Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development o...Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development of technologies for highthroughput sequencing,a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi.The intratumour microbiome is being revealed as an influential contributor to carcinogenesis.The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression,diagnosis,and treatment,chemotherapy resistance,and immune response.A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies.This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer,the intratumour localization,the interaction with the tumour microenvironment,and strategies for improving the outcome of pancreatic cancer treatment.Thus,this review offers new perspectives for improving the prognosis of pancreatic cancer.展开更多
BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of ...BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.展开更多
Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE com...Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.展开更多
Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-different...Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.展开更多
BACKGROUND Phyllodes tumours(PTs)are fibroepithelial breast tumours,which can be classified as benign,borderline or malignant,according to their histological characteristics.While various huge borderline or malignant ...BACKGROUND Phyllodes tumours(PTs)are fibroepithelial breast tumours,which can be classified as benign,borderline or malignant,according to their histological characteristics.While various huge borderline or malignant PTs have been previously described,a benign PT with a pulmonary nodule mimicking malignancy has not yet been reported.In order that doctors may have a comprehensive understanding of super-giant benign PTs(≥20 cm),we also performed a literature review to summarize the clinical features,differential diagnosis,and treatment of this disease.CASE SUMMARY A 42-year-old woman with severe anaemia presented with a rapidly enlarging right breast mass,measuring approximately 30 cm×25 cm×20 cm that was first noticed 1 year previously.A region of skin ulceration and necrosis(20 cm×15 cm)was observed on the lateral side of the mass.Computed tomography(CT)of the chest revealed a pulmonary nodule,which initially suggested a diagnosis of metastasis.CT showed that the boundaries between the pectoralis major and the mass were blurred,which was presumed to be due to tumour invasion.However,two core needle biopsies of the mass showed no evidence of malignancy.Following these results,the tumour was removed by mastectomy of the right breast.Interestingly,postoperative pathology finally proved the diagnosis of a benign PT.After 1 year of follow-up,wedge resection of the small pulmonary nodule was performed,and it was confirmed that the lung nodule was actually adenocarcinoma rather than metastatic breast cancer.The patient recovered very well without any postoperative treatment.CONCLUSION This case is unique in that the giant breast mass initially mimicking a malignantclinical presentation was eventually pathologically confirmed to be a benign PT,which misled the diagnosis and complemented the atypical features of benign PTs.The pathological and immunohistochemical results were important in the differential diagnosis.In addition,total mastectomy should be recommended due to difficulty in the precise diagnosis of PTs,especially in large breast masses.In the literature,almost one-half of super-giant benign cases were thought to be malignant tumours before surgery.This finding is a reminder to consider all conditions in order to make an accurate diagnosis and avoid excessive treatment.展开更多
Gastrointestinal stromal tumour (GIST) is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resect...Gastrointestinal stromal tumour (GIST) is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resection of the rectum for a low-risk GIST. The patient was not given adjuvant chemotherapy with imatinib and is still disease-free 30 mo after surgery. The authors conclude that although rectal GIST is extremely uncommon, it should be included in differential diagnosis when a tumour in the rectum is detected. Biopsy of the tumour is essential, since this makes it possible to reach a sure preoperative diagnosis based on the immunohistological features of the CD117 and CD34. Although complete surgical resection with negative tumour margins is the principal curative procedure for primary and non-metastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients with rectal GIST.展开更多
