Serous Stage Research Articles

GESTATIONAL PYELONEPHRITIS ACCORDING TO SAMARKAND INDICATORS

In pyelonephritis, the pathogenic factor affecting the chronic stage of inflammation loses its leading role; processes that influence changes in the rheological properties of blood and microcirculation play an important role, which leads to the development of a chronic condition. occurs -the causes of this disease are a risk factor for the mother and fetus, leading to perinatal losses.In patients with acute pyelonephritis, significant changes are observed in the hemostatic system, clinical and laboratory parameters. The above changes intensify during the transition from the serous stage of kidney inflammation to the purulent stage.

STATE OF HEARING FUNCTION AND EUSTACHIAN TONSILS IN PATIENTS WITH SECRETORY OTITIS MEDIA AT DIFFERENT STAGES OF ITS DEVELOPMENT

The problem of hearing pathology is relevant as we have seen the number of those patients increasing yearly. According to the literature, about 30% of all cases of hearing loss are related to middle ear pathology. The cause of the development of many forms of hearing loss is the dysfunction of the Eustachian tube which can lead to retraction of the tympanic membrane, development of secretory otitis media or even adhesive otitis media that can be the reason for constant conductive hearing loss, and require surgical intervention to restore mechanism of sound conduction.
 Prevention and treatment of hearing disorders is not only a medical, but also a social-economic problem. In our researches, we’ve decided to study the peculiarities of hearing impairment in patients with secretory otitis media in different stages of its development, depending on the condition of the tubal tonsils and lymphoid tissue around the orifice of the Eustachian tube.
 The aim. Study the relationship between the state of auditory function and pathomorphological changes of the tubal tonsils and lymphoid tissue around the orifice of the Eustachian tube in patients with secretory otitis media in different stages of its development.
 Material and methods. There were examined 89 patients, age between 18 and 65 years old, with secretory otitis media. All patients were performed a detailed collection of complaints, disease anamnesis, examination of the ENT-organs – by a routine method and with the help of endoscopic and microscopic equipment, as well as pure-tone audiometry and tympanometry. Patients were divided into III groups. Group I – 21 patients with catarrhal stage of secretory otitis media, group II – 38 patients with serous stage, group III – 30 patients with mucous stage.
 The results. When examining patients with secretory otitis media during nasopharyngeal endoscopy, the changes in the tubal tonsils and surrounding area in the form of inflammation, hypertrophy, or hyperplasia were found. The form of these changes affects the nature of the disease stage. According to pure-tone audiometry, the average hearing thresholds at speech frequencies by air conductivity in all patients were significantly increased. At the same time, in patients of group III with mucous exudate in the middle ear space, average hearing thresholds by bone conduction were slightly increased, which is associated with significantly restricted or absent movement of the tympanic membrane and ossicular chain in the presence of thick mucous exudate.
 Conclusions. Analyzing the patients’ complaints, clinical picture, data of otoscopy, endoscopy of the nasal cavity and nasopharynx, data of pure-tone audiometry and tympanometry – there was determined a cause-and-effect relationship between the condition of the tubal tonsils, the stage of secretory otitis media and, accordingly, hearing impairment in the examined patients. The performed studies indicate that one of the reasons for the development of secretory otitis media in adults may be pathomorphological changes in the tubal tonsils and lymphoid tissue surrounding the orifice of the Eustachian tube, namely their pathomorphological changes: inflammation, hypertrophy, or hyperplasia. Inflammation of the tubal tonsils, as a rule, is the cause of the development of the catarrhal and serous stage of secretory otitis media, and their hypertrophy or hyperplasia leads to the long-term dysfunction of the Eustachian tube, which in turn is the cause of the mucous stage of secretory otitis media.

Primary peritoneal carcinoma and ovarian carcinoma - a ten-year comparative analysis.

Primary peritoneal carcinoma (PPC) at presentation often masquerades as epithelial ovarian carcinoma (OC) but behaves different with respect to treatment response, recurrence patterns and has inferior outcomes. The objective of this study is to compare the clinicopathological features and survival outcomes of PPC and OC. Prospectively maintained database of patients presenting to the gynecologic oncology department at a tertiary hospital was reviewed between 1st January 2010 and 31st December 2020. A comparative analysis of high-grade serous stage III/IV PPC and OC was done. Demographics, treatment details, complications and survival outcomes were collected from electronic medical records. 151 OC and 69 PPC patients were included. A higher proportion of women with PPC had reduced performance status prior to hysterectomy with salpingo-oophorectomy, a shorter symptom to treatment interval, and large volume ascites. A significantly lower number of women with PPC (4.3 vs. 46.1%; P < 0.001) underwent primary cytoreduction, had a lower median surgical complexity score (3 vs. 4; P < 0.001) but higher recurrence rates (66.7 vs. 47.0%; P = 0.041) as compared to the patients with OC. The median progression-free survival (PFS) was 18 (15-20) months in PPC and 23 (17-28) months in OC patients (log-rank P = 0.034), while the median overall survival (OS) was similar (44 vs. 48 months; log-rank P = 0.696). The presence of extraperitoneal disease and interval cytoreduction was associated with shorter PFS. Suboptimal cytoreduction and delay in adjuvant chemotherapy beyond 6 weeks post-surgery was associated with reduced OS. PPC is an aggressive disease with lower PFS compared to OC. Commonly presenting with large volume carcinomatosis, it is not amenable for primary cytoreduction, making the usage of neoadjuvant chemotherapy a common practice and pragmatic approach.

