Sm Cancer Research Articles

Development of artificial intelligence for the detection and staging of esophageal cancer

: Computer-assisted diagnosis (CAD) using deep learning, based on convolutional neural networks (CNNs), is rapidly developing in modern society and clinical practice. In the medical field of endoscopy, a CAD system can be used in the detection and staging of superficial esophageal cancer. In the detection of superficial esophageal squamous cell carcinoma (ESCC), several studies were reported as using still images of conventional white-light endoscopy and narrow-band imaging (NBI). The sensitivity of CAD systems is over 90%, and in some reports, higher than that of expert endoscopists. In addition, there is a report using video for a validation set that showed good performance. In diagnosing invasion depth, there are reports using conventional white-light imaging, NBI, and magnifying endoscopy with NBI using still images; there are also reports of intrapapillary capillary loop pattern identification using still images. Using white-light endoscopy and NBI, CAD systems showed sensitivity of 84.1–95.4%, specificity of 73.3–79.2%, and accuracy of 80.9–92.9% for differentiating SM1 cancers from SM2 or SM3 cancers in pathology. Additional systems could accurately classify intrapapillary capillary loop patterns as normal or abnormal, with comparable performance to experienced endoscopists. As for esophageal adenocarcinoma (EAC) that arises in Barrett’s esophagus (BE), there are detection reports that show favorable performance. Furthermore, the CAD system from one report identified the location suitable for biopsy; this is helpful for endoscopists because of the difficulty in determining the location of early EAC in BE. Although these studies are still only at research level, excellent performance has been achieved for detecting and staging of superficial esophageal carcinoma by CAD systems. In the near future, CAD systems will support us in detecting and staging esophageal cancers in daily clinical practice, leading to a better prognosis.

Long-term prognosis of curative endoscopic submucosal dissection for early colorectal cancer according to submucosal invasion: a multicenter cohort study

BackgroundEndoscopic submucosal dissection (ESD) can provide a high en bloc resection rate and has been widely applied as curative treatment for early colorectal cancer (ECC). However, surgical treatment is occasionally required, and reports on the long-term prognosis of ESD are insufficient. This study aimed to investigate the long-term outcomes of ECC removal by ESD, including local recurrence and metastasis.MethodsThis multicenter study was conducted retrospectively on 450 consecutive patients with ECC who were treated with ESD between November 2003 and December 2013. Clinical, pathological, and endoscopic data were collected to determine tumor depth, resection margin, lymphovascular invasion, and recurrence.ResultsThe median follow-up period was 53.8 (12–138 months). The en bloc resection rate was 85.3% (384) and in intramucosal cancer being 84.1% and in superficial submucosal invasion (SM1) cancer being 89.8% (p = 0.158). The curative resection rate was 76.0% (n = 342), and there was no statistical difference between the two groups (77.3% vs. 71.4%, p = 0.231). The overall recurrence free survival rate (RFS) was 98.7% (444/450). In patients with curative resection, there was no statistically significant difference in RFS according to invasion depth (intramucosal: 99.3% vs. SM1: 97.1%, p = 0.248).ConclusionsPatients with curatively resected ECC treated with ESD showed favorable long-term outcomes. Curatively resected SM1 cancer has a RFS similar to that of intramucosal cancer.

Application of convolutional neural networks for evaluating the depth of invasion of early gastric cancer based on endoscopic images.

Recently, artificial intelligence (AI) has been used in endoscopic examination and is expected to help in endoscopic diagnosis. We evaluated the feasibility of AI using convolutional neural network (CNN) systems for evaluating the depth of invasion of early gastric cancer (EGC), based on endoscopic images. This study used a deep CNN model, ResNet152. From patients who underwent treatment for EGC at our hospital between January 2012 and December 2016, we selected 100 consecutive patients with mucosal (M) cancers and 100 consecutive patients with cancers invading the submucosa (SM cancers). A total of 3508 non-magnifying endoscopic images of EGCs, including white-light imaging, linked color imaging, blue laser imaging-bright, and indigo-carmine dye contrast imaging, were included in this study. A total of 2288 images from 132 patients served as the development dataset, and 1220 images from 68 patients served as the testing dataset. Invasion depth was evaluated for each image and lesion. The majority vote was applied to lesion-based evaluation. The sensitivity, specificity, and accuracy for diagnosing M cancer were 84.9% (95% confidence interval [CI] 82.3%-87.5%), 70.7% (95% CI 66.8%-74.6%), and 78.9% (95% CI 76.6%-81.2%), respectively, for image-based evaluation, and 85.3% (95% CI 73.4%-97.2%), 82.4% (95% CI 69.5%-95.2%), and 83.8% (95% CI 75.1%-92.6%), respectively, for lesion-based evaluation. The application of AI using CNN to evaluate the depth of invasion of EGCs based on endoscopic images is feasible, and it is worth investing more effort to put this new technology into practical use.

