Survival Outcomes and Prognostic Predictors in Patients With Malignant Struma Ovarii

Background: Malignant struma ovarii (MSO) is an extremely rare ovarian malignant tumor and there is limited data on the survival outcomes and prognostic predictors of MSO. The objectives of this study were to investigate the disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) rates of patients with MSO, and also evaluate the prognostic factors in this population.Methods: A retrospective study was conducted and 194 cases of MSO were selected. DFS was assessed by the logistic regression, OS by the Kaplan–Meier method, and DSS was evaluated by the Cox regression.Results: The median age of these patients was 46.0 years; 142 cases (73.2%) were confined to the ovary and 52 cases (26.8%) had extraovarian metastasis at the initial diagnosis of MSO. During the follow-up, 75.3% of these patients showed no evidence of disease and 18.0% were alive with disease. Only 13 deaths occurred, with 10 attributed to MSO. The 5, 10, and 15-year OS rates were 91.4, 87.7, and 83.5%, respectively. The 5, 10, and 15-year DSS rates were 93.8, 90.0, and 85.7%, respectively. Logistic regression revealed that International Federation of Gynecology and Obstetrics (FIGO) stage IV was the only risk factor for DFS [p < 0.001; odds ratio (OR) 7.328; 95% CI 3.103–16.885, FIGO stage IV vs. stage I; p = 0.021; OR 4.750, 95% CI 1.264–17.856, FIGO stage IV vs. stage II-III]. The multivariate Cox regression analysis showed that poor differentiation was the only risk factor for both OS (p = 0.005, OR 6.406; 95% CI 1.730–23.717) and DSS (p = 0.001, OR 9.664; 95% CI 2.409–38.760), while age ≥45 years was the prognostic predictor for OS (p = 0.038, OR 4.959; 95% CI 1.093–22.508).Conclusion: Survival outcomes were excellent in patients with MSO, irrespective of the treatment strategy, FIGO stage IV, age ≥45 years, and poor differentiation of tumors were the independent risk factors.

Endoscopic Versus Surgical Therapy for Early Esophagogastric Junction Adenocarcinoma Based on Lymph Node Metastasis Risk: A Population-Based Analysis

BackgroundIn this study, we aimed to compare the prognosis and lymph node metastasis (LNM) risk in patients with early-stage esophagogastric junction (EGJ) adenocarcinoma after endoscopic treatment (ET) or radical surgery.MethodsWe collected data from eligible patients based on the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Logistic regression analysis was used to determine independent predictors of LNM (examination of at least 16 lymph nodes). Cox regression analysis and propensity score-matched (PSM) analysis were subsequently utilized to compare the overall survival (OS) and cancer-specific survival (CSS) of patients treated with ET or radical surgery.ResultsIn total, 3708 patients were identified. Among them, 856 patients had greater than or equal to 16 examined lymph nodes (LNs) (LNE≥16). The LNM rates were 18.8% in all patients 8.3% in T1a patients and 24.6% in T1b patients. Independent predictors of LNM were submucosal invasion, tumor size ≥3cm and decreasing differentiation (P<0.05). The LNM rate decreased to approximately 5.3% in T1b tumors with well differentiation and tumor size <3cm. However, the LNM incidence increased to 17.9% or 33.3% in T1a tumors with poor differentiation or with both tumor size≥3cm and poor differentiation. Cox regression analysis demonstrated CSS was not significantly different in early-stage EGJ adenocarcinoma patients undergoing ET and those treated with radical surgery (HR= 1.004, P=0.974), which were robustly validated after PSM analysis. Moreover, subgroup analysis stratified by T1a and T1b showed similar results.ConclusionsThe findings of this study indicated ET as an alternative to radical surgery in early EGJ adenocarcinoma.

Who Will Benefit Most From PD-L1 Detection and Immunotherapy in Non-small Cell Lung Cancer?

