Fecal calprotectin showed a significant correlation with the intestinal inflammation evaluated with BAE even in patients with only small intestinal disease. FC is useful for the evaluation of CD including both the small and large intestines.

Background and aimsThe recent advancement of next-generation sequencing (NGS) has enabled the identification of cancerrelated somatic aberrations in advanced gastric cancer. However, these remain unclear in early gastric cancers, especially in intramucosal gastric cancers. Patients and methods Thirty-one well-differentiated (tub1) intramucosal gastric cancers obtained by endoscopic submucosal dissection (ESD) from 29 patients were analyzed. After precise collection of tumors and non-tumors from formalin-fixed paraffin-embedded tissues using laser-captured microdissection (LCM), target sequencing analysis of 50 cancer-related genes was performed using an Ion-Proton sequencer. Results The most frequent hotspot mutation was found in TP53 (17 lesions, 54.8%) followed by the Wnt-signaling pathway genes, APC and CTNNB1 (6 lesions, 19.4%). The mutations in TP53 and the Wnt-signaling genes were mutually exclusive (p = 0.004). There was a tendency that H. pylori infection (p = 0.082) and macroscopic protrusion (p = 0.095) was associated with the presence of these mutations. Only 10 lesions (59%) among 17 lesions with proven TP53 mutations were positive for p53 immunostaining demonstrating the superiority of the mutational analysis. In addition, focal gene amplification of ERBB2 (16%) was found frequently in these early stage lesions. Conclusions Using LCM and NGS, mutations in TP53 and the Wnt-signaling pathway were frequently found and were mutually exclusive in the earliest stage of gastric carcinogenesis.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

We undertook the statistical analysis on the three categories. Surprisingly, no tumor derived parameter contributed to the overall survival. Background liver disease-derived parameter rather than tumor-derived parameter was found to define the prognosis of patients with advanced HCC treated by sorafenib.

Background and Aim Although high expression of Dickkopf‐4 (DKK‐4) in colorectal cancer has been reported in previous studies, its impact on clinicopathological features, including the prognosis and mechanism of expression, has not been well clarified to date. Methods (i) DKK‐4 protein expression was analyzed by immunohistochemical staining with anti‐DKK‐4 antibody using archived formalin‐fixed paraffin‐embedded specimens obtained at surgery from 122 patients with colorectal cancer, and its association with clinicopathological findings was also investigated. (ii) The association between intratumoral DKK‐4 protein expression and somatic hotspot mutations in cancer‐associated genes in 40 patients was investigated using a next‐generation sequencer. Results In cross‐section, DKK‐4 protein expression in colorectal tissue was related to an adenocarcinoma of a histologically differentiated type (tub1/tub2, P = 0.032) and distant metastasis (P = 0.012). Longitudinally, however, DKK‐4 was not an independent prognostic factor determining overall survival (OS). On the other hand, in patients with metastasis, high DKK‐4 protein was independently associated with short OS (P = 0.013). In addition, colorectal cancer tissue with high DKK‐4 protein expression was associated with hotspot mutations in Wnt/β catenin‐signaling molecules (APC, CTNNB1, and FBXW7, P = 0.03). Conclusion Intratumoral DKK‐4 expression, by partly reflecting the Wnt/β catenin pathway, is strongly associated with the advancement of colorectal cancer and OS in colorectal cancer patients with metastasis, although further studies are needed.

Background and AimsNext generation sequencing (NGS) has revealed a great deal about cancer-related somatic changes in esophageal squamous cell neoplasia; however, the changes in the very early stages remain unclear.ResultsTP53 (87%) and CDKN2A (20%) hot spot mutations were frequently found in early lesions. TP53 was the most common mutation (LGIN/HGIN, 86%; EP, 83%; LPM, 95%; MM/SM1, 80%), followed by CDKN2A (29%, 28%, 16% and 10%, respectively); the frequency of other mutations increased as the disease advanced (p < 0.01). Copy number variation analysis revealed copy number aberrations in multiple genes, including PIK3CA amplification (48%). NGS was superior to p53 immunostaining for detecting TP53 mutations (74% vs. 87%); in combination, the two tests improved detectability to 94%. Clinically, smoking was associated with the occurrence of TP53 mutations in these early lesions (p = 0.049).Materials and MethodsFifty-four early esophageal neoplasia lesions from 47 patients treated by endoscopic resection (low-grade intraepithelial neoplasia [LGIN], n = 1; high-grade intraepithelial neoplasia [HGIN] n = 7; invasion limited to epithelium [EP/M1], n = 18; lamina propria mucosae [LPM/M2], n = 19; muscularis mucosae [MM/M3], n = 8; and upper third of the SM [SM1], n = 2) were isolated from formalin-fixed paraffin-embedded tissue specimens by laser-capture microdissection. Target sequencing of 50 cancer-related genes was performed with an Ion Proton sequencer; their association with the clinical characteristics was investigated.ConclusionsMutations of TP53 and CDKN2A, and PIK3CA amplification were common in early esophageal squamous neoplasia, while other mutations accumulated with disease progression. An understanding of these molecular events might provide a molecular basis for early lesion treatment.

