A case of Podocytic Infolding Glomerulopathy with SLE and literature review

Background Podocytic infolding glomerulopathy (PIG) is a rare pathological change which was characterized by the microspheres or microtubular structures in the thickened glomerular basement membrane (GBM). Only a few dozen cases have been reported worldwide so far. Here we present a case of PIG with systemic lupus erythematosus. Case presentation A 61-year-old Chinese female was diagnosed with systemic lupus erythematosus with clinical manifestations of proteinuria, pleural effusion, seroperitoneum, anemia, leukopenia, thrombocytopenia, antinuclear antibody positive, and hypocomplementemia. She also had benign ovarian tumor and Epstein-Barr virus infection. Renal biopsy immunofluorescent staining showed IgM and C3 were granularly deposited along the capillary wall instead of typical “full house” features. Electron microscopy showed lots of microspheres structures were seen in the thickened GBM. Conclusion We present a case of PIG in a patient with systemic lupus erythematosus. The mechanisms of PIG are unknown, but may be associated with connective tissue disease and podocyte injury.

Ovarian Masses-Applicable IOTA ADNEX Model versus Morphological Findings for Accurate Diagnosis and Treatment

A common problem in gynecological practice is the differential diagnosis of the ovarian masses. The clinician must apply the IOTA (International Ovarian Tumor Analysis) ADNEX (Assessment of Different Neoplasia in the Adnexa) model criteria to evaluate the risk of benign, borderline or malignant tumors. The aim of this study was to verify if the IOTA ADNEX model is a practical tool to be used before surgery and if there is a significant difference between IOTA ADNEX criteria and histological findings. A prospective single center study was performed between January 2017 and December 2019 in Obstetrics and Gynecology Hospital “Cuza-Voda”, Iasi, Romania. The study included 230 patients between 17 and 74 years old diagnosed with persistent adnexal masses. We applied the IOTA ADNEX model protocol predicting the risk of benign, borderline or malignant masses. The golden standard remains the histological diagnosis of the surgically removed mass. The patients that had been diagnosed using ultrasonography with persistent adnexal masses between 30 and 291 mm were operated on in our clinic. In our study. the majority of patients had benign ovarian tumor mass, these being 223 (96.96%) patients, from whom, according to IOTA ADNEX protocol, the correspondence was: 91.8–99.7% at risk of benign tumors, 0.3–4.5% at risk of borderline tumors and 0.3–8.2% at risk of malignant masses. Unexpected findings were obtained from the malignant group that included five patients (2.17%) with the following correspondence: 96.1–99% at risk of benign tumors, 0.6–2.4% at risk of borderline tumors and 1–3.9% at risk of malignant masses. After applying the IOTA ADNEX model criteria, the patients with a suspicion of malignant disease were correctly guided towards surgical treatment in an oncological center. In our hospital, surgical treatment was only proposed to those patients with high suspicion of benign masses.

OCT4 Promotes Ovarian Cancer Cell Metastasis and Angiogenesis via Modulating VEGFR2/LRPPRC Pathway

Background: Due to its high ability of metastasis, ovarian cancer remains the most lethal gynecological malignancy, yet its underlying mechanism remains unconfirmed. Objectives: The main purpose is to probe into the role and regulation mechanism of octamer-binding transcription factor 4 (OCT4) in angiogenesis and metastasis in ovarian cancer.Methods: Immunohistochemistry (IHC) and immunofluorescence in epithelial ovarian cancer specimens and benign ovarian tumor samples were performed, followed by RNA-sequencing and examination of angiogenesis, cell migration and invasion in OCT4 knockdown cell lines and the controls. Co-Immunoprecipitation (Co-IP), mass spectrometry, immunoblotting, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses were conducted along with models of zebrafishes and nude mice of transplanted tumors to gain insights into the specific functions and mechanisms of action of OCT4 in ovarian cancer.Results: Firstly, we discovered that OCT4 expression was enhanced in ovarian cancer tissues significantly, especially in the metastatic lesions, indicating that OCT4 might be a key for the metastasis of ovarian cancer. Furtherly, we observed and verified that OCT4 promoted cell migration and invasion, and induced angiogenesis in vitro and in vivo. Mechanistically, OCT4 modulated the transcription of leucine‑rich PPR motif‑containing protein (LRPPRC)，and furtherly interacted with vascular endothelial growth factor receptor 2 (VEGFR2)/LRPPRC complex and ultimately triggered the downstream FAK/AKT signaling pathway . Conclusions: Together, through models of ovarian cancer cells, zebrafishes and tumor-transplanted mice, this study highlighted the importance of OCT4/LRPPRC/VEGFR2 signaling axis in metastasis of ovarian cancer and angiogenesis. Thus, our finding supplied a potential novel molecular-targeted approach for the treatment of ovarian cancer.

