BACKGROUND The use of radiofrequency ablation(RFA)has been reported in the treatment of gastric low-grade intraepithelial neoplasia(LGIN).However,its efficacy and prognostic risk factors have not been well analyzed.AI...BACKGROUND The use of radiofrequency ablation(RFA)has been reported in the treatment of gastric low-grade intraepithelial neoplasia(LGIN).However,its efficacy and prognostic risk factors have not been well analyzed.AIM To explore the efficacy and prognostic risk factors of RFA for gastric LGIN in a large,long-term follow-up clinical study.METHODS The clinical data of 271 consecutive cases from 198 patients who received RFA for treatment of gastric LGIN at the Chinese PLA General Hospital from October 2014 to October 2020 were reviewed in this retrospective study.Data on operative parameters,complications,and follow-up outcomes including curative rates were recorded and analyzed.RESULTS The curative rates of endoscopic RFA for gastric LGIN at 3 mo,6 mo,and 1-5 years after the operation were 93.3%,92.8%,91.5%,90.3%,88.5%,85.7%,and 83.3%,respectively.Multivariate analyses revealed that Helicobacter pylori(H.pylori)infection and disease duration>1 year had a significant effect on the curative rate(P<0.001 and P=0.013,respectively).None of patients had bleeding,perforation,infection,or other serious complications after RFA,and the main discomfort was postoperative abdominal pain.CONCLUSION RFA was safe and effective for gastric LGIN during long-term follow-up.H.pylori infection and disease course>1 year may be the main risk factors for relapse of LGIN after RFA.展开更多
As a drug-mechanical combination technology,photodynamic(PDT)can achieve accurate and taurgeted therapy for maligmant tumors and benign diseases through the production of reactive oxygen species,oxygen free radicals o...As a drug-mechanical combination technology,photodynamic(PDT)can achieve accurate and taurgeted therapy for maligmant tumors and benign diseases through the production of reactive oxygen species,oxygen free radicals or singlet oxygen by photosensitizers at specific wavelengths.Compared with traditional surgery,it has the advantages of selective killing.repeatable teatment,preserving target organ fiunction and so on.The purpose of this study was to explore the clinical value of photodynamic therapy in cervical precancerous lesions by taking the patients with low-grade cervical intaepithelial neoplasia(CIN1)with high-risk human papillomavinus(HR HPV)persistent infection diagnosed by"three-step diagnosis and teatment procedure"as an example.Using HiPorfn as a photosensitizer,photodynamic therapy was performed 48 hours after intavenous drip.Set laser wavelength 630nm,light dose density 137.58J/cm^2,ansmission efficiency 1.42,output power 2w.3cm columnar optical fber was placed around the 2cm in the cervical canal to cover all the lesions,and the inadiation time was 900s(600s in the cervical canal and 300s outside the cervical canal).The patients were given oxygen inhalation for 6 hours after operation,and the patients were observed for itching and other discomfort,and paid attention to avoid light.Photodynamic therapy was performed again in the same way on the second day.After two months of treatment,pathological biopsy showed chronic cervicitis,indicating that the disease had been effectively controlled.Theoretically,although the patient is not the absolhute indication of photodynamic therapy(hat is,meeting CIN Ⅱ or CIN Ⅲ,having fertility requirements and not undergoing surgery),this therapy can remove not only the superficial lesions inside and outside the cervix,but also the potential lesions not found under colposcopy.It can also block the persistent infection of HPV by.inhbting the expression of HPV18,E6 and E7mRNA in Hela cells.In combination with Baofukang suppository,it can block HPV infection.Increase the negative conversion rate of cervical HPV and reduce the probablity of recurence after CIN1 cure.For youmng female patients with persistent HR-HPV infection and fertility requirements,photodynamic therapy is an effective choice for clinical treatment of CIN1.展开更多
Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the Unit...Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus(HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPVmediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.展开更多
Gastric adenocarcinoma generally culminates via the inflammation-metaplasia-dysplasia-carcinoma sequence progression. The prevalence of gastric adenomas shows marked geographic variation. Recently, the rate of diagnos...Gastric adenocarcinoma generally culminates via the inflammation-metaplasia-dysplasia-carcinoma sequence progression. The prevalence of gastric adenomas shows marked geographic variation. Recently, the rate of diagnosis of low-grade dysplasia(LGD) has increased due to increased use of upper endoscopy. Many investigators have reported that gastric highgrade dysplasia has high potential for malignancy and should be removed; however, the treatment for gastric LGD remains controversial. Although the risk of LGD progression to invasive carcinoma has been reported to be inconsistent, progression has been observed during follow-up. Additionally, the rate of upgraded diagnosis in biopsy-proven LGD is high. Therefore, endoscopic resection(ER) may be useful in the treatment and diagnosis of LGD, especially if lesions are found to have risk factors for upgraded histology after ER, such as large size, surface erythema or depressed morphology. Fatal complications in endoscopic submucosal dissection(ESD) are extremely low and its therapeutic and diagnostic outcomes are excellent. Therefore, ESD should be applied preferentially instead of endoscopic mucosal resection.展开更多
Objective: To explore the clinical significance of the quantitative detection of human papillomavirus(HPV) E6/E7 mRN A in triage of patients with atypical squamous cells of undetermined significance(ASC-US) and low-gr...Objective: To explore the clinical significance of the quantitative detection of human papillomavirus(HPV) E6/E7 mRN A in triage of patients with atypical squamous cells of undetermined significance(ASC-US) and low-grade squamous intraepithelial lesion(LSIL).Methods: A cross-sectional screening study was conducted among women who underwent outpatient gynecological screening at the Obstetrics and Gynecology Hospital of Fudan University from September 2015 to July 2016. A total of 500 patients from our hospital with ASC-US or LSIL based on cytology testing were subjected to HPV DNA and HPV E6/E7 mRNA quantitative analysis.Results: The specificity of the HPV E6/E7 mRNA test for detecting ≥high-grade squamous intraepithelial lesion(HSIL+) was statistically higher than that of the HPV DNA test(61.3% vs. 40.0%, P< 0.05), whereas there was no significant difference in the sensitivity of HPV E6/E7 mRNA test and HPV DNA test(90.0% vs. 95.0%, P > 0.05). The positive rates of HPV in the participants tested by HPV E6/E7 mRNA and HPV DNA were, respectively, 42.8%(214/500) and 62.8%(314/500), with statistical significance(P < 0.05).Conclusions: The HPV E6/E7 mRNA test was slightly less sensitivity than that of the HPV DNA test for diagnosing HSIL+ in patients with ASC-US and LSIL, but the difference was not significant, although the specificity of the former was significantly higher. HPV E6/E7 mRNA detection can effectively reduce overdiagnosis and overtreatment of patients with ASC-US and LSIL and has important clinical value in triage of patients with ASC-US and LSIL.展开更多
Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over t...Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the crit...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.展开更多
