Molecular analysis in combination with iodine staining may contribute to the risk prediction of esophageal squamous cell carcinoma

Purpose Mucosal iodine staining has improved the detection of precancerous lesions of the esophagus. However, this method is unable to exactly evaluate the risk status of the lesions. In the present study, we conducted a molecular analysis combining the iodine staining in esophageal squamous cell carcinomas (ESCC) and different premalignant lesions of the esophagus in order to improve the early diagnosis of ESCC. Methods Tumorous and precancerous lesions were procured as iodine-unstained areas in the resected specimens of ESCC patients by means of Lugol’s iodine staining. Loss of heterozygosity (LOH) was detected with 35 microsatellite markers frequently reported to be deleted in ESCC. The markers with high frequency of LOH in tumorous and precancerous lesions of the same patient were subjected to further detection in iodine-unstained biopsy samples from the population screening in ESCC high-incidence region. Results Common alterations were observed at D3S3644, D3S1768, D3S3040, D3S4542, RPL14, D9S169, D13S171 and D13S263 in both cancer tissues and precancerous lesions around tumors. Interestingly, D3S3644, D3S1768, D3S3040, D3S4542, RPL14 and D13S263 were also found with high frequency of LOH in iodine-staining abnormal lesions from the population screening. Most importantly, LOH frequency increased with histological severity. Conclusion Our data suggest that detection of these six markers in combination with iodine staining might contribute to the prediction for the risk of ESCC development and for the diagnosis of patients in preclinical and preneoplastic phase of the disease.     

Pink-color sign in esophageal squamous neoplasia,and speculation regarding the underlying mechanism

AIM:To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions. METHODS:In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pinkcolor sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed. RESULTS:A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range:2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0.0001). Univariate analyses found that absence of the keratinous     

Risk appraisal and endoscopic screening for esophageal squamous cell carcinoma in Japanese populations

Epidemiological studies have shown several strong predictors for selecting Japanese persons at high risk for esophageal squamous cell carcinoma (ESCC). (1) Alcohol consumption and tobacco smoking synergistically increase the risk, and a low intake of green and yellow vegetables or fruit and a low body mass index also increase the risk of ESCC. (2) The presence of esophageal distinct iodine-unstained lesions and melanosis are associated with an increased risk of ESCC. (3) The combination of alcohol consumption and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) and less-active homozygous alcohol dehydrogenase-1B (ADH1B) increases the risk of ESCC in a multiplicative fashion. (4) The results of a simple flushing questionnaire predict the ALDH2 phenotype with a high accuracy. (5) High mean corpuscular volume (MCV), which is induced by heavy drinking, high acetaldehyde exposure, heavy smoking, and poor nutrition, may be useful in identifying high-risk persons. Endoscopic screening with esophageal iodine staining in Japanese high-risk populations yields very high rates of early ESCC. Treatment of early ESCC by endoscopic mucosectomy has become a widespread practice in Japan and has succeeded in improving the outcome of this high-mortality cancer. New evidence concerning ALDH2/ADH1B/alcohol flushing/MCV-related cancer susceptibility has renewed interest in alcohol and acetaldehyde as important subjects for cancer research and has served as a powerful tool for cancer prevention and cancer screening of Japanese subjects. Review articles on this topic also appeared in the previous issue (Volume 4 Number 3). An editorial related to this article is available at .     

Clinicopathological features of narrow‐band imaging endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms

