Raman spectroscopy for early real-time endoscopic optical diagnosis based on biochemical changes during the carcinogenesis of Barrett's esophagus

Raman spectroscopy is a spectroscopic technique based on the inelastic scattering of monochromatic light that represents the molecular composition of the interrogated volume to provide a direct molecular fingerprint. Several investigations have revealed that confocal Raman spectroscopy can differentiate non-dysplastic Barrett's esophagus from esophageal high-grade dysplasia and adenocarcinoma with high sensitivity and specificity. An automated on-line Raman spectral diagnostic system has made it possible to use Raman spectroscopy to guide accurate target biopsy instead of multiple random forceps-biopsies,this novel system is expected to improve in vivo precancerous diagnosis and tissue characterization of Barrett's esophagus.

Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett's esophagus

AIM:To determine whether magnified observation of short-segment Barrett’s esophagus(BE)is useful for the detection of specialized intestinal metaplasia(SIM).METHODS:Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to×80.The magnified images were analyzed with respect to their pit-patterns,which were simultaneously classified into five epithelial types[Ⅰ(small round),Ⅱ(straight),Ⅲ(long oval),Ⅳ(tubular),Ⅴ(villous)]by Endo’s classification.Then,a 0.5%solution of methylene blue(MB)was sprayed over columnar mucosa.The patterns of the magnified image and MB staining were analyzed.Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy.RESULTS:Three of five patients with a typeⅤ(villous)epithelial pattern had SIM,whereas 21 patients with a non-typeⅤepithelial patterns did not have SIM.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of pit-patterns in detecting SIM were 100%,91.3%,92.3%,60%and100%,respectively(P=0.004).Three of the 12 patients with positive MB staining had SIM,whereas 14patients with negative MB staining did not have SIM.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of MB staining in detecting SIM were 100%,60.9%,65.4%,25%and100%,respectively(P=0.085).The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemar’s test(P=0.0391).CONCLUSION:The magnified observation of a shortsegment BE according to the mucosal pattern and its classification can be predictive of SIM.

Primary malignant melanoma of the esophagus:A case report

BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE SUMMARY In this paper,we report a case of a 73-year-old male with PMME.The patient complained of progressive dysphagia accompanied by substantial weight loss.Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach.Histopathological biopsy revealed melanocytes in the esophageal mucosa.Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs,such as the skin.Through this case report and literature review,we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathoge-nesis as well as cutting-edge therapeutic advances.CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis.Clinicians should raise their awareness and be able to identify early lesions.

Primary adenosquamous carcinoma of the esophagus

AIM:To investigate the clinical characteristics,diagnosis,treatment,and prognosis of primary adenosquamous carcinoma(ASC)of the esophagus.METHODS:A total of 4015 patients with esophageal carcinoma underwent surgical resection between January 1995 and June 2012 at the Cancer Hospital of Shantou University Medical College.In 37 cases,the histological diagnosis was primary ASC.Clinical data were retrospectively analyzed from these 37 patients,who underwent transthoracic esophagectomy with lymphadenectomy.Theχ2or Fisher’s exact test was used to compare the clinicopathological features between patients with ASC and those with squamous cell carcinoma(SCC).The Kaplan-Meier and Log-Rank methods were used to estimate and compare survival rates.A Cox proportional hazard regression model was used to identify independent prognostic factors.RESULTS:Primary esophageal ASC accounted for0.92%of all primary esophageal carcinoma cases(37/4015).The clinical manifestations were identical to those of other types of esophageal cancer.All of the 24patients who underwent preoperative endoscopic biopsy were misdiagnosed with SCC.The median survival time(MST)was 21.0 mo(95%CI:12.6-29.4),and the1-,3-,and 5-year overall survival rates were 67.5%,29.4%,and 22.9%,respectively.In multivariate analysis,only adjuvant radiotherapy(HR=0.317,95%CI:0.114-0.885,P=0.028)was found to be an independent prognostic factor.The MST for ASC patients was significantly lower than that for SCC patients[21.0 mo(95%CI:12.6-29.4)vs 46.0 mo(95%CI:40.8-51.2),P=0.001].In subgroup analyses,the MST for ASC patients was similar to that for poorly differentiated SCC patients.CONCLUSION:Primary esophageal ASC is a rare disease that is prone to be misdiagnosed by endoscopic biopsy.The prognosis is poorer than esophageal SCC but similar to that for poorly differentiated SCC patients.

