Real-time contrast-enhanced ultrasound-guided percutaneous biopsy in the diagnosis of ovarian metastasis of gallbladder carcinoma: a case report.

BACKGROUND: Multiple-organ primary tumors can invade the ovary through lymphatic and hematogenous routes, presenting as ovarian Krukenberg tumors, but these rarely originate from the gallbladder. Krukenberg tumors can present similar to primary ovarian tumors; however, their treatments are completely different. PATIENT CONCERNS: A 62-year-old Chinese woman presented with abdominal distension for six months and weight loss of five kilograms for two months. DIAGNOSES: Based on multiple imaging examinations, the patient was preliminarily diagnosed with a malignant tumor of unknown origin with multiple metastases (omentum). To identify the origin of the malignancy, the patient underwent real-time contrast-enhanced ultrasound-guided percutaneous biopsy. The results revealed a perihepatic hypoechoic lesion and right adnexal mass that were both metastatic adenocarcinomas from the gallbladder. INTERVENTIONS: The patient initially received chemotherapy with gemcitabine and cisplatin instead of surgery. However, the tumor increased in size on re-examination after two cycles, so the treatment was shifted to a combination regimen with durvalumab for six cycles. OUTCOMES: The treatment proceeded smoothly, with no recurrence or obvious progression of the cancer during follow-up. CONCLUSIONS: Differentiating between primary and metastatic ovarian tumors is important. Early diagnosis and effective treatment options are essential for patient survival. CEUS-guided percutaneous biopsy is a valuable procedure for patients with multiple metastases who cannot tolerate surgery.

High Expression of ERK-related RASGRF2 predicts Poor prognosis in patients with Stomach Adenocarcinoma and correlates with M2 macrophage.

Background: The role of RASGRF2 has been verified in the development of various cancers. However, its roles in stomach adenocarcinoma (STAD) are still under investigation. Methods: RASGRF2 transcript-level data and the associated clinical information from patients with STAD were extracted from The Cancer Genome Atlas (TCGA). Diagnostic and prognostic values of RASGRF2 were analyzed using receiver-operator characteristics (ROC) analysis, correlation analysis, and survival analysis in conjunction with a prognostic model. In addition, gene expression profiles, differentially-expressed genes for co-varying expression, and a differential expressed genes (DEG) protein-protein interaction network for influential nodes were also analyzed. To identify the molecular role of RASGRF2 in STAD, gene ontology (GO) term, Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway, and gene set enrichment analysis (GSEA)-mediated functional module enrichment analyses were conducted. The relationship between RASGRF2 and gene signature-based predicted immune cell infiltration patterns were also investigated. To validate the bioinformatic findings, RASGRF2 protein expression was investigated in vitro using western blot and immunohistochemistry. Furthermore, relationships among RASGRF2 protein expression, clinicopathologic characteristics, and patient survival were analyzed. Results: Bioinformatic analysis revealed a significantly higher RASGRF2 transcript level in STAD tissue, which was positively associated with the T stage, histological type, histological grade, and TP53 status. Moreover, the RASGRF2 transcript level indicated poor overall survival in STAD patients (hazard ratio = 1.47, P = 0.023). Multivariate Cox regression analysis showed that primary therapy outcome, age, and RASGRF2 transcript level were independent prognostic factors for survival, and the C-index of a nomogram was 0.695. Additionally, 159 genes were differentially expressed according to RASGRF2 transcript levels; 15 exhibited co-varying expression, and 13 were identified as influential nodes. The DEG-list was significantly enriched for several GO terms, biological pathways, and functional modules, including MAPK, RAS, ERK, and immunoregulatory pathways. RASGRF2 transcript levels were significantly positively correlated with infiltration levels of Tem, Macrophages, pDCs, and NK cells. Validation analysis showed similar results for the RASGRF2 protein expression level in both in vitro analyses. Conclusion: Bioinformatic predictions combined with in vitro validation suggest that RASGRF2 plays diagnostic and prognostic roles and serves as a negative protective molecular factor in STAD patients.

Two-Years Prospective Follow-Up Study of Subacute Thyroiditis.

Purpose: The aim of the present prospective follow-up study was to explore the early indicators of hypothyroidism and the final changes in thyroid volume in subacute thyroiditis (SAT) patients. Methods: We enrolled 61 SAT patients and followed them up for 2 years to assess the incidence of hypothyroidism and changes in thyroid volume. Binary logistic regression and receiver operating characteristic (ROC) curves were used for data analysis. Results: During the 2 years follow-up period, we found that the volumes of the thyroid gland in SAT patients at 1 and 2 years were significantly smaller than those in the healthy control group, which were significantly smaller compared to the initial thyroid volumes after SAT onset (p < 0.001). Also, the thyroid volumes of SAT patients with hypothyroidism were significantly smaller than those of SAT patients without hypothyroidism. The early maximum thyroid-stimulating hormone (TSH) values (within 3 months after SAT onset) were closely related to the incidence of hypothyroidism at 2 years. The OR value was 1.18 (95% CI = 1.01-1.38, p = 0.032). The early maximum TSH value had a maximum area under the ROC curve (AUC) of 0.866 for the development of hypothyroidism 2 years after SAT onset vs. euthyroidism (p < 0.001). Conclusions: The thyroid volumes of patients increased significantly after the onset of SAT, while during the follow-up these volumes decreased; the thyroid volumes at 1 and 2 years were significantly smaller than those of normal healthy subjects, especially in SAT patients with hypothyroidism. Furthermore, the early maximum TSH value could be used as an effective indicator of the development of hypothyroidism 2 years after the onset of SAT.

