Barrett's esophagus with high grade dysplasia is associated with non-esophageal cancer

AIM To study factors associated with esophageal and nonesophageal cancer morbidity among Barrett's esophagus(BE) patients. METHODS A cohort study within a single tertiary center included 386 consecutive patients with biopsy proven BE, who were recruited between 2004-2014. Endoscopic and histologic data were prospectively recorded. Cancer morbidity was obtained from the national cancer registry. Main outcomes were BE related(defined as esophagus and cardia) and non-BE related cancers(all other cancers). Cancer incidence and all-causemortality were compared between patients with highgrade dysplasia(HGD) and with low-grade or no dysplasia(non-HGD) using Kaplan-Meier curves and cox regression models.RESULTS Of the 386 patients, 12 had HGD, 7 had a BE related cancer. There were 75(19.4%) patients with 86 cases of lifetime cancers, 76 of these cases were non-BE cancers. Seven(1.8%) and 18(4.7%) patients had BE and non-BE incident cancers, respectively. Twelve(3.1%) patients had HGD as worst histologic result. Two(16.7%) and 16(4.4%) incident non-BE cancers occurred in the HGD and non-HGD group, respectively. Ten-year any cancer and non-BE cancer free survival was 63% and 82% in the HGD group compared to 93% and 95% at the non-HGD group, respectively. Log-rank test for patients with more than one endoscopy, assuring longer follow up, showed a significant difference(P < 0.001 and P = 0.017 respectively). All-cause mortality was not significantly associated with BE HGD.CONCLUSION Patients with BE and HGD, may have a higher risk for all-cause cancer morbidity. The implications on cancer prevention recommendations should be further studied.

Photodynamic therapy for high-grade dysplasia of bile duct via a choledochoscope

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia,it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy.Here we describe a patient with a progressive dysplastic lesion in the common bile duct,which developed from moderate-high to highgrade dysplasia in approximately 2 mo.The patient refused major surgery.Therefore,endoscopic-assisted photodynamic therapy was performed.The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic.This report is the first to describe the successful treatment of highgrade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.

Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma in Barrett's esophagus: An Italian experience

AIM: To evaluate endoscopic mucosal resection (EMR)in patients with high-grade dysplasia (HGD) and/or intramucosal cancer (IMC) in Barrett's esophagus (BE).METHODS: Between June 2000 and December 2003,39 consecutive patients with HGD (35) and/or IMC (4)underwent EMR. BE ＞30 mm was present in 27 patients.In three patients with short segment BE (25.0%), HGDwas detected in a normal appearing BE. Lesions had a mean diameter of 14.8±10.3 mm. Mucosal resection was carried out using the cap method.RESULTS: The average size of resections was 19.7±9.4×14.6±8.2 mm. Histopathologic assessment postresection revealed 5 low-grade dysplasia (LGD) (12.8%),27 HGD (69.2%), 2 IMC (5.1%), and 5 SMC (-12.8%).EMR changed the pre-treatment diagnosis in 10 patients (25.6%). Three patients with SMC underwehtsurgery.Histology of the surgical specimen revealed 1 T0N0 and 2 T1N0 lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo, respectively. A metachronous lesion was detected after 25 mo in one patient with HGD. Intra-procedural bleeding, controlled at endoscopy,occurred in four patients (10.3%). After a median followup of 34.9 mo, all patients remained in remission.CONCLUSION: In the medium term, EMR is effective and safe to treat HGD and/or IMC within BE and is a valuable staging method. It could become an alternative to surgery.

Barrett's esophagus with high-grade dysplasia:Focus on current treatment options

High-grade dysplasia(HGD) in Barrett's esophagus(BE) is the critical step before invasive esophageal adenocarcinoma.Although its natural history remains unclear,an aggressive therapeutic approach is usually indicated.Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium.In healthy patients with reasonable life expectancy,vagal-sparing esophagectomy,with associated low mortality and low early and late postoperative morbidity,is considered the treatment of choice for BE with HGD.Patients unfit for surgery should be managed in a less aggressive manner,using endoscopic ablation or endoscopic mucosal resection of the entire BE segment,followed by lifelong surveillance.Patients eligible for surgery who present with a long BE segment,multifocal dysplastic lesions,severe reflux symptoms,a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment,either surgical or endoscopic.

