑尾B超联合腹部增强MRI、CT或PET/CT检查可明显提高阑尾黏液腺癌的诊断率；CEA、CA199、CA125、CA242检测有助于阑尾黏液腺癌的术前诊断。

, correspAuthors=冯燕, authorNote=null, correspAuthorsNote=
冯燕，E-mail：
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许明芳，副主任医师，主要从事DNA损伤修复方面的研究。E-mail：

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许明芳，副主任医师，主要从事DNA损伤修复方面的研究。E-mail：

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许明芳，副主任医师，主要从事DNA损伤修复方面的研究。E-mail：

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Am J Pathol, 1999, 154(6): 1849-1855., articleTitle=Molecular genetic evidence supporting the clonality and appendiceal origin of Pseudomyxoma peritonei in women, refAbstract=null), Reference(id=1211268834208649333, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, doi=null, pmid=null, pmcid=null, year=2004, volume=91, issue=3, pageStart=304, pageEnd=311, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=González-Moreno S, Sugarbaker PH, journalName=Br J Surg, refType=null, unstructuredReference=González-Moreno S, Sugarbaker PH. Right hemicolectomy does not confer a survival advantage in patients with mucinous carcinoma of the appendix and peritoneal seeding[J]. 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J Clin Oncol, 2012, 30(20): 2449-2456., articleTitle=Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, refAbstract=null), Reference(id=1211268834825212044, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, doi=null, pmid=null, pmcid=null, year=1999, volume=6, issue=8, pageStart=727, pageEnd=731, url=null, language=null, rfNumber=[30], rfOrder=29, authorNames=Sugarbaker PH, Chang D, journalName=Ann Surg Oncol, refType=null, unstructuredReference=Sugarbaker PH, Chang D. Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy[J]. Ann Surg Oncol, 1999, 6(8): 727-731., articleTitle=Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy, refAbstract=null), Reference(id=1211268834909098127, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, doi=null, pmid=null, pmcid=null, year=2019, volume=4, issue=10, pageStart=761, pageEnd=770, url=null, language=null, rfNumber=[31], rfOrder=30, authorNames=Klaver CEL, Wisselink DD, Punt CJA, journalName=Lancet Gastroenterol Hepatol, refType=null, unstructuredReference=Klaver CEL, Wisselink DD, Punt CJA, et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial[J]. Lancet Gastroenterol Hepatol, 2019, 4(10): 761-770., articleTitle=Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial, refAbstract=null)], funds=[Fund(id=1211268829880128484, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, awardId=2019XLC3061, language=EN, fundingSource=Science and Technology Innovation Capability Improvement Project of Army Medical University(2019XLC3061), fundOrder=null, country=null), Fund(id=1211268830010151915, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, awardId=2019XLC3061, language=CN, fundingSource=陆军军医大学科技创新能力提升专项(2019XLC3061), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1211268823152464528, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, xref=null, ext=[AuthorCompanyExt(id=1211268823156658834, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, companyId=1211268823152464528, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China), AuthorCompanyExt(id=1211268823165047442, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, companyId=1211268823152464528, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=陆军军医大学大坪医院肿瘤科，重庆 400042)])], figs=[ArticleFig(id=1211268827980108634, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Fig.1, caption=Microscopic features of primary AMAC (HE), figureFileSmall=vxHKizdfIo5APUoTb8H4/w==, figureFileBig=2naBRw9GGo41UY46U4H+3g==, tableContent=null), ArticleFig(id=1211268828110132067, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=图1, caption=阑尾黏液腺癌镜下特征(HE)

A. 低倍镜下见异型黏液腺体呈浸润性生长，阑尾正常结构消失，肿瘤浸润周围脂肪组织，肿瘤细胞可见丰富的细胞外黏液；B. 高倍镜下腺体异型性明显，腺体排列极向紊乱，肿瘤细胞染色质增粗，核仁可见，腺体周围促纤维增生明显

, figureFileSmall=vxHKizdfIo5APUoTb8H4/w==, figureFileBig=2naBRw9GGo41UY46U4H+3g==, tableContent=null), ArticleFig(id=1211268828294681464, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Fig.2, caption=Effect of tumor staging and R0 resection on survival time of patients with AMAC, figureFileSmall=guk4nL/RmgzZFMUVW4GOtQ==, figureFileBig=0WDHceI4fGIuAkeWmby5Hw==, tableContent=null), ArticleFig(id=1211268828378567548, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=图2, caption=肿瘤分期及R0切除对阑尾黏液腺癌患者生存期的影响

A. R0切除对生存期的影响；B. 肿瘤分期对生存期的影响

, figureFileSmall=guk4nL/RmgzZFMUVW4GOtQ==, figureFileBig=0WDHceI4fGIuAkeWmby5Hw==, tableContent=null), ArticleFig(id=1211268828466647940, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Tab.1, caption=