To reveal clinicopathological features of narrow‐band imaging (NBI) endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms. If a lesion diameter was smaller or same compared with a width of closed biopsy forceps, a lesion was defined to be an ultraminute lesion. Twenty‐five consecutive patients with 33 ultraminute esophageal lesions that were removed by endoscopic mucosal resection were included in the present study. We conducted two questionnaire surveys of six endoscopists by their retrospective review of endoscopic still images. The six endoscopists evaluated the endoscopic findings of the ultraminute lesions on still images taken by conventional white‐light imaging endoscopy and non‐magnified NBI endoscopy in the first questionnaire, and taken by magnified NBI endoscopy in the second questionnaire. An experienced pathologist who was unaware of any endoscopic findings made histological diagnosis and evaluated immunoexpression of p53 and Ki67. The 33 ultraminute lesions were all determined to be either 11 high‐grade intraepithelial neoplasias (HGIENs) or 22 low‐grade intraepithelial neoplasias (LGIENs). The tumor diameters were histologically confirmed to be <3 mm. All of the ultraminute tumors were visualized as unstained areas and brownish areas by real‐time endoscopy with Lugol dye staining and non‐magnified NBI endoscopy, respectively. All of the ultraminute IENs were visualized as brownish areas by real‐time non‐magnified NBI endoscopy. Three of the 25 patients with the ultraminute IENs (12%) had multiple brownish areas (more than several areas) in the esophagus on real‐time non‐magnified NBI endoscopy. All of the ultraminute IENs were visualized as unstained areas by real‐time Lugol chromoendoscopy. Twenty of the 25 patients (80%) had multiple unstained areas (more than several areas) in the esophagus on real‐time Lugol chromoendoscopy. The first questionnaire survey revealed that a significantly higher detection rate of the ultraminute IENs on non‐magnified NBI endoscopy images compared with conventional white‐light imaging endoscopy ones (100% vs. 72%, respectively: P < 0.0001). The second questionnaire survey revealed that presence rates of any magnified NBI endoscopy findings were not significantly different between HGIENs and LGIENs. Proliferation, dilation, and various shapes of intrapapillary capillary loops indicated remarkably high presence rates of more than 90% in both HGIENs and LGIENs. Six of 22 LGIENs (27%) and 3 of 11 HGIENs (27%) show a positive expression for p53. None of peri‐IEN epithelia was positive for p53. A mean of Ki67 labeling index of LGIENs was 33% and that of HGIENs 36%. Ki67 labeling index was significantly greater in the LGIENs and HGIENs compared with that in the peri‐IEN epithelia. There were no significant differences in p53 expression and Ki67 labeling index between the HGIENs and LGIENs. Non‐magnified/magnified NBI endoscopy could facilitate visualization and characterization of ultraminute esophageal squamous IENs. The ultraminute HGIENs and LGIENs might have comparable features of magnified NBI endoscopy and immunohistochemistry.     

Endoscopic mucosal resection for early esophageal cancer and esophageal dysplasia

BACKGROUND/AIMS: Advances in diagnostic technology have led to increased detection of early esophageal cancer, which is suitable for endoscopic treatment. We performed endoscopic esophageal mucosal resection of such cancer and dysplasia using the endoscopic esophageal mucosal resection tube and evaluated the clinical benefit of this technique. METHODOLOGY: Twenty-nine patients with esophageal mucosal cancer (27 cases with 33 lesions) or dysplasia (2 cases with 2 lesions) diagnosed between September 1992 and March 1998 were assessed endoscopically for the depth and extent of invasion by double staining with toluidine blue and iodine. Endoscopic ultrasonography was also performed to assess the depth of invasion in 22 cases with 22 lesions. RESULTS: The 35 esophageal lesions comprised 27 esophageal carcinomas and 8 areas of dysplasia. Twenty of the 35 lesions were resected en bloc and 15 were resected piecemeal. Subsequent surgery was performed for 5 cases with 7 lesions out of 10 cases with 15 lesions that were histopathologically diagnosed as m3 or more invasive. No recurrence has been detected in 24 evaluable cases (including 1 who died of another disease, 2 in whom surgery could not be performed due to complications, and 3 who refused subsequent surgery). No patients died of esophageal cancer after a mean follow-up period of 30.9 +/- 18.9 months. The 4-year survival rate was 100% in the m2 or less invasive group of 19 cases with 20 lesions, 75% in the m3 or higher invasive group of 5 cases with 8 lesions and 100% in the surgery group of 5 cases with 7 lesions (NS). No serious complications occurred except for 1 patient. Circumferential mucosal resection was done in this patient, resulting in esophageal stenosis, which responded to esophageal dilation. CONCLUSIONS: Esophageal mucosal resection using the endoscopic esophageal mucosal resection tube is safe and beneficial for early esophageal cancer and dysplasia.     