Esophageal resection for high-grade dysplasia and intramucosal carcinoma: When and how?

High-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in the setting of Barrett’s esophagus have traditionally been treated with esophagectomy. However, with the advent of endoscopic mucosal resection and endoscopic ablative therapies, endoscopic therapy at centers with expertise is now an established treatment of Barrett’s-esophagus-related neoplasia, including HGD and IMC. Esophagectomy is today reserved for more selected cases with submucosal invasion, evidence for lymph node metastasis, or unsuccessful endoscopic therapy.

Management of esophageal mucosa with high-grade dysplasia

Objective:Early detection and treatment in patients with esophageal cancer is the most effective way to improve the prognosis. Patients with high-grade dysplasia(HGD) in esophageal mucosa might be involved with early esophageal cancer,but the management of the disease is controversial. The purpose of our study was to explore the management of esophageal mucosa with HGD. Methods:We retrospectively analyzed 10 patients with HGD in esophageal mucosa,who underwent esophagectomy in Cancer Hospital of Fudan University from 1999 to 2006. The surgical approach,postoperative morbidity,in-hospital complications and pathological results of the patients were analyzed. Basing on our data together with other studies,we aimed at looking for an appropriate management for patients with HGD. Results:Of the 10 patients who received esophagectomy,the pathological results showed that 2(20%) cases were in situ carcinoma and 8(80%) cases were invasive cancer with no regional lymph nodes involved. 30-day mortality was 0. One patient experienced cervical anastomotic leakage,but healed in 2 weeks. There was no pulmonary complication. Conclusion:Most patients with HGD actually have occult carcinoma. High percentage of patients with HGD would develop into cancer during their lifetime. Esophagectomy is now a selective approach for the treatment of the patients with HGD.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists

AIM To evaluate annual incidence of low grade dysplasia(LGD) progression to high grade dysplasia(HGD) and/or esophageal adenocarcinoma(EAC) when diagnosis was made by two or more expert pathologists.METHODS Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies(n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate(AIR) of progression to HGD and or EAC was 10.35%(95%CI: 7.56-13.13) and progression to EAC was 5.18%(95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65%(95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42%(95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63%(95%CI: 13.98-43.27). CONCLUSION When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.

Study of Cofactors Associated with Precancerous High-Grade Cervical Lesions at the Teaching Hospital Gabriel Touré, 2010 to 2015

Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospective case-control study without matching. Women with high grade dysplasia were the cases while those with a normal screening test represented the controls. The study took place at the Gabriel Touré University Hospital Center in Bamako. We included 351 cases and 420 controls. The capture and analysis were performed using the SPSS 20 software. A univariate and multivariate logistic regression analysis was performed for the analysis of risk cofactors. The statistical tests used were the odds ratio and its confidence interval and the statistical significance threshold was set at p Results: In univariate analysis, the co-factors statistically significantly associated with the occurrence of high-grade dysplasia were parity 0.6 (0.5 - 0.9), gestational 0.7 (0.5 - 0.9), smoking of the spouse 3.4 (1.1 - 11.3), the non-schooling 1.4 (1.2 - 2.1). In multivariate analysis after adjusting for confounding factors, two co-factors have significantly increased the risk of high-grade dysplasia: lack of schooling 1.4 (1.2 - 2.0) and polygamy 1.5 (1.4 - 2.5). Conclusion: At the end of this study, polygamy and lack of schooling were the main risk factors. The prevention of cervical cancer will go through the education of girls and women as well as communication for behavioral change and social change.

Squamous cell carcinoma after radiofrequency ablation for Barrett's dysplasia

Barrett’s oesophagus(BO)is a usually indolent condition that occasionally requires endoscopic therapy.Radiofrequency ablation(RFA)is an effective endoscopic treatment for high grade dysplasia(HGD)and intramucosal cancer in BO.It has a good efficacy,durability and safety profile although complications can occur.Here we describe a case of RFA in a patient with high grade dysplasia.Although the response to treatment was initially very good with the development of neosquamous epithelium,the patient very rapidly developed a squamous cell cancer of the oesophagus confirmed on radiology,histology and immunohistochemistry.Sanger sequencing confirmed that the original HGD and the squamous cell cancer(SCC)were derived from separate clonal origins.The report highlights the fact that SCC of the oesophagus has been noted after endoscopic ablation for BO previously and suggest that ablation of BO may encourage the clonal expansion of cells carrying carcinogenic mutations once a dominant clonal population has been eradicated.