Background: Lung cancer is one of the most lethal cancers worldwide, but studies have shown that the higher the expression of programmed cell death protein 1 ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), the more likely it will benefit from anti-PD-L1 immunotherapy. The purpose of our study was to collect and analyze abundant clinical samples in order to provide evidence for clinicians and patients who might consider anti-PD-L1 immunotherapy while jointly formulating treatment plans.Methods: On the one hand, we obtained cases from The Cancer Genome Atlas (TCGA)database, including 498 squamous cell carcinoma of lung cancer (LUSC) patients and 515 adenocarcinoma of lung cancer (LUAD) patients. A heat map of gene expression was drawn. On the other hand, PD-L1 expression was detected in 1,008 NSCLC patients with immunohistochemistry staining (IHC), and we studied the correlation between PD-L1 expression and clinicopathological characteristics.Results: PD-L1 expression was higher in LUSC than in LUAD at the mRNA level in the TCGA database. In univariate analysis, PD-L1 expression was higher in patients who were males, were LUSC, were smokers, had a tumor diameter >3 cm, had poor differentiation, or had stage III~IV disease. In multivariate analysis, PD-L1 expression was higher in patients who were LUSC or in poor differentiation.Conclusion: PD-L1 expression was higher in patients who were LUSC or in poor differentiation. We recommend that PD-L1 detection can be mandated for patients who might be suitable candidates for immunotherapy.

Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis

Plasmodium vivax malaria is one of the most lethal infectious diseases, with 7 million infections annually. One of the roadblocks to global malaria elimination is the lack of highly sensitive, specific, and accurate diagnostic tools. The absence of diagnostic tools in particular has led to poor differentiation among parasite species, poor prognosis, and delayed treatment. The improvement necessary in diagnostic tools can be broadly grouped into two categories: technologies-driven and omics-driven progress over time. This article discusses the recent advancement in omics-based malaria for identifying the next generation biomarkers for a highly sensitive and specific assay with a rapid and antecedent prognosis of the disease. We summarize the state-of-the-art diagnostic technologies, the key challenges, opportunities, and emerging prospects of multi-omics-based sensors.

Impact of chemotherapy and radiotherapy on the survival of elderly esophageal cancer patients undergoing surgery: a SEER database analysis

Background Esophageal cancer (EC) is a common and lethal carcinoma; however, the effectiveness and feasibility of the chemo- and radio-therapy (CRT) for the elderly patients (≥ 70 years) with surgery have not been fully discussed. The purpose of this study was to investigate the potential effect of CRT on the prognosis. Methods A total of 1085 patients (534 CRT patients vs. 551 non-CRT patients) from 1998 to 2016 were collected from the Surveillance, Epidemiology, and End Results database according to the inclusion and exclusion criteria. Using the competing risk regression and survival analysis, an overall estimation of the effectiveness of CRT was performed on a well-balanced cohort via performing propensity score matching. Then, the specific impact of CRT on high- (n = 557) and low-risk (n = 528) cohorts derived from the nomogram’s risk quantification for every patient were further evaluated respectively. Additionally, the advantages of the nomogram model and the conventional tumor, node, metastasis (TNM, 6th revision) staging system were compared. Results A better survival outcome was observed among patients receiving both surgery and CRT than those who underwent surgery alone (HR: 0.55, 95% CI 0.45–0.68, P < 0.001), especially for those with tumors characterized by poor differentiation, large tumor size, advanced T staging, lymphatic metastasis, and distant metastasis (HR: 0.48, 95% CI 0.39–0.59, P < 0.001), while no benefit was observed among the low-risk patients. Furthermore, the newly established nomogram model might be better than the TNM (6th revision) staging system but more data needed. Conclusion Aggressive treatments, such as surgery, chemotherapy, and radiotherapy, were considered effective for selected elderly patients with EC according to the newly established nomogram model.