305 RISK OF GENERALIZATON IN PATIENTS WITH HIGH-RISK EARLY ESOPHAGEAL CANCER: RETROSPECTIVE ANALYSIS OF PROSPECTIVELY COLLECTED DATA INCLUDING LYMPH-NODE MICROMETASTASES ASSESSMENT

Abstract Esophagectomy is a standard of care for patients with "high-risk" early esophageal cancer (HRC) despite a growing evidence that endoscopic treatment may be a safe alternative. Our aims were 1. to prospectively evaluate the long-term results of endoscopic and surgical treatments in consecutive patients with HRC and 2. to determine the risk of lymph node (LN) metastases and micrometastases in patients with HRC. Methods HRC was defined as any cancer with submucosal (sm) invasion or mucosal cancer with at least one of the following: poor differentiation, invasion to blood or lymphatic vessels and high tumor cell dissociation (TCD3). All patients (n = 69) underwent endoscopic resection (ER or ESD) and after the histopathological diagnosis of HRC, patients without contraindications were referred to surgery (n = 30). The remaining patients (n = 39) continued in endoscopic treatment, if necessary. All resected LNs were stained for hematoxylin–eosin to evaluate metastases and immunohistochemistry was used for the detection of micrometastases or isolated tumor cells. Results Eighteen patients (26%) had T1a and 51 (74%) had T1b cancer; 51 had adenocarcinoma (AC) and 18 had squamous cell carcinoma (SCC). The median follow-up was 32 months (3–120). No patient with mucosal invasion (15 AC, 3 SCC) experienced LN involvement. Among 17 patients with sm1 invasion, only 2 (12%, both AC)experienced generalization or LN involvement. The further rates of LN involvement were 0% (0/5) in sm2 AC, 50% (3/6) in sm2 SCC, 25% (4/16) in sm3 AC and 29% (2/7) in sm3 SCC. 60% (18/30) of surgically treated patients would have been completely cured by endoscopy (Table 1). Conclusion The risk of LN metastases/micrometastases was lower than expected. No patients with high-risk mucosal cancer or low-risk sm1 cancer experienced lymph node involvement. Endoscopic treatment provided long-term remission (or cure) in considerable number of patients and it may represent a valid alternative to surgery in patients with high-risk early esophageal cancer.

Preoperative Diagnosis and Indications for Endoscopic Resection of Superficial Esophageal Squamous Cell Carcinoma.

Endoscopic resection (ER) is the mainstay of treatment for superficial esophageal squamous cell carcinoma (SESCC) instead of esophagectomy because of its minimal invasiveness and favorable clinical outcomes. Developments in endoscopic submucosal dissection have enabled en bloc resection of SESCCs regardless of size, thus reducing the risk of local recurrence. Although ER for SESCC is effective, metastasis may subsequently occur. Additionally, extensive esophageal ER confers a risk of postoperative esophageal stricture. Therefore, accurate assessment of the invasion depth and circumferential extent of SESCCs is important in determining the indications for ER. Diagnostic accuracies for SESCC invasion differ between epithelial (EP)/lamina propria (LPM), muscularis mucosa (MM)/submucosal (SM1), and SM2 cancers. ER is strongly indicated for clinically diagnosed (c)EP/LPM cancers because 90% of these are as pathologically diagnosed (p)EP/LPM, which has a very low risk of metastasis. Remarkably, the diagnostic accuracy for cMM/SM1 differs significantly with lateral spread of cancer. Eighty percent of cMM/SM1 cancers with ≤3/4 circumferential spread prove to be pEP/LPM or pMM/SM1, which have very low or low risk of metastasis. Thus, these are adequate candidates for ER. However, given the relatively low proportion of pEP/LPM or pMM/SM1 and high risk of subsequent stricture, ER is not recommended for whole circumferential cMM/SM1 cancers. For cMM/SM1 cancers that involve >3/4 but not the whole circumference, ER should be considered on a lesion-by-lesion basis because the risk of post-ER stricture is not very high, but the proportion of pEP/LPM or pMM/SM1 is relatively low. ER is contraindicated for cSM2 cancers because 75% of them are pSM2, which has high risk of metastasis.

Prognostic factors for ESD of early gastric cancers: a systematic review and meta-analysis.