Screening of the general population for esophageal cancer and gastric cardia cancer using an occult blood bead detector supplemented by fiberogastroscopy was able to detect 103 cases with early esophageal cancer and g...Screening of the general population for esophageal cancer and gastric cardia cancer using an occult blood bead detector supplemented by fiberogastroscopy was able to detect 103 cases with early esophageal cancer and gastric cardia cancer at Yangzhong County where the incidence was high from Apr. 1986 to Feb. 1992. Among them, there were 47 cancers of esophagus and 56 cancers of gastric cardia through pathological verification.. They took 17.1% (103/604) of the correspouding esophageal and gastric cardia caucers. We thought that about 90% of early esophageal and gastric cardia cancers have symptoms. We should couduct screening for high risk group in the area where the incidence is high at regular intervals. Besides, it is also important to strengthen propaganda for cancer prevention and self-protection for population, to emphasize the diagnosis and recognition of early cancer for medical workers.展开更多
Endometriosis is a debilitating problem with pain in the short term and high risk of infertility later. It is an oestrogen-dependent condition found in about 10% of women of reproductive age, about 1/3 of infertile wo...Endometriosis is a debilitating problem with pain in the short term and high risk of infertility later. It is an oestrogen-dependent condition found in about 10% of women of reproductive age, about 1/3 of infertile women and as high as 80% of women with chronic pelvic pain. The condition is not well understood and thus associated with misdiagnosis and delayed diagnosis. Higher rates of misdiagnosis occur in blacks and this is especially for pelvic tumors-fibroids and ovarian tumors. We present here the case of a 30-year-old nullipara, who had an umbilical nodule (Sister Mary Joseph’s) and was found on imaging to have a pelvic tumor which was suspected to be an ovarian cancer. Diagnostic laparoscopy during the menstrual phase however revealed endometriosis in early stage. Misdiagnosis of endometriosis has potential to distort the course of the disease and endanger fertility prospects;early laparoscopic evaluation of patients with unclear pelvic pathologies would help to prevent this occurrence.展开更多
中国疾病预防控制中心数据显示,肝癌位居我国恶性肿瘤死因第2位,是死亡率较高的恶性肿瘤。肝癌具有早期诊断困难(约50%漏诊)、恶性程度高、异质性强及进展迅速等特点,早期诊断可提升治疗效果,延长患者生存期。肝癌的主要病理类型为肝细...中国疾病预防控制中心数据显示,肝癌位居我国恶性肿瘤死因第2位,是死亡率较高的恶性肿瘤。肝癌具有早期诊断困难(约50%漏诊)、恶性程度高、异质性强及进展迅速等特点,早期诊断可提升治疗效果,延长患者生存期。肝癌的主要病理类型为肝细胞肝癌(hepatocellular carcinoma,HCC),其肿瘤标志物包括甲胎蛋白(α-fetoprotein,AFP)、维生素K缺乏或拮抗剂Ⅱ诱导的凝血酶原(protein induced by vitamin K deficiency or antagonist-Ⅱ,PIVKA-Ⅱ)、α-L-岩藻糖苷酶(α-L-fucosidase,AFU)等,检测简单且高效,但由于HCC的异质性,部分患者的标志物水平未出现异常,52%的小型HCC(<3 cm)患者为AFP阴性,影响HCC诊断的准确率。一些新型肿瘤标志物已被发现,包括循环肿瘤细胞(circulating tumour cell,CTC)、循环游离核酸(包括循环游离DNA(circulating cell-free DNA,cfDNA)和微小RNA(microRNA,miRNA)以及外泌体等。90.81%的CTC阳性HCC患者(包括早期疾病患者),在随访3~5个月后可检测到非常小的HCC结节,表明CTC与HCC特征高度相关,术后监测CTC水平可在临床检测到复发结节出现之前预测HCC复发;cfDNA可作为HCC早期诊断的有效工具,而检测ctDNA内的突变可指导靶向治疗;miRNA可作为诊断疾病和监测疾病进展、预后情况的生物标志物;联合检测AFP与lncRNAs Panel(包含3种循环外泌体来源的长链非编码RNA,即ENSG00000248932.1、ENST00000440688.1、ENST00000457302.2)显示出比单独检测AFP更高的灵敏度和特异度(曲线下面积为0.910和0.408),可预测HCC的发生并动态监测HCC的转移。但这类新型肿瘤标志物仍具有一定的局限性,如由于这类标志物通常以较低水平存在,可能会导致较高的假阴性,并且缺乏标准化的分析前变量和分析变量,在稳定性方面具有局限性。这类肿瘤标志物目前仍不建议独立用于HCC的早期筛查、监测或是在临床上大规模应用,仅可作为传统诊断方法的补充。本文将对近年来肿瘤标志物在HCC诊断中的研究进展进行综述,总结传统肿瘤标志物(AFP、PIVKA-Ⅱ和AFU等)效能,介绍新型肿瘤标志物(CTC、cfDNA、ctDNA、miRNA和外泌体等)的研究进展及临床应用,并对未来提升HCC诊断准确率进行展望。展开更多
文摘Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development of technologies for highthroughput sequencing,a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi.The intratumour microbiome is being revealed as an influential contributor to carcinogenesis.The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression,diagnosis,and treatment,chemotherapy resistance,and immune response.A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies.This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer,the intratumour localization,the interaction with the tumour microenvironment,and strategies for improving the outcome of pancreatic cancer treatment.Thus,this review offers new perspectives for improving the prognosis of pancreatic cancer.