Esophageal melanosis, an endoscopic finding associated with squamous cell neoplasms of the upper aerodigestive tract, and inactive aldehyde dehydrogenase-2 in alcoholic Japanese men

Background Esophageal melanosis is often observed in alcoholic Japanese men, in whom the prevalence of squamous cell dysplasia and carcinoma (SCC) in the upper aerodigestive tract are high. This study evaluated the associations of esophageal melanosis with these neoplasms, and the factors contributing to the development of esophageal melanosis in this population.Methods Endoscopic screening was combined with esophageal iodine staining in 1535 alcoholic Japanese men (aged 40–79 years), of whom 1007 underwent aldehyde dehydrogenase-2 (ALDH2) genotyping.Results Fifty patients (3.3%) were diagnosed with esophageal melanosis, which had a higher incidence in those with noncancerous distinct iodine-unstained lesions (DIULs; 16/268; 6.0%), esophageal SCC (9/66; 13.6%), and oropharyngolaryngeal SCC (4/19; 21.1%) than in cancer- and DIUL-free controls (24/1182; 2.0%). The presence of esophageal melanosis was associated with higher risks for noncancerous DIULs, esophageal SCC, and oropharyngolaryngeal SCC (odds ratios, 2.81, 6.54, and 14.77, respectively). Men with the inactive ALDH2*1/2*2 genotype had a higher risk for esophageal melanosis (2.66-fold), as well as for DIULs and SCCs.Conclusions The presence of esophageal melanosis in alcoholic Japanese men could indicate a high risk for DIULs and SCCs in the upper aerodigestive tract. The high incidence of esophageal melanosis may be partially linked to high acetaldehyde exposure, a consequence of drinking alcohol in persons with inactive ALDH2.     

Clinicopathological features of minute pharyngeal lesions diagnosed by narrow-band imaging endoscopy and biopsy

AIM: To evaluate the utility of magnified narrow-band imaging (NBI) endoscopy for diagnosing and treating minute pharyngeal neoplasia.METHODS: Magnified NBI gastrointestinal examinations were performed by the first author. A magnification hood was attached to the tip of the endoscope for quick focusing. Most of the examinations were performed under sedation. Magnified NBI examinations were performed for all of the pharyngeal lesions that had noticeable brownish areas under unmagnified NBI observation, and an intrapapillary capillary loop (IPCL) classification was made. A total of 93 consecutive pharyngeal lesions were diagnosed as IPCL type IV and were suspected to represent dysplasia. Sixty-two lesions of approximately 1 mm in diameter were biopsied in the clinic, and 17 lesions with larger diameters were resected by endoscopic submucosal dissection (ESD) at the Hiroshima University Hospital. In addition to the histological diagnoses, the lesion diameters were microscopically measured in 45 of the 62 biopsies. Thirty-four of the 62 biopsied patients received endoscopic follow up.RESULTS: Minute pharyngeal lesions were diagnosed in 93 of approximately 3000 patients receiving magnified NBI examinations at the clinic. Of the 93 patients with IPCL type IV lesions, 80 were men, and 13 were women. Fifty-six were drinkers, and 57 were smokers. Two had esophageal cancer. Twenty-one lesions were located on the posterior hypopharyngeal wall, and 72 lesions were located on the posterior oropharyngeal wall. All 93 lesions were flat and showed similar findings in the magnified and unmagnified NBI examinations. Although almost all of the IPCL type IV lesions showed faint redness when examined under white light, it was difficult to diagnose the lesions using only this technique because the contrast was weaker than that achieved in the NBI examinations. Of the 93 lesions, only 3 had diameters greater than 2.1 mm. Sixty-two lesions of approximately 1 mm were biopsied in the clinic, whereas 17 larger lesions were treated by ESD at the Hiroshima University Hospital. Of the 79 pharyngeal lesions that were biopsied or resected by ESD, 5 were histologically diagnosed as high-grade dysplasia, 39 were diagnosed as low-grade dysplasia, and 39 were determined to be non-dysplastic lesions. There were no cancerous lesions. Histologically, abnormal cell size variations and increased nuclear size were observed in all of the high-grade dysplasia lesions, while the incidence of these findings in the low-grade dysplasia lesions was low. Of the 62 biopsied lesions, 45 were microscopically measurable. The measured diameters ranged from 0.1 to 2.0 mm. The dysplasia ratios increased with the diameters. A follow-up endoscopic examination of the 34 biopsied patients found the rate of complete resection by biopsy to be 79%. The largest lesion in which complete resection was expected was a low-grade dysplasia of 1.9 mm in diameter.CONCLUSION: Minute pharyngeal lesions suspected to be dysplasia that are identified by NBI magnifying endoscopy should be biopsied to determine the diagnosis and further treatment.     