Confocal Laser Endomicroscopy in the Field of Esophageal Diseases

Confocal laser endomicroscopy (CLE) is a new endoscopic imaging technology that allows real-time, high-resolution observation of tomographic images of mucosal cells and subcellular levels in vivo, detecting microscopic structural changes in mucosal morphology, and its in vivo immediate pathological diagnostic capability can avoid delays in mucosal pathological diagnosis and reduce the pain caused by repeated biopsies. CLE is known as “optical biopsy” and compared with other endoscopic techniques, it has obvious advantages. CLE systems include probe-based confocal laser endomicroscopy (pCLE) and endoscope-based confocal laser endomicroscopy (eCLE). Since 2006, CLE has been widely used for the evaluation of various lesions in the digestive system, including esophageal, gastric, and colonic neoplasia, pancreatic cysts and solid lesions, and inflammatory bowel disease. The advent of CLE has made in vivo microscopic imaging possible, which has changed the endoscopic screening and diagnosis of multiple gastrointestinal (GI) lesions. However, the value of its use in GI diseases is still controversial. In this review, we focus on the application of CLE in the field of esophageal diseases.

Barrett食管的内镜介入治疗

Barrett食管(Barrett’s esophagus,BE)是被公认的食管腺癌的癌前病变,食管腺癌的发生率呈快速上升趋势,因此,对癌前病变进行有效地干预是降低食管腺癌发病率和控制死亡率的关键。目前,BE的治疗方法主要有抑酸药物治疗、外科食管切除术、内镜介入治疗等。近年来多种内镜介入治疗技术应用于BE和食管腺癌的治疗,取得了较好的效果。本文就BE各种内镜介入治疗方法作一概述。

食管上皮高度不典型增生的处理

背景与目的：改善食管癌患者预后的最有效方法是早期诊断、早期治疗。食管上皮高度不典型增生患者可能存在早期癌变，处理方法存在争议。本研究探讨对内镜活检病理诊断为食管上皮高度不典型增生患者的处理。方法：对我院1999-2006年间10例术前内镜活检病理诊断为食管上皮高度不典型增生患者的术式、手术后并发症和疗效的分析，结合文献报道食管上皮高度不典型增生的处理方法，以探讨内镜活检病理诊断为食管上皮高度不典型增生病例的合适的处理措施。结果：10例内镜活检病理诊断为食管上皮高度不典型增生的患者经食管切除术后，病理证实原位癌2例（20％），浸润性癌8例（80％），区域淋巴结转移率为零，手术后30d内死亡率为零，围手术期颈部吻合口漏1例，经处理后2周漏口愈合。1例术后因非肿瘤疾患死亡，其余患者均长期无瘤生存（术后存活时间3～66个月）。结论：根据我们的临床资料，结合文献报道，认为大部分食管上皮高度不典型增生患者已经存在原位癌或浸润性癌，且相当部分高度不典型增生患者会转变成浸润性癌。外科切除食管目前是胸外科较成型术式，手术风险小，术后患者预后好，是食管内镜活检病理诊断为高度不典型增生患者的合适的治疗方法。

Barrett's食管微创治疗的研究进展

Barrett's食管(Barrett's esophagus,BE)是公认的癌前病变,高度异型增生(high-grade dysplasia,HGD)的出现是进展为食管腺癌的关键.在我国食管腺癌的发生率正呈快速上升趋势.因此对BE中出现HGD患者的治疗引起了广泛重视.随着医疗技术及医疗科技的发展,各种微创治疗方法不断涌现,但由于治疗方法的个体化,及缺乏远期效果的评估,对大部分患者来说治疗方法的选择还没有明确的指南.本篇综述的目的是简单介绍各种内镜治疗方法,比较这些方法的治疗效果,分析影响治疗效果的相关因素,以期为该病的治疗提供指导.