Diagnosis and treatment characteristics of mucinous ovarian tumors

Ovarian tumors occupy a special place in gynecological pathology due to their great diversity, diagnostic difficulties, specifying their evolutionary nature, establishing the prognosis and treatment. Ovarian mucinous tumors are a group of rare formations, with a cell of as yet undefined origin, but with an apparent progression from benign to borderline and carcinoma. The treatment of a benign ovarian tumor is surgical. Material and methods. The research in question was performed on a group of 50 patients, who were treated in the gynecology department of the IMSP Oncological Institute of the Republic of Moldova, with the diagnosis of mucinous ovarian tumors. Results. The study analyzed data on the diagnosis and treatment of mucinous ovarian tumors. The clinical diagnosis showed a unilateral ovarian involvement in 41 cases (82%) compared to the bilateral one registered in 9 patients (18%). All tumors were large and irregularly shaped. In the case of laboratory diagnosis in assessing the benign or malignant tumor potential, the tumor marker CA-125 was performed, in 41 patients the index was within the norm range from 0-35U / ml and only in 9 cases were there insignificant increases of 50-100U / ml. Ultrasonographic diagnosis is an important method in detecting mucinous ovarian tumors. The treatment of patients is surgical and, depending on the appearance of the tumor intraoperatively and age, they had a radical or less radical character. Conclusions. The most common clinical signs were fullness in the pelvis, dysuria, pain in the lumbar or sacral region. As usual, the mucous ovarian tumors are large. The CA-125 tumor marker was in most cases within the normal range. Imaging investigations are informative and some of them applied to all patients in the study. Endoscopic diagnostic methods are less informative in mucinous ovarian tumors due to bulky formations and the risk of effusion of the mucin into the abdominal cavity.

Estimating the Risk of Malignancy in Adnexal Masses: Validation of the ADNEX Model in the Hands of Non-expert Ultrasonographers in a Gynecological Oncology Center in China

Background: The diagnosis of adnexal masses depends more on ultrasonography. This study aim to validate the diagnostic accuracy of the International Ovarian Tumor Analysis (IOTA) ADNEX model in the preoperative diagnosis of adnexal masses in the hands of non-expert ultrasonographers in a gynecological oncology center in China. Methods: This was a single oncology center, retrospective diagnostic accuracy study from 620 patients. All patients underwent surgery and the histopathological diagnosis was used as reference standard. The masses were divided into five types according to the ADNEX model: benign ovarian tumor, borderline ovarian tumor (BOT), Stage-I ovarian cancer (OC), Stages-II-IV OC and ovarian metastasis. Receiver-operating characteristics (ROC) curve analysis was used to evaluate the ability of the ADNEX model to classify tumors into different histological types with and without Cancer antigen 125 (CA 125) results. Results: Of the 620 women, 402 (64.8%) had a benign ovarian tumor and, 218 (35.2%) had a malignant ovarian tumor, including 86 (13.9%) with BOT, 75 (12.1%) with Stage-I OC, 53 (8.5%) with Stages-II-IV OC and 4 (0.6%) with ovarian metastasis. The AUC of the model to differentiate between benign and malignant adnexal masses was 0.97 (95% CI, 0.96–0.98). Performance was excellent for the discrimination between benign vs Stage II-IV OC, benign vs ovarian metastasis with AUCs of 0.99 (95% CI, 0.99-1.00) and 0.99 (95% CI, 0.98-1.00), respectively. Performance of the model was less effective at distinguishing between BOT and Stage I OC and between BOT and ovarian metastasis, with AUC of 0.54 (95% CI, 0.45–0.64) and 0.66 (95% CI, 0.56–0.77), respectively. When including CA125 in the model, performance in discriminating between Stages II–IV OC with stage I OC and ovarian metastasis were improved (AUC increased from 0.88 to 0.94, P = 0.01; 0.86 to 0.97, p = 0.01, respectively). Conclusions: The IOTA ADNEX model has excellent performance in differentiating benign and malignant adnexal masses in the hands of non-expert ultrasonographers with limited experienced in China. Between classification different subtypes of ovarian cancers, the model has difficulty to differentiate BOT from stage I OC, BOT from ovarian metastases.

