Abstract
Background: The findings of a recent analysis on microRNAs (miRNAs) suggest that circulating miRNAs have potential as biomarkers of esophageal squamous cell carcinoma (ESCC). In order to ...identify specific miRNAs of ESCC, we analyzed the circulating miRNAs of patients who underwent endoscopic mucosal resection (EMR) and esophagectomy. Method: After obtaining written informed consent, we collected paired (pre and post treatment) blood samples from 60 superficial ESCC patients and 42 pretreatment advanced ESCC patients between 2011 and 2015. Samples were divided into training (40 superficial ESCC and 22 advanced ESCC) and test (15 superficial ESCC and 20 advanced ESCC) cohorts according to the period at which they were obtained (between 2011 and 2013 and between 2014 and 2015). Fifty-five patients underwent EMR and were confirmed as stage 0 or Stage 1a. Microarray analyses of blood samples were performed using the 3D-Gene miRNA microarray platform (Toray). Normalization was achieved using the Quantile method, and poor quality samples were excluded from the analysis. Any two clinical groups were compared using a two-sided Student’s t-test. miRNAs exhibiting significant differences were subsequently evaluated using a logistic regression analysis (LRA). Multivariate LRA, Akaike’s Information Criterion (AIC), and Receiver Operating Characteristic (ROC) analyses were performed in order to evaluate the diagnostic power of miRNA combinations. In all series, we used post-EMR patients as control cases.
Results: Twelve miRNAs (miR-6722-5p, 489, 4525, 409-3p, 6088, 3678-5p, 197-5p, 4281, 5090, 3173-3p, 762, and 1470) were selected as discriminant markers (S-combination: AUC 1.00) of superficial ESCC, while 4 miRNAs (miR-4723-3p, 4646-3p, 2392, and 1236-3p) were selected as discriminant markers (A-combination: AUC 1.00) of advanced ESCC in the training cohort. There were no overlap miRNAs between the two combinations. In the test cohort, the S-combination discriminated superficial ESCC (AUC 1.00), while the A-combination discriminated advanced ESCC (AUC 1.00) from post-EMR patients. Furthermore, the S-combination discriminated advanced ESCC in the test cohort (AUC 1.00). However, the A-combination did not clearly discriminate superficial ESCC (AUC 0.833).
Conclusion: Our results suggest that selected miRNAs are useful biomarkers for the discrimination of ESCC. However, biomarkers of superficial ESCC and advanced ESCC may differ.
Citation Format: Yutaka Shimada, Yoshinori Takei, Tomoyuki Okumura, Takuya Nagata, Haruka Fujinami, Miwako Arima, Tetsuya Abe, Yasumasa Niwa, Masahiro Tajika, Tetsuo Sudo, Kazuharu Shimizu. Circulating microRNA expression profiles as a novel diagnostic biomarker for esophageal squamous cell carcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4430. doi:10.1158/1538-7445.AM2017-4430
The Japan Gastroenterological Endoscopy Society has developed endoscopic submucosal dissection/endoscopic mucosal resection guidelines. These guidelines present recommendations in response to 18 ...clinical questions concerning the preoperative diagnosis, indications, resection methods, curability assessment, and surveillance of patients undergoing endoscopic resection for esophageal cancers based on a systematic review of the scientific literature.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Iodine staining is mainly performed to screen for superficial esophageal cancer and to evaluate the extent of lesions. The normal esophageal mucosa stained with iodine consisted of aggregations of ...papillary patterns with small white spots. Changes in the color tone of iodinestain reflect the thickness and degree of damage of the prickle-cell layer, which reacts with iodine. Whitish thickened areas of reflex esophagitis were darkly stained with iodine. Red regions retained their papillary structures and were unstained with iodine and poorly demarcated. Unstained regions suggestive of cancer are characterized by irregular positively stained areas of various sizes within a poorly demarcated unstained region. Dense aggregates of abnormal vessels proliferate up to near the surface. As iodine staining fades, the lesion becomes redder than the surround region, often resulting in positive pink-color signs. Pink-color signs also become positive when papillary vessel proliferation is caused by inflammation. The regions with chronic inflammation and repeated cellular regeneration may be difficult to distinguish from cancer. Basal-layer-type CIS present with poorly demarcated areas unstained with iodine. PC signs are often negative. Papillary structures of different sizes and the formation of poorly demarcated regions can be used to distinguish CIS from inflammatory disease. Iodine staining properties and microvascular patterns should be evaluated to diagnose CIS as well as inflammatory lesions.
