Carbohydrate Antigen 19-9 Is an Invasive Malignancy Preoperative Prognostic Factor for Intraductal Papillary Mucinous Neoplasms

<b><i>Introduction:</i></b> This study aimed to determine the preoperative clinicophysiological and postoperative clinicopathological predictors of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN). <b><i>Methods:</i></b> This was a retrospective observational study. We included 121 patients (73 men and 48 women; mean age: 68.7 years) who had undergone pancreatic resection for IPMN between 2007 and 2018. These patients were grouped into invasive carcinoma (IPMN-INV, <i>N</i> = 21) and low/high-grade IPMN (IPMN-LG/HG, <i>N</i> = 100) groups. Univariate and multivariate analyses of clinicophysiological parameters were carried out. These parameters were also compared between the IPMN-INV/HG (<i>N</i> = 53) and IPMN-LG (<i>N</i> = 68) groups. Survival analyses according to macroscopic type and IPMN subtypes were performed. <b><i>Results:</i></b> On univariate analysis, age (<i>p</i> = 0.038), carbohydrate antigen (CA) 19-9 (<i>p</i> &#x3c; 0.001), IPMN macroscopic type (<i>p</i> = 0.001), IPMN subtype (<i>p</i> &#x3c; 0.001), pancreatic duct diameter (<i>p</i> &#x3c; 0.001), and mural nodule (<i>p</i> = 0.042), between IPMN-INV and IPMN-LG/HG were found to be significant prognostic factors of malignancy. CA 19-9 was found to be an independent prognostic factor of IPMN malignancy on multivariate analysis (<i>p</i> = 0.035). The 1-, 3-, and 5-year overall survival (OS) rates of the IPMN-INV and IPMN-LG/HG groups were 94.4/100%, 94.4/100%, and 67.2/100%, respectively. The OS rate in the IPMN-LG/HG group was significantly higher than that in the IPMN-INV group (<i>p</i> &#x3c; 0.001). On univariate analysis, platelet (<i>p</i> = 0.043), CA 19-9 (<i>p</i> = 0.039), prognostic nutritional index (<i>p</i> = 0.034), platelet/lymphocyte ratio (<i>p</i> = 0.01), IPMN macroscopic type (<i>p</i> &#x3c; 0.001), IPMN subtype (<i>p</i> &#x3c; 0.001), pancreatic duct diameter (<i>p</i> = 0.036), and mural nodule (<i>p</i> = 0.032) between IPMN-INV/HG and IPMN-LG were found to be significant prognostic factors of malignancy. On multivariate analysis, CA 19-9 was found to be an independent prognostic factor (<i>p</i> = 0.042) between IPMN-INV/HG and IPMN-LG of malignancy. The 1-, 3-, and 5-year OS rates of the IPMN-INV/HG and IPMN-LG groups were 97.9/100%, 97.9/100%, and 82.6/100%, respectively. The OS rate was significantly higher in the IPMN-LG group than in the IPMN-INV/HG group (<i>p</i> = 0.03). No significant differences in survival were observed in patients with macroscopic tumors (<i>p</i>= 0.544). <b><i>Conclusion:</i></b> CA 19-9 is an independent invasive malignancy predictor of IPMN.

Diagnostic Ability of Magnifying Narrow-Band Imaging for the Extent of Early Gastric Cancer: A Systematic Review and Meta-Analysis

Background. Accurate delineation of tumor margin is essential for complete resection of early gastric cancer (EGC). The objective of this study is to assess the performance of magnifying endoscopy with narrow-band imaging (ME-NBI) for the accurate demarcation of EGC margins. Methods. We searched PubMed, EMBASE, Web of Science, and Cochrane Library databases up to March 2020 to identify eligible studies. The diagnostic accuracy of ME-NBI for EGC margins was calculated, and subgroup analyses were performed based on tumor size, depth of tumor invasion, tumor-occupied site, macroscopic type, histological type, Helicobacter pylori (H. pylori), and endoscopists’ experience. Besides, we also evaluated the negative and positive resection rates of the horizontal margin (HM) of EGC after endoscopic submucosal dissection (ESD) and surgery. Results. Ten studies comprising 1018 lesions were eligible in the databases. The diagnostic accuracy of ME-NBI for the demarcation of EGC margins was 92.4% (95% confidence interval (CI): 86.7%-96.8%). According to ME-NBI subgroup analyses, the rate of accurate evaluation of EGC margins was not associated with H. pylori infection status, tumor size, depth of tumor invasion, tumor-occupied site, macroscopic type, histological type, and endoscopists’ experience, and no statistical differences were found in subgroup analyses. Moreover, the negative and positive resection rates of HM after ESD and surgery were 97.4% (95% CI: 92.1%-100%) and 2.6% (95% CI: 0.02%-7.9%), respectively. Conclusions. ME-NBI enables a reliable delineation of the extent of EGC.