Serum Levels of S100A11 and MMP-9 in Patients with Epithelial Ovarian Cancer and Their Clinical Significance

Objective. To investigate the serum levels of calgizzarin (S100A11) and matrix metalloproteinase-9 (MMP9) in patients with epithelial ovarian cancer (EOC) and determine their clinical significance. Methods. Serum levels of S100A11 and MMP9 were detected in patients with EOC, patients with benign ovarian tumor, and healthy women. The correlation between the two markers and clinicopathological characteristics of ovarian cancer was analysed. Results. The serum levels of S100A11 and MMP-9 in patients with EOC were higher than those in patients with benign ovarian tumor and in healthy women, and the expression levels of S100A11 and MMP-9 were positively correlated. S100A11 and MMP-9 were correlated with tumor staging, postoperative residual foci, ascites volume, serum CA125 level, chemotherapy response, and lymph node metastasis, while S100A11 and MMP-9 were not associated with the bilevel classification, histological type, age, and degree of differentiation. Conclusion. S100A11 and MMP-9 were both highly expressed in the serum of patients with EOC and were associated with cancer development, invasion, and metastasis. Therefore, they can be used as an important reference maker in the diagnosis and treatment of ovarian cancer.

LARGE BENIGN OVARIAN TUMOR MIMICKING LATE STAGE MALIGNANT OVARIAN TUMOR

Ovarian fibrothecoma is a rare, benign neoplasm of the sex cords and stroma of the ovary. Patients may present with abdominal pelvic pain and / or distension, and sometimes postmenopausal bleeding. Large tumors (> 10cm) are often associated with pleural and peritoneal effusion mimicking an advanced ovarian malignancy (Deimon –Meigs syndrome). We report 2 cases of giant fibrothecoma associated with ascites and pleurisy. Both patients were postmenopausal. The ovarian tumor was discovered during an increase in abdominal volume in the first patient and as part of the etiological workup of encysted pleurisy in the second. The clinical examination made it possible to objectify a tumor with abdominopelvic development of size greater than 10 cm, the clinical examination also noted, in the two patients, a right basithoracic dullness in favor of a pleurisy and an ascites of average abundance suggesting in the first place a malignant tumor of the ovary, with peritoneal carcinoma. the two patients underwent a pelvic ultrasound, supplemented by an abdominal pelvic CT scan objectifying the presence of a large ovarian mass with pleural and peritoneal effusions. Exploratory laparotomy was required in both patients and underwent an extemporaneous examination which was consistent with the definitive pathological examination in both patients. Both patients underwent total hysterectomy with bilateral adnexectomy and omentectomy with multiple biopsies as the clinical picture was highly suggestive of malignancy. The postoperative follow-up was simple with total regression of peritoneal and pleural effusions in the two cases of Demons-Meigs syndrome. The definitive pathological examination revealed a fibrothecoma. Fibrothecal tumors remain a real challenge from a diagnostic and therapeutic point of view. The fear of cancer is even greater in the presence of Demons-Meigs syndrome. The management of these tumors requires a good clinical and radiological analysis, and it is the histological examination that confirms the diagnosis. The surgery corresponds, in post-menopausal patients, to a hysterectomy with bilateral adnexectomy, while conservative treatment by unilateral adnexectomy is entirely justified in young women who still want fertility.

Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment

Immunotherapy is expected to become the most promising new treatment for ovarian cancer owing to its immunogenicity. However, immunosuppression in the tumor microenvironment is a major obstacle to the efficacy of tumor therapy. Studies have found different metabolism ways of regulatory T cells (Tregs) in the cancer environment may be related to the immunosuppression and Toll-like receptor 8 (TLR8) can reverse the suppression function of Tregs. But it is still unclear that if the TLR8-mediated function reversal is associated with the change of glucose metabolism of Tregs. It was found that the positive expression rates of Glut1, HIF-1α, and Ki67 in CD4+ Treg cells of OC were significantly higher than that in benign ovarian tumor and HC, and also significantly higher than that in CD4+ Teffs of OC. What’s more, compared with CD4+ Teff group, CD4+ Tregs highly expressed seven genes and three proteins related to glucose metabolism and had higher levels of glucose uptake and glycolysis. After activating TLR8 signal of CD4+ Tregs, the proliferation level of naive CD4+ T cells was higher than that of the control group. At the same time, the expression levels of eight genes and five proteins related to glucose metabolism in CD4+ Treg cells with TLR8 activated were decreased and levels of glucose uptake and glycolysis were also lower. Furthermore, TLR8 signaling also downregulated the mTOR pathway in CD4+ Tregs. CD4+ Tregs pretreated with 2-deoxy-d-Glucose (2-DG) and galloflavin also attenuated the inhibition of Teffs proliferation. Although CD4+ Tregs pretreated with 2-DG and galloflavin before activating TLR8 signal had no significant difference compared with the group only treated with inhibitors, which suggested TLR8-mediated reversal of CD4+ Treg cells inhibitory function in ovarian cancer cells co-cultured microenvironment had a causal relationship with glucose metabolism.

Meigs’ syndrome mimicking heart failure with preserved ejection fraction: a case report

Background Meigs’ syndrome is a rare disease characterized by a triad of presentations, including benign ovarian tumor, ascites, and pleural effusion. However, a clinical diagnosis of Meigs’ syndrome remains challenging because pleural and ascitic effusions can be common findings in a variety of underlying conditions. Furthermore, these findings can often be misdiagnosed as pleural and peritoneal dissemination caused by potentially malignant tumors, leading to the administration of improper treatment. Case presentation We described a case of an 85-year-old postmenopausal female patient with atypical Meigs’ syndrome presenting with right-sided pleural effusion, notable leg edema, and trivial ascites, which was initially mistaken as heart failure with preserved ejection fraction. However, pleural effusion was totally ineffective against diuretic therapy. Subsequently, thoracentesis yielded serosanguineous exudative effusion. Moreover, refractory pleural effusions and abdominal/pelvic computed tomography and magnetic resonance imaging findings strongly suggested bilateral malignant ovarian tumors with pleural dissemination. Repetitive negative cytological results allowed the patient to undergo bilateral salpingo-oophorectomy. Finally, a definitive diagnosis of Meigs’ syndrome was made by confirming the presence of a benign mitotically active cellular fibroma of the ovary by pathology and that pleural effusion resolved following tumor resection. Conclusions Our case highlights the clinical importance of assessing Meigs’ syndrome in the diagnostic workup of pleural effusion in postmenopausal female patients. Given the favorable prognosis of Meigs’ syndrome, clinicians should consider surgical resection, even with potentially malignant ovarian tumors with accompanying pleural effusion, ascites, or both.

Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer

Ovarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiation between malignant and benign tumors, monitoring the progression of the disease, and identification of patients that will respond to implemented treatment. Our study is aimed at evaluating the profile of IL-6 in the plasma and peritoneal fluid (PF) of patients with various clinical manifestations of OC (n=78). We also examined the relationship between IL-6 and PD-L1/PD-L2 positive CD45+CD14+ inflammatory cell (MO/MA) levels in three OC environments (TME): peripheral blood (PB), PF, and tumor (TT) and their clinical and prognostic relevance in OC patients. The expression of PD-L1/PD-L2 molecules was analyzed by flow cytometry. The IL-6 levels were determined by ELISA. We found an elevated level of PD-L1/PD-L2 positive MO/MA in TT compared to PB (p<0.0001). Significantly higher (p<0.0001) levels of IL-6 were observed in PF of the OC patients than in the benign ovarian tumor group (n=31). Additionally, we found higher IL-6 levels in PF than in the plasma of the OC patients. Interestingly, accumulation of IL-6 was observed in PF of patients with low-differentiated OC and correlated with worse prognosis. Moreover, we observed correlations between the level of IL-6 and CD45+CD14+ cells and between CD45+CD14+PD-L1+ cells and the IL-6 level in PF. For the first time, we discovered that the higher percentage of CD45+CD14+PD-L2+ cells in PF predicts better survival of OC patients. Our study suggests that CD45+CD14+PD-L2+ cells and IL-6 may be predictive biomarkers for OC patients. Understanding how the composition of TME changes during OC development and progression is a prerequisite for projecting new therapeutic strategies. Overall, further validation research is warranted.