Endoscopic treatment of esophageal mucosal carcinomas: indications and outcomes

The indications for endoscopic mucosal resection (EMR) and treatment outcomes are discussed for 402 patients (336 men and 66 women with 527 lesions) who had squamous-cell carcinoma of superficial type and with no lymph-node metastasis (N0) on clinical evaluation. The patients were followed-up for at least 2 years after EMR, conducted between January 1988 and December 2004. They were classified according to the depth of tumor invasion as follows: m1 cancer in 179 patients, m2 in 137, m3 in 61, and sm1 in 25. The number of lesions treated at the initial session of EMR was one in 317 patients (79%) and multiple lesions in 85 (21%). For the resection technique, a two-channel scope method was used in 318 patients (79%) and the cap method in 84 (21%). In patients with m3 or sm1 cancers, additional treatments included follow-up observations in 62 patients (72%) (m3 in 52 and sm1 in 10), chemoradiotherapy or radiotherapy in 17 (20%) (m3 in 7 and sm1 in 10), chemotherapy in 3 (3%) (m3 in 2 and sm1 in 1), and surgery in 4 (5%) (sm1 in 4). With regard to complications, only 5 patients (1.2%) with difficult-to-control bleeding were considered to have bleeding; a hemostatic clip was used in 1, a Sengstaken-Blakemore tube insertion in 1, and repeated argon plasma coagulation (APC) in 3. Of the 402 patients undergoing EMR, 1 (0.2%) had perforation. Despite no evidence of esophageal perforation, mediastinal emphysema occurred in 10 patients (2.3%) who underwent piecemeal resection because of large lesions. Of the 34 patients with mucosal defects occupying more than three quarters of the circumference of the esophagus, 29 (85%) had esophageal strictures. Local recurrence was found in 19 (5.4%) of the 349 patients in whom esophageal mucosal cancer was clinically considered to be completely resected and treatment completed. All patients with local recurrence had undergone piecemeal resection. Of the 402 patients who underwent EMR, 71 (18%) had a total of 111 metachronous esophageal cancers. Among the 71 patients with metachronous esophageal cancers, EMR was performed in 67 patients (107 lesions); 104 lesions were mucosal cancers and 3 were submucosal cancers (1 sm1 cancer and 2 sm2 cancers). Regarding prognosis: (1) m1 and m2 cancer: Of the 316 patients who underwent EMR for m1 or m2 cancer, 12 (4%) had local recurrence. There were 39 deaths (12%). Two patients refused further treatment after EMR, and finally died of advanced esophageal cancer. (2) m3 and sm1 cancer: Local recurrence was found in 7 (11%) of 61 patients with m3 cancer. Lymph-node metastasis was found in 2 patients (3%) and bone metastasis was found in 1. There were 17 deaths (28%); 3 patients died of recurring esophageal cancer. Lymph-node metastasis was found in 3 (12%) of 25 patients with sm1 cancer. There were 7 deaths (28%); no patient died of esophageal cancer.     

