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AimsAccurate histopathological evaluation of the endoscopic submucosal dissection (ESD) specimens is essential for clinicians to guide further triage and management. This study aimed to report a novel processing technique for large ESD (≥4 cm) specimens.Methods92 patients with colorectal neoplasms who had undergone ESD were included. 46 ESD specimens were treated with conventional handling process, while the rest 46 cases were given the optimised method. Macrobiocassettes and L-shaped embedding moulds were applied in the optimised method. We evaluated the efficacy of this improved procedure in terms of the number of paraffin blocks, storage space and time consumption of pathological assessment.ResultsThe average diameter of ESD specimens was 4.5±0.4 cm and 4.7±0.5 cm in the control and test group (p=0.023), respectively. In control group, 398 paraffin blocks of 46 cases were obtained. With the same cases number and larger lesion size, only 276 blocks were achieved in test group (p<0.001). As for the storage space, the total volume of paraffin blocks and slides (4554.0 cm3and 1207.5 cm3) of optimised method was significantly reduced compared with the control group (6208.8 cm3and 1741.3 cm3) (p=0.001, p<0.001). In addition, the optimised method was superior to the conventional one in shortening time consumption of pathological assessment (164.5 min and 269.0 min, p<0.001).ConclusionsThe optimised technique not only reduced the workload and storage space, but also facilitated accurate pathological assessment.

Background: pT1b esophageal squamous cell carcinoma (ESCC) patients treated by endoscopic resection (ER) required additional treatment with surgical resection (SR) or chemoradiotherapy (CRT) according to 2020 Japan Gastroenterological Endoscopy Society (JGES) guideline. Given the evidences for this recommendation were largely based on small-size studies, our study collected 166 cases of ER-treated pT1b patients in order to investigate the efficacy of additional SR as compared to ER-alone treatment. Methods: A multi-institutional retrospective study in China was conducted. The pT1b ESCC treated by ER + SR (n= 42) and ER-alone (n= 124) from 2007 to 2018 were recruited. Meanwhile, patients with positive lymphovascular invasion (LVI(+)) and/or with positive vertical margin (VM(+)) were put into high-risk group, and those with both VM(−) and LVI(−) were selected into low-risk group. The clinicopathological parameters, lymph node metastasis (LNM), and survival between ER + SR and ER-alone groups were analyzed. Results: In high-risk group, concurrent LNM revealed in surgically resected specimens accounted for 52.6% cases in ER + SR group. After surgical removal, the incidence of post-resection LNM dropped down to 5.6%. However, in low-risk group, patients with ER + SR treatment did not exhibit any concurrent LNM in surgically resected specimens, and the incidence of their overall LNM was similar to that in ER-alone group (0% vs. 2.8%, p= 1.000). More importantly, these cases demonstrated significantly shorter overall survival (OS) than that in ER-alone group (81.8% and 100.0%, respectively, at 3 years; log-Rank: P= 0.010). Conclusions: For ER-treated pT1b patients in high-risk group, additional SR is strongly recommended. However, for those in low-risk group, additional SR does not generate much benefit for clearance of LNM, but brings harm to shorten their OS. Therefore, additional SR is not recommended for ER-treated pT1b patient in low-risk group.

Chemoradiation and targeted therapies are the major treatments for colorectal cancer (CRC); however, molecular properties associated with therapy resistance are incompletely characterized. Here, we profile the proteome of 254 tumor tissues from patients with CRC undergoing chemotherapy, chemoradiation, or chemotherapy combined with targeted therapy. Proteome-based classification reveals four subtypes featured with distinct biological and therapeutic characteristics. The integrative analysis of CRC cell lines and clinical samples indicates that immune regulation is significantly associated with drug sensitivity. HSF1 can increase DNA damage repair and cell cycle, thus inducing resistance to radiation, while high expression of HDAC6 is negatively associated with response of cetuximab. Furthermore, we develop prognostic models with high accuracy to predict the therapeutic response, further validated by parallel reaction monitoring (PRM) assay in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemoradiation and targeted therapy in CRC.