Clinicopathological and Prognostic Characteristics of Esophageal Spindle Cell Squamous Cell Carcinoma: An Analysis of 43 Patients in a Single Center

ObjectiveEsophageal spindle cell squamous cell carcinoma (ESCSCC) is a distinct subtype of esophageal carcinoma with unique morphologic and clinicopathologic features. This study aimed to characterize the clinicopathologic manifestations and postoperative prognostic factors of ESCSCC.MethodsIn this study, 43 ESCSCC patients who underwent esophagectomy at Sun Yat-sen University Cancer Center between January 2001 and December 2014 were identified. 200 patients with conventional squamous cell carcinoma during the same period were sampled as a control. Hematoxylin and eosin-stained slides and available data were reviewed, and pertinent clinicopathologic features were retrospectively analyzed.ResultsAmong the ESCSCC patients, the median age was 60.5 years, with a male-to-female ratio of 2.58:1. The five-year disease-free survival and cancer-specific survival rates were 51.6 and 55.5%, respectively. In the univariate analysis, drinking abuse, tumor size, macroscopic type, perineural invasion, pT, preoperative blood white blood cell count, preoperative blood neutrophil count, and preoperative blood neutrophil to lymphocyte ratio were significantly correlated with the cancer-specific survival and disease-free survival of the ESCSCC patients. The multivariate analysis showed that macroscopic type, perineural invasion, and preoperative blood neutrophil to lymphocyte ratio were independent prognostic factors for cancer-specific survival; macroscopic type, perineural invasion, tumor size, and pT were independent prognostic factors for disease-free survival. Moreover, the combined prognostic model for cancer-specific survival (including macroscopic type, perineural invasion, and preoperative blood neutrophil to lymphocyte ratio), the combined prognostic model for disease-free survival (including macroscopic type, perineural invasion, and tumor size) significantly stratified patients according to risk (low, intermediate, and high) to predict cancer-specific survival, disease-free survival, respectively. In terms of esophageal conventional squamous cell carcinoma cohort, there was no significant difference in long-term outcome when compared with ESCSCC. Though five independent prognostic variables (macroscopic type, perineural invasion, preoperative blood neutrophil to lymphocyte ratio, tumor size, and pT) were indentified in ESCSCC, univariate analysis demonstrated that perineural invasion, preoperative blood neutrophil to lymphocyte ratio were correlated with esophageal conventional squamous cell carcinoma on cancer-specific survival; whereas only perineural invasion on disease-free survival.ConclusionsThe proposed two new prognostic models might aid in risk stratification and personalized management for patients with esophageal spindle cell squamous cell carcinoma who received radical surgery.

Short-term results of a phase II study of preoperative docetaxel/cisplatin/S-1 therapy for locally advanced gastric cancer

Background A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer. Methods Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%. Results Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3–4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively. Conclusions Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.

The clinicopathological features of submucosal invasive non-ampullary duodenal carcinoma

Background Little is known about submucosal invasive non-ampullary duodenal carcinoma because of its extreme rarity, so we investigated the clinicopathological features, comparing submucosal invasive carcinoma (SM-Ca) with mucosal carcinoma (M-Ca) and advanced carcinoma (Ad-Ca). Methods We retrospectively analyzed 165 sporadic non-ampullary duodenal carcinomas (SNADCs) at 4 institutions between January 2003 and December 2018. In addition, we compared the mucin phenotype between SM-Ca and M-Ca. Results There were only 11 cases (7%) of SM-Ca, while there were 70 cases of M-Ca (42%) and 84 cases of Ad-Ca (51%). Although the distribution of M-Ca was almost equal between the oral and anal sides of the papilla of Vater, all SM-Ca was located on the oral-Vater (P = 0.013) and Ad-Ca tended to be located on the oral-Vater (P = 0.020). Mixed macroscopic type was more frequent in SM-Ca than in M-Ca (64% vs. 10%, P < 0.001). There was no significant difference in tumor diameter between M-Ca and SM-Ca, but 45% of SM-Ca were ≤ 10 mm. 73% (8/11) of SM-Ca were classified as gastric phenotype and no lesions were intestinal phenotype, whereas most M-Ca were intestinal phenotype (67%, 8/12). Conclusions SM-Ca was highly associated with tumor location (oral-Vater) and gastric mucin phenotype, different from M-Ca. The possibility of SM-Ca should be considered when superficial SNADCs are located on oral-Vater and have mixed macroscopic type even if tumor diameters are ≤ 10 mm.