Study on endoscopic esophageal mucosal resection with ligating device. I--Clinical study

BACKGROUND/AIMS: EEMRL (endoscopic esophageal mucosal resection with a ligating device) has become increasingly popular. In this article, we review 13 clinical cases of EEMRL. METHODOLOGY: Since 1993, we have performed EEMRL to treat 15 lesions in 13 patients. Twelve squamous cell carcinomas (mucosal cancer in 10 and submucosal cancer in 2) were included among the 15 lesions. RESULTS: EEMRL failed to achieve complete resection of the 2 submucosal lesions (3.0 and 2.8 cm in maximum diameter). However, esophageal lesions could be removed successfully when 2.5 cm or less in maximum diameter. The procedure was not associated with any complication. CONCLUSIONS: Our clinical study showed that this technique may be indicated for esophageal cancer with a maximum diameter < or = 2.5 cm and confined to the mucosa. EEMRL is a technically easy and minimally invasive therapy which could be useful for the treatment of early esophageal cancer.     

Expression of a plant－associated human cancer antigen in normal,premalignant and malignant esophageal tissues

AIM: To study the relationship between the expression profiles of a plant-associated human cancer antigen and carcinogenesis of esophagus and its significance. METHODS: We analyzed expression of a plant-associated human cancer antigen in biopsy specimens of normal (n=29),mildly hyperplastic (n=29), mildly (n=30), moderately (n=27)and severely dysplastic (n=29) and malignant esophageal (n=30) tissues by immunohistochemistry. RESULTS: The plant-associated human cancer antigen was mainly confined to the cytoplasm and showed diffuse type of staining. Positive staining was absent or weak in normal (0/30) and mildly hyperplastic tissue samples (2/29), while strong staining was observed in severe dysplasia (23/29) and carcinoma in situ (24/30). There was significant difference of its expression between normal mucosa and severely dysplastic tissues (P＜0.001) or carcinoma in situ (P＜0.001). Significant difference was also observed between mild dysplasia and severe dysplasia (P＜0.001) or carcinomain situ (P＜0.001). An overall trend toward increased staining intensity with increasing grade of dysplasia was found. There was a linear correlation between grade of lesions and staining intensity (r=0.794,P＜0.001). Samples from esophageal cancer showed no higher levels of expression than those in severely dysplastic lesions (P＞0.05). CONCLUSION: The abnormal expression of this plantassociated human cancer antigen in esophageal lesions is a frequent and early finding in the normal-dysplasiacarcinoma sequence in esophageal carcinogenesis. It might contribute to the carcinogenesis of esophageal cancer. The abnormal expression of this plant-associated human cancer antigen in esophageal lesion tissues may serve as a potential new biomarker for early identification of esophageal cancer.     

Early diagnosis of esophageal cancer.

The doubling time of esophageal cancer, as measured by x-ray films, was studied retrospectively. The average doubling time of 19 lesions in 18 cases was 6.7 months, but in three cases the lesions doubled within a month. The developing time of depth of invasion in esophageal cancer in 19 lesions were: from mucosa to submucosa, 16 +/- 7.8 months; submucosa to advanced adventitia, 6.6 +/- 3.8 months; mucosa to advanced adventitia, 21.1 +/- 6.8 months. Lugol-staining endoscopy was effective in detecting not only lesions but also margin lines. Capsulated brushing cytology is also effective and the diagnostic rate was 94.5% in total, and 84.4% in superficial cancer. For early detection of esophageal cancer it is most desirable to have examinations once every six months and a combination of these three methods is recommended.     

