Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus–Di?erences in Etiology, Epidemiology and Prevention

In Germany, esophageal carcinoma is one of the ten most frequent causes of death. Normally the disease is found in men over the age of 50. Although squamous cell carcinoma (SCC) of the esophagus has been more commonly diagnosed over the past 30 years, there is increasing incidence of esophageal adenocarcinoma (AC) in Western industrialized countries. For SCC the known etiological risk factors are nicotine and alcohol abuse. For AC, they are moderate nicotine and alcohol consumption as well as gastro-esophageal re?ux and obesity.

A case of rapidly progressing leiomyosarcoma combined with squamous cell carcinoma in the esophagus

Esophageal leiomyosarcoma is a rare tumor that accounts for less than 1%of all malignant esophageal tumors.Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma.We experienced a case of leiomyosarcoma combined with squamous cell carcinoma that progressed very rapidly.

Determination of esophageal squamous cell carcinoma and gastric adenocarcinoma on raw tissue using Raman spectroscopy

BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.

Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population

AIM: To investigate the relation of human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in Iranian patients as compared to normal controls. METHODS: Using MY09/MY11 consensus primers, we compared the prevalence of a HPV L1 gene in tumor tissues from 38 ESCC cases and biopsied tissues from 38 endoscopically normal Iranian individuals. We also compared the presence of HPV16 and HPVA18 in the same samples using type-specific E6/E7 primers. RESULTS: Fourteen (36.8%) of the 38 ESCC samples but only 5 (13.2%) of the 38 control samples were positive for the HPV L1 gene (P= 0.02). Five (13.2%) of the ESCC samples but none of the control samples were positive for the HPV16 E6/E7 gene (P= 0.05). Three (7.9%) of the ESCC samples and 5 (13.2%) of the control samples were positive for the HPV18 E6/E7 gene (P= 0.71). CONCLUSION: Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor contributing to the high incidence of ESCC in Iran and other high-incidence areas of the world.

Preoperative sorting of circulating T lymphocytes in patients with esophageal squamous cell carcinoma: Its prognostic significance

AIM: To elucidate the immunologic parameters for the outcome of patients with malignant tumors, especially esophageal squamous cell carcinoma (ESCC) associated with high malignant potential. METHODS: Clinicopathologic features were compared between patients with lower and higher CD4 and CD8 values as well as CD4/CD8 ratio in peripheral blood. RESULTS: The survival rate of patients with higher CD4 value was significantly better than that in patients with lower CD4 value (P = 0.039). The survival rate of patients with higher CD8 value was significantly worse than that of patients with lower CD8 value (P = 0.026). Similarly, the survival rate of patients with higher CD4/ CD8 ratio was significantly better than that of patients with lower CD4/CD8 ratio (P = 0.042). Additionally, multivariate analysis demonstrated that lower CD8 and lower CD4/CD8 ratio were factors independently associated with worse prognosis of patients. CONCLUSION: All the immunologic parameters can predict the outcome of patients with ESCC.

Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer

AIM： To assess the proteome of normal versus tumor tissue in squamous cell carcinoma of the esophagus （SCCE） in Iranian patients and compare our results with former reports by using proteomics. METHODS： Protein was extracted from normal and tumor tissues. Two dimensional electrophoresis was carried out and spots with differential expression were identified with mass spectrometry. RNA extraction and RT-PCR along with immunodetection were performed. RESULTS： Fourteen proteins were found whose expression levels differed in tumor compared to normal tissues. Mass spectrometric analysis resulted in the identification of β-tropomyosin （TMβ）, myosin light chain 2 （and its isoform）, myosin regulatory light chain 2, peroxyredoxin 2, annexin I and an unknown polypeptide as the down regulated polypeptides in tumor tissue. Heat shock protein 70 （HSP70）, TPM4-ALK fusion oncoprotein 2, myosin light polypeptide 6, keratin I, GH16431p and calreticulin were the up-regulated polypeptides found in tumor tissue. Several of these proteins, such as TMβ, HSP70, annexin Ⅰ, calreticulin, TPM4-ALK and isoforms of myosins, have been well recognized in tumorigenesis of esophageal or other types of cancers. CONCLUSION： Our study not only supports the involvement of some of the formerly reported proteins in SCCE but also introduces additional proteins found to be lost in SCCE, including TMβ.

S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells

AIM： To investigate a potential role of S100A4 in esoph- agus squamous cell carcinoma metastasis （ESCCs）.METHODS： Expression of $100A4 and E-cadherin were analyzed in frozen sections from ESCCs （metastasis, n = 28; non-metastasis, n = 20） by reverse transcrip- tion-polymerase chain reaction, quantitative polymerase chain reaction and immunohistochemistry. To explore the influence of $100A4 on esophageal cancer invasion and metastasis, $100A4 was overexpressed or silenced by $100A4 siRNA in TE-13 or Eca-109 cells/n vitro and /n vivo.