Background and study aims Gastric neoplasms are one of the leading types of cancer in the world and early detection is essential to improve prognosis. Endoscopy is the gold-standard diagnostic procedure and allows adequate treatment in selected cases. Endoscopic submucosal dissection (ESD) has been reported to safely address most early gastric cancers (EGCs), with high curability rates. However, data on prognostic factors related to ESDs of EGCs are conflicting. Therefore, we aimed to systematically review the available literature and to perform a meta-analysis to identify the relevant prognostic factors in this context. Methods We performed this study according to PRISMA guidelines. Comparative studies assessing the relationship between curative resection or long-term curability rates and relevant prognostic factors were selected. Prognostic factors were demographic data, lesion features (location, morphology of the lesion, size, and depth of invasion), histological findings, Helycobacter pylori (HP) infection, presence of gastric a atrophy and body mass index (BMI). Finally, we also evaluated risk factors related to metachronous gastric neoplasm. Results The initial search retrieved 2829 records among which 46 studies were included for systematic review and meta-analysis. The total sample comprised 28366 patients and 29282 lesions. Regarding curative resection, pooled data showed no significant influence of sex [odds ratio (OR): 1.15 (0,97, 1.36) P = 0.10 I 2 = 47 %] , age [OR: 1.00 (0.61, 1.64) P = 1.00 I 2 = 58 %], posterior vs non-posterior location [OR: 1.35 (0.81, 2.27) P = 0.25 I 2 = 84 %], depressed vs von-depressed macroscopic type[OR: 1.21 (0.99, 1.49) P = 0.07 I 2 = 0 %], non-upper vs upper location [OR: 1.41 (0.93, 2.14) P = 0.10 I 2 = 77 %] and BMI [OR: 0.84 (0.57; 1.26) P = 0.41 I 2 = 0 %]. Differentiated neoplasms presented greater chance of cure compare to undifferentiated [OR: 0.10 (0.07, 0.15) P < 0.00001 I 2 = 0 %]. Ulcerated lesions had lower curative rates compared to non-ulcerated [OR: 3.92 (2.81, 5.47) P < 0.00001 I 2 = 44 %]. Lesions smaller than 20 mm had greater chance of curative resection [OR: 3.94 (3.25, 4.78) P < 0.00001 I 2 = 38 %]. Bleeding during procedure had lower curative rates compared to non-bleeding [OR: 2.13 (1.56, 2.93) P < 0.0001 I 2 = 0 %]. Concerning long-term cure, female gender [OR 1.62 (1.33, 1.97) P < 0.00001 I 2 = 0 %] and the mucosal over SM1 cancers were protective factors [OR: 0.08 (0.02, 0.39) P = 0.002 I 2 = 86 %]. Gastric atrophy [OR: 0.60 (0.45, 0.81) P = 0.0006 I 2 = 42 %] and the pepsinogen I/pepsinogen II ratio [OR 2.29 (1.47, 3.57) P = 0.0002 I 2 = 0 %] were risk factors to metachronous gastric neoplasm. Conclusions Ulcerated lesions, histology, bleeding and size > 20 mm are prognostic factors concerning curative resection. Regarding long-term cure, female gender and mucosal over SM1 cancer are predictive factors. Gastric atrophy and the pepsinogen ratio are risk factors for metachronous gastric neoplasm.

Magnification endoscopy in combination with acetic acid enhancement and narrow-band imaging for the accurate diagnosis of colonic neoplasms.

Background and study aims Magnification endoscopy with narrow-band imaging (NBIME) and NBIME with acetic acid enhancement (A-NBIME) enable visualization of the vascular and microstructural patterns of colorectal polyp. We compared the diagnostic accuracy and reproducibility of white light endoscopy (WLE), NBIME, and A-NBIME for predictive histologic diagnosis. Patients and methods Consecutive colorectal polyps (N = 628; 38 hyperplasias, 488 adenomas, 72 M-SM1 cancers, and 30 SM2 cancers) were photographed with WLE, NBIME, and A-NBIME. Endoscopic images were independently reviewed by three experts, according to the traditional criteria for WLE, the Japan NBI Expert Team classification for NBIME, and pit pattern classification for A-NBIME to compare diagnostic accuracy and interobserver diagnostic agreement among modalities. Results The specificity (95 % confidence interval) of hyperplasia and SM2 cancer with WLE were 98.2 % (96.8 %–99.1%) and 99.4 % (98.5 %–99.9 %), respectively, showing high accuracy for endoscopic resection without magnifying observation. Diagnostic accuracy of WLE, NBIME, and A-NBIME was 80.8 % (77.4 %–83.8 %), 79.3 % (75.9 %–82.4 %), and 86.1 % (83.2 %–88.7 %), respectively, showing the highest accuracy for A-NBIME among modalities ( P < .05). NBIME showed a lower PPV for M-SM1 cancer ( P < .05), as with WLE ( P = .08) compared to A-NBIME. Fleiss’s kappa values for WLE, NBIME, and A-NBIME diagnosis were 0.43 (0.39 – 0.46), 0.52 (0.49 – 0.56) and 0.65 (0.62 – 0.69), respectively, showing insufficient reproducibility of WLE and superiority of A-NBIME among modalities. Conclusion WLE showed high accuracy for endoscopic resection of colorectal polyps in expert diagnosis. NBIME demonstrated a higher diagnostic reproducibility than WLE. A-NBIME showed possible superiority among modalities in both diagnostic accuracy and reproducibility.