Neuroendocrine carcinoma admixed adenocarcinoma of cervix: A case report of young female

Neuroendocrine carcinoma coexisted with adenocarcinoma in cervix is very rare. This disease has a very poor prognosis and so far no standard treatment has been obtained. A 35-years-old woman seeks medical attention with chief complaint of bleeding per vagina outside of menstruation. Ultrasound shows cervical mass of 4.2 cm × 2.9 cm. Microscopic biopsy suggestive of a mixture of neuroendocrine cervical carcinoma and adenocarcinoma, moderate-poor differentiation. Several immunohistochemical staining of the biopsy tissue was done to detect neuroendocrine and adenocarcinoma. In biopsy tissue, P63 immunohistochemical staining was performed to detect squamous cell carcinoma with negative results. Furthermore chromogranin, synaptophycin, CD 56, NSE, and P40 immunohistochemical staining were performed to detect neuroendocrine with positive results and so did CK 19, CEA, and CK 7 staining to detect positive adenocarcinomas. This rare case had a positive immunohistochemical staining of both neuroendocrine carcinoma and adenocarcinoma cervix. Patient received definitive concurrent chemo-radiotherpay.

Combination of IL-34 and AFP improves the diagnostic value during the development of HBV related hepatocellular carcinoma

Background IL34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBVHCC). Methods Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBVHCC patients. Serum IL34 and MCSF were measured. Hepatic IL34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined. Results Serum IL34 was 1.7, 1.3 or 2.3-fold higher in HBVHCC than that of CHB, HBV related cirrhosis, or healthy control, which was inhibited following transhepatic arterial chemoembolization (TACE) in HBVHCC patients. Intrahepatic IL34 was higher in HBVHCC than that of the other three groups. Intra-hepatic IL34 was associated with high HBVDNA, HBeAg−, poor differentiation and small tumor size of HBVHCC patients. Intra-hepatic TAMs in HBVHCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBVDNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBVHCC among CHB patients. Conclusions Circulating and intra-hepatic IL34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBVHCC.

Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

Degenerated, Undifferentiated, Rearranged, Lost: High Variability of Sex Chromosomes in Geometridae (Lepidoptera) Identified by Sex Chromatin

Sex chromatin is a conspicuous body that occurs in polyploid nuclei of most lepidopteran females and consists of numerous copies of the W sex chromosome. It is also a cytogenetic tool used to rapidly assess the W chromosome presence in Lepidoptera. However, certain chromosomal features could disrupt the formation of sex chromatin and lead to the false conclusion that the W chromosome is absent in the respective species. Here we tested the sex chromatin presence in 50 species of Geometridae. In eight selected species with either missing, atypical, or normal sex chromatin patterns, we performed a detailed karyotype analysis by means of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The results showed a high diversity of W chromosomes and clarified the reasons for atypical sex chromatin, including the absence or poor differentiation of W, rearrangements leading to the neo-W emergence, possible association with the nucleolus, and the existence of multiple W chromosomes. In two species, we detected intraspecific variability in the sex chromatin status and sex chromosome constitution. We show that the sex chromatin is not a sufficient marker of the W chromosome presence, but it may be an excellent tool to pinpoint species with atypical sex chromosomes.

Emerging strategies to target RAS signaling in human cancer therapy

RAS mutations (HRAS, NRAS, and KRAS) are among the most common oncogenes, and around 19% of patients with cancer harbor RAS mutations. Cells harboring RAS mutations tend to undergo malignant transformation and exhibit malignant phenotypes. The mutational status of RAS correlates with the clinicopathological features of patients, such as mucinous type and poor differentiation, as well as response to anti-EGFR therapies in certain types of human cancers. Although RAS protein had been considered as a potential target for tumors with RAS mutations, it was once referred to as a undruggable target due to the consecutive failure in the discovery of RAS protein inhibitors. However, recent studies on the structure, signaling, and function of RAS have shed light on the development of RAS-targeting drugs, especially with the approval of Lumakras (sotorasib, AMG510) in treatment of KRASG12C-mutant NSCLC patients. Therefore, here we fully review RAS mutations in human cancer and especially focus on emerging strategies that have been recently developed for RAS-targeting therapy.