文摘BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.
文摘Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.
文摘Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.
基金We would like to thank Dr. Xiao-Song Chen (Ruijin Hospital) for additional editorialassistance.
文摘BACKGROUND Phyllodes tumours(PTs)are fibroepithelial breast tumours,which can be classified as benign,borderline or malignant,according to their histological characteristics.While various huge borderline or malignant PTs have been previously described,a benign PT with a pulmonary nodule mimicking malignancy has not yet been reported.In order that doctors may have a comprehensive understanding of super-giant benign PTs(≥20 cm),we also performed a literature review to summarize the clinical features,differential diagnosis,and treatment of this disease.CASE SUMMARY A 42-year-old woman with severe anaemia presented with a rapidly enlarging right breast mass,measuring approximately 30 cm×25 cm×20 cm that was first noticed 1 year previously.A region of skin ulceration and necrosis(20 cm×15 cm)was observed on the lateral side of the mass.Computed tomography(CT)of the chest revealed a pulmonary nodule,which initially suggested a diagnosis of metastasis.CT showed that the boundaries between the pectoralis major and the mass were blurred,which was presumed to be due to tumour invasion.However,two core needle biopsies of the mass showed no evidence of malignancy.Following these results,the tumour was removed by mastectomy of the right breast.Interestingly,postoperative pathology finally proved the diagnosis of a benign PT.After 1 year of follow-up,wedge resection of the small pulmonary nodule was performed,and it was confirmed that the lung nodule was actually adenocarcinoma rather than metastatic breast cancer.The patient recovered very well without any postoperative treatment.CONCLUSION This case is unique in that the giant breast mass initially mimicking a malignantclinical presentation was eventually pathologically confirmed to be a benign PT,which misled the diagnosis and complemented the atypical features of benign PTs.The pathological and immunohistochemical results were important in the differential diagnosis.In addition,total mastectomy should be recommended due to difficulty in the precise diagnosis of PTs,especially in large breast masses.In the literature,almost one-half of super-giant benign cases were thought to be malignant tumours before surgery.This finding is a reminder to consider all conditions in order to make an accurate diagnosis and avoid excessive treatment.
文摘Gastrointestinal stromal tumour (GIST) is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resection of the rectum for a low-risk GIST. The patient was not given adjuvant chemotherapy with imatinib and is still disease-free 30 mo after surgery. The authors conclude that although rectal GIST is extremely uncommon, it should be included in differential diagnosis when a tumour in the rectum is detected. Biopsy of the tumour is essential, since this makes it possible to reach a sure preoperative diagnosis based on the immunohistological features of the CD117 and CD34. Although complete surgical resection with negative tumour margins is the principal curative procedure for primary and non-metastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients with rectal GIST.
文摘Screening of the general population for esophageal cancer and gastric cardia cancer using an occult blood bead detector supplemented by fiberogastroscopy was able to detect 103 cases with early esophageal cancer and gastric cardia cancer at Yangzhong County where the incidence was high from Apr. 1986 to Feb. 1992. Among them, there were 47 cancers of esophagus and 56 cancers of gastric cardia through pathological verification.. They took 17.1% (103/604) of the correspouding esophageal and gastric cardia caucers. We thought that about 90% of early esophageal and gastric cardia cancers have symptoms. We should couduct screening for high risk group in the area where the incidence is high at regular intervals. Besides, it is also important to strengthen propaganda for cancer prevention and self-protection for population, to emphasize the diagnosis and recognition of early cancer for medical workers.