The first diagnosis of 30 cases of primary AMAC [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
项目首诊情况
症状
 腹部包块1(3.3)
 肿瘤标志物增高3(10.0)
 腹痛或腹胀26(86.7)
诊断
 合并卵巢占位8(26.7)
 急慢性阑尾炎12(40.0)
科室
 消化科1(3.3)
 妇科9(30.0)
 胃肠外科20(66.7)
), ArticleFig(id=1211268828558922633, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=表1, caption=

30例阑尾黏液腺癌患者首诊情况[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
项目首诊情况
症状
 腹部包块1(3.3)
 肿瘤标志物增高3(10.0)
 腹痛或腹胀26(86.7)
诊断
 合并卵巢占位8(26.7)
 急慢性阑尾炎12(40.0)
科室
 消化科1(3.3)
 妇科9(30.0)
 胃肠外科20(66.7)
), ArticleFig(id=1211268828638614418, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Tab.2, caption=

The preoperative imaging examination of 30 cases of primary AMAC

, figureFileSmall=null, figureFileBig=null, tableContent=
检查项目检查患者[例(%)]影像诊断为阑尾肿瘤(例)
1项检查8(26.7)
 B超8(26.7)2
2项检查20(66.7)
 B超+CT16(53.4)10
 B超+MRI3(10.0)2
 B超+PET/CT1(3.3)1
3项检查1(3.3)
 B超+PET/CT+CT1(3.3)1
4项检查1(3.3)
 B超+PET/CT+CT+MRI1(3.3)1
), ArticleFig(id=1211268828789609367, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=表2, caption=

30例阑尾黏液腺癌患者术前影像学检查情况

, figureFileSmall=null, figureFileBig=null, tableContent=
检查项目检查患者[例(%)]影像诊断为阑尾肿瘤(例)
1项检查8(26.7)
 B超8(26.7)2
2项检查20(66.7)
 B超+CT16(53.4)10
 B超+MRI3(10.0)2
 B超+PET/CT1(3.3)1
3项检查1(3.3)
 B超+PET/CT+CT1(3.3)1
4项检查1(3.3)
 B超+PET/CT+CT+MRI1(3.3)1
), ArticleFig(id=1211268828894466972, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Tab.3, caption=

CT or MRI characteristics of 30 cases of primary AMAC

, figureFileSmall=null, figureFileBig=null, tableContent=
影像学表现例数
阑尾结节样改变3
阑尾囊性改变3
阑尾壁增厚6
阑尾炎4
阑尾穿孔1
阑尾周围脓肿3
肠壁水肿1
网膜腹膜增厚4
腹膜结节样改变8
腹腔淋巴结增大3
腹盆腔积液4
), ArticleFig(id=1211268829011907494, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=表3, caption=

30例阑尾黏液腺癌患者CT或MRI影像学表现

, figureFileSmall=null, figureFileBig=null, tableContent=
影像学表现例数
阑尾结节样改变3
阑尾囊性改变3
阑尾壁增厚6
阑尾炎4
阑尾穿孔1
阑尾周围脓肿3
肠壁水肿1
网膜腹膜增厚4
腹膜结节样改变8
腹腔淋巴结增大3
腹盆腔积液4
), ArticleFig(id=1211268829133542326, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Tab.4, caption=

Changes of tumor markers of 30 cases of primary AMAC (n)

, figureFileSmall=null, figureFileBig=null, tableContent=
变化情况CEACA199CA125CA242
升高1~5倍7675
升高5~10倍3321
升高10倍以上8411
合计1813107
), ArticleFig(id=1211268829234205627, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=表4, caption=

30例阑尾黏液腺癌患者的肿瘤标志物变化情况(例)

, figureFileSmall=null, figureFileBig=null, tableContent=
变化情况CEACA199CA125CA242
升高1~5倍7675
升高5~10倍3321
升高10倍以上8411
合计1813107
), ArticleFig(id=1211268829339063235, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Tab.5, caption=

Surgical procedures for 30 patients with AMAC

, figureFileSmall=null, figureFileBig=null, tableContent=
术式例数
阑尾切除方式
 单纯阑尾切除16
 右半结肠切除13
 回盲部结肠切除1
合并切除大小网膜及转移灶10
合并切除附件9
合并切除小肠2
因肿瘤巨大或腹膜转移广泛仅行活检或减灭术2
淋巴结清扫情况
 是10
 否20
术中腹腔热灌注2
术中氟尿嘧啶药泵植入术1
), ArticleFig(id=1211268829448115148, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=表5, caption=

30例阑尾黏液腺癌患者术式情况

, figureFileSmall=null, figureFileBig=null, tableContent=
术式例数
阑尾切除方式
 单纯阑尾切除16
 右半结肠切除13
 回盲部结肠切除1
合并切除大小网膜及转移灶10
合并切除附件9
合并切除小肠2
因肿瘤巨大或腹膜转移广泛仅行活检或减灭术2
淋巴结清扫情况
 是10
 否20
术中腹腔热灌注2
术中氟尿嘧啶药泵植入术1
), ArticleFig(id=1211268829540389842, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=EN, label=Tab. 6, caption=