Nicotine enhances migration and invasion of human esophageal squamous carcinoma cells which is inhibited by nimesulide

AIM： To study the effect of nicotine on the migration and invasion of human esophageal squamous carcinoma cells and to investigate whether nimesulide can inhibit the effect of nicotine.METHODS： The esophageal squamous carcinoma cell line （TE-13） was treated with different concentrations of nicotine （100 μg/mL and 200 μg/mL） or 200 μg/mL nicotine plus 100 μmol/L nimesulide. Cell migration and invasion were measured using migration and invasion chamber systems. COX-2 expression was determined by Western blotting. Matrix metalloproteinase-2 （MMP-2） was analyzed by zymography and ELISA.RESULTS： Nicotine （100 μg/mL, 200 μg/mL） enhanced TE-13 cells migration and invasion, and increased the protein expression of COX-2 and the activity of MMP-2. Nicotine （200 μ/mL） stimulated TE-13 cells migration and invasion which were partly blocked by nimesulide. This was associated with decreased protein expression of COX-2 and decreased activity and protein expression of MMP-2. CONCLUSION： Nicotine enhances the migration and invasion of the esophageal squamous carcinoma cell line, and nimesulide partly blocks the effect ofnicotine-enhanced esophageal squamous carcinoma cell migration and invasion.

An extremely rare case of pancreatic metastasis of esophageal squamous cell carcinoma

We report a rare case of a 68-year-old male with metachronous pancreatic metastasis that was resected2 years after salvage esophagectomy for local recurrence of esophageal squamous cell carcinoma(ESCC).Two years and 8 mo ago,he had undergone definitive chemoradiotherapy for the lower thoracic ESCC and achieved a complete response.Chemoradiotherapy used the protocol of the Japan Clinical Oncology Group trial 9906.Approximately 8 mo later,he developed a local recurrence of the ESCC and underwent thoracoscopic salvage esophagectomy followed by reconstruction with a conduit colon graft via a subcutaneous route.Recently,a tumor of the pancreatic body was found on routine follow-up computed tomography(CT).The tumor diameter was 15 mm on CT,and the maximum standardized uptake value of the lesion was 5.49at 18F-2-fluoro-2-deoxy-D-glucose positron-emission tomography,strongly suggesting pancreatic cancer.In addition,all tumor markers were within the reference intervals.Therefore,distal pancreatectomy was performed with the resultant histological diagnosis being confirmed as pancreatic metastasis of the ESCC.He was treated with adjuvant chemotherapy,and there has been no evidence of recurrence 9 mo after the surgery.Resection of pancreatic metastasis offers a good prognosis and should be considered for solitary ESCC metastasis.

Quantitative measurement of contrast enhancement of esophageal squamous cell carcinoma on clinical MDCT

AIM: To investigate contrast-enhanced computed tomography (CECT) for discriminating esophageal squamous cell carcinoma (ESCC) from normal esophagus and evaluating outcomes within tumors after chemoradiotherapy (CRT). METHODS: Sixty-four patients with surgical ESCC served as group A, and underwent thoracic contrast-enhanced scan with 16-section multidetector row CT 1 wk before surgery. Thirty-five patients with advanced ESCC receiving 4-wk CRT and showing response to CRT served as group B, and underwent CT scans similar with group A 4 wk after completion of CRT. In group A, differences in CT attenuation values (in HU) between the preoperative ESCC and background normal esophageal wall (delta CT1), or between different background normal esophageal walls (delta CT2) were compared. Furthermore, delta CT1 between group A and B was also compared. RESULTS: In group A, mean delta CT1 was higher than delta CT2 (23.86 ± 10.59 HU vs 6.24 ± 3.06 HU, P < 0.05). When a delta CT1 of 10.025 HU was employed at a cut-off value to discriminate ESCC from normal esophagus, a sensitivity of 89.1% and specificity of 90.6% were achieved. Mean delta CT1 was lower in group B than in group A (9.25 ± 10.86 vs 23.86 ± 10.59, P < 0.05), and a delta CT1 of 15.45 HU was obtained at a cut-off value to assess the CRT changes with a sensitivity of 76.6% and specificity of 77.1%. CONCLUSION: CECT might be a clinical technique for discriminating ESCC from normal esophagus, and evaluating outcome in the tumors treated with CRT.