AMACR/P504S在胃黏膜高度异型增生诊断中的价值

目的观察AMACR/P504S在正常胃黏膜、不确定性异型增生、低度异型增生、高度异型增生和胃肠型腺癌中的表达,探讨其在胃黏膜高度异型增生诊断中的价值。方法应用免疫组化EnVision法检测20例无异型增生、30例不确定性异型增生、25例低度异型增生、30例高度异型增生和20例肠型腺癌中AMACR/P504S的表达。结果 AMACR/P504S在无异型增生和不确定性异型增生的胃黏膜中均为阴性表达,在低度异型增生中AMACR/P504S阳性率为4.0%,高度异型增生和肠型腺癌中阳性率分别为73.3%和55%,AMACR/P504S在高度异型增生中的表达明显高于低度异型增生(P<0.01),与肠型腺癌无差异(P>0.05)。AMACR/P504S对高度异型增生诊断的特异性为98.7%,敏感性为73.3%。结论 AMACR/P504S可作为胃黏膜高度异型增生与低度异型增生和不确定性异型增生鉴别诊断的免疫标记物。

DOK3 PTK7在不同级别结肠腺瘤组织中的表达及意义探讨

目的分析对接蛋白3(DOK3)和蛋白酪氨酸激酶7(PTK7)在不同级别结肠腺瘤组织中的表达情况,探讨其在结肠癌的发生、发展机制中的作用。方法收集2015-01~2018-12广西壮族自治区南溪山医院经病理科确诊的结肠腺瘤伴低级别异型增生(LGD)标本22例,结肠腺瘤伴高级别异型增生(HGD)标本23例,结肠癌标本22例,瘤旁非肿瘤黏膜组织标本20例。采用免疫组织化学染色法检测不同类型标本DOK3和PTK7的表达情况。结果DOK3和PTK7均主要表达于腺上皮的胞浆和胞膜。瘤旁非肿瘤黏膜和LGD组织的DOK3高表达率均显著高于HGD和结肠癌组织(P<0.05);HGD组织的DOK3高表达率也显著高于结肠癌组织(P<0.05)。结肠癌和HGD组织的PTK7高表达率均显著高于瘤旁非肿瘤黏膜和LGD组织(P<0.05);结肠癌组织的PTK7高表达率也显著高于HGD组织(P<0.05)。结论DOK3可能是作为抑癌因子,而PTK7作为促癌因子参与结肠癌的发生、发展。

超声内镜诊断Barrett食管的研究进展

Barrett食管(BE)是食管腺癌发病的最危险因素。超声内镜(EUS)能清晰地显示食管壁各层的结构。大量研究表明,EUS可显示BE食管壁黏膜层和黏膜下层增厚,但目前不推荐用EUS诊断BE,和鉴别BE是否存在异型增生。EUS在评估有重度异型增生或有食管黏膜下层癌的BE患者及其食管壁肿瘤侵犯程度和局部淋巴结转移方面有重要意义,虽然其准确性现在还存在争议,但其可为BE患者选择进一步治疗的方案提供重要依据。

食管鳞癌及其前驱病变9q基因杂合子缺失的研究

目的:通过对食管黏膜高级别不典型和鳞状细胞癌中的等位基因杂合子缺失(LOH)的检测,以期发现9q上与食管鳞癌密切相关的抑癌基因。方法:应用显微切割、PCR扩增、凝胶电泳、AgNO3染色等技术,对照分析正常组织、高级别不典型增生和癌组织中的LOH的变化,并就各位点的杂合性丢失率与患者的临床病理参数分别进行单因素分析。结果:①在食管高级别不典型增生和癌组织中,3个微卫星位点的LOH率分别为D9S303(31%,38%)、D9S753(29%,43%)、D9S242(11%,17%)。②应用SPSS软件对3个微卫星序列的等位基因LOH率与患者的性别、组织学分化及是否有淋巴结转移进行单因素分析,差异均无显著性(P>0.05)。结论:①从正常鳞状上皮到不典型增生再到癌变的过程中存在基因的异常累积。②9q末端可能存在与食管鳞癌的发生发展相关的抑癌基因。