Treatment of 7 AMAC patients with intestinal obstruction*

, figureFileSmall=null, figureFileBig=null, tableContent=
组别肠梗阻例数发生时间(月)肿瘤切除术式梗阻原因治疗方式治疗结局
单次手术组(n=20)32.1阑尾切除术单纯性非手术治疗好转
2.4腹腔镜探查+网膜结节活检术肿瘤进展非手术治疗好转
4.7右半结肠癌根治术+小肠部分切除+小肠系膜转移结节切除+大网膜切除+淋巴结清扫单纯性非手术治疗好转
二次手术组(n=10)48.5阑尾切除术+肠系膜结节活检术肿瘤复发非手术治疗好转
9.7右半结肠切除+大网膜切除+双侧卵巢切除+腹腔热灌注+淋巴结清扫单纯性非手术治疗好转
35.7右半结肠癌根治术单纯性非手术治疗好转
0.3右半结肠根治性切除术+大网膜切除术单纯性非手术治疗好转
), ArticleFig(id=1211268829657830361, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211268820677825145, language=CN, label=表6, caption=

7例阑尾黏液腺癌术后发生肠梗阻患者的治疗情况*

, figureFileSmall=null, figureFileBig=null, tableContent=
组别肠梗阻例数发生时间(月)肿瘤切除术式梗阻原因治疗方式治疗结局
单次手术组(n=20)32.1阑尾切除术单纯性非手术治疗好转
2.4腹腔镜探查+网膜结节活检术肿瘤进展非手术治疗好转
4.7右半结肠癌根治术+小肠部分切除+小肠系膜转移结节切除+大网膜切除+淋巴结清扫单纯性非手术治疗好转
二次手术组(n=10)48.5阑尾切除术+肠系膜结节活检术肿瘤复发非手术治疗好转
9.7右半结肠切除+大网膜切除+双侧卵巢切除+腹腔热灌注+淋巴结清扫单纯性非手术治疗好转
35.7右半结肠癌根治术单纯性非手术治疗好转
0.3右半结肠根治性切除术+大网膜切除术单纯性非手术治疗好转
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原发性阑尾黏液腺癌30例临床特征分析
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许明芳 , 蹇丹 , 彭红 , 何娟 , 陈骞 , 钱程远 , 戴楠 , 单锦露 , 王东 , 冯燕 *
解放军医学杂志 | 临床研究 2021,46(1): 42-48
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解放军医学杂志 | 临床研究 2021, 46(1): 42-48
原发性阑尾黏液腺癌30例临床特征分析
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许明芳 , 蹇丹, 彭红, 何娟, 陈骞, 钱程远, 戴楠, 单锦露, 王东, 冯燕*
作者信息
  • 陆军军医大学大坪医院肿瘤科，重庆 400042

    • 许明芳，副主任医师，主要从事DNA损伤修复方面的研究。E-mail：

通讯作者:

冯燕，E-mail：
Clinical features of 30 cases of primary appendiceal mucinous adenocarcinoma
Ming-Fang Xu , Dan Jian, Hong Peng, Juan He, Qian Chen, Cheng-Yuan Qian, Nan Dai, Jin-Lu Shan, Dong Wang, Yan Feng*
Affiliations
  • Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China
出版时间: 2021-01-28 doi: 10.11855/j.issn.0577-7402.2021.01.08
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摘要
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目的 分析原发性阑尾黏液腺癌的临床特点，探讨该病的诊断方式及治疗原则。方法 选取陆军军医大学大坪医院2011年10月—2019年9月收治的30例原发性阑尾黏液腺癌患者，回顾分析其人口学、影像学、血液学、病理学特征及治疗方式等临床资料。结果 30例患者的主要临床表现为右下腹疼痛，术前诊断为急、慢性阑尾炎者12例，合并卵巢占位者8例。术前行常规阑尾B超并联合多项影像学(腹部CT、MRI、PET/CT)检查的诊断率(68.2%)明显高于单纯B超检查(25.0%)，差异有统计学意义(P=0.049)。肿瘤标志物中以癌胚抗原(CEA)、糖类抗原199(CA199)、糖类抗原125(CA125)、糖类抗原242(CA242)升高最为常见，对阑尾黏液腺癌的诊断价值最高。二次扩大手术肠梗阻发生4例，而未行二次手术者肠梗阻发生3例(Fisher's确切概率法，P=0.181)。手术R0切除患者平均生存期为(57.5±9.5)个月，中位生存期59.0个月，未R0切除患者平均生存期为(29.8±4.1)个月，中位生存期33.0个月(χ2=1.255，P=0.263)。结论 阑尾B超联合腹部增强MRI、CT或PET/CT检查可明显提高阑尾黏液腺癌的诊断率；CEA、CA199、CA125、CA242检测有助于阑尾黏液腺癌的术前诊断。

