Total hysterectomy versus radical hysterectomy in neuroendocrine cervical cancer: a SEER-database analysis.

PURPOSE: We conducted this study to evaluate the efficacy of total hysterectomy versus radical hysterectomy in the treatment of neuroendocrine cervical cancer (NECC). METHODS: Eligible NECC patients were identified from the Surveillance, Epidemiology and End Results (SEER) database. Demographic characteristics, clinical treatment and survival of the patients were collected. The overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan-Meier analysis with log-rank test. RESULTS: A total of 286 patients were included, with 104 patients undergoing total hysterectomy and 182 patients undergoing radical hysterectomy. The 5-year OS were 50.8% in the total hysterectomy group and 47.5% in the radical hysterectomy group (p = 0.450); and the corresponding 5-year CSS were 51.6% and 49.1% (p = 0.494), respectively. Along with surgery, radiotherapy was given to 49.0% of patients in the total hysterectomy group and 50.5% in the radical hysterectomy group; and chemotherapy was administered to 77.9% of patients in the total hysterectomy group and 85.7% in the radical hysterectomy group. Unexpectedly, in patients who received adjuvant radiotherapy with or without chemotherapy, the OS was superior in the total hysterectomy group compared with the radical hysterectomy group (p = 0.034). While in patients who received chemotherapy alone and those who received neither radiotherapy nor chemotherapy, the OS still remained comparable between the total hysterectomy and radical hysterectomy group. CONCLUSION: Compared with radical hysterectomy, total hysterectomy was not associated with compromised survival prognosis in patients with NECC. Total hysterectomy has the potential to be a surgical alternative in the multimodal management of NECC.

Identification of an immune-based mRNA-lncRNA signature for overall survival in cervical squamous cell carcinoma.

Aim: To better predict the survival of cervical squamous cell carcinoma (CESC) patients, we aimed to construct a signature according to different immune infiltration. Methods: We downloaded the RNA sequences of CESC patients from the Cancer Genome Atlas database. By using single-sample gene set enrichment analysis, we separated the samples into high- and low-immunity groups. Then we separated the samples into training and testing datasets and performed the following analyses: univariate, least absolute shrinkage and selection operator analysis, multivariate Cox regression analyses and weighted gene coexpression network analysis using R software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes studies were performed using the Database for Annotation, Visualization and Integrated Discovery website. Results & conclusion: We finally identified a signature with three mRNAs and two lncRNAs: ADGRG5, HSH2D, ZMAT4, RBAKDN and LINC00200. In short, our study constructed an mRNA-lncRNA signature related to immune infiltration to better predict the survival of CESC patients.

Lay abstract Cervical squamous cell carcinoma is a prevalent cancer type among females. Our study was to construct a signature which can predict the overall survival time in cervical squamous cell carcinoma patients. We performed some analysis of genetic expression patterns using a public database of genetic data, and successfully constructed the model which holds a good prediction value.

Rare case of tonsillar and subcutaneous metastasis from neuroendocrine cervical cancer.

Neuroendocrine cervical carcinoma (NECC) is a rare type of cervical cancer, with high tendency of lymphatic and distant metastasis and poor prognosis. Herein, we reported a rare case of relapsed NECC metastasizing to palatine tonsil and subcutaneous adipose tissue in multiple regions, which reflects the aggressive biological behavior of NECC.

Cisplatin-induced immune modulation in ovarian cancer mouse models with distinct inflammation profiles.

The backbone of ovarian cancer treatment is platinum-based chemotherapy and aggressive surgical debulking. New therapeutic approaches using immunotherapy via immune checkpoint blockade, which have demonstrated clinical efficacy in other tumor types, have been less promising in ovarian cancer. To increase their clinical efficacy, checkpoint inhibitors are now being tested in clinical trials in combination with chemotherapy. Here, we evaluated the impact of cisplatin on tumor immunogenicity and its in vivo roles when used alone or in combination with anti-PD-L1, in two novel murine ovarian cancer cell models. The 2F8 and its platinum-resistant derivative 2F8cis model, display distinct inflammatory profiles and chemotherapy sensitivities, and mirror the primary and recurrent human disease, respectively. Acute and chronic exposure to cisplatin enhances tumor immunogenicity by increasing calreticulin, MHC class I, antigen presentation and T-cell infiltration. Cisplatin also upregulates PD-L1 expression in vitro and in vivo, demonstrating a dual, paradoxical immune modulatory effect and supporting the rationale for combination with immune checkpoint blockade. One of the pathways activated by cisplatin treatment is the cGAS/STING pathway. Chronic cisplatin treatment led to upregulation of cGAS and STING proteins in 2F8cis compared to parental 2F8 cells, while acute exposure to cisplatin further increases cGAS and STING levels in both 2F8 and 2F8cis cells. Overexpression of cGAS/STING modifies tumor immunogenicity by upregulating PD-L1, MHC I and calreticulin in tumor cells. Anti-PD-L1 alone in a platinum-sensitive model or with cisplatin in a platinum-resistant model increases survival. These studies have high translational potential in ovarian cancer.

Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain.

PURPOSE: Recent studies have shown that abnormal distribution of pelvic nerves contributes to endometriosis-associated pain. However, the relationship between neurogenesis and pain severity in endometriosis still remains uncertain, which makes it an enigma for both gynecologists as well as neuropathologists. In this study, we tried to explore a special phenomenon, perineural invasion (PNI), in deep infiltrating endometriosis (DIE) and investigated the correlation between PNI- and DIE-associated pain. PATIENTS AND METHODS: The study was conducted in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Sun Yat-sen University from June 2012 to January 2015. In total, 64 patients with DIE were enrolled. They received laparoscopically surgical resection of endometriotic lesions. The Kruskal-Wallis and Mann-Whitney tests were used for comparisons of enumeration data. Spearman rank correlation was used for linear analysis. RESULTS: Immunohistochemical analysis demonstrated that PNI was commonly found in DIE lesions. Patients were divided into PNI (+) group and PNI (-) group. The visual analog scale scores of dysmenorrhea, dyspareunia, and chronic pelvic pain were higher in PNI (+) group than in PNI (-) group. Also, we found significantly increased density of newly formed nerve fibers as well as microvessels in lesions of PNI (+) group. Further, double immunofluorescence showed a closely spatial nerve-vessel network in the endometriotic lesion of PNI (+) group. More importantly, correlation analysis revealed positive relation between the density of newly formed nerve fibers in the lesion and the density of microvessels in lesions of PNI (+) group. CONCLUSION: This study suggests that PNI in endometriotic lesions plays an important role in endometriosis-associated pain, mainly through a mechanism named "neuroangiogenesis".