Comparison of endoscopic therapies for rectal neuroendocrine tumors: endoscopic submucosal dissection with myectomy versus endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been a valuable treatment of choice for rectal neuroendocrine tumors (NETs). However, the vertical margin may remain positive after ESD because the neuroendocrine tumors develop in a submucosal tumor (SMT)-like way. Endoscopic submucosal dissection with myectomy (ESD-ME), a new method for rectal NETs, may overcome this problem. METHODS: From August 2013 to August 2020, the medical records of 69 patients (72 rectal neuroendocrine tumors) who received endoscopic submucosal dissection (ESD) or endoscopic submucosal dissection with myectomy (ESD-ME) for rectal NETs were investigated retrospectively. The characteristics of the patients and tumors, the rate of complete resection, and the rate of complications were analyzed retrospectively. RESULTS: The ESD-ME group contained 27 patients (12 males, 15 females; age range 29-72 years) and the ESD group contained 42 patients (21 males, 21 females; age range 29-71 years). Both groups had similar mean rectal neuroendocrine tumor diameters (ESD-ME 6.1 ± 1.8 mm, ESD 6.7 ± 2.6 mm; P = 0.219). The procedure time was not different significantly between groups (ESD-ME 21.1 ± 6.3, ESD 19.3 ± 3.1; P = 0.115). The endoscopic complete resection rate did not differ significantly between the ESD-ME and ESD groups (100% for each). The histological complete resection rate was 100% (27 of 27) in the ESD-ME group and 81.0% (34 of 42) in the ESD group (P = 0.043). Delayed bleeding occurred in 1 ESD-ME patient (3.7%) and in 2 ESD patients (4.8%) (P = 1.000). Perforation occurred in 1 ESD-ME patient (3.7%) and the patient was successfully managed by conservative measure, and there was no perforation after ESD (P = 0.391). CONCLUSIONS: When compared with ESD, ESD-ME resulted in a higher histological complete resection rate, had a similar complication rate, and took similar time to perform. ESD-ME can be considered an effective and safe resection method for rectal NETs < 16 mm in diameter without metastasis.

Serum interleukin-33 levels in patients with gastric cancer.

BACKGROUND: Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines, and it is closely related to IL-18, one of the best characterized members of the IL-1 family. It's been demonstrated that elevated levels of IL-18 are involved in a wide variety of tumors, especially in gastric cancer. AIMS: The purpose of this study was to determine the correlations between serum IL-33 levels and the clinicopathologic features in gastric cancer patients. METHODS: Serum samples were collected from 68 patients with gastric cancer and 57 controls. Serum IL-33 levels were measured by ELISA. Classical tumor markers of CEA and CA19-9 levels were routinely detected by chemiluminescence immunoassay. Western blot analysis was used to detect IL-33 expression in gastric cancer tissue samples and cell lines. The relationship between serum levels of IL-33 and clinical characteristics in patients was analyzed. RESULTS: IL-33 levels in the serum of gastric cancer patients were significantly elevated in comparison with that of healthy volunteers. Furthermore, higher serum levels of IL-33 in gastric cancer patients were found to correlate with several poor prognostic factors like depth of invasion, distant metastasis and advanced stage (stage III/IV). On the other hand, serum IL-33 levels did not correlate with CEA and CA19-9. The expression of IL-33 protein was upregulated in carcinoma tissues in comparison with matched normal tissues, and no statistically significant difference was found between the four gastric cancer cell lines and human gastric epithelial cell line GES-1. CONCLUSIONS: Serum IL-33 may be a useful biomarker for predicting the prognosis of gastric cancer.

Epigenetic inactivation and tumor suppressor activity of HAI-2/SPINT2 in gastric cancer.

Hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2) encodes Kunitz-type protease inhibitor that regulates HGF activity. Inspection of the human HAI-2/SPINT2 locus uncovered a large and dense CpG island within the 5' region of this gene. Analysis of cultured human gastric tumor lines indicated that HAI-2/SPINT2 expression is either undetectable or in low abundance in several lines; however, enhanced gene expression was measured in cells cultured on the DNA demethylating agent 5-aza-2'-deoxycytidine. Bisulfite DNA sequencing confirmed the densely methylated HAI-2/SPINT2 promoter region. Forced expression of HAI-2/SPINT2 induced cell apoptosis, suppressed anchorage independent growth in vitro and tumor growth in vivo. We investigated HAI-2/SPINT2 aberrant methylation in patients with gastric cancer. The HAI-2/SPINT2 methylation was found preferentially in cancerous tissues (30 of 40, 75%) compared with nontumor tissues (no methylation was detected), indicating that this aberrant characteristic is common in gastric malignancies. In conclusion, epigenetic inactivation of HAI-2/SPINT2 is a common event contributing to gastric carcinogenesis and may be a potential biomarker for gastric cancer.

Upregulation and CpG island hypomethylation of the TRF2 gene in human gastric cancer.

The telomere-binding protein TRF2 regulates both telomere protection and telomere length. The fact that TRF2 is up-regulated in some tumors indicates that TRF2 plays a role in cancer. However, the role of TRF2 in gastric cancer has not been fully understood. The aim of this study is to evaluate the expression pattern of TRF2 in gastric cancer and examine the potential mechanism of TRF2 regulation. Our study revealed that the expression of TRF2 analyzed by immunohistochemistry was significantly higher in gastric cancers compared to noncancerous tissues. Moreover, TRF2 methylation was detected in six of 30 (20%) primary gastric cancers and 18 of 30 (60%) paired normal tissues, and the downregulation of TRF2 was strongly correlated with the methylation status (P < 0.001). Our results suggest that hypomethylation might contribute to the upregulation of TRF2 in gastric cancers and this overexpression may play a role in the pathogenesis of gastric cancers.

Frequent promoter hypermethylation and transcriptional downregulation of BTG4 gene in gastric cancer.

The BTG4 gene belongs to the BTG family of genes endowed with antiproliferative properties. In this study, we have found that BTG4 undergoes promoter CpG island hypermethylation-associated inactivation in gastric cancer and 5'-aza-2'-deoxycytidine (DAC) treatment restores BTG4 expression. We also found BTG4 levels were significantly reduced in primary gastric cancer but not in normal gastric tissues. BTG4 reexpression in gastric cancer causes growth inhibition of colony assays and nude mice. Taken together, our data support BTG4 as a candidate tumor suppressor gene that is epigenetically silenced in the majority of gastric cancers.