阑尾  /  黏液腺癌  /  肿瘤标志物

Objective To analyze the clinical features of primary appendiceal mucinous adenocarcinoma (AMAC), and investigate the diagnosis and treatment principles of the disease. Methods Thirty cases of primary AMAC from October 2011 to September 2019 in Daping Hospital of the Army Medical University were retrospectively analyzed, including demography, imaging, hematology, pathology and treatment method. Results The main clinical features of the 30 cases were right lower abdominal pain. Of whom 12 cases were diagnosed as acute or chronic appendicitis before operation, and 8 cases were as combined with ovarian space occupying. Preoperative routine abdominal B ultrasonography combined with other imaging examinations (including abdominal CT, MRI and PET/CT) obviously improved the diagnostic accuracy (68.2%) than that with B ultrasonography alone(25.0%, P=0.049). Carcinoembryonic antigen (CEA) and carbohydrate antigens (CA199, CA125 and CA242) were the most common tumor markers, which had the highest diagnostic value for AMAC. Intestinal obstruction occured in four patients undergoing stage Ⅱ extended surgery, while in only three patients without undergoing stage Ⅱ extended surgery (Fisher's exact test, P=0.181). The mean survival time of patients with R0 resection was (57.5±9.5) months and the median survival time was 59.0 months. The mean survival time of patients without R0 resection was (29.8±4.1) months and the median survival time was 33.0 months (χ2=1.255, P=0.263). Conclusions Appendiceal B ultrasound combined with abdominal enhanced MRI, CT or PET/CT can significantly improve the diagnostic rate of appendiceal mucinous adenocarcinoma. The monitoring of CEA, CA199, CA125, CA242 is helpful for the preoperative diagnosis of appendiceal mucinous adenocarcinoma.