食管早期癌和癌前病变超声内镜诊断及内镜下食管黏膜切除术的临床研究

目的探讨食管早期癌和癌前病变超声内镜诊断价值及内镜下食管黏膜切除术的临床治疗价值。方法 61例食管早期癌和癌前病变行超声内镜检查探测病变浸润深度,位于黏膜层及黏膜肌层的食管早期癌和癌前病变行内镜下食管黏膜切除术（EMR）,位于黏膜下层的食管早期癌行外科手术治疗。EMR术28例,外科手术33例。比较超声内镜和术后病理判断病变浸润深度。结果超声内镜判断食管黏膜内癌的特异性和敏感性为94.1%（48/51）、98.0%（48/49）;黏膜下癌的特异性和敏感性为80.0%（8/10）、72.7%（8/11）;鉴别黏膜内癌及黏膜下癌浸润深度准确率为91.8%（56/61）。28例EMR术后病理：14例食管早期癌和12例食管黏膜中重度异型增生完全切除,完全切除成功率为92.9%（26/28）,观察3～45个月无复发。结论超声内镜能较准确鉴别食管早期癌和癌前病变浸润深度,黏膜切除术治疗食管早期癌和癌前病变是安全有效的内镜治疗方法。     

色彩增强技术联合放大内镜诊断食管浅表性病变

目的 应用色彩增强技术(FICE)联合内镜观察食管病变后食管上皮乳头内毛细血管袢(IPCL)的改变,探讨FICE在食管病变诊断中的价值.方法 对患者先行普通胃镜检查,发现食管病变后再利用富士能EG-590ZW内镜行FICE观察,分析食管病变后食管上皮IPCL改变,并研究了31例浅表性食管病变的IPCL与病理组织学之间关系.结果 (1)FICE放大观察将IPCL分为4型:Ⅰ型IPCL分布均匀,形态规则,见于正常食管;Ⅱ型IPCL延长,主要见于食管炎;Ⅲ型IPCL出现扩张、波浪样弯曲、管径粗细不均以及不规则形态改变中的2至3种改变,主要见于食管上皮异型增生;Ⅳ型IPCL出现扩张、波浪样弯曲、管径粗细不均以及不规则形态改变中所有4种变化,主要见于食管鳞癌.(2)17例食管炎中15例IPCL表现为Ⅱ型、2例表现为Ⅲ型;10例食管上皮异型增生中8例IPCI表现为Ⅲ型、2例表现为Ⅳ型,表现为Ⅳ型的2例均为重度食管上皮异型增生;1例sml食管鳞癌IPCL表现为Ⅲ型;3例进展期食管鳞癌均表现为Ⅳ型.结论 FICE联合内镜能清楚显示食管黏膜IPCL,通过应用FICE联合内镜观察食管病灶的IPCL变化,可以很好地确定食管浅表性病变的性质,对食管肿瘤性病变的诊断具有重要的应用价值.     

Feasibility of endoscopic mucosal resection as salvage treatment for patients with local failure after definitive chemoradiotherapy for stage IB,II, and III esophageal squamous cell cancer

Local failure after definitive chemoradiotherapy (CRT) for stage IB, II, and III esophageal cancer is one of the causes of poor outcome. Endoscopic mucosal resection (EMR) is an effective treatment for superficial esophageal cancer. However, its feasibility as a salvage treatment for local recurrent or residual tumors after definitive CRT for stage IB, II, and III esophageal cancer remains unclear. Between January 2000 and February 2008, 274 patients with stage IB, II, and III esophageal squamous cell cancer excluding T4 received definitive CRT at the National Cancer Center Hospital, Japan. Of these patients, nine patients with local recurrence after achieving complete response and two patients with residual tumor underwent salvage EMR. The technique of salvage EMR involved a strip biopsy method. We retrospectively reviewed the 11 patients (13 lesions). Characteristics of all 11 patients were as follows: median age of 69 (range: 45–78); male/female: 10/1; baseline clinical stage (Union for International Cancer Control 7th) IB/IIA/IIB/III: 1/3/7/0. The depth of resected tumor was limited to the mucosal layer in seven lesions and submucosal in six lesions. En bloc resection was performed on six lesions (46%). The vertical margin was free of cancer cells in 11 lesions (84.6%). No major complications, such as hemorrhage requiring blood transfusion and perforation, were experienced. At a median follow‐up period of 38.9 months (range: 5.3–94 months) after salvage EMR, no recurrence was detected in six patients (54%). Local recurrence was detected in five patients (27%). Of these patients, two had lung metastasis simultaneously, and one was also detected lung metastasis 2 months after the detection of local recurrence. The 5‐year survival rate after salvage EMR was 41.6%. Salvage EMR is a feasible treatment option for local recurrent or residual lesions after definitive chemotherapy and/or radiotherapy for stage IB, II, and III esophageal squamous cell cancer.     