Irregularly branched microvessels as visualized by magnifying endoscopy: a reliable marker for predicting deep submucosal invasion of superficial esophageal squamous cell carcinoma.

Background and study aims Magnifying endoscopy with narrow-band imaging (M-NBI) is reported to be useful in diagnosing invasion depth of superficial esophageal squamous cell carcinoma (SCC), but accurate diagnosis of deep submucosal invasion (SM2) has remained difficult. However, we discovered that irregularly branched microvessels observed with M-NBI are detected in SM2 cancers with high prevalence. Thus, this retrospective study aimed to investigate the diagnostic performance of irregularly branched microvessels as visualized by M-NBI for predicting SM2 cancers. Patients and methods Patients with superficial esophageal SCC lesions that were endoscopically or surgically resected at our hospital between September 2005 and December 2014 were included. Endoscopic findings by M-NBI of these lesions were presented to an experienced endoscopist who was unaware of the histopathological diagnosis and who then judged whether irregularly branched microvessels were present. Using the invasion depth according to postoperative histopathological diagnosis as the gold standard, we determined the diagnostic performance of the presence of irregularly branched microvessels as an indicator for SM2 cancers. Results A total of 302 superficial esophageal SCC lesions (228 patients) were included in the analysis. When irregularly branched microvessels were used as an indicator of SM2 cancers, the diagnostic accuracy was 94.0 % (95 % confidence interval [CI]: 91.1–96.1 %), sensitivity was 79.4 % (95 % CI: 66.6–88.4 %), specificity was 95.9 % (95 % CI: 94.3–97.0 %), positive predictive value was 71.1 % (95 % CI: 59.6–79.1 %), and negative predictive value was 97.3 % (95% CI: 95.7–98.5 %). Conclusions Irregularly branched microvessels may be a reliable M-NBI indicator for the diagnosis of cancers with deep submucosal invasion.

The possibility of endoscopic treatment of cN0 submucosal esophageal cancer: results from a surgical cohort

BackgroundWe analyzed the pathological characteristics and recurrence pattern of cN0 submucosal esophageal cancer after esophagectomy and conducted risk stratification to determine the feasibility of performing endoscopic resection for cN0pT1b esophageal squamous cell malignancies.MethodsWe retrospectively enrolled 167 patients who underwent right-sided transthoracic esophagectomy and extended thoracic/abdominal two-field lymphadenectomy. Patients with pathologically confirmed lymph node metastasis or tumor recurrence constituted the high-risk group for endoscopic submucosal resection, and the remainder were defined as low risk. Factors affecting lymphatic metastasis and long-term recurrence were identified by univariate and multivariate analyses.ResultsPostoperative pathology showed that five patients (5/167; 3%) had lymph node metastases. Follow-up ranged from 12–60 months, with a median of 29 months. A total of 17 patients (10.2%) had recurrences during follow-up, including three patients with pathologic nodal metastasis (pN +) found at surgery. Invasion depth, differentiation, and tumor size differed significantly in high-risk patients. Overall 3-year survival rates were 94.2% (low-risk) and 40.9% (high-risk) (p < 0.01). Twenty-one patients with sm1 cancer, high tumor differentiation, and tumor length < 2 cm had no lymph node metastasis or lymphovascular invasion, and none of these patients experienced recurrence.ConclusionsEndoscopic submucosal resection alone may be feasible for patients with small (≤ 2 cm) clinically N0 submucosal esophageal squamous cell carcinoma with low invasion depth (sm1) and higher differentiation, but prospective studies are required for confirmation. Other patients require surgical resection with extended two-field thoracic/abdominal lymphadenectomy.