appendix  /  mucinous adenocarcinoma  /  tumor markers
许明芳, 蹇丹, 彭红, 何娟, 陈骞, 钱程远, 戴楠, 单锦露, 王东, 冯燕. 原发性阑尾黏液腺癌30例临床特征分析. 解放军医学杂志, 2021 , 46 (1) : 42 -48 . DOI: 10.11855/j.issn.0577-7402.2021.01.08
Ming-Fang Xu, Dan Jian, Hong Peng, Juan He, Qian Chen, Cheng-Yuan Qian, Nan Dai, Jin-Lu Shan, Dong Wang, Yan Feng. Clinical features of 30 cases of primary appendiceal mucinous adenocarcinoma[J]. Medical Journal of Chinese People’s Liberation Army, 2021 , 46 (1) : 42 -48 . DOI: 10.11855/j.issn.0577-7402.2021.01.08
正文
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阑尾黏液腺癌的发病率极低，文献报道，经年龄调整后，每年每100万人中约发生0.12例阑尾黏液腺癌[1]。由于该病起病隐匿，无肿瘤相关特异表现，临床表现与急、慢性阑尾炎相似，故容易误诊，多在术中探查发现或术后经病理证实，加之临床上对该病的认识不足，其诊断及治疗规范也尚待提高。因此，有必要对该病的临床特征进行系统分析，并应争取行Ⅰ期根治手术，尽量避免再次行Ⅱ期扩大手术，以提高术前及术中的诊断正确率。本研究对陆军军医大学大坪医院收治的30例阑尾黏液腺癌的临床病理资料进行回顾分析，以期提高对该病的临床诊治能力。
1 资料与方法
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1.1 一般资料
选取陆军军医大学大坪医院2011年10月—2019年9月收治的原发性阑尾黏液腺癌30例，其中男11例，女19例；发病年龄40~74岁，中位年龄59岁。所有患者均行手术治疗，并经病理诊断为阑尾黏液腺癌。收集患者初诊时采集的吸烟史、家族史、合并症、首发症状等情况。
1.2 影像学检查
收集患者术前影像学检查情况，包括阑尾B超、腹部平扫或增强CT、腹部平扫或增强MRI，以及全身PET/CT检查。
1.3 血液学检查
收集患者术前所行血常规、肝肾功能、生化、凝血功能及肿瘤标志物等检查指标。肿瘤标志物包括癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原242(CA242)、糖类抗原199(CA199)、甲胎蛋白(AFP)、神经元特异性烯醇化酶(NSE)、总前列腺特异抗原(T-PSA)等。血清肿瘤标志物水平高于正常参考值即为阳性，肿瘤标志物阳性界定值为CEA>5.0 ng/ml、CA125>35.0 U/ml、CA242>20.0 U/ml、CA199>35.0 U/ml、AFP>15.0 ng/ml、NSE>25.0 ng/ml、T-PSA>4.0 ng/ml。
1.4 病理学检查
所有患者均行组织病理学检查。首先行HE染色检查，根据初步结果进一步行免疫组化检查，并进行病理学分级。免疫组化指标包括Ki-67、CEA、CK20、Villin、CDX-2、CK、CK7、CK19、CK20、P16、P53、Muc-2、EMA、Her-2、PD-L1、WT-1、Calretinin、CD56、CgA及Syn等。
1.5 治疗情况
所有患者均行手术治疗，根据术中所见及术后分期情况选择是否行术后辅助全身化疗及腹腔灌注化疗。
1.6 统计学处理
采用SPSS 17.0软件进行统计分析。计数资料以例(%)表示，两组间比较采用χ2检验或Fisher确切概率法；生存期资料以$\bar{x}±s$表示，采用Cox比例风险模型分析生存期的影响因素，Kaplan-Meier法分析不同因素对生存期的影响。P<0.05为差异有统计学意义。
2 结果
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2.1 患者一般资料
根据美国癌症协会(AJCC)第7版的阑尾腺癌分期，本组30例阑尾黏液腺癌中，Ⅰ期0例，Ⅱ期9例，Ⅲ期4例，Ⅳ期17例(1例为肝转移，9例为子宫及附件转移，其余均为腹膜转移)。病理分级：低分化(高级别)4例，中分化5例，高分化(低级别)11例，未进行病理分级10例。有吸烟史4例，吸烟指数200~1040。有肿瘤家族史4例(分别为父亲肺癌、父亲直肠癌、母亲肺癌、母亲胃癌)。基础合并胆囊结石5例、高血压9例、糖尿病2例。首诊症状、诊断及科室分布见表1。
2.2 影像学检查结果