Atrophic gastritis: Risk factor for esophageal squamous cell carcinoma in a Latin-American population

AIM: To study the association between atrophic gastritis (AG) and esophageal squamous cell carcinoma (ESCC) in a Latin-America population. METHODS: A case-control study was performed at two reference Brazilian hospitals including patients diagnosed with advanced ESCC and dyspeptic patients who had been subjected to upper gastrointestinal endoscopy, with biopsies of the gastric antrum and body.All cases with ESCC were reviewed by a single pathologist, who applied standard criteria for the diagnosis of mucosal atrophy, intestinal metaplasia, and dysplasia, all classified as AG. The data on the patients' age, sex, smoking status, and alcohol consumption were collected from clinical records, and any missing information was completed by telephone interview. The association between AG and ESCC was assessed by means of univariate and multiple conditional logistic regressions. RESULTS: Most patients were male, and the median age was 59 years (range: 37-79 years) in both the ESCC and control groups. Univariate analysis showed that an intake of ethanol greater than 32 g/d was an independent risk factor that increased the odds of ESCC 7.57 times (P = 0.014); upon multiple analysis, alcohol intake of ethanol greater than 32 g/d exhibited a risk of 4.54 (P = 0.081), as adjusted for AG and smoking. Smoking was shown to be an independent risk factor that increased the odds of ESCC 14.55 times (P = 0.011) for individuals who smoked 0 to 51 packs/year and 21.40 times (P = 0.006) for those who smoked more than 51 packs/year. Upon multiple analyses, those who smoked up to 51 packs/year exhibited a risk of 7.85 (P = 0.058), and those who smoked more than 51 packs/ year had a risk 11.57 times higher (P = 0.04), as adjusted for AG and alcohol consumption. AG proved to be a risk factor that increased the odds of ESCC 5.33 times (95%CI: 1.55-18.30, P = 0.008) according to the results of univariate conditional logistic regression. CONCLUSION: There was an association by univariate conditional logistic regression between AG and ECSS in this sample of Latin-American population.

Is endoscopic ultrasound examination necessary in the management of esophageal cancer?

Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.

Coexistence of esophageal superficial carcinoma and multiple leiomyomas:A case report

Leiomyomas are the most common benign tumors of the esophagus. They usually occur as a single lesion or as two or three nodules. Only two cases of esophageal multiple leiomyomas comprising more than 10 nodules have been reported previously. Moreover, there have been few reports of esophageal squamous cell carcinoma overlying submucosal tumors. We describe a 71-yearold man who was diagnosed as having a superficial esophageal cancer coexisting with two or three leiomyoma nodules. During surgery, 10 or more nodules that had not been evident preoperatively were palpable in the submucosal and muscular layers throughout the esophagus. As intramural metastasis of the esophageal cancer was suspected, we considered additional lymphadenectomy, but had to rule out this option because of the patient＇s severe anoxemia. Microscopic examination revealed that all the nodules were leiomyomas （20 lesions, up to 3 cm in diameter）, and that invasion of the carcinoma cells was limited to the submucosal layer overlying a relatively large leiomyoma. This is the first report of superficial esophageal cancer coexisting with numerous solitary leiomyomas. Multiple minute leiomyomas are often misdiagnosed as intramural metastasis, and a leiomyoma at the base of a carcinoma lesion can also be rnisdiagnosed as tumor invasion. The present case shows that accurate diagnosis is required for the management of patients with coexisting superficial esophageal cancer and multiple leiomyomas.

Have patients with esophagitis got an increased risk of adenocarcinoma? Results from a population-based study

AIM: To examine an increased risk of esophageal adenocarcinoma is restricted to patients who develop Barrett's esophagus or whether esophagitis per se is a risk factor for adenocarcinoma.METHODS: A population-based cohort of patients with histological evidence of esophagitis without Barrett's esophagus was constructed using electronic pathology reports relating to all esophageal biopsies in Northern Ireland between 1993 and 1996. Person-years of followup and incident cases of esophageal cancer were calculated by linking the cohort to death files and the Northern Ireland Cancer Registry records. Standardized incidence ratios (SIR) were calculated for esophageal cancers (adenocarcinoma, squamous cell carcinoma (SCC), and histologically unspecified cancers).RESULTS: A total of 2 013 patients in the cohort provided 13 559 patient-years of follow-up (mean follow-up 6.7 years). None of the patients developed adenocarcinoma. Three patients developed SCC, and six developed histologically unspecified cancers. The SIR for all esophageal cancers and for SCC were 2.73 (95%CI 1.25-5.19) and 2.93 (95%CI 0.61-8.59), respectively. In a sensitivity analysis in which all unspecified esophageal cancers were treated as adenocarcinomas, the SIR for adenocarcinoma was 2.64 (0.97-5.75).CONCLUSION: The risk of adenocarcinoma is not elevated in patients with histological evidence of esophagitis without Barrett's esophagus; however, these patients may have a moderately increased risk of SCC.Further studies are required to confirm these findings,which suggest that Barrett's esophagus, not esophagitis,is the key precursor lesion in the development of adenocarcinoma.