P48 MEDIASTINOSCOPY-ASSISTED ESOPHAGECTOMY FOR AN UPPER THORACIC SQUAMOUS CELL CARCINOMA IN A PATIENT WITH LIVER CIRRHOSIS

Abstract Background The standard treatment for T1a esophageal cancer (EC) is endoscopic submucosal dissection (ESD), whereas in T1b cancer is esophagostomy with lymph node dissection performed. The lesions infiltrated into the middle one-third (SM2) have in 36% of cases lymph node metastasis. Moreover, 41% of patients with SM2 cancer and lymphovascular invasion can develop recurrent cancer. Surgical resection is the recommended treatment. However, surgery could deteriorate the general condition and quality of life of patients with several chronic diseases. Hence, it is necessary to develop less invasive surgical approaches for this category of patients [1-2]. Methods Mediastinoscopy-assisted esophagectomy (MAE) is one of the less invasive surgical approaches for EC patients with severe co-morbidities [3]. MAE facilitates direct visualization of the mediastinal organs and dissection of the mediastinal lymph nodes [3]. Thoracotomy could be avoided in MAE with less retention time and reduced volume of drainage in 24 h. However, MAE is still not widely performed because of the controversy about lymphadenectomy. This disadvantage could be covered by improving the surgical technique and instruments [4, 5]. Results A 49-year-old man with Child Pugh Class A liver cirrhosis and portal hypertension underwent MAE with side to end anastomosis after ESD of an upper (23-30 cm) pT1b (SM2) well differentiated squamous cell carcinoma with lymphovascular invasion. The considerations for the mediastinoscopy-assisted esophagostomy were the presence of co-morbidities, not having lymph node metastasis in the clinical stage and the presence of lymphovascular invasion in the specimen. After esophagectomy, pathological investigation revealed squamous cell carcinoma in-situ (Tis, 12 x 8 mm) of the upper part of esophagus with no ductal involvement, absence of lymphovascular invasion and no lymph node metastasis (0/9). The patient had no postoperative complications. Conclusion MAE is a feasible and less invasive surgical approach in EC patients with severe co-morbidities, although there is a limitation in curative dissection of the mediastinal nodes. Direct vision of the mediastinal structures during MAE predicts organ injury and may affect postoperative morbidity and mortality.

Endoscopic Submucosal Dissection with/without Adjuvant Therapy for the Treatment of cT1N0M0 Esophageal Neoplasms Turned Out to be pT1b Cancers after the Endoscopic Resection

Background and Aim: After endoscopic submucosal dissection (ESD) for esophageal neoplasms, some patients would have the diagnosis of submucosal (pT1b) cancers. How to manage these patients appropriately after the ESD has not been well elucidated. The aim of this study is to report the outcomes of the patients with pT1b esophageal cancers, with or without adjuvant therapy after the ESD. Patients and Methods: This is a retrospective observational study. Between May 2013 and November 2017, 23 patients (25 lesions) undergoing ESD with the results of pT1b esophageal squamous cell carcinomas were enrolled in this study. After the ESD, our protocol was to give the patients adjuvant therapy (surgery or chemoradiotherapy) for the following criteria: positive vertical resection margins,lymphovascular (LV) invasion in the resected specimens, and SM2 cancers (tumor invasion to submucosa deeper than 200 μm). Those patients did not meet the criteria or refused adjuvant therapy were followed-up closely. Results: The mean patient age was 56.3 year (range, 45-75 year). The mean resected specimen length was 4.6 cm (range, 1.5-9.5 cm). The en block resection rate for the ESD was 100%. Four patients had positive vertical resection margins, resulting in an en blockplus R0 resection rate of 82.6% (19/23). Four other patients had LV invasion in the resected specimens. These eight patients (34.8%) were regarded as incomplete treatment by the ESD and seven of them received adjuvant therapy. None had tumor recurrence during the mean follow-up of 30.1 months. Two of the remaining 15 patients with R0 resection without LV invasion eceived adjuvant therapy based on the protocol. The other 13 patients received close observations only, including 11 patients with SM2 cancers. None had tumor recurrence during the mean follow-up of 23.6 months. Conclusions: ESD with/without adjuvant therapy based on the final pathological results may be an alternative treatment for patients with pT1b esophageal cancers.

Su1718 FEASIBILITY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL NEOPLASIA IN ANASTOMOSIS SITE

