BACKGROUND AND AIM:Esophageal squamous cell carcinoma (ESCC) in patients with no history of tobacco smoking or alcohol consumption accounts for approximately 5% of all ESCCs. This study aimed to clarify the clinicopathological features of superficial ESCCs in patients with no history of tobacco smoking or alcohol consumption. METHODS:Clinical data and pathological features of 108 superficial ESCCs in endoscopic submucosal dissection (ESD) specimens obtained from 102 patients with no history of tobacco smoking or alcohol consumption (NTNA group) were reviewed. For comparison, the clinicopathological features of 767 superficial ESCCs in ESD specimens from 544 patients with history of tobacco smoking and alcohol consumption (TA group) were also reviewed. Factors analyzed included age, sex, synchronous/metachronous cancer, gastroesophageal reflux disease (GERD), tumor size, tumor site, macroscopic type, Lugol-voiding lesion (LVL) grade, invasion depth, and lymphovascular invasion. LVLs were graded as A (no lesions), B (1-9 lesions), and C (> 9 lesions). RESULTS:The univariate analysis revealed that female predominance (p < 0.01), absence of synchronous/metachronous cancer (p < 0.01), grade A LVLs (p < 0.01), presence of GERD (p < 0.01), tumor location in the middle thoracic esophagus (p < 0.05), tumor location at the posterior wall (p < 0.05), and 0-IIa macroscopic type (p < 0.01) were significantly more frequently observed in NTNA group than in TA group. Multivariate analysis identified female predominance (OR 68.2, p < 0.001), LVL grade A (OR 50.6, p < 0.001), and 0-IIa macroscopic type (OR 7.2, p < 0.001) as significant features in the NTNA group. CONCLUSIONS:This study demonstrated the unique clinicopathological features of ESCCs in patients with NTNA.

INTRODUCTION:Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been controversial. METHODS:We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER. RESULTS:A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15-3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09-11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1-233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% ( P < 0.0001), 80.5% vs 53.3% ( P < 0.0001), and 98.5% vs 93.1% ( P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups. DISCUSSION:pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.

Background and study aims We investigated the effect of adding magnifying blue laser imaging (BLI), magnifying narrow-band imaging (NBI), and iodine staining to white light imaging in diagnosis of early esophageal squamous cell carcinoma (EESCC) in high-risk patients. Patients and methods Between May 2013 and March 2016, two parallel prospective cohorts of patients received either primary WLI followed by NBI-magnifying endoscopy (ME) or primary WLI followed by BLI-ME, were studied. At the end of screening, both groups underwent iodine staining. The percentage of patients with newly detected esophageal malignant lesions in each group and the diagnostic ability of image-enhanced endoscopy (IEE)-ME were evaluated. Results There are 258 patients assigned to the NBI-ME group and 254 patients assigned to the BLI-ME group. The percentage of patients with one or more malignant lesions detected in the WLI + NBI-ME examination was similar in the WLI + BLI-ME examination (15 of 258 patients or 5.81 % vs. 14 of 254 patients or 5.51 %). However, four of 19 lesions in the NBI-ME group and six of 21 lesions in the BLI-ME group were overlooked and were detected by iodine staining. NBI-ME and BLI-ME showed similar accuracy in differentiation of cancerous lesions from non-cancerous lesions in diagnosis of EESCC (NBI/BLI: sensitivity, 87.5/89.5; specificity, 78.9/76.6; accuracy, 80.8/79.5; positive predictive value, 53.8/53.1; negative predictive value, 95.7/96.1). Conclusions Both NBI and BLI were useful for detection of EESCC. However, because some lesions were overlooked by even NBI and BLI, high-risk patients may benefit from use of iodine staining during endoscopic screening of EESCC (UMIN000023596).

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.

Cervical esophageal cancer (CEC) is an uncommon disease. Thus, the clinical data from CEC patients have not been sufficient to establish a standard treatment.

