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.

Ruxolitinib Alleviates Inflammation, Apoptosis, and Intestinal Barrier Leakage in Ulcerative Colitis via STAT3.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa with increasing prevalence and limited management. Ruxolitinib is a new anti- JAK/STAT3 biologic agent that has shown potential in protecting against colitis. METHODS: We first constructed an in vivo UC model and an in vitro colonic epithelial cell inflammation model. Ruxolitinib was administered via gavage in mice. After treatment, colon tissues, cells, and cell lysates were collected and prepared for histological evaluation, immunohistochemistry, immunofluorescence staining, quantitative reverse-transcriptase polymerase chain reaction, Western blotting, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining, and cytokine analysis. STAT3 expression was silenced and overexpressed via small interfering RNA and overexpression plasmid transfection, respectively, and quantitative reverse-transcriptase polymerase chain reaction was used to examine the downstream effects. RESULTS: Ruxolitinib administration significantly alleviated colitis both in vivo and in vitro, as manifested by reduced body weight loss, shortened colon lengths, relieved disease activity (measured by the disease activity index), and prolonged survival. A mechanistic study showed that ruxolitinib attenuated nuclear factor kappa B-induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage, and thereby reduced colitis activity in vivo. STAT3 knockdown partially reversed the protective effect of ruxolitinib against colitis, while STAT3 overexpression exaggerated the reductions in proinflammatory cytokine levels upon ruxolitinib treatment. CONCLUSIONS: We demonstrate that ruxolitinib alleviates colitis by inhibiting nuclear factor kappa B-related inflammation and apoptosis in addition to restoring epithelial barrier function via STAT3, providing a new strategy for UC treatment.

We studied the effect and mechanism of ruxolitinib on ulcerative colitis. We discovered that ruxolitinib administration significantly alleviated murine colitis by relieving disease activity and prolonged survival through intestinal epithelial cell nuclear factor kappa B­induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage via STAT3.

The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis.

BACKGROUND: Cervical cancer is the second deadliest gynecologic malignancy, characterized by apparently precancerous lesions and cervical intraepithelial neoplasia (CIN), and having a long course from the development of CIN to cervical cancer. Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a well-documented tumor suppressor gene and is commonly methylated in cervical cancer. However, the relationship between methylated CDKN2A and carcinogenesis in cervical cancer is inconsistent, and the diagnostic accuracy of methylated CDKN2A is underinvestigated. In this study, we attempted to quantify the association between CDKN2A methylation and the carcinogenesis of cervical cancer, and its diagnostic power. METHODS: We systematically reviewed four electronic databases and identified 26 studies involving 1,490 cervical cancers, 1,291 CINs, and 964 controls. A pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was calculated to evaluate the association between methylated CDKN2A and the carcinogenesis of cervical cancer. Specificity, sensitivity, the area under the receiver operating characteristic curve, and the diagnostic odds ratio were computed to assess the effect of methylated CDKN2A in the diagnosis of cervical cancer. RESULTS: Our results indicated an upward trend in the methylation frequency of CDKN2A in the carcinogenesis of cervical cancer (cancer vs control: OR =23.67, 95% CI =15.54-36.06; cancer vs CIN: OR =2.53, 95% CI =1.79-3.5; CIN vs control: OR =9.68, 95% CI =5.82-16.02). The specificity, sensitivity, area under the receiver operating characteristic curve, and diagnostic odds ratio were 0.99 (95% CI: 0.97-0.99), 0.36 (95% CI: 0.28-0.45), 0.93 (95% CI: 0.91-0.95), and 43 (95% CI: 19-98), respectively. CONCLUSION: Our findings indicate that abnormal CDKN2A methylation may be strongly correlated with the pathogenesis of cervical cancer. Our results also demonstrate that CDKN2A methylation might serve as an early detector of cervical cancer. These findings require further confirmation.