Role of endoscopy in caustic injury of the esophagus

Caustic injury of the esophagus is a problematic condition challenging endoscopists worldwide. Althoughthe caustic agents and motives are different among countries and age groups, endoscopy still plays an invaluable role in diagnosis and treatment. Endoscopy can determine the severity of caustic ingestion which is of great importance in choosing appropriate treatment. However, some aspects of endoscopy in diagnosis of caustic injury remain controversial. Whether or not all patients need endoscopy, when to perform endoscopy and how to assess the severity are just some examples of these controversies. Due to lack of randomized controlled trials, many findings and suggestions are inconclusive. Computerized tomography scan of the chest and abdomen gains popularity in assessing the severity of caustic injury and avoiding unnecessary surgery. If esophageal stricture eventually develops, endoscopic dilatation is a mainstay. Maneuvers such as steroid injection and esophageal stent may be used in a refractory stricture. Nevertheless, some patients have to undergo surgery in spite of vigorous attempts with esophageal dilatation. To date, caustic injury remains a difficult situation. This article reviews all aspects of caustic injury of the esophagus focusing on endoscopic role. Pre-endoscopic management, endoscopy and its technique in acute and late phase of caustic injury including the endoscopic management of refractory stricture, and the treatment outcomes following each endoscopic intervention are thoroughly discussed. Finally, the role of endoscopy in the long term follow-up of patients with esophageal caustic injury is addressed.

Primary malignant melanoma of the esophagus:A case report

Primary malignant melanoma of the esophagus(PMME)is a malignant tumor which occurs in the melanin cells of esophageal mucosal epithelial basal layer.PMME is a rare disease with an extremely poor prognosis.PMME represents only 0.1%to 0.2%of all esophageal malignant tumors.Dysphagia,retrosternal or epigastric discomfort or pain is the most frequent symptom at presentation.Retrosternal,epigastric discomfort,melena or hematemesis are the major clinical manifestations.The tumor is often located from the middle to lower thoracic esophagus.The characteristic endoscopic finding of PMME is a polypoid lesion that is usually pigmented.Immunohistochemical examination with positive results of S100 protein,HMB45 and neuron-specific enolase allow a definitive diagnosis.PMME metastasizes via hematogenic and lymphatic pathways.Esophagectomy is believed to be an effective approach for localized PMME.Five-year survival rates of 37%or higher have been achieved recently.Herein,we report a case of an 65-year-old female admitted for progressive difficulty in swallowing for more than 4 mo.After upper gastrointestinal endoscopy and biopsy,upper gastrointestinal series and computed tomography examination,the patient accepted radical esophagectomy,and the postoperative pathologic and immunohistochemical examination showed PMME.

Endoscopic diagnosis of cervical esophageal heterotopic gastric mucosa with conventional and narrow-band images

AIM:To compare the diagnostic yield of heterotopic gastric mucosa(HGM)in the cervical esophagus with conventional imaging(CI)and narrow-band imaging(NBI).METHODS:A prospective study with a total of 760patients receiving a CI examination(mean age 51.6years;47.8%male)and 760 patients undergoing NBI examination(mean age 51.2 years;45.9%male).The size of HGM was classified as small(1-5 mm),medium(6-10 mm),or large(>1 cm).A standardized questionnaire was used to obtain demographic characteristics,social habits,and symptoms likely to be related to cervical esophageal HGM,including throat symptoms(globus sensation,hoarseness,sore throat,and cough)and upper esophageal symptoms(dysphagia and odynophagia)at least 3 mo in duration.The clinicopathological classification of cervical esophageal HGM was performed using the proposal by von Rahden et al.RESULTS:Cervical esophageal HGM was found in 36of 760(4.7%)and 63 of 760(8.3%)patients in the CI and NBI groups,respectively(P=0.007).The NBI mode discovered significantly more small-sized HGM than CI(55%vs 17%;P<0.0001).For the 99 patients with cervical esophageal HGM,biopsies were performed in 56 patients;37(66%)had fundic-type gastric mucosa,and 19 had antral-type mucosa.For the clinicopathological classification,77 patients(78%)were classified as HGMⅠ(asymptomatic carriers);21 as HGMⅡ(symptomatic without morphologic changes);and one as HGMⅢ(symptomatic with morphologic change).No intraepithelial neoplasia or adenocarcinoma was found.CONCLUSION:NBI endoscopy detects more cervical esophageal HGM than CI does.Fundic-type gastric mucosa constitutes the most common histology.One-fifth of patients have throat or dysphagic symptoms.

Management strategies of Barrett's esophagus

Barrett's esophagus is a condition resulting from chronic gastro-esophageal reflux disease with a documented risk of esophageal adenocarcinoma. Current strategies for improved survival in patients with Barrett's adenocarcinoma focus on detection of dysplasia. This can be obtained by screening programs in high-risk cohorts of patients and/or endoscopic biopsy surveillance of patients with known Barrett's esophagus (BE). Several therapies have been developed in attempts to reverse BE and reduce cancer risk. Aggressive medical management of acid reflux, lifestyle modifications, antireflux surgery, and endoscopic treatments have been recommended for many patients with BE. Whether these interventions are cost-effective or reduce mortality from esophageal cancer remains controversial. Current treatment requires combinations of endoscopic mucosal resection techniques to eliminate visible lesions followed by ablation of residual metaplastic tissue. Esophagectomy is currently indicated in multifocal high-grade neoplasia or mucosal Barrett's carcinoma which cannot be managed by endoscopic approach.