文摘Endometriosis is a debilitating problem with pain in the short term and high risk of infertility later. It is an oestrogen-dependent condition found in about 10% of women of reproductive age, about 1/3 of infertile women and as high as 80% of women with chronic pelvic pain. The condition is not well understood and thus associated with misdiagnosis and delayed diagnosis. Higher rates of misdiagnosis occur in blacks and this is especially for pelvic tumors-fibroids and ovarian tumors. We present here the case of a 30-year-old nullipara, who had an umbilical nodule (Sister Mary Joseph’s) and was found on imaging to have a pelvic tumor which was suspected to be an ovarian cancer. Diagnostic laparoscopy during the menstrual phase however revealed endometriosis in early stage. Misdiagnosis of endometriosis has potential to distort the course of the disease and endanger fertility prospects;early laparoscopic evaluation of patients with unclear pelvic pathologies would help to prevent this occurrence.
文摘中国疾病预防控制中心数据显示,肝癌位居我国恶性肿瘤死因第2位,是死亡率较高的恶性肿瘤。肝癌具有早期诊断困难(约50%漏诊)、恶性程度高、异质性强及进展迅速等特点,早期诊断可提升治疗效果,延长患者生存期。肝癌的主要病理类型为肝细胞肝癌(hepatocellular carcinoma,HCC),其肿瘤标志物包括甲胎蛋白(α-fetoprotein,AFP)、维生素K缺乏或拮抗剂Ⅱ诱导的凝血酶原(protein induced by vitamin K deficiency or antagonist-Ⅱ,PIVKA-Ⅱ)、α-L-岩藻糖苷酶(α-L-fucosidase,AFU)等,检测简单且高效,但由于HCC的异质性,部分患者的标志物水平未出现异常,52%的小型HCC(<3 cm)患者为AFP阴性,影响HCC诊断的准确率。一些新型肿瘤标志物已被发现,包括循环肿瘤细胞(circulating tumour cell,CTC)、循环游离核酸(包括循环游离DNA(circulating cell-free DNA,cfDNA)和微小RNA(microRNA,miRNA)以及外泌体等。90.81%的CTC阳性HCC患者(包括早期疾病患者),在随访3~5个月后可检测到非常小的HCC结节,表明CTC与HCC特征高度相关,术后监测CTC水平可在临床检测到复发结节出现之前预测HCC复发;cfDNA可作为HCC早期诊断的有效工具,而检测ctDNA内的突变可指导靶向治疗;miRNA可作为诊断疾病和监测疾病进展、预后情况的生物标志物;联合检测AFP与lncRNAs Panel(包含3种循环外泌体来源的长链非编码RNA,即ENSG00000248932.1、ENST00000440688.1、ENST00000457302.2)显示出比单独检测AFP更高的灵敏度和特异度(曲线下面积为0.910和0.408),可预测HCC的发生并动态监测HCC的转移。但这类新型肿瘤标志物仍具有一定的局限性,如由于这类标志物通常以较低水平存在,可能会导致较高的假阴性,并且缺乏标准化的分析前变量和分析变量,在稳定性方面具有局限性。这类肿瘤标志物目前仍不建议独立用于HCC的早期筛查、监测或是在临床上大规模应用,仅可作为传统诊断方法的补充。本文将对近年来肿瘤标志物在HCC诊断中的研究进展进行综述,总结传统肿瘤标志物(AFP、PIVKA-Ⅱ和AFU等)效能,介绍新型肿瘤标志物(CTC、cfDNA、ctDNA、miRNA和外泌体等)的研究进展及临床应用,并对未来提升HCC诊断准确率进行展望。