术前所有患者均行阑尾B超检查，行2项影像学检查20例，行3项影像学检查1例，行4项影像学检查1例。其中，22例(73.3%)患者术前行2项以上影像学检查(表2)。阑尾B超影像学特征表现为：阑尾占位、炎性阑尾伴周边炎性渗出。CT影像学表现为：阑尾占位(结节样改变、壁增厚)、阑尾炎、阑尾穿孔、周围脓肿、肠壁水肿、网膜腹膜增厚、腹膜占位、腹盆腔积液；阑尾占位的靶病灶最长径范围3.7~18.8 cm。MRI影像学主要表现为：阑尾占位(可见肠壁增厚、不均匀强化)、周围淋巴结肿大，其中1例行MRI检查未见异常(表3)。30例患者中行术前PET/CT检查3例，显示右腹部盲肠后外侧局限性肠壁增厚1例，右侧附件区占位(但未发现阑尾异常代谢增高影)1例，未见阳性发现1例。单项B超检查的阑尾肿瘤诊断率为25.0%(2/8)；多项影像学联合检查的阑尾肿瘤诊断率为68.2%(15/22)。B超联合其他影像学检查的诊断率明显高于单项B超检查(P=0.049)。
2.3 血液学检查结果
患者行血常规分析结果提示白细胞异常增高3例，均为轻度增高，均<12.0×109/L，血红蛋白92~135 g/L，血小板(81~384)×109/L，D-二聚体102~1754 μg/L，其余生化及凝血功能指标均在正常范围内。
行肿瘤标志物检查的30例中，未检测到肿瘤标志物增高10例；肿瘤标志物异常增高20例，其中仅1项增高5例，2项增高6例，3项增高6例，4项增高3例。增高的标志物中，以CEA、CA199、CA125及CA242最为常见，其中CEA异常升高18例，C199异常升高13例，CA125异常升高10例、CA242异常升高7例，具体变化情况见表4。术前肿瘤标志物增高的患者，手术后肿瘤标志物均有不同程度的下降，行R0切除后肿瘤标志物降至正常，当肿瘤出现进展或复发时，肿瘤标志物再次升高。
2.4 病理结果分析
30例患者均获得组织病理标本。大体表现：盆壁胶冻样组织，小肠、肠系膜及大网膜可见粟粒样广泛癌结节(直径0.3~2.0 cm，质地硬，呈饼状，白色絮状物)，子宫及其附件/盆壁可见粟粒样广泛癌结节，邻近肠道黏膜上可见布满黏液样小泡，腹腔内淋巴结肿大转移，腹腔积液为胶冻样液体(图1)。免疫组化分析13例患者的Ki-67阳性比例为1%~90%，中位值为5%，CEA、CK20、Villin、CDX-2、CK、CK7、CK19、P16、P53、Muc-2、EMA、Her-2、PD-L1均有阳性表达。
2.5 治疗结果
2.5.1 手术治疗
所有患者均行手术治疗，其中腹腔镜为第一手术方式25例，剖腹探查为第一手术方式5例，剖腹探查后转开腹手术1例，因首诊为阑尾炎2个月内行Ⅱ期扩大手术10例。首次手术治疗及二次扩大手术治疗后，评估达到R0切除16例，行淋巴结清扫10例。术中行腹腔热灌注治疗2例，均采用奥沙利铂200 mg，术后行腹腔热灌注化疗(HIPEC)或普通灌注化疗7例，所用药物包括顺铂、奈达铂、替加氟、5-氟尿嘧啶、重组人血管内皮抑制素、重组人5型腺病毒、白细胞介素-2等，术后热灌注疗程为1~6个周期。因肿瘤反复腹腔内复发行5次手术治疗1例，行3次手术治疗2例(表5)。
术后发生肠梗阻7例，首次梗阻时间为术后0.3~35.7个月，中位时间4.7个月，其中6例肠梗阻发生在术后10个月内，仅1例首次肠梗阻时间发生在术后3年。肠梗阻原因包括单纯性术后粘连5例及肿瘤复发或进展2例。首诊为阑尾炎2个月内行Ⅱ期扩大手术的10例患者中，发生肠梗阻4例，未行二次手术的20例患者仅发生肠梗阻3例，两组肠梗阻发生率差异无统计学意义(Fisher's确切概率法，P=0.181，表6)。所有肠梗阻均未采取手术治疗，予以胃肠减压、留置经鼻肠梗阻导管、禁食水、维持水电解质平衡、肠外营养等治疗后好转。
2.5.2 化疗
术后病理证实有淋巴结转移、分期在Ⅲ期及以上、术后肿瘤标志物未恢复正常或未达到R0切除的患者共11例，接受了全身术后辅助化疗，共完成44个周期的辅助化疗。一线辅助化疗方案包括：紫杉醇类+铂类(如多西他赛+洛铂、紫杉醇+卡铂、紫杉醇脂质体+奈达铂)8个周期(18.2%)，紫杉醇类+氟尿嘧啶类(紫杉醇脂质体+替加氟)1个周期(2.3%)，铂类+阿霉素类(顺铂+阿霉素脂质体)1个周期(2.3%)，奥沙利铂+氟尿嘧啶类(奥沙利铂+替加氟/卡培他滨/5-氟尿嘧啶)34个周期(77.2%)，其中化疗联合或不联合抗血管生成类药物(重组人血管内皮抑制素/贝伐珠单抗)9个周期。11例患者的无进展生存期(PFS)为1.8个月~7年。随后发生病情进展的原因主要为合并网膜/系膜新发结节及腹腔积液、吻合口周围新发结节、回盲部复发、输尿管新发结节、腹壁新发结节。
病情进展后采用的后线化疗方案主要为：奥沙利铂/伊立替康/奈达铂+替吉奥/替加氟/卡培他滨，联合或不联合抗血管生成类药物(重组人血管内皮抑制素/贝伐珠单抗/安罗替尼)。局部腹腔内灌注治疗方案为洛铂+恩度、顺铂+5-氟尿嘧啶。接受术后辅助化疗的11例患者中，疗效评估达部分缓解(PR)7例，完全缓解(CR)4例。
2.6 生存随访
30例患者首次治疗时均痊愈或症状缓解后出院，住院时间7~16 d，平均11 d。所有患者术后均获随访，随访截止日期2019年10月31日，其中失访6例，死亡5例，死亡患者的总生存期(OS)为10~26个月，死亡患者术前均出现腹盆腔内及腹膜广泛转移，粘连较重，接受右半结肠及阑尾切除、腹盆腔探查松解术，部分女性患者接受了子宫及附件切除手术，术后给予腹腔灌注化疗及辅助化疗。其余19例随访11~82个月，生存期(50.0±7.5)个月，中位生存期59.0个月，其中未R0切除患者生存期(29.8±4.1)个月，中位生存期33.0个月，R0切除患者生存期(57.5±9.5)个月，中位生存期59.0个月，采用Kaplan-Meier法对是否R0切除进行分层分析，结果显示差异无统计学意义(χ2=1.255，P=0.263)。此外，采用Kaplan-Meier生存分析方法，对不同分期(Ⅱ期9例，Ⅲ期4例，Ⅳ17例)的患者进行分层分析，结果显示其生存期差异无统计学意义(χ2=2.289，P=0.318)，尽管本组病例中分期及R0切除对生存期的影响在统计学上无明显差异，但呈现出差异趋势(图2)。