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

Predicting invasion depth of superficial esophageal squamous cell carcinoma is crucial in determining the precise indication for endoscopic resection because the rate of lymph node metastasis increases in proportion to the invasion depth of the carcinoma. Previous studies have shown a close relationship between microvascular patterns observed by Narrow Band Imaging magnifying endoscopy and invasion depth of the superficial carcinoma. Thus, the Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating invasion depth of superficial esophageal squamous cell carcinomas. We conducted a prospective study to evaluate the diagnostic values of type B vessels in the pretreatment estimation of invasion depth of superficial esophageal squamous cell carcinomas utilizing JES classification, the criteria of which are based on the degree of irregularity in the microvascular morphology. Type A microvessels corresponded to noncancerous lesions and lack severe irregularity; type B, to cancerous lesions, and exhibit severe irregularity. Type B vessels were subclassified into B1, B2, and B3, diagnostic criteria for T1a-EP or T1a-LPM, T1a-MM or T1b-SM1, and T1b-SM2 tumors, respectively. We enrolled 211 patients with superficial esophageal squamous cell carcinoma. The overall accuracy of type B microvessels in estimating tumor invasion depth was 90.5 %. We propose that the newly developed JES magnifying endoscopic classification is useful in estimating the invasion depth of superficial esophageal squamous cell carcinoma.

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.

With the development of a new endoscopy system using LASER light as the light source, the LASERO system, Blue Laser Imaging (BLI) has been added to the various digital image enhancement techniques already available. We studied the usefulness and ability of the diagnosis of the superficial esophageal cancer use of the LASEREO system and magnifying endoscopy with BLI. One of the most important features of this system is the clarity of white-light images, which has made it easy to observe delicate color tone changes, and the borders of the lesions were clearly visualized. The BLI mode images are also bright, making it possible to obtain sharp, bright close-up images even in magnifying observation. The ability to recognize the micro vessels and to evaluate the micro-vascular patterns, accuracy rate of the depth of cancer invasion did not substantially differ between BLI and NBI.

The definition of early carcinoma of the esophagus has changed with time on the basis of new data. As from 2007 an early carcinoma is defined as an intramucosal carcinoma with or without metastasis. In the subclassification based on invasion depth, m1 and m2 squamous cell carcinomas have no metastasis and are considered curable by endoscopic resection alone, whereas less than 10% of m3 carcinomas and some 20% of sm1 squamous cell carcinomas have lymph node metastasis. In this article the relationship between various histopathological findings and the incidence of lymph node metastasis is reviewed. The m3 and sm1 superficial squamous cell carcinomas showing 0-I and 0-III types, large tumors over 50 mm in size or those showing vessel permeation have higher incidences of lymph node metastasis. In the field of gastrointestinal surgical pathology pathologists are now expected to not only diagnose the presence or absence of malignancy but also to investigate in detail many of the histological factors related to the prevalence of lymph node metastasis.

An upper gastrointestina(l GI) series revealed a diverticulum in the anterior wall of the middle thoracic esophagus of a 72-year-old man. Endoscopy revealed a type 0-IIc lesion in the esophageal diverticulum. The margin of the lesion was unclear. Biopsy proved that it was squamous cell carcinoma. Endoscopic ultrasonography showed that the deepest layer of the tumor was the lamina propria mucosae (cT1a-LPM) and that the underlying muscularis propria was thinning. No distant metastasis or regional lymph node metastasis was detected. Diverticulectomy or endoscopic submucosal dissection (ESD) was out of indication due to the unclear margin and thin muscularis propria. We conducted mediastinoscopy-assisted esophagectomy. The pathological diagnosis of the resected specimen was moderately differentiated squamous cell carcinoma with invasion to the lamina propria mucosae (pT1a-LPM). Pathological examination proved the thinning of the underlying muscularis propria in the diverticulum. The patient is alive without recurrence at 6 months after surgery.