: A questionnaire‐based survey of cases of superficial esophageal cancer with histological features other than squamous cell carcinoma (SCC) was conducted prior to The 37th Conference of the Japanese ...Research Society for Early Esophageal Cancer and Chromoendoscopy. The data of cases resected between 1986 and 1996 at 25 Japanese institutions were evaluated. Among 2,381 cases of superficial esophageal cancer, 93 patients (3.9%) were diagnosed with histological features other than SCC. These included 6 cases of mucosal cancer and 87 cases of submucosal cancer, and were referred to as superficial nonsquamous cell carcinoma (NSCC). Most cases were grossly classified as O‐I type. Elevated tumors, which included O‐I and O‐lla types, accounted for 80% of all lesions. Many cases of adenoid cystic carcinoma (ACC), adenosquamous carcinoma (ASC), basaloid carcinoma (BSC) and undifferentiated carcinoma (UND) were classified as O‐lpl or O‐lsep types. Almost all cases of carcinosarcoma (CASA) and malignant melanoma (MM) were classified as O‐lp type. A small number of O‐llc type tumors were observed and diagnosed as adenocarcinoma (AC), ACC ASC and BSC. All cases of AC were classified as unilocular tumor, and many cases were observed at the abdominal esophagus. However, the superficial esophageal tumors could not be differentiated by endoscopic features. The frequency of lymph node metastasis was slightly higher in UND and MM (60%), while the other histological types of esophageal cancer had an equivalent frequency to SCC (20–40%). Although the frequency of tumor recurrence was usually approximately 20%, the frequency of recurrent UND and MM was as high as 50–60%. Distant organ metastasis was the most commonly observed pattern of tumor metastasis. The five‐year survival rate was approximately 60%, and there were no significant differences in the survival rate among the patients. However, the prognosis of UND and MM tended to be poor. (Dig Endosc 1999; 11: 12–23)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The patient was a 75-year-old woman who had dysphagia. Upper gastrointestinal endoscopy revealed a semipedunculated, superficial polypoid type (0-Ip) lesion, 4 cm in diameter, in the lumen of the ...middle thoracic esophagus. A superficial slightly depressed type (0-IIc) lesion (about 25 mm) was present around the polypoid lesion. Magnifying endoscopy showed abnor-mal microvessels. Biopsy revealed carcinosarcoma. Endoscopic ultrasonography disclosed no enlargement of the cervical, thoracic, or abdominal lymph nodes. The patient was given a 0-Ip+IIc type esophageal carcinosarcoma invading the muscularis mucosae (m3) and the surface layer of the submucosa (sml). Endoscopic mucosal resection (EMR) was performed. This was the first case of carcinosarcoma that we radically treated by EMR.
A 59-years-old man was referred to our hospital for treatment of gastric cancer. Esophagogastroduodenoscopy revealed that the lesion was depressed, 10 mm in diameter, and was located at the anterior ...wall of the lower gastric body. Signet-ring cell carcinoma was diagnosed using endoscopic biopsy. The lesion was diagnosed as the expanded indication lesion of endoscopic submucosal dissection (ESD) , and ESD was performed. The cancer invaded the submucosa to a depth of 1800 µm and vertical margins were negative ; however, the cancer cells were in close proximity to the vertical margins. The lesion was diagnosed as a non-curative resection. Additional gastrectomy was performed. The gastrectomy specimen revealed that residual cancer cells had invaded the muscularis propria. Since it was possible that the invasive cancer persisted in the deeper tissues of the submucosa, additional gastrectomy was suggested.
Background: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) was developed to attain endosonographic image in real time in endoscopic biopsy, just like in percutaneous biopsy ...with ultrasonic or computer-tomographic images. Results of EUS-FNAB in esophageal and mediastinal diseases were evaluated and clinical indications of this technique were investigated. Methods : The study was performed in 58 patients, consisting of 30 with esophageal or mediastinal tumors and 28 requiring mediastinal lymph node examination. The intruments were linear array EUS transducer PEF-703FA and 21G Endosonopsy. The aspirated material was recovered on a filter paper and was formalin-fixed to be examined histopath-ologically. Results : The tumors measured 6mm to 60mm (mean 29mm). Collection of tissue was successful in 95% of the patients, and diagnostic accuracy was 95%. The biopsy specimen was satisfactory to establish histological diagnosis in every case of 27 patients with malignant diseases. No complication was experienced. Conclusion : EUS-FNAB is indicated in cases where technique of EUS-guided puncture is required, or is considered optimum in view of the safety, and in cases where histological diagnosis is critical for the decision of treatment program. In many cases of mediastinal diseases, not even a detection of lesion is feasible without this technique, let alone a collection of tissue. EUS-FNAB is thus performed as first choice to obtain biopsy specimen in such cases. To patients with esophageal cancer, EUS-guided lymph node puncture is applied in order to assess the appropriateness of endoscopic mucosal resection (EMR), to follow-up the patients after EMR and chemo-radiotherapy (CRT), and to evaluate the efficacy of Neoadjuvant CRT.
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