3 讨论
收起
3.1 流行病学特征
阑尾黏液性肿瘤在美国的发病率不断上升，从1973年的0.6/100万上升到2011年的2.8/100万，年增长率为3.1%[2]，且患者确诊年龄趋于年轻化[3]。最近一项来自日本的单中心回顾性研究发现，在常规的阑尾切除标本中约有2.3%被诊断为阑尾原发性或继发性恶性肿瘤[4]，0.2%~0.3%被诊断为阑尾黏液性肿瘤[5]。包括术后早期腹腔化疗(EPIC)及HIPEC在内的阑尾黏液性肿瘤治疗目前仍无明确的指南依据。阑尾黏液性肿瘤的临床进展速度由诊断时的分期及反映细胞分化的组织学特征决定[5-9]。
3.2 临床特征
阑尾肿瘤患者可出现非特异性的临床表现，从而延误诊断[10-11]。急性阑尾炎样表现主要为右下腹部疼痛，由于阑尾膨胀增粗所致，是疾病早期最常见的临床表现[12]。特别是当肿瘤阻塞阑尾口时，可表现为阑尾炎或阑尾穿孔。Carr等[13]报道，32%的阑尾增生性息肉及肿瘤患者术前诊断为急性阑尾炎，而23%的患者是偶然诊断的。本研究的30例患者中有12例(40%)被初诊为急、慢性阑尾炎，初诊误诊比例略高于国外文献报道，主要原因考虑为该部分初诊患者大部分在当地下级医院行急诊手术，术前诊断手段有限，少有CT或MRI辅助检查。阑尾黏液性肿瘤影像学上常见的特征为阑尾壁不规则增厚、软组织结节、浸润或肿块，同时大网膜、腹腔、肠、腹部及盆腔脏器也可能有黏液或软组织影表现[14]，B超能够观察到阑尾本身的结构与形态异常，但因为肠管气体等原因，对大网膜、肠壁、子宫及其附件的观察受到很大局限，而CT、MRI及PET/CT对肿瘤的血供、侵犯性生长、远处转移等恶性行为有良好的判断作用。因此，联合检查能够提高阑尾黏液腺癌的诊断率。本组病例的体会是若阑尾B超提示有占位，形态呈结节样改变，周围有炎性渗出或与周围组织结构界限模糊等影像表现，应联合腹部或盆腔CT/MRI，必要时联合PET/CT进行检查。患者病程进展至晚期可表现为腹围进行性增大，主要由黏液性腹水在腹腔内积聚所致。该阶段的其他临床表现还包括慢性腹痛、体重减轻、贫血等肿瘤消耗特征，肝、肺的远处转移并不常见[11,15]，本研究中也仅有1例出现肝转移，未发现肺转移、脑转移及骨转移患者。尽管患者通常伴有腹膜、浆膜及网膜的黏液肿瘤种植，但肠梗阻并不是一种常见的首发症状[9,16]，本研究中的肠梗阻也主要是后期二次扩大手术后的继发性肠梗阻。二次手术后合并梗阻的患者初次手术往往接受了右半结肠切除术或联合大网膜相关手术，如大网膜切除或网膜结节切除等，手术范围及创面较大，术后腹腔或盆腔粘连严重，是二次手术后合并梗阻的主要原因。另外，本研究中观察到肿瘤局部复发造成肠腔狭窄，提示肿瘤复发是二次手术后合并梗阻的另一重要原因。
3.3 病理及分子特征
阑尾恶性肿瘤的病理类型主要包括黏液上皮性肿瘤、神经内分泌肿瘤(典型类癌)、杯状/前杯状细胞或复合类癌、淋巴瘤、腺癌、淋巴样及间质肉瘤。组织学上，约65%的阑尾肿瘤为神经内分泌细胞起源，其中腺癌(包括黏液性、印戒性或非黏液性)约占20%[2,5]。
阑尾黏液性肿瘤中最常见的是低级别阑尾黏液性肿瘤(LAMN)，是阑尾黏膜的腺瘤性改变[17-18]。Ronnett等[19-20]最初将阑尾黏液性肿瘤分为3种主要类型：弥散性腹膜腺瘤病(DPAM)、腹膜黏液性癌病(PMCA)及不确定或不一致特征的PMCA(PMCAI/D)。Bradley等[12]进一步将DPAM及PMCAI/D分为3种不同的亚型：①分化良好的黏液性腺癌(G1，高分化DPAM)；②黏液腺癌(G2，中分化PMCA-I型)；③高级别黏液腺癌(G3，低分化PMCA型)。本研究中的30例患者涵盖了上述3种病理类型。
阑尾黏液性肿瘤的诊断在很大程度上取决于病理检查中是否有黏液蛋白的存在。阑尾黏液腺癌中CK20呈弥漫性阳性表达(100%)，CK7常呈阴性表达(71%)，MUC5AC呈阳性表达(86%)，DPC4也呈阳性表达(100%)[21-22]。本研究中部分患者病理标本行多个免疫指标检测，但检测项目无统一标准，其中CK20等阳性率较高的指标与文献报道相仿。Szych等[23]发现，累及腹膜的16例阑尾黏液性肿瘤均检测出KRAS突变，而未累及腹膜的16例阑尾黏液性肿瘤中11例癌旁组织发生KRAS突变，表明KRAS突变是阑尾黏液性肿瘤形成的早期驱动因素之一，但不足以驱动后期的腹膜播散。
3.4 手术治疗
行单纯阑尾切除术后，若发现肿瘤累及右半结肠，或肿瘤累及阑尾周围区域、穿孔，肿瘤直径≥2 cm，组织学分化程度差，或肿瘤侵及固有肌，应考虑行右半结肠切除手术[24]。因为上述任何危险因素均可使患者面临局部复发率更高的风险，故阑尾肿瘤的术前诊断及术中确诊对选择合理术式具有重要意义。本研究对术前拟诊为阑尾恶性肿瘤的患者均行右半结肠切除术。尽管在本组小样本的研究中是否R0切除对生存期的影响无统计学差异，但观察到R0切除的患者生存期明显延长。因此，通过右半结肠根治术、大网膜/附件切除及淋巴结清扫等扩大手术完全切除病灶仍是阑尾黏液腺癌治疗的关键。