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 16–84 years) 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.

Imatinib mesylate resistance occurs in some patients with gastrointestinal stromal tumors (GISTs) during the course of treatment. In this study, we investigated the relationship between microRNAs (miRNAs) and imatinib-resistant GISTs, and the effect of miR-518a-5p on PIK3C2A in imatinib-resistant GISTs. A total of 20 matched-pair GIST samples from imatinib-resistant patients were included in the study. Each of the paired tumor specimens were from the same patient who had surgical removal of GISTs preimatinib and postimatinib treatment. Seven pairs of tissues were resected for microarray analysis, and the remaining 13 pairs were utilized for miRNAs analysis. Target genes were selected based on bioinformatics from multiple biological databases. Luciferase reporter assays were used to confirm the binding of miR-518a-5p to PIK3C2A 3′UTR. GIST882R-NC, 882R-miR-518a-5p-OE, and 882R-miR-518a-5p-KD cell lines were constructed using lentiviral vectors. miR-518a-5p and PIK3C2A expression in 882R-NC, 882R-OE, and 882R-KD cells was assessed by real-time PCR and western blotting. A cell counting kit was used to detect the influence of miR-518a-5p to cell proliferation. TUNEL staining was applied to detect the influence of miR-518a-5p to cell apoptosis. Microarray analysis showed that miR-518a-5p was downregulated in imatinib-resistant GISTs, and the expression of miR-518a-5p was confirmed with good concordance between real-time PCR and miRNA microarray results. Luciferase reporter assays indicated that miR-518a-5p bound to the PIK3C2A 3′UTR. Compared with 882R-OE, PIK3C2A expression was significantly increased in 882R-KD cells. MiR-518a-5p reduced 882R proliferation and promoted 882R apoptosis. In conclusion, PIK3C2A is a gene-specific target of miR-518a-5p in imatinib mesylate-resistant GISTs. Low expression of miR-518a-5p is likely to upregulate PIK3C2A and affect the cellular response to the drug, causing resistance to imatinib in GISTs.

Imatinib mesylate resistance occurs in some patients with gastrointestinal stromal tumors (GISTs) during the course of treatment. In this study, we investigated the relationship between microRNAs (miRNAs) and imatinib-resistant GISTs, and the effect of miR-518a-5p on PIK3C2A in imatinib-resistant GISTs. A total of 20 matched-pair GIST samples from imatinib-resistant patients were included in the study. Each of the paired tumor specimens were from the same patient who had surgical removal of GISTs preimatinib and postimatinib treatment. Seven pairs of tissues were resected for microarray analysis, and the remaining 13 pairs were utilized for miRNAs analysis. Target genes were selected based on bioinformatics from multiple biological databases. Luciferase reporter assays were used to confirm the binding of miR-518a-5p to PIK3C2A 3′UTR. GIST882R-NC, 882R-miR-518a-5p-OE, and 882R-miR-518a-5p-KD cell lines were constructed using lentiviral vectors. miR-518a-5p and PIK3C2A expression in 882R-NC, 882R-OE, and 882R-KD cells was assessed by real-time PCR and western blotting. A cell counting kit was used to detect the influence of miR-518a-5p to cell proliferation. TUNEL staining was applied to detect the influence of miR-518a-5p to cell apoptosis. Microarray analysis showed that miR-518a-5p was downregulated in imatinib-resistant GISTs, and the expression of miR-518a-5p was confirmed with good concordance between real-time PCR and miRNA microarray results. Luciferase reporter assays indicated that miR-518a-5p bound to the PIK3C2A 3′UTR. Compared with 882R-OE, PIK3C2A expression was significantly increased in 882R-KD cells. MiR-518a-5p reduced 882R proliferation and promoted 882R apoptosis. In conclusion, PIK3C2A is a gene-specific target of miR-518a-5p in imatinib mesylate-resistant GISTs. Low expression of miR-518a-5p is likely to upregulate PIK3C2A and affect the cellular response to the drug, causing resistance to imatinib in GISTs.