Objective:Penile neoplasia,usually of squamous histogenesis,is currently classfied into human papillomavirus(HPV)-related or-dependent and non-HPV-related or-indepen dent.There are distinct morphological differences a...Objective:Penile neoplasia,usually of squamous histogenesis,is currently classfied into human papillomavirus(HPV)-related or-dependent and non-HPV-related or-indepen dent.There are distinct morphological differences among the two groups.New research studies on penile cancer from Northern countries showed that the presence of HPV is corre lated with a better prognosis than virus negative people,while studies in Southern countries had not confirmed,perhaps due to differences in staging or treatment.Methods:We focused on the description of the HPV.related carcinomas of the penis.The approach was to describe common clinical features followed by the pathological features of each entity or subtype stressing the characteristics for differential diagnosis,HPV genotypes,and prognostic features of the invasive carcinomas.Similar structure was followed for penile intraepithelial neoplasia,except for prognosis because of the scant evidence available.Results:Most of HPV-related lesions can be straightforwardly recognized by routine hematoxylin and eosin stains,but in some cases surrogate p16 immunohistochemical staining or molecular methods such as in situ hybridization or polymerase chain reaction can be utilized.Currently,there are eight tumor invasive variants associated with HPV,as follows:basaloid,warty,warty-basaloid,papillary basaloid,clear cell,medullary,lymphoepithelioma-like,and giant condylomas with malignant transformation.Conclusion:This review presents and describes the heterogeneous clinical,morphological,and genatypic features of the HPV-related subtypes of invasive and non-invasive penile neoplasia.展开更多
目的探究食管鳞状上皮内瘤变发生风险的预测因素,构建列线图预测模型。方法回顾性收集2016年01月至2021年12月在扬州大学附属医院诊断为食管鳞状上皮内瘤变患者126例,以及同期于健康管理中心进行体检者344例,收集患者一般临床资料、血...目的探究食管鳞状上皮内瘤变发生风险的预测因素,构建列线图预测模型。方法回顾性收集2016年01月至2021年12月在扬州大学附属医院诊断为食管鳞状上皮内瘤变患者126例,以及同期于健康管理中心进行体检者344例,收集患者一般临床资料、血常规检测、肿瘤标志物、病变资料。确定食管鳞状上皮内瘤变的独立预测因子,构建列线图预测模型、绘制受试者操作特征(receiver operating characteristic,ROC)曲线,计算得出Harrell一致性指数(C-index)并采用Bootstrap自抽样法,对模型进行内部验证并绘制校准曲线及决策曲线。结果为构建食管上皮内瘤变的风险预测模型,经PSM法匹配后,本研究共纳入96例食管鳞状上皮内瘤变患者及96例健康对照。多因素Logistic回归分析显示,血红蛋白(HGB)计数、血小板(PLT)计数、血小板分布宽度(PDW)、NLR水平是食管鳞状上皮内瘤变的独立预测因子。根据以上四项指标构建的列线图模型曲线下面积(area under curve,AUC)为0.787。Bootstrap内部验证的C-index值为0.771,提示该食管鳞状上皮内瘤变风险预测模型的识别能力、一致性和临床净获益良好。结论基于HGB、PLT、PDW及NLR建立的列线图预测模型可有效鉴别有无食管鳞状上皮内瘤变病变人群,对诊断食管癌前病变有辅助价值。展开更多
Background:Differentiated vulvar intraepithelial neoplasia(dVIN)is a non-human papilloma virus(HPV)-related high-grade precursor lesion to vulvar squamous cell carcinoma(vSCCa).Although TP53 gene mutations have been i...Background:Differentiated vulvar intraepithelial neoplasia(dVIN)is a non-human papilloma virus(HPV)-related high-grade precursor lesion to vulvar squamous cell carcinoma(vSCCa).Although TP53 gene mutations have been identified in 80%of dVIN,its role in dVIN pathogenesis as well as malignant transformation is still being poorly understood.Poor reproducible diagnostic criteria and ambiguous p53 immunostaining patterns,along with morphologic discordance still pose a diagnostic challenge.Methods:A series of 60 cases of dVIN-related vSCCa along with adjacent dVIN were evaluated.Clinicopathological features as well as immunohistochemical results were recorded on the resection-confirmed dVIN-related vSCCa.Results:The average age of the patients was 71 years.Thirty-five cases(58.4%)of dVIN-related vSCCa were moderately differentiated,fourteen cases(23.3%)were poorly differentiated,and the remaining eleven cases(18.3%)were well-differentiated.Twenty-nine cases(48.3%)were found to have lichen sclerosus adjacent to dVIN.In terms of p53 and p16 expression in dVIN-related vSCCa and the adjacent dVIN,fifty-five(91.7%)dVIN showed mutant p53 immunostaining pattern with strong positive expression in 80%cases(basal/para-basal expression)and null pattern expression in 11.7%cases.Five(8.3%)dVIN showed p53 wild-type staining pattern.The wild-type pattern were seen in 5%of vSCCa and p53 null pattern were seen in 13.3%vSCCa.Six cases demonstrated atypical staining patterns:two cases showed p53 null expression in dVIN but p53 overexpression in invasive carcinoma;three cases exhibited p53 null expression in invasive carcinoma,with the adjacent dVIN showing basal and para-basal mutant(2 cases)and wild-type(1 case)p53 expression patterns.A single case demonstrated p53 wild-type pattern in dVIN and overexpression in invasive carcinoma.In addition,65%dVIN were p16 negative and 31.7%dVIN had patchy p16 staining.Conclusion:Clinical and prognostic value of the ambiguous/inconsistent patterns are uncertain and molecular studies are needed for further characterization.展开更多