Clinicopathological Characteristics and Prognosis of Upper Gastric Cancer Patients in China: A 32-Year Single-Center Retrospective Clinical Study

Purpose. Upper or proximal gastric cancer occurs in the upper third of the stomach between the cardia and a line connecting the greater and lesser curvatures. As it differs from other gastric cancers in pathology and prognosis, we evaluated patient and disease characteristics that might guide improved treatment and survival of upper gastric cancer. Methods. We conducted a retrospective analysis of 649 patients with upper gastric cancer and 1551 patients with lower gastric cancer and R0 radical surgery at our institution between January 1980 and December 2012. Results. Survival after radical surgery for upper gastric cancer was 77.8% at 1 year, 49.6% at 3 years, and 41.1% at 5 years. The corresponding rates for lower gastric cancer were 85.9%, 60.0%, and 57.2% (p<0.001). Upper gastric cancer had a poor prognosis. Sex (p=0.036), tumor diameter (p=0.001), macroscopic type (p<0.001), pTM stage (p<0.001), tissue differentiation type (p=0.003), and serosal invasion (p=0.034) were independently associated with lymph node metastasis. The macroscopic type (p=0.045), lymphovascular tumor emboli (p=0.021), and pTNM stage were independently associated with recurrence and metastasis. Survival of 333 patients with D2 total gastrectomy was 81.3% at 1 year, 54.4% at 3 years, and 45.2% at 5 years. The corresponding rates for 316 proximal gastrectomy patients were 75.4%, 44.9%, and 36.7%. Radical total gastrectomy had better survival than radical proximal resection. Conclusions. Upper gastric cancers were more aggressive, had a worse prognosis, and were more prone to recurrence and metastasis compared with lower gastric cancers. Survival was better after total gastrectomy than after proximal resection.

RA08.04: IMPORTANT ENDOSCOPIC AND HISTOPATHOLOGICAL CHARACTERISTICS FOR PREDICTING SUBMUCOSAL TUMOR INVASION IN SUPERFICIAL BARRETT ADENOCARCINOMA

Background Predicting the depth of invasion of superficial Barrett adenocarcinoma (s-BA) is important for choosing an appropriate treatment. This study aimed to evaluate the endoscopic and histopathological characteristics related to s-BA submucosal invasion. Methods We retrospectively reviewed 67 lesions in 63 cases with pathologically defined s-BA (SSBE, n = 56; LSBE, n = 7) that underwent endoscopic resection at our hospital from January 2004 to December 2017. Initial treatment included endoscopic mucosal resection (EMR) (n = 4), endoscopic submucosal dissection (ESD) (n = 99), and surgery (n = 33). We grouped 133 lesions into two groups based on depth of tumor invasion: group M comprised 87 intramucosal tumors and group SM comprised 49 submucosal tumors. We defined characteristic criteria for submucosal invasion as follows: tumor size ≥ 21 mm, complex macroscopic type; composed of > 2 macroscopic types, biopsy-por; biopsy specimens including poorly differentiated adenocarcinoma. Endoscopic ultrasound (EUS) was performed only in cases in which predicting the depth of tumor invasion was difficult. Results In group M, the median tumor diameter was 13 (range, 1–82) mm and included 68 SSBEs and 19 LSBEs. In group SM, the median tumor diameter was 23 (range, 4–55) mm and included 41 SSBEs and 8 LSBEs. Tumors larger than 21 mm were seen in 12 (13.8%) patients in group M and 25 (51.0%) in group SM. Complex macroscopic type tumors were present in 20 patients (23.0%) in group M and 30 (61.2%) in group SM. Biopsy-por was present in 2 (2.3%) in group M and 12 (24.5%) in group SM. Multivariate analysis indicated the above three characteristics as independent predictors of submucosal invasion; in particular, biopsy-por was highly significant (P < 0.001, odds ratio, 10.81). EUS was performed in 55 lesions including 28 tumors invading the submucosa. Sensitivity, specificity, positive predictive value, and negative predictive value of EUS for predicting submucosal invasion were 46.4%, 70.4%, 61.9%, and 57.5%, respectively. Conclusion Tumor size ≥ 21 mm, complex macroscopic type, and biopsy specimens including poorly differentiated adenocarcinoma were independent predictors of submucosal invasion. Specificity of EUS was relatively high for cases that were difficult to predict depth of tumor invasion. Disclosure All authors have declared no conflicts of interest.