内镜下双重色素法联合超声内镜对食管早期癌及癌前病变的诊断价值

目的:探讨美蓝和卢戈氏碘液双重染色法联合超声内镜对食管早期癌及癌前病变的诊断价值．方法:对96例可疑食管病变患者行食管黏膜染色,先用 20 g／L美蓝喷洒,再用30 g/L卢戈氏碘溶液喷洒于病变区观察;对美蓝染色区和卢戈氏碘不染色区进行活组织病理检查．食管癌及重度不典型增生、Barrett食管等癌前病变者再次行超声内镜检查．结果:确诊为食管癌7例,其中早期癌2例;不典型增生14例 (轻度7例,中度4例,重度3例);Barrett食管3例;溃疡8例;炎症36例．双重染色法总阳性率达70．8％．超声内镜对判断食管癌及癌前病变的浸润深度及纵隔淋巴结转移准确率达 92．3％(12／13)．结论:双重色素法(色素内镜)联合超声内镜有助于食管疾病,特别是早期癌及癌前病变的诊断,值得推广．     

内镜下碘染色用于江苏淮安地区食管疾病筛查1983例研究

目的探讨内镜下碘染色在食管癌高发区的食管早癌内镜筛查中的重要临床价值。 方法2014至2016年在江苏省淮安市清浦区武墩镇及盐河镇等对1983例40～60岁人群进行食管癌内镜筛查,对比碘染色前后食管黏膜颜色和形态的变化,并对黏膜染色异常者行活检病理检查。 结果740例患者共835处病灶接受食管组织活检,有273例于碘染色前发现(白光状态下),碘染色后再发现562例。其中碘染后新发现5例黏膜内癌,205例各种异型增生,2组比较差异有统计学意义(P<0.05),表明碘染色后食管癌及癌前病变的检出率明显高于染色前。 结论内镜下食管黏膜碘染色可明显提高筛查过程中食管癌及癌前病变的检出率,且因其价格低廉,操作简单,值得临床推广应用。     

Application of a Video Microscope to Observe the Gastric Mucosal Surface,Especially in Early Gastric Cancer

Abstract: The surface of cancerous mucosa in 30 surgically resected cases of early gastric cancer (22 differentiated and 8 undifferentiated adenocarcinoma) was observed through a video microscope. The mucosal surface showed characteristic findings of a pit pattern, composed of elevations and depressions of the surface, as previously reported when a dissecting microscope was used. The pit patterns of the cancerous mucosa were classified into five types under 200 × magnification: oval or round (type I), tubular or slightly branching (type II), irregular sulcus (tupe Ill), mesh-like (type IV) and non-structural or destroyed (type V). Most differentiated cancers had type I to 1V pit patterns, in contrast with undifferentiated cancers which mostly had a type V pit pattern. Our observations suggest that a video microscope is useful to observe magnified gastrointestinal mucosal lesions and to recognize the characteristic features of the surface such as the pit pattern.     

Fluorescence induced with 5-aminolevulinic acid for the endoscopic detection and follow-up of esophageal lesions.