基金Supported by National Key R&D Program of China,No.2016YFC1303601
文摘BACKGROUND The use of radiofrequency ablation(RFA)has been reported in the treatment of gastric low-grade intraepithelial neoplasia(LGIN).However,its efficacy and prognostic risk factors have not been well analyzed.AIM To explore the efficacy and prognostic risk factors of RFA for gastric LGIN in a large,long-term follow-up clinical study.METHODS The clinical data of 271 consecutive cases from 198 patients who received RFA for treatment of gastric LGIN at the Chinese PLA General Hospital from October 2014 to October 2020 were reviewed in this retrospective study.Data on operative parameters,complications,and follow-up outcomes including curative rates were recorded and analyzed.RESULTS The curative rates of endoscopic RFA for gastric LGIN at 3 mo,6 mo,and 1-5 years after the operation were 93.3%,92.8%,91.5%,90.3%,88.5%,85.7%,and 83.3%,respectively.Multivariate analyses revealed that Helicobacter pylori(H.pylori)infection and disease duration>1 year had a significant effect on the curative rate(P<0.001 and P=0.013,respectively).None of patients had bleeding,perforation,infection,or other serious complications after RFA,and the main discomfort was postoperative abdominal pain.CONCLUSION RFA was safe and effective for gastric LGIN during long-term follow-up.H.pylori infection and disease course>1 year may be the main risk factors for relapse of LGIN after RFA.
文摘As a drug-mechanical combination technology,photodynamic(PDT)can achieve accurate and taurgeted therapy for maligmant tumors and benign diseases through the production of reactive oxygen species,oxygen free radicals or singlet oxygen by photosensitizers at specific wavelengths.Compared with traditional surgery,it has the advantages of selective killing.repeatable teatment,preserving target organ fiunction and so on.The purpose of this study was to explore the clinical value of photodynamic therapy in cervical precancerous lesions by taking the patients with low-grade cervical intaepithelial neoplasia(CIN1)with high-risk human papillomavinus(HR HPV)persistent infection diagnosed by"three-step diagnosis and teatment procedure"as an example.Using HiPorfn as a photosensitizer,photodynamic therapy was performed 48 hours after intavenous drip.Set laser wavelength 630nm,light dose density 137.58J/cm^2,ansmission efficiency 1.42,output power 2w.3cm columnar optical fber was placed around the 2cm in the cervical canal to cover all the lesions,and the inadiation time was 900s(600s in the cervical canal and 300s outside the cervical canal).The patients were given oxygen inhalation for 6 hours after operation,and the patients were observed for itching and other discomfort,and paid attention to avoid light.Photodynamic therapy was performed again in the same way on the second day.After two months of treatment,pathological biopsy showed chronic cervicitis,indicating that the disease had been effectively controlled.Theoretically,although the patient is not the absolhute indication of photodynamic therapy(hat is,meeting CIN Ⅱ or CIN Ⅲ,having fertility requirements and not undergoing surgery),this therapy can remove not only the superficial lesions inside and outside the cervix,but also the potential lesions not found under colposcopy.It can also block the persistent infection of HPV by.inhbting the expression of HPV18,E6 and E7mRNA in Hela cells.In combination with Baofukang suppository,it can block HPV infection.Increase the negative conversion rate of cervical HPV and reduce the probablity of recurence after CIN1 cure.For youmng female patients with persistent HR-HPV infection and fertility requirements,photodynamic therapy is an effective choice for clinical treatment of CIN1.