PS02.090: WHY BARRETT’S ESOPHAGEAL ADENOCARCINOMAS WERE FOUND AS WIDE LESIONS

Background Barrett's esohageal adenocarcinoma(BEA) originated from Long-segment Barrett's esophagus(LSBE) were found to be larger lesions than BEA from Short-segment Barrett's esophagus(SSBE). In Japan, superficial BEA were found and treated by ESD. However, most of superficial BEA in Japan are originated from SSBE. We investigated about the differences between BEA from SSBE and LSBE. Methods We examined macroscopic appearance and histology for superficial BEA. And we compared with BEA between SSBE and LSBE.And then we examined imminohistochemical study using p53 for operated specimens of superficial BEA. Results The multiple lesions were presented only LSBE cases. Operations were the far more common treatment for LSBE. The ratio of lesions involving more than one-half of the lumen was significantly larger in LSBE cases. The percentage of type 0-IIb was only 3.2%(3/95) for SSBE, whereas 32.6%(15/46) for LSBE (P < 0.05). When we placed each macroscopic type into one of two groups (Elevated and Flat or depressed type), we found that elevated types accounted for 63.2%(60/95) in SSBE cases. In LSBE cases, 50.0%(23/46) were of the flat or depressed type. In SSBE, simple macroscopic types accounted for 69.5%(66/95). Whereas, in LSBE cases, 50.0%(23/46) were of complex macroscopic types (P < 0.05). The lesions with accompanied type 0- IIb accounted for 2.1%(2/95) of SSBE and 21.7%(10/46) of LSBE(P < 0.05). The more common macroscopic type of T1b invasion was type 0- IIa + IIc. p53 immunohistochemical study was done for an operated specimen. This case was operated for superficial BEA. p53 was strongly positive on adenocarcinoma. However, we could find p53 strongly positive part on other part of the specimens. There were three part of p53 positive are in this operated specimens. These parts were not defined adenocarcinoma by HE stained. Conclusion Most superficial BEA originated from SSBE could be distinguished by the elevated lesions. Whereas, in cases of LSBE, flat type lesions including the accompanied type 0- IIb and multiple lesions, operation cases, the ratios of lesions involving a large range and the complex macroscopic types were significantly higher. When we diagnose and treat superficial BEA, it is necessary to consider the differences between SSBE and LSBE, such as macroscopic types. Disclosure All authors have declared no conflicts of interest.

Gene expression profiling of Japanese gastric cancer patinets using Asian Cancer Research Group classification.

72 Background: Gastric cancer is well known as having heterogeneous features. Recently, the Asian Cancer Research Group (AGRG) had proposed a new classification scheme based on the gene expression profile of the tumor. However, the genomi/expression profiling of gastric cancer in Japanese patients is still unknown. We started a comprehensive molecular profiling study that analyzes genome and transcriptome of tumor obtained from cancer patients admitted to Shizuoka Cancer Center from 2014. We already had evaluated more than 1,500 samples from various type of cancer. Among them, 104 gastric cancer patients were analyzed. Methods: Fresh surgically resected tumor/normal samples and peripheral blood were obtained and whole-exome sequencing (Ion Proton, Life Technologies) and gene expression profiling (DNA microarray, Agilent Technologies) were performed. Patients were grouped based on the gene expression profile according to AGRG classification, and clinicopathological features were compared among the group. Results: Patients were classified into MSI in 14, MSS/EMT in 15, MSS/TP53+ in 38 and MSS/TP53- in 37, respectively. There was no significant difference of sex among the group. Age was significantly younger in MSS/EMT and MSS/TP53-. In MSI, tumor tended to be located at antrum, and differentiated type tumor was predominant. In MSS/EMT, advanced T stage (T4) and undifferentiated type of tumor was predominant. In MSS/TP53+, relatively less advanced stage and localized macroscopic type tumor was predominant. In MSS/TP53-, relatively advanced stage and invasive macroscopic type tumor was predominant. Although the follow-up period is insufficient, relapse-free survival was the worst in MSS/EMT and no patient recurred in MSI. Conclusions: Classification of gene expression profiling based on ACRG was possible in Japanese gastric cancer. Distribution and tumor characteristics were almost identical to ACRG cohort. Gene -expression profiling may be comprehensively used for tumor classification and further clinical trials of molecular targeting agents.