BACKGROUND: The aim of this study was to investigate the use of orally administered 5-aminolevulinic acid (ALA) for in vivo photodynamic diagnosis and follow-up of premalignant and malignant esophageal lesions. METHODS: Twenty-two patients with known or treated malignant and precancerous esophageal lesions were sensitized with orally administered ALA (15 mg/kg). Six patients had Barrett's esophagus, with or without severe dysplasia, 5 squamous cell cancer or early-stage (uT1N0M0) adenocarcinoma, 1 advanced-stage (uT3N1) adenocarcinoma, and 1 patient a lesion with an appearance that suggested esophageal cancer. Nine patients underwent photodynamic diagnosis for follow-up after treatment of esophageal cancer with curative intent; 6 had no macroscopically visible lesion and 3 a barely visible lesion under standard (white-light) endoscopy. Photodynamic diagnosis was conducted 6 to 7 hours after oral administration of ALA by using a special light source capable of delivering either white or violet-blue light. Red fluorescence was detected with a charged coupled device camera attached to a fiberoptic endoscope. Corresponding endoscopic, fluorescence, and microscopic findings were compared. RESULTS: By using histology as the reference standard (n = 86 biopsies), 85% of the biopsy sites with premalignant or malignant histopathology exhibited red fluorescence, whereas only 25% were detected with white-light endoscopy. CONCLUSION: ALA-induced fluorescence might be useful for the early endoscopic detection of malignant esophageal lesions and follow-up after treatment of such lesions with curative intent.     

MICROVASCULAR PATTERNS OF ESOPHAGEAL MICRO SQUAMOUS CELL CARCINOMA ON MAGNIFYING ENDOSCOPY

Background: Recently, esophageal microcancers have been frequently diagnosed and are receiving increasing attention as initial findings of cancer. We examined whether the clinicopathological features and microvascular patterns of esophageal microcancers on magnifying endoscopy are useful for diagnosis. Methods: Magnifying endoscopy was performed to examine the histopathological features of 55 esophageal cancers measuring ≤10 mm in diameter (34 small cancers, 16 microcancers, and five supermicrocancers). Results: Although some lesions were detected only on iodine staining, most were detected on conventional endoscopic examination. Most small cancers and microcancers were m1 or m2; some were m3 or sm2. Supermicrocancers were dysplasia or m1 cancer. As for the microvascular pattern, most m1 and m2 cancers showed type 3 vessels, while most submucosal cancers showed type 4 vessels. Conclusions: Microvascular patterns on magnifying endoscopy are useful for the differential diagnosis of benign and malignant esophageal cancers and for estimating the depth of tumor invasion. The shape of small lesions is often altered considerably by biopsy. Residual tumor may persist unless the basal layer of the lesion is included in biopsy specimens, even in microcancers. Consequently, endoscopic mucosal resection, without biopsy, is being performed in increasing numbers of patients with lesions suspected to be cancer on the basis of their microvascular patterns.     

CYPIA1, GSTs and mEH polymorphisms and susceptibility to esophageal carcinoma： Study of population from a high- incidence area in north China

AIM: To characterize cytochrome P4501A1 (CYPIA1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain reaction (PCR) and PCR based restriction fragment length polymorphisms (PCRRFLP) were used to detect polymorphism changes of CYP,GSTs and mEH on esophageal cancerous and precancerous lesions as well as in case control group. All the examination samples were obtained from Linzhou (formerly Linxian), Henan Province, the highest incidence area for esophageal. RESULTS: The frequency of CYP1A1 3‘‘ polymorphism in case control group (26/38, 68 %) was significantly higher than in esophageal squamous cell carcinoma~roup (ESCC) (29/62, 47 %) (P&lt;0.05). A significant difference in the incidence of mEH slow allele variant was observed between case control group (15/38, 39 %) and esophageal dysplasiagroup (22/32, 69 %) or ESCC group (39/62, 63 %) (P&lt;0.05). However, no significant difference was observed among different groups in the polymorphisms of CYPIA1 exon 7, GSTM1, GSTT1, GSTP1 and mEH fast allele. CONCLUSION: The present results suggest that CYPIA1 3‘‘ polymorphism may be one of the promising protectivef actors and its wild gene type may be an indicator for higher susceptibility to esophageal cancer, mEH slow allele variant,associated with the progression of esophageal precancerous lesions, may conthbute to the high susceptibility to esophageal carcinoma.