Metachronous colorectal lesions are sometimes occur in anastomosis site following surgical resection. Due to poor endoscopic maneuverability caused by adhesions in addition to severe postoperative fibrosis, lesions located at anastomotic sites are hard to treat, even with minimally invasive methods such as colorectal endoscopic submucosal dissection (ESD). The feasibility of ESD for colorectal lesion in an anastomotic site following colorectal surgery has not been assessed. In this retrospective study, we evaluated the treatment outcomes of ESD for colorectal lesion in an anastomotic site following colorectal surgery. Of 675 lesions (649 cases) treated with ESD at the Keio University Hospital between May 2010 and June 2017, 9 lesions (8 cases) of anastomotic sites following colorectal surgery were treated with ESD. Colorectal lesion in an anastomotic site was defined as a lesion expanding to an anastomotic site or a lesion requiring resection including an anastomotic site. Patient background (lesion site, macroscopic type, tumor size, histological type, and depth of invasion) and outcomes of treatment (procedure duration, en bloc resection rate, R0 resection rate, and the presence or absence of complications) were examined in this study. The mean age of patients in this study was 63.2 years. The lesions consisted of 4 in the transverse colon, 3 in the rectum, 1 in the anal canal, and 1 in the ileal pouch. The median tumor size (diameter) was 25 mm (range, 12 to 90 mm). The macroscopic types were Is (1 lesion), IIa (7 lesions), and IIc (1 lesion). The pathological diagnoses were adenoma (3 lesions), M cancer (4 lesions), SM cancer (1 lesion), and MP cancer (1 lesion). The median procedure duration was 50 minutes (range, 15 to 150 minutes), the en bloc resection rate was 88.9%, and the R0 resection rate was 66.7%. The only complication was postoperative bleeding. No perforation was observed. A high en bloc resection rate was achieved with ESD for lesions in the anastomotic site without perforation. Although a low R0 resection rate remains a challenge, this probably reflects the difficulty of making a preoperative diagnosis of lesions in the anastomotic site. This approach could avoid repetitive surgical resection. ESD by highly skilled endoscopists appears to be a feasible treatment for colorectal lesion in an anastomotic site.

Pilot study on probe-based confocal laser endomicroscopy for colorectal neoplasms: an initial experience in Japan.

The aim of this pilot study is to investigate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) in the evaluation of depth of invasion in colorectal lesions. Patients with colorectal lesions eligible for either endoscopic treatment or surgery were enrolled in the study. Tumor's depth of invasion was classified as mucosal or slight submucosal (M-SM1) and deep submucosal invasion or deeper (SM2 or deeper). White light endoscopy (WLE), magnifying narrow band imaging (M-NBI), and magnifying chromoendoscopy (M-CE) were used to assess colorectal lesions, and pCLE was used to identify tumor's features related to SM2 or deeper. The diagnostic classification of depth of invasion was obtained by correlating pCLE findings with histology results (on-site diagnosis). All colorectal lesions were stratified by a second endoscopist who was blinded to any clinical and histological information with the use of WLE, M-NBI, M-CE,and pCLE (off-line review). A total of 22 colorectal lesions were analyzed: seven were adenoma, ten intramucosal cancer, and five SM2 or deeper cancer. With respect to pCLE findings, loss of crypt structure was seen in all SM2 or deeper cancers and only in one M-SM1 lesion. Sensitivity, specificity, and accuracy of WLE, M-NBI, and M-CE in off-line review were 60/94/86, 60/94/86, and 80/94/91%, respectively. Sensitivity/specificity/accuracy of pCLE in off-line review were 80/94/91%, respectively. The inter-observer agreement of pCLE between on-site diagnosis and off-line review was 0.64 (95%CI 0.27-1.0). pCLE may represent a useful tool to evaluate the depth of invasion in colorectal lesions.

Predictive Factors for Lymph Node Metastasis in Submucosal Invasive Colorectal Carcinoma: A New Proposal of Depth of Invasion for Radical Surgery.

Patients with lymph node metastasis (LNM) in submucosal invasive colorectal carcinoma (SM cancer) require additional surgical treatment after endoscopic dissection. However, because additional radical resection after endoscopic local resection may be unnecessary for cases without LNM, more specific criteria are required in order to diminish the incidence of further radical resection after endoscopic dissection. A total of 492 patients with biopsy-proven SM cancer who underwent curative surgery between January 2008 and December 2012 were collected and were divided into LNM group and no LNM group. The cutoff value for the depth of submucosal invasion was analyzed by a receiver operating characteristic (ROC) curve. In this retrospective study, the association between LNM and clinicopathologic factors was analyzed by logistic regression analysis. The depth of submucosal invasion of 1900μm was determined as the cutoff value by ROC curve. Significant, independent predictive factors for LNM included the depth of submucosal invasion>1900μm (odds ratio [OR] 7.5; 95% confidence interval [CI] 3.1-18.3; p<0.001), venous invasion (OR 2.4; 95% CI 1.1-5.5; p=0.03), and poorly differentiated/mucinous adenocarcinoma (OR 6.3; 95% CI 1.3-30.8; p=0.02). Our study demonstrates that the depth of submucosal invasion (>1900μm), vascular invasion and poorly differentiated/mucinous carcinoma were predictive factors of LNM in patients with SM cancer. These predictors may help to reduce the incidence of unnecessary surgery after endoscopic resection.

Indication for endoscopic treatment based on the risk of lymph node metastasis in patients with Siewert type II/III early gastric cancer.