3.5 化疗及腹腔热灌注治疗
LAMN伴阑尾外播散患者的3、5、7及10年总生存率分别为100%、86%、60%及45%[25]。在前瞻性随机对照研究中，尚未评估辅助化疗对局部切除的阑尾黏液性肿瘤的作用。在特定的高危情况下，如肿瘤分化差(印戒细胞癌成分)、有淋巴结受累或穿孔的证据时，通常建议使用5-氟尿嘧啶为基础的辅助化疗。辅助化疗不推荐用于低级别分化好的黏液性肿瘤，只应在肿瘤表现出浸润性特征(如淋巴管或淋巴结受累)或具有混合型组织学的特殊情况下考虑[25]。本研究术后行辅助化疗的患者中，仍随访到后期出现进展的患者，进展原因主要为腹腔内肿瘤原位复发、吻合口复发及网膜系膜转移，几乎未出现远处实质脏器转移。
对于阑尾黏液腺癌伴腹膜转移瘤的治疗，20世纪90年代Sugarbaker[26]、Jacquet等[27]提出了在Ⅰ期积极腹膜切除后，随即在术中继续进行HIPEC的治疗方式。HIPEC的目的是在局部腹腔内提供高浓度的热化疗，但全身效应很小。热化疗通常用于已行完全肿瘤细胞减灭术(cytoreductivesurgery，CRS)的患者，这些患者仅有微小残留肿瘤或无残留，术中在整个腹部灌注高剂量的热化疗药物(温度控制在40~42 ℃)以清除残留的微小肿瘤。在阑尾黏液性肿瘤的腹腔灌注治疗中，最常用的药物是丝裂霉素C(10~12.5 mg/m2)[28-29]、草酸铂(460 mg/m2)、顺铂及5-氟尿嘧啶，多采用单用或不同方式的联合用药[29]。只有达到R0切除时，CRS及HIPEC联合应用才可能使DPAM患者的5年生存率达到86%，PMCA患者的5年生存率达到50%[30]。若减瘤手术清除不完全，患者5年生存率则下降至20%，HIPEC可明显改善患者PFS，但未改善OS[29]。2019年，柳叶刀子刊The Lancet Gastroenterology & Hepatology在线发表的一项来自荷兰的多中心、随机对照试验(COLOPEC)[31]，探索了局部晚期结肠癌患者采用HIPEC治疗的效果，发现在T4或穿孔性结肠癌患者中采用奥沙利铂行HIPEC治疗不能提高18个月时的无腹膜转移生存率。目前，阑尾黏液腺癌的治疗方案主要参照结直肠癌，因此，HIPEC对于包括阑尾黏液腺癌在内的阑尾黏液性肿瘤可能有一定效果，但也存在一定争议，尚缺乏随机对照试验研究的证据。由于本院设备的限制，本组患者中仅2例行HIPEC治疗，其余均为腹腔灌注化疗，且灌注用药种类繁杂，其经验也有待进一步积累。
3.6 随访
参照阑尾肿瘤诊疗指南，采用单纯阑尾切除术治疗直径<2 cm的肿瘤，无需常规监测。对于肿瘤直径>2 cm、淋巴结受累、局部区域性扩散或远处转移，以及行右半结肠切除术治疗者，应常规行病史询问、体格检查及影像学检查。建议术后3~12个月复查血清肿瘤标志物，同时考虑行CT或MRI。第1年后，建议每6~12个月随访一次，包括问诊及体格检查，同时考虑复查血清肿瘤标志物并行CT或MRI。这种每年一次的随访频率应该持续10年。
综上所述，阑尾黏液性肿瘤是一组发病率呈上升趋势且具有异质性的肿瘤，治疗方案的制定主要以肿瘤分期及组织学特征为基础。低级别肿瘤早期采用原发灶切除术治疗，晚期采用腹膜扩大切除术及可能的HIPEC治疗。高级别阑尾黏液性肿瘤的治疗可选择腹腔扩大切除手术、HIPEC及术前化疗[25]等，但疗效仍需前瞻性临床试验证实。此外，也应该积极推进相应的基础研究，探寻分子靶向药物及免疫检查点抑制剂在阑尾黏液腺癌中的应用。
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doi: 10.11855/j.issn.0577-7402.2021.01.08
  • 接收时间：2020-03-20
  • 首发时间：2025-12-26
  • 出版时间：2021-01-28
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  • 收稿日期：2020-03-20
  • 修回日期：2020-08-09
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Science and Technology Innovation Capability Improvement Project of Army Medical University(2019XLC3061)
陆军军医大学科技创新能力提升专项(2019XLC3061)
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    陆军军医大学大坪医院肿瘤科，重庆 400042

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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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