局部进展期食管鳞状细胞癌新辅助化疗联合免疫治疗反应的基线CT Logistic回归预测模型研究

目的:建立并验证局部进展期食管鳞状细胞癌(ESCC)新辅助化疗联合免疫治疗前的增强CT对治疗反应性预测的Logistic回归模型。方法:回顾性分析148例局部进展期ESCC患者的CT影像资料及临床资料,患者均接受新辅助化疗联合免疫治疗,并按3∶1的比例分为训练集(n=114)和验证集(n=34)。单因素统计分析训练集治疗前相关指标与ESCC新辅助治疗后反应性的关系;多因素Logistic回归分析治疗反应性的独立预测因素,并构建Logistic预测模型。受试者工作特征(ROC)曲线分析模型的预测效能,并在验证集通过Kappa检验验证回归模型的预测效能。结果:单因素分析显示,训练集治疗前cT分期、淋巴结转移、原发肿瘤体积(GTV)及转移淋巴结体积(GVAMN)在有和无反应患者的差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,cT分期、淋巴结转移和GTV是治疗反应性的独立预测因素(P<0.05)。ROC曲线分析显示,基于独立预测因素构建的Logistic回归模型在训练集中预测治疗反应性的曲线下面积为0.831,Kappa检验显示在验证集,预测模型效能表现良好(Kappa=0.641)。结论:基于治疗前cT分期、淋巴结转移和GTV建立的Logistic回归模型,对预测局部进展期ESCC新辅助化疗联合免疫治疗后的反应性有重要价值。

口腔微生物与食管疾病关系的研究进展

口腔微生物与人类疾病的相关性是近年来的研究热点。口腔微生物除了与口腔疾病具有密切关系外,还与消化道其他器官疾病密切相关,其中食管疾病很少受到关注。本文旨在总结当前口腔微生物组与食管疾病之间关联的证据,这些证据表明与胃食管反流病、巴雷特食管、食管鳞状细胞癌和食管腺癌相关的口腔微生物组具有独有的特征,这种从较高革兰阳性菌比例到革兰阴性菌更占优势的转变被认为与食管疾病的发生发展有关。口腔微生物组改变与食管疾病的关联机制可能是由于革兰阴性菌脂多糖的表达,特别是福赛斯坦纳菌和牙龈卟啉单胞菌参与食管癌发展的信号通路。识别口腔微生物组的改变将会促进临床对食管疾病病因、发病机制和进展的理解,促进新诊断方法出现,并为制订个性化治疗方案奠定基础。

Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract

Esophageal atresia(EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia(72%) and gastroesophageal reflux(GER)(67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.

Human papilloma virus and esophageal carcinoma in a Latin-American region

AIM:To investigate the presence of high-risk human papilloma virus (HPV) in esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican population.METHODS: Cases with a pathological diagnosis of squamous cell carcinoma of the esophagus were obtained from Department of Pathology files, at the National Cancer Institute in Mexico City during the period between 2000 and 2008. Slides from each case were reviewed and cases with sufficient neoplastic tissue were selected for molecular analysis. DNA was extracted from paraffin-embedded tissue samples for polymerase chain reaction analysis to detect HPV DNA sequences. Demographic and clinical data of each patient were retrieved from corresponding clinical records.RESULTS: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected in one case. Unfortunately, HPV genotype could not be established in three cases due to lack of material for direct sequencing, although universal primers detected the presence of HPV generic sequences. No low-risk HPV genotypes were found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage. Male patients were most commonly affected and the male:female ratio in HPV-positive ESCC increased two- fold in comparison with HPV-negative cases (6.5:1 vs 3.1:1).CONCLUSION: High prevalence of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV-associated ESCC is more common in areas with higher ESCC incidence rates.

Artificial intelligence technique in detection of early esophageal cancer

Due to the rapid progression and poor prognosis of esophageal cancer(EC),the early detection and diagnosis of early EC are of great value for the prognosis improvement of patients.However,the endoscopic detection of early EC,especially Barrett's dysplasia or squamous epithelial dysplasia,is difficult.Therefore,the requirement for more efficient methods of detection and characterization of early EC has led to intensive research in the field of artificial intelligence(AI).Deep learning(DL)has brought about breakthroughs in processing images,videos,and other aspects,whereas convolutional neural networks(CNNs)have shone lights on detection of endoscopic images and videos.Many studies on CNNs in endoscopic analysis of early EC demonstrate excellent performance including sensitivity and specificity and progress gradually from in vitro image analysis for classification to real-time detection of early esophageal neoplasia.When AI technique comes to the pathological diagnosis,borderline lesions that are difficult to determine may become easier than before.In gene diagnosis,due to the lack of tissue specificity of gene diagnostic markers,they can only be used as supplementary measures at present.In predicting the risk of cancer,there is still a lack of prospective clinical research to confirm the accuracy of the risk stratification model.