Because of the poor prognosis of proximal gastric cancers, there is debate as to whether the conventional indications for endoscopic resection can be used. Among subjects who underwent surgery for esophagogastric junction or gastric cardia cancer, 256 patients with T1 type II/III of the Siewert classification were included in this study. The association of lymph node metastasis (LNM) with each variable was analyzed using logistic regression models. A receiver operating characteristic curve was used to determine the discriminatory ability of the model. Propensity score-matched non-cardia cancer patients were selected to compare LNM and long-term survival rates. Of the 256 patients with T1 Siewert II/III gastric cancer, 21 (8.2%) had LNM. Because there was no LNM in T1a cancers, risk factors were analyzed only in patients with T1b. Tumor size (OR 1.42, 95% CI 1.10-1.82, P=0.007) and lymphovascular invasion (LVI) (OR 5.13, 95% CI 1.88-14.06, P=0.002) were determined to be predictors of LNM (sensitivity=66.7% and specificity=81.6%). Among patients without LVI, the groups with negligible risk for LNM were mucosa-confined cancer, or SM1 cancer with a tumor size ≤3cm. No LNM was observed in patients satisfying the absolute or extended criteria for endoscopic resection of early gastric cancers. LNM and long-term survival rates of patients with Siewert II/III did not differ significantly compared with matched non-cardia cancer patients. Tumor size and LVI were associated with LNM in patients with early Siewert type II/III gastric cancer, and the expanded indication for endoscopic resection may be used.

A retrospective study of endoscopic resection for 368 patients with early esophageal squamous cell carcinoma or precancerous lesions.

To retrospectively investigate the clinicopathological features and prognosis of early esophageal squamous cell neoplasm (ESCN) treated with endoscopic resection (ER), especially, to compare the prognosis in patients with sm2 cancer and non-sm2 cancer. From 2007 to 2013, 368 patients were included in our analysis. The patients were 252 (68.5%) men and 116 (31.5%) women with a median age of 61 (range 16-84years) years. Hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia, m1, m2, m3, sm1, and sm2 were diagnosed in 47 (12.8%), 27 (7.3%), 34 (9.2%), 61 (16.6%), 54 (14.7%), 38 (10.3%), 63 (17.1%), 12 (3.3%), and 32 (8.7%) cases. The mean (range) follow-up time was 29 (0-84) months. The cumulative overall 1-, 3-, and 5-year metachronous esophageal lesion rates were 4.1, 12.9, and 32.6%. The incidence of lymph node or distant metastasis was 1.54% in m3, 6.25% in sm2, and 0 in other subgroups. The overall 1-, 3-, and 5-year survival rates were 99.5, 97.3, and 87.5%. There was significant difference between sm2 and non-sm2 patients in metastatic rate (P=0.021); however, no difference existed between m3 patients and sm2 patients (P=0.252). The difference of metachronous esophageal lesion (P=0.401) and survival (P=0.634) between sm2 and non-sm2 patients was not obvious. Our study showed that ER was an effective and relatively safe treatment for superficial ESCN. ER is still appropriate in select sm2 patients. To monitor the second primary cancer in sm2 is necessary during the follow-up.

Diagnostic performance of conventional endoscopy in the identification of submucosal invasion by early gastric cancer: the "non-extension sign" as a simple diagnostic marker.

The ability to differentiate between mucosal (M) or microinvasive submucosal (SM1: depth of less than 500µm) and invasive submucosal (SM2: depth of 500µm or more) cancer is paramount when choosing the method of treatment for early gastric cancer (EGC). The "non-extension sign" relates to a localized increase in thickness and rigidity due to massive submucosal invasion by a cancer. The present study sought to assess the ability of conventional endoscopy (CE) to correctly identify SM2 cancer using only the non-extension sign. This is a retrospective study based on a prospectively collected database. EGCs had been diagnosed according to invasion depth as M-SM1 or SM2. In terms of the endoscopic diagnostic criterion, lesions positive for the non-extension sign were classified as SM2 cancers, while those negative for the non-extension sign were classified as M-SM1 cancers. Histopathological findings were used as the gold standard. We examined a total of 863 lesions from 704 patients, comprising 104 true-positive, 733 true-negative, 9 false-positive, and 17 false-negative lesions. This yielded a sensitivity of 92.0% (95% confidence interval (CI), 87.0-97.0%), a specificity of 97.7% (95% CI, 96.7-98.8%), a positive predictive value of 85.9% (95% CI, 79.7-92.1%), a negative predictive value of 98.8% (95% CI, 98.0-99.6%), and a diagnostic accuracy of 96.9% (95% CI, 95.8-98.1%). The non-extension sign may be useful for accurately determining the suitability of minimally invasive endoscopic treatment. Nevertheless, considering the limitations of retrospective analysis, a further prospective study is warranted to confirm the diagnostic reliability of the non-extension sign.