Down-regulated miR-22 as predictive biomarkers for prognosis of epithelial ovarian cancer.

BACKGROUND: Recent studies have demonstrated that microRNA-22 (miR-22) was deregulated in many types of cancers and was involved in various cellular processes related to carcinogenesis. However, the clinical significance and prognostic value of miR-22 in epithelial ovarian cancer (EOC) haven't been investigated. METHODS: 109 pairs of fresh EOC tissue and matched adjacent normal tissue specimens were collected between May 2007 and March 2013. Real-time quantitative RT-PCR assay was performed to evaluate the expression levels of miR-22. The chi-square test was used to assess miR-22 expression with respect to clinicopathological parameters. The survival curves of the patients were determined using the Kaplan-Meier method and Cox regression, and the log-rank test was used for statistical evaluations. RESULTS: miR-22 expression in EOC tissues was significantly lower than that in matched normal adjacent tissues (mean ± SD: 1.944 ± 1.026 vs. 4.981 ± 1.507, P<0.0001). Low miR-22 expression level was correlated with FIGO stage (P=0.006), tumor grade (P=0.03), and lymph node metastases (P=0.01). Kaplan-Meier analysis with the log-rank test indicated that low miR-22 expression had a significant impact on overall survival (44.4% vs. 64.5%; P=0.005) and progression-free survival (23.5% vs. 52.6%; P=0.004). CONCLUSIONS: Our data demonstrated that the expression of miR-22 was downregulated in EOC, and associated with overall survival as well as progression-free survival, suggesting that miR-22 could serve as an efficient prognostic factor for EOC patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_178.

ATAD2 is highly expressed in ovarian carcinomas and indicates poor prognosis.

The purpose of this study was to explore the expression of ATAD2 in ovarian tumor tissue as well as its relationship with degree of malignancy. Tumor tissue from 110 cases of ovarian cancer was collected in accordance with the Declaration of Helsinki for evaluation of ATAD2 expression immunohistochemistry, quantitative PCR (qPCR) and Western blotting. The correlation between the ATAD2 expression and and the prognosis of ovarian cancer was evaluated by Cox regression model. In addition, HO-8910 and OVCAR-3 cells were transfected with two siRNAs targeting ATAD2. Cell viability was evaluated with MTT assay, and cell migration by transwell migration assay. ATAD2 was shown to be highly expressed in 65.5% (72/110) of ovarian cancer cases, both at transcriptional and protein levels. Moreover, highly expression was positively correlated with degree of malignancy. Knock-down of ATAD2 in HO-8910 and OVCAR-3 cells was found to reduce cell migration. In addition, follow-up visits of the patients demonstrated that the 5-year survival rate was lower in patients with high expression of ATAD2. Our study suggested that ovarian tumor tissue may have highly expressed ATAD2, which is associated with tumor stage, omentum-metastasis, ascites and CA-125. Increased ATAD2 may play important roles in tumor proliferation and migration. ATAD2 could serve in particular as a prognostic marker and a therapeutic target for ovarian cancer.

Peritoneal metastases: evaluation with contrast-enhanced ultrasound.

OBJECTIVES: The aim of this study is to evaluate the contrast-enhanced ultrasound (CEUS) features of peritoneal metastases. MATERIALS AND METHODS: Unenhanced ultrasound and CEUS were conducted in 25 patients who had confident diagnoses of peritoneal metastases after ultrasound-guided biopsies of peritoneum. B-mode sonograms, color Doppler, CEUS pattern and quantitative analysis of blood perfusion in peritoneal metastases were successively evaluated. RESULTS: Peritoneum became markedly thickened and was well seen as a heterogeneous omental cake at B-mode ultrasound. Color Doppler only detected dotted or strip-like blood flow scattered in the thickened peritoneum and no blood signal was found in any metastatic nodule. At CEUS, the thickened peritoneum enhanced diffusely and parameters of time-intensity curves did not show any significant difference among variant metastases groups. All the metastatic nodules in the peritoneum showed fast radial enhancement and became homogeneous with adjacent parenchyma. These nodules soon became hypoechoic and the contour of the nodule was clearly shown during the wash-out phase. In all the nodules, the time to peak was shorter and peak intensity was higher compared with the peripheral tissue. CONCLUSION: CEUS played a good role in the evaluation of microcirculation and angiogenesis of peritoneal metastases and metastatic nodules in thickened peritoneum.