DIAGNOSIS AND SURGICAL TREATMENT OF 103 PATIENTS WITH EARLY ESOPHAGEAL CANCER AND CARDIAC CANCER OF STOMACH

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.

Artificial intelligence in Barrett’s esophagus: A renaissance but not a reformation

Esophageal cancer remains as one of the top ten causes of cancer-related death in the United States.The primary risk factor for esophageal adenocarcinoma is the presence of Barrett’s esophagus(BE).Currently,identification of early dysplasia in BE patients requires an experienced endoscopist performing a diagnostic endoscopy with random 4-quadrant biopsies taken every 1-2 cm using appropriate surveillance intervals.Currently,there is significant difficulty for endoscopists to distinguish different forms of dysplastic BE as well as early adenocarcinoma due to subtleties in mucosal texture and color.This obstacle makes taking multiple random biopsies necessary for appropriate surveillance and diagnosis.Recent advances in artificial intelligence(AI)can assist gastroenterologists in identifying areas of likely dysplasia within identified BE and perform targeted biopsies,thus decreasing procedure time,sedation time,and risk to the patient along with maximizing potential biopsy yield.Though using AI represents an exciting frontier in endoscopic medicine,recent studies are limited by selection bias,generalizability,and lack of robustness for universal use.Before AI can be reliably employed for BE in the future,these issues need to be fully addressed and tested in prospective,randomized trials.Only after that is achieved,will the benefit of AI in those with BE be fully realized.

食管测压联合食管24 h pH监测对胃食管反流相关性胸痛的诊断价值

目的探讨食管测压联合食管24 h pH监测对胃食管反流相关性胸痛的诊断价值。方法选取通辽市医院2017年6月至2021年12月接收的疑似胃食管反流引起的相关性胸痛患者145例,男92例,女53例,采用食管测压联合食管24 h pH进行监测,以是否胃食管反流分为胃食管反流组与无反流组。收集两组患者的年龄、性别、蠕动收缩百分数、pH<4反流次数、最长反流持续时间等资料,采用t、χ2检验进行统计比较,通过多因素logistic回归分析、受试者工作特征曲线(ROC)分析上述指标与胃食管反流相关性胸痛的相关性。结果145例疑似胃食管反流相关性胸痛患者,经诊断为胃食管返流36例,无返流109例。经多因素logistic回归分析发现,蠕动收缩百分数、pH<4反流次数、最长反流持续时间均是胃食管反流引起的相关性胸痛的影响因素[比值比(OR)=3.155、2.998、3.459,P=0.003、0.012、0.001]。经ROC分析,食管测压、pH<4反流次数、最长反流持续时间联合预测胃食管反流引起的相关性胸痛的灵敏度与曲线下面积(AUC)均高于各指标单独预测时(P=0.001、0.001、0.004),联合预测的特异度与各指标单独预测时差异无统计学意义(P=0.852)。结论食管测压联合食管24 h pH监测对于胃食管反流引起的相关性胸痛的诊断、治疗具有重要意义,值得临床推广应用。

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.

儿童食管腐蚀伤并发症的诊治分析

目的总结儿童食管腐蚀伤并发症的诊断及治疗经验。方法本研究为回顾性研究,收集2017年10月至2019年5月由首都医科大学附属北京儿童医院收治的14例食管腐蚀伤病例作为研究对象,总结患儿摄入腐蚀剂后的并发症、治疗和预后情况。结果14例患儿中,并发食管狭窄12例,其中短段食管狭窄8例,长段食管狭窄4例;14例均行胃镜下球囊扩张术,共扩张188次,有效率为66.7%(8/12),8例短段食管狭窄均扩张成功,4例长段食管狭窄扩张无效。并发食管气管瘘5例,其中3例因纽扣电池导致食管气管瘘的患儿经保守治疗后自愈。结论儿童食管腐蚀伤可造成食管狭窄,大多可经反复扩张治愈,狭窄段的长度会影响扩张治疗结果。纽扣电池所致食管气管瘘有自愈的可能,可于保守治疗失败后再行手术治疗。

颈段食管异物穿孔诊治

食管异物在临床上较为常见。食管的第一狭窄是异物最易嵌顿处。因此,临床上食管异物最多见于颈段食管。引发的食管穿孔可导致食管周围脓肿、纵隔炎等,严重者可危及生命,处理比较棘手[1]。2013年1月~2014年8月,笔者所在科收治颈部食管异物伴穿孔8例,均顺利出院,现报道如下。1.1临床资料。本组病例共8例,男4例,女4例,年龄25~87岁,平均61.5岁。