文摘Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus(HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPVmediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.
文摘Gastric adenocarcinoma generally culminates via the inflammation-metaplasia-dysplasia-carcinoma sequence progression. The prevalence of gastric adenomas shows marked geographic variation. Recently, the rate of diagnosis of low-grade dysplasia(LGD) has increased due to increased use of upper endoscopy. Many investigators have reported that gastric highgrade dysplasia has high potential for malignancy and should be removed; however, the treatment for gastric LGD remains controversial. Although the risk of LGD progression to invasive carcinoma has been reported to be inconsistent, progression has been observed during follow-up. Additionally, the rate of upgraded diagnosis in biopsy-proven LGD is high. Therefore, endoscopic resection(ER) may be useful in the treatment and diagnosis of LGD, especially if lesions are found to have risk factors for upgraded histology after ER, such as large size, surface erythema or depressed morphology. Fatal complications in endoscopic submucosal dissection(ESD) are extremely low and its therapeutic and diagnostic outcomes are excellent. Therefore, ESD should be applied preferentially instead of endoscopic mucosal resection.
基金supported by the Shanghai Science and Technology Committee Project(No.16411950200).
文摘Objective: To explore the clinical significance of the quantitative detection of human papillomavirus(HPV) E6/E7 mRN A in triage of patients with atypical squamous cells of undetermined significance(ASC-US) and low-grade squamous intraepithelial lesion(LSIL).Methods: A cross-sectional screening study was conducted among women who underwent outpatient gynecological screening at the Obstetrics and Gynecology Hospital of Fudan University from September 2015 to July 2016. A total of 500 patients from our hospital with ASC-US or LSIL based on cytology testing were subjected to HPV DNA and HPV E6/E7 mRNA quantitative analysis.Results: The specificity of the HPV E6/E7 mRNA test for detecting ≥high-grade squamous intraepithelial lesion(HSIL+) was statistically higher than that of the HPV DNA test(61.3% vs. 40.0%, P< 0.05), whereas there was no significant difference in the sensitivity of HPV E6/E7 mRNA test and HPV DNA test(90.0% vs. 95.0%, P > 0.05). The positive rates of HPV in the participants tested by HPV E6/E7 mRNA and HPV DNA were, respectively, 42.8%(214/500) and 62.8%(314/500), with statistical significance(P < 0.05).Conclusions: The HPV E6/E7 mRNA test was slightly less sensitivity than that of the HPV DNA test for diagnosing HSIL+ in patients with ASC-US and LSIL, but the difference was not significant, although the specificity of the former was significantly higher. HPV E6/E7 mRNA detection can effectively reduce overdiagnosis and overtreatment of patients with ASC-US and LSIL and has important clinical value in triage of patients with ASC-US and LSIL.
文摘Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.
基金Supported by National Natural Foundation of China,No.821742232019 Chinese and Western Medicine Clinical Collaborative Capacity Building Project for Major Difficult Diseases,No.2019-ZX-005。
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.
文摘Objective:Penile neoplasia,usually of squamous histogenesis,is currently classfied into human papillomavirus(HPV)-related or-dependent and non-HPV-related or-indepen dent.There are distinct morphological differences among the two groups.New research studies on penile cancer from Northern countries showed that the presence of HPV is corre lated with a better prognosis than virus negative people,while studies in Southern countries had not confirmed,perhaps due to differences in staging or treatment.Methods:We focused on the description of the HPV.related carcinomas of the penis.The approach was to describe common clinical features followed by the pathological features of each entity or subtype stressing the characteristics for differential diagnosis,HPV genotypes,and prognostic features of the invasive carcinomas.Similar structure was followed for penile intraepithelial neoplasia,except for prognosis because of the scant evidence available.Results:Most of HPV-related lesions can be straightforwardly recognized by routine hematoxylin and eosin stains,but in some cases surrogate p16 immunohistochemical staining or molecular methods such as in situ hybridization or polymerase chain reaction can be utilized.Currently,there are eight tumor invasive variants associated with HPV,as follows:basaloid,warty,warty-basaloid,papillary basaloid,clear cell,medullary,lymphoepithelioma-like,and giant condylomas with malignant transformation.Conclusion:This review presents and describes the heterogeneous clinical,morphological,and genatypic features of the HPV-related subtypes of invasive and non-invasive penile neoplasia.