饮食习惯与食管上皮高度异型增生及食管癌发病关系的病例对照研究

目的探讨食管癌高发区河北省武安地区居民饮食习惯与食管上皮高度异型增生及食管癌发病之间的关系,为食管癌的早期预防提供依据。方法按1:4配比行病例对照研究,采用统一的调查表,对病例和对照组的饮食习惯进行问卷调查。应用多因素logistic回归分析探讨不同饮食习惯对食管上皮高度异型增生及食管癌发病的影响。结果分析结果显示烫饮食习惯、食用霉变食物以及经常食用葱蒜为食管上皮高度异型增生及食管癌发病的危险因素,而经常食用新鲜蔬菜、水果以及饮茶则为保护因素。其中食用霉变食物、新鲜蔬菜及饮茶与发病之间的关联具有统计学意义。结论在河北省武安地区,食管上皮高度异型增生以及食管癌发病的危险因素有其地域特点,因此对于武安地区食管癌的预防工作应当结合本地区特点,因地制宜的进行。

Radiofrequency ablation for early oesophageal squamous neoplasia:Outcomes form United Kingdom registry

AIM:To report outcomes on patients undergoing radiofrequency ablation(RFA)for early oesophageal squamous neoplasia from a National Registry.METHODS:A Prospective cohort study from 8 tertiary referral centres in the United Kingdom.Patients with squamous high grade dysplasia(HGD)and early squamous cell carcinoma(ESCC)confined to the mucosa were treated.Visible lesions were removed by endoscopic mucosal resection(EMR)before RFA.Following initial RFA treatment,patients were followed up 3monthly.Residual flat dysplasia was treated with RFA until complete reversal dysplasia(CR-D)was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond.The main outcome measures were CR-D at 12 mo from start of treatment,long term durability,progression to cancer and adverse events.RESULTS:Twenty patients with squamous HGD/ESCC completed treatment protocol.Five patients(25%)had EMR before starting RFA treatment.CR-D was 50%at12 mo with a median of 1 RFA treatment,mean 1.5(range 1-3).Two further patients achieved CR-D with repeat RFA after this time.Eighty per cent with CR-D remain dysplasia free at latest biopsy,with median follow up 24 mo(IQR 17-54).Six of 20 patients(30%)progressed to invasive cancer at 1 year.Four patients(20%)required endoscopic dilatations for symptomatic structuring after treatment.Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient.The other 2 patients required only a single dilatation to achieve an adequate symptomatic response.One patient developed cancer during follow up after end of treatment protocol.CONCLUSION:The role of RFA in these patients re-mains unclear.In our series 50%patients responded at12 mo.These figures are lower than limited published data.

Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis

AIM:To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer(CC)or high grade dysplasia(HGD).METHODS:This is a single center(Lenox Hill Hospital)retrospective cohort and descriptive study of extensive ulcerative colitis(UC)for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis.Data analyzed included:duration of UC,date of diagnosis of(CC)or(HGD),number of surveillance colonoscopies,and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal.Two subgroups of patients were compared:group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD.RESULTS:Of 115 patients with longstanding UC reviewed,68 patients met the inclusion criteria.Twenty patients were in group 1 and 48 in group 2.We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation.Overall,histological disease activity in the absence of gross/endoscopic disease was found in 31.2%(95%CI:28%-35%)of colonoscopies performed on the entire cohort of 68 patients.Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients,88%(95%CI:72%-97%)vs 59%(95%CI:53%-64%).Only 3/20(15%)of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity(i.e.,no endoscopic or histological activity)as compared to 37/48(77%)of patients in group 2,and only 3.3%(95%CI:0.09%-8.3%)of colonoscopies in group 1 had no histological inflammation compared to23%(95%CI:20%-27%)in group 2.CONCLUSION:Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrate persistent histological inflammation in the absence of gross mucosal disease.Our findings support including the elimination of histological inflammation in the definition of mucosal healing,and support this endpoint as an appropriate goal of therapy because of its risk of increasing dysplasia and colon cancer.