Die Definition der Plattenepithelfrühkarzinome des Ösophagus hat sich im Laufe der Zeit geändert. Seit 2007 wird das Frühkarzinom als intramukosales Karzinom mit oder ohne Metastasen definiert. In der Subklassifikation der Invasionstiefe weisen mukosale m1- und m2-Plattenepithelkarzinome praktisch keine Metastasen auf und gelten als endoskopisch heilbar. Dagegen bilden 10% der m3-Karzinome und etwa 20% der sm1-Plattenepithelkarzinome Lymphknotenmetastasen aus. In der vorliegenden Arbeit wird die Beziehung zwischen verschiedenen histopathologischen Befunden bei m3- und sm1-Plattenepithelkarzinomen und dem Auftreten von Lymphknotenmetastasen bewertet. Nach der Paris-Klassifikation und der Größe werden endoskopisch folgende Typen unterschieden: 0-I- und 0-III-Typen sowie große Tumoren über 50 mm Größe. Tumoren mit Gefäßeinbrüchen weisen ebenfalls eine höhere Inzidenz von Lymphknotenmetastasen auf. Wichtig für Pathologen ist, dass von klinischer Seite in der Magen-Darm-Pathologie erwartet wird, dass histologisch nicht nur eine Malignitätsbewertung durchgeführt, sondern auch im Detail auf Risikofaktoren für Lymphknotenmetastasen eingegangen wird.

The usefulness of magnified endoscopy for the diagnosis of invasion depth of esophageal squamous cell carcinoma (SCC) has been reported. There are two different classifications established by Inoue and Arima. However, both classifications are a little bit complicated for beginners. Therefore, Japan esophageal society decided to put the two classifications together and make a new classification. Aim: The aim of this study is to clarify the usefulness of this new classification for the diagnosis of invasion depth of esophageal SCC. Design: A prospective multicenter study. Patients and Methods: New classification; this new classification is composed of two major criteria. One is the shape and width of vessels and the other is the size of avascular area (AVA). The vessels observed by magnified endoscopy were classified into two groups, Type A and B. Type A is the vessels with mild or no atypia of intra papillary capillary loops (IPCL). And Type B is that with atypia including dilatation, meandering, caliber change and uneven form in each vessel. A lesion with Type A and B vessels strongly suggests intraepithelial neoplasia (IN) and SCC, respectively. Type B was sub-classified into 3 groups, B1, B2 and B3. Type B1, B2 and B3 were composed by loop like, non-loop and large vessels 3 times or more than B2, respectively. And, the invasion depth of B1, B2 and B3 was diagnosed as T1aEP or LPM, T1aMM or T1bSM1 and T1bSM2, respectively. AVA was defined as an area without or poor in vessels. AVA was divided into three groups according to the size. AVA-small, AVA-middle and AVA-large were defined as 0.5mm or less, between 0.5 and 3mm and 3mm or larger. Each AVA suggested the invasion depth as T1aEP or LPM, T1aMM or T1bSM1 and T1bSM2, respectively. A prospective study on diagnosis of the invasion depth according to the new classification had been carried out by Saku central, Osaka, Sendai, Niigata University and Saitama cancer center hospital. 210 consecutive patients who had superficial esophageal SCC and treated by ESD were enrolled to this study. All of the cases were diagnosed using this new classification, and the endoscopic findings and pictures were recorded. The invasion depth was diagnosed as T1aEP or LPM, T1aMM or T1bSM1 and T1bSM2. T1bSM1 was defined as submucosal invaded cancer 200 micrometer or less. Result159 of 172 lesions diagnosed as T1aEP-LPM were correct (92%). The remaining 7 and 6 lesions were T1aMM-SM1 and T1bSM2. 21 of 28 lesions diagnosed as T1aMM-T1bSM1 were correct (75%). And remaining 4 and 3 lesions was T1aEP-LPM and T1bSM2, respectively. 10 of 10 lesions diagnosed as T1bSM2 was correct (100%). The average of accuracy was 90% (190/210). Conclusion: The new classification of magnified endoscopy is simple and useful for diagnosis of invasion depth of esophageal SCC.