食管结核消化内镜下特点和临床分析

目的通过对食管结核的消化内镜下表现和其他临床资料的分析,提高消化内镜对此病的诊断率。方法回顾分析南昌大学第一附属医院2004年1月～2009年7月确诊的12例食管结核患者,并复习国内文献。结果患者主要临床表现为吞咽困难6例,胸骨后烧灼痛4例,上腹部不适2例,低热盗汗3例。病变位于食管中段10例,下段2例。以溃疡为主要表现者7例,隆起性病变为主要表现者5例。超声内镜6例患者中,4例病变深达肌层,2例全层结构破坏。内镜下行电子染色及卢戈染色2例,均着色。11例经内镜下活检病理确诊,1例手术确诊。结论食管结核好发于中青年,病变部位主要位于食管中下段,电子胃镜下主要表现为隆起型和溃疡型,易误诊为食管癌和黏膜下肿瘤。通过电子胃镜下活检及染色,结合超声内镜能明显提高该病的诊断率。

食管黏膜下巨大血肿2例并文献复习

病例1：患者为老年男性,因＂胸痛3个月＂于2016-02-22入住青岛大学附属医院心内科。胸痛为心前区闷痛,界限不清,步行10 min左右即可发作,休息后可缓解,偶伴胸闷,无其他不适。于当地医院行冠状动脉CT血管造影,提示冠状动脉左前降支狭窄约75%,拟诊不稳定性心绞痛。

经食管心脏电生理检查在宽QRS波心动过速鉴别诊断中的应用价值

目的比较经食管心脏电生理检查术与其他各无创鉴别方法诊断宽QRS波心动过速(WCT)的优劣。方法入选接受经食管心脏电生理检查并诱发心动过速成功,最后行心内电生理检查确诊的161例患者,平均年龄(36.43±14.24)岁。分析心动过速时体表心电图,采用Brugada四步法以及经食管心脏电生理检查对WCT进行鉴别诊断。所有患者均行心内电生理检查明确诊断,并对以上鉴别WCT方法的敏感性、特异性、阳性预测值、阴性预测值进行统计。结果 161例WCT患者中心内电生理检查诊断提示有94例为室性心动过速(VT),Brugada四步法有74例(准确率78.7%),经食管心脏电生理检查92例(准确率97.9%)。经食管心脏电生理检查比Brugada四步法对鉴别WCT的VT有着更高的敏感性(P<0.01)和阴性预测值(P<0.01)。而且经食管调搏终止心动过速成功率在室上性心动过速患者远高于VT患者(P<0.01)。结论在无创鉴别诊断WCT的方面,经食管心脏电生理检查显著优于Brugada四步法。

食管癌肉瘤的诊断和治疗(附18例分析)

总结两家医院自1969年12月～1995年4月手术治疗食管（贲门）恶性肿瘤7920例，共发现食管癌肉瘤18例，发生率为0．23％。资料表明，平均发病年龄54．7岁，男性多见，男女之比为2．6：1。临床症状主要为缓慢加重的吞咽困难，好发于食管中段，X线表现为食管腔内巨大充盈缺损。病变处食管梭形膨大，很少见到周围软组织块影。食管镜检查可见食管腔内息肉样肿物突出，活检报告多为鳞癌。病理特征为癌与肉瘤两种成分并存，无鳞状上皮癌与肉瘤之间的过渡形态。手术切除率高，极少转移，预后较好。

食管原发性恶性黑色素瘤5例临床病理学观察

目的观察食管原发性恶性黑色素瘤（primary malignant melanoma of esophagus，PMME）的影像学、病理组织学和免疫表型特征，探讨其临床病理学特征、诊断、鉴别诊断及治疗。方法对5例PMME行HE及免疫组化染色，并结合相关文献对其临床表现、影像学、组织学形态、免疫表型、治疗和预后进行观察分析。结果5例患者均为老年男性，平均年龄63．4岁，临床均表现为进食不畅，症状呈进行性加重。肿瘤细胞呈巢片状或条索状排列，细胞圆形或多角形，胞质丰富红染，胞质内见黑色素颗粒，细胞核大小不一，核居中或偏位，核仁明显，病理性核分裂象易见。免疫表型：瘤细胞弥漫表达HMB-45、Melan-A、S-00，CK阴性，Ki-67增殖指数40％～45％。结论PMME非常罕见，恶性程度高，预后差。免疫组化染色有助于其诊断，需与低分化癌、食管癌肉瘤、食管淋巴瘤、神经内分泌癌、食管平滑肌瘤等进行鉴别。