Background and Aim Genetic indicators of endoscopic resection for colorectal carcinoma remain inconclusive. This study analyzed genetic changes in early colorectal tumors that could inform decisions for endoscopic procedures. Methods A total of 83 colorectal tumors from 81 patients, including adenoma (n = 7), Tis–T1a (n = 22), T1b (n = 14), and advanced carcinoma (n = 40), were analyzed. Tis tumors (n = 16) and some T1 carcinomas (n = 11) were analyzed as mixed adenomas and carcinomas. Lesions were laser‐capture microdissected for DNA extraction, and targeted sequencing of 50 cancer‐related genes was performed. Genetic data were then correlated with clinical records, including magnifying endoscopic findings. Results Numbers of gene alteration rates in TP53 and SMAD4 increased with tumor progression from adenoma to carcinoma. Frequencies of mutant variants in TP53 (P = 0.004) and rates of copy number loss in SMAD4 (P = 0.006) increased in carcinoma components of mixed tumors compared to adenoma components. Moreover, adenoma components of T1b carcinomas had higher TP53 mutation rates than Tis or T1a carcinomas (P = 0.011) and pure adenomas (P = 0.026). Gene alterations in TP53 (P = 0.0055) and SMAD4 (P = 0.0055) increased in cases with irregular surface patterns of magnifying endoscopic findings. Conclusions Numbers of copy number variations and TP53 and SMAD4 alterations were related to colorectal tumor progression. TP53 alteration rates in adenoma components were high in T1b carcinomas, warranting complete treatment with en bloc resection. Magnifying endoscopic findings might reflect the genetic status of colorectal tumors.

Background and Aim There are no globally approved, distinguishing criteria enabling the classification of gastric adenomas and intramucosal carcinomas for differential diagnosis of noninvasive neoplasia (NIN). Methods Next‐generation sequencing of 50 cancer‐related genes was undertaken on 68 pathologically diagnosed microdissected gastric neoplasms (25 adenomas, 27 intramucosal carcinomas, and 16 submucosal carcinomas) obtained during endoscopic submucosal dissection. Findings from magnifying endoscopy with narrow‐band imaging (M‐NBI) of 52 NINs (the 25 adenomas and 27 intramucosal carcinomas) were compared with these data. Results Among all 68 neoplasms, the most frequently mutated genes were APC (76% in adenoma, 11.1% in intramucosal carcinoma, and 0% in submucosal carcinoma; P < 0.001) and TP53 in intramucosal and submucosal carcinomas (8% in adenoma, 48.1% in intramucosal carcinoma, and 75% in submucosal carcinoma; P < 0.001). Dividing the NIN neoplasms into five groups according to their mutational status (A1: APC mutation, A2: APC + α mutation, B: APC + TP53 mutation, C: TP53 mutation, D: no mutation in either APC or TP53) resulted in almost identical diagnoses by pathology and M‐NBI for groups A1 (12/13, 92%), C (12/13, 92%), and D (16/17, 94%) but not for groups A2 (3/7, 43%) or B (0/2, 0%). This finding implies that NINs with the APC + α mutation have carcinoma‐like endoscopic features despite most being judged as adenomas by pathology. Conclusion A diagnosis of NINs by pathology or M‐NBI in the subset of gastric tumors classified by cancer‐related mutations is not completely identical, suggesting the possible additional role of M‐NBI in diagnosing NINs. Further studies are needed to confirm this.

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