Clinicopathological Outcomes of Patients with Early Gastric Cancer after Non-Curative Endoscopic Submucosal Dissection

Background: Endoscopic submucosal dissection (ESD) was developed to resect early gastric cancer (EGC), which could not be resected by conventional endoscopic mucosal resection, and the indications for ESD are expanding to include more types of EGCs. Favorable long-term outcomes of ESD for EGCs that meet the expanded curability criteria have been reported. However, the outcomes of non-curative ESD are not known in detail. Summary: We analyzed the outcomes of 165 EGCs in 165 patients after non-curative ESD, as well as the clinical course. Of these patients, 109 underwent additional surgical resection (group S) and 56 patients were followed up without additional surgery (group F). The complete resection rate was 90.7% (39/43) for intramucosal cancer (M), 97.3% (36/37) for minimally submucosal invasive cancer (SM1), and 74.1% (63/85) for deep submucosal invasive cancer (SM2). The lymph node metastasis rate was 0% for M, 5.4% for SM1, and 10.6% for SM2 cancers. Regarding long-term survival, although the number of patients who died of another disease was significantly higher in group F than in group S, there was no significant difference in overall survival between the groups. Key Message: The resectability of ESD for ECGs with an invasion depth of M to SM1 after non-curative ESD was excellent, and lesions without lymphovascular invasion did not metastasize or recur, resulting in a favorable prognosis. Our data may help in deciding whether additional surgery should be performed for borderline lesions after non-curative ESD. Furthermore, we suggest the possibility of further expanding the indications for ESD.

The role of tumor size in surgical decision making after endoscopic resection for early gastric cancer

Endoscopic resection (ER) is curative treatment option for early gastric cancer (EGC). Additional surgery is required when the tumor pathology is beyond ER indication. It is unclear whether tumor size can be correlated with indications for surgery after ER. Therefore, we aimed to access the role of tumor size for surgical decision making after ER. We reviewed clinicopathological data from 3246 patients underwent gastrectomy for EGC. The patients were classified into three groups as follows: the ulcer-negative intramucosal cancer with undifferentiated histology, ulcerative intramucosal cancer with differentiated histology, and minute submucosal (SM1) cancer with differentiated histology. The probability of additional surgery after ER was defined as at least one positive result for lymph node metastasis, lymphovascular invasion or perineural invasion. The probability was compared between individual tumor size and ER size criteria in each group using area under receiver operating characteristic curves. The probabilities of ulcer-negative intramucosal cancer with undifferentiated histology, SM1 cancer with differentiated histology and ulcerative intramucosal cancer with differentiated histology were 4.2, 22.1 and 2.5%. In the ulcerative intramucosal cancer with differentiated histology group, these probabilities increased when the difference in tumor size was >1mm compared with ER size criteria. The probability was not increased when there was a >10-mm tumor size difference compared with ER size criteria in the other two groups. Tumor size was correlated with ER criteria in patients with ulcerative intramucosal cancer with differentiated histology after ER but was not strictly correlated with ER criteria in the other two patient groups. However, further study may be necessary to validate our results in the future.

Poorly Differentiated Carcinoma Component in Submucosal Layer Should be Considered as an Additional Criterion for Curative Endoscopic Resection of Early Gastric Cancer.

Some studies have reported lymph node metastasis (LNM) in early gastric cancer (EGC) cases meeting the expanded criteria for endoscopic resection. Therefore, we investigated whether a minor poorly differentiated carcinoma (PDC) component in the submucosal (SM) layer affects LNM in differentiated EGC. We performed surgery in 1096 patients with differentiated SM gastric cancer and compared the clinicopathologic features of node-positive (n = 194) and node-negative (n = 902) differentiated SM cancer, with special reference to the portion of PDC component in the SM layer. When we categorized patients by the proportion of PDC component in the SM layer, we found 840 patients had <5 % and 256 patients had ≥5 % PDC components in the SM layer. The ≥5 % group was significantly associated with younger age, female sex, moderate differentiation, deep SM invasion, lymphovascular invasion (LVI), perineural invasion, and LNM. In multivariate analysis, middle third location, moderate differentiation, SM2 invasion, size >2 cm, LVI, and PDC components in the SM layer were independent risk factors for LNM. When we limited the depth of invasion to SM1, the incidence of LNM was significantly higher in the ≥5 % group. On multivariate analysis, tumor size >2 cm, moderate differentiation, LVI positivity, and ≥5 % PDC components in the SM1 layer were independent risk factors for LNM in SM1 cancer. The PDC component in the SM layer of differentiated EGC was an independent risk factor of LNM, which might constitute a supplementary criterion in the expanded indications for endoscopic resection in differentiated EGC.