文摘目的探究食管鳞状上皮内瘤变发生风险的预测因素,构建列线图预测模型。方法回顾性收集2016年01月至2021年12月在扬州大学附属医院诊断为食管鳞状上皮内瘤变患者126例,以及同期于健康管理中心进行体检者344例,收集患者一般临床资料、血常规检测、肿瘤标志物、病变资料。确定食管鳞状上皮内瘤变的独立预测因子,构建列线图预测模型、绘制受试者操作特征(receiver operating characteristic,ROC)曲线,计算得出Harrell一致性指数(C-index)并采用Bootstrap自抽样法,对模型进行内部验证并绘制校准曲线及决策曲线。结果为构建食管上皮内瘤变的风险预测模型,经PSM法匹配后,本研究共纳入96例食管鳞状上皮内瘤变患者及96例健康对照。多因素Logistic回归分析显示,血红蛋白(HGB)计数、血小板(PLT)计数、血小板分布宽度(PDW)、NLR水平是食管鳞状上皮内瘤变的独立预测因子。根据以上四项指标构建的列线图模型曲线下面积(area under curve,AUC)为0.787。Bootstrap内部验证的C-index值为0.771,提示该食管鳞状上皮内瘤变风险预测模型的识别能力、一致性和临床净获益良好。结论基于HGB、PLT、PDW及NLR建立的列线图预测模型可有效鉴别有无食管鳞状上皮内瘤变病变人群,对诊断食管癌前病变有辅助价值。
文摘Background:Differentiated vulvar intraepithelial neoplasia(dVIN)is a non-human papilloma virus(HPV)-related high-grade precursor lesion to vulvar squamous cell carcinoma(vSCCa).Although TP53 gene mutations have been identified in 80%of dVIN,its role in dVIN pathogenesis as well as malignant transformation is still being poorly understood.Poor reproducible diagnostic criteria and ambiguous p53 immunostaining patterns,along with morphologic discordance still pose a diagnostic challenge.Methods:A series of 60 cases of dVIN-related vSCCa along with adjacent dVIN were evaluated.Clinicopathological features as well as immunohistochemical results were recorded on the resection-confirmed dVIN-related vSCCa.Results:The average age of the patients was 71 years.Thirty-five cases(58.4%)of dVIN-related vSCCa were moderately differentiated,fourteen cases(23.3%)were poorly differentiated,and the remaining eleven cases(18.3%)were well-differentiated.Twenty-nine cases(48.3%)were found to have lichen sclerosus adjacent to dVIN.In terms of p53 and p16 expression in dVIN-related vSCCa and the adjacent dVIN,fifty-five(91.7%)dVIN showed mutant p53 immunostaining pattern with strong positive expression in 80%cases(basal/para-basal expression)and null pattern expression in 11.7%cases.Five(8.3%)dVIN showed p53 wild-type staining pattern.The wild-type pattern were seen in 5%of vSCCa and p53 null pattern were seen in 13.3%vSCCa.Six cases demonstrated atypical staining patterns:two cases showed p53 null expression in dVIN but p53 overexpression in invasive carcinoma;three cases exhibited p53 null expression in invasive carcinoma,with the adjacent dVIN showing basal and para-basal mutant(2 cases)and wild-type(1 case)p53 expression patterns.A single case demonstrated p53 wild-type pattern in dVIN and overexpression in invasive carcinoma.In addition,65%dVIN were p16 negative and 31.7%dVIN had patchy p16 staining.Conclusion:Clinical and prognostic value of the ambiguous/inconsistent patterns are uncertain and molecular studies are needed for further characterization.