Cancer-specific and overall survival in African American women with endometrial cancer: a SEER-Medicare study

<h3>Objectives:</h3> To compare the overall survival (OS) and cancer specific survival (CSS) by race for women with stage I-III endometrial cancer (EC) by histologic subtype. <h3>Methods:</h3> This is a retrospective cohort study of women with stage I-III endometrioid, serous, clear cell, and carcinosarcoma who underwent hysterectomy as primary surgical staging as identified within the SEER-Medicare database. Endometrial cancer cases diagnosed between 2000 and 2015 with Medicare enrollment data from 1999-2016 were included. Demographics, cancer data, and survival outcomes were collected. Demographic and treatment factors by race were compared using descriptive analyses. OS and CSS outcomes were stratified by race, stage and histology, then analyzed using log rank tests and multivariate cox modeling (adjusting for age, geographic region, Charlson comorbidity index, post-operative treatment sequencing, FIGO stage, and grade). <h3>Results:</h3> 24,142 total patients were included in this dataset. 85.5% were White, and 8.5% were BlackBlack. 19,351 stage I, 1,484 stage II, and 3,307 stage III cases were identified. Black women were diagnosed at a younger age bracket (40-69yo) than White patients for endometrioid stage I (40% vs 35%), II (37% vs 31%), and III (31% vs 28%); serous stage I (45% vs 31%) and III (42% vs 28%), and carcinosarcoma stage I (39% vs 27%), p<0.05 all. Charlson comorbidity indexes were significantly higher for BlackBlack patients with endometrioid stages I (p<0.001), II (p=0.001), and III (p=0.02) and serous stage I (p<0.0001) and III (p=0.02). Receipt of adjuvant therapy did not differ by race for any stage or histology except for stage III endometrioid where Black women were less likely to receive adjuvant treatment (61.2% vs 70.1% White p=0.03). For stage I, BlackBlack patients had worse CSS and OS for all histologies except clear cell in unadjusted and adjusted analyses (Table I). For stage II, only CSS for endometrioid carcinoma differed by race in unadjusted analyses, whereas OS did not. For stage III, BlackBlack patients with endometrioid carcinoma had worse CSS and OS in unadjusted analyses, but significant survival differences only remained for CSS in the adjusted model. <h3>Conclusions:</h3> Prior studies have reported that BlackBlack women with endometrial cancer have worse survival consistently across stage and histology. However, we did not find this effect when evaluating by CSS and OS. For stage I, BlackBlack women had consistently worse CSS likely related to the disease itself and worse OS in adjusted analyses likely related to poorer overall health outcomes across all histologic subtypes except for clear cell. For stage II and III, racial disparities were seen only for CSS in endometrioid patients in the adjusted analyses, but not OS; and this may have been related to BlackBlack women with stage III cancer receiving less adjuvant therapy. When stratified by stage and histology, BlackBlack women with EC were diagnosed at younger age and with more comorbidities. Overall these findings emphasize the need to intervene in the early stage population, where a disparity exists and the largest population of women is affected.

Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer

ObjectiveMebendazole and other anti-parasitic drugs are being used off-prescription based on social media and unofficial accounts of their anti-cancer activity. The purpose of this study was to conduct a controlled evaluation of mebendazole's therapeutic efficacy in cell culture and in vivo models of ovarian cancer. The majority of ovarian cancers harbor p53 null or missense mutations, therefore the effects of p53 mutations and a mutant p53 reactivator, PRIMA-1MET (APR246) on mebendazole activity were evaluated. MethodsMebendazole was evaluated in cisplatin-resistant high grade serous stage 3C ovarian cancer patient derived xenograft (PDX) models: PDX-0003 (p53 null) and PDX-0030 (p53 positive), and on ovarian cancer cell lines: MES-OV (p53 R282W), ES2 (p53 S241F), A2780 (p53 wild type), SKOV3 parental (p53 null) and isogenic sublines, SKOV3 R273H p53 and SKOV3 R248W p53. Drug synergy and mechanisms were evaluated in cell cultures using isobolograms, clonogenic assays and western blots. Prevention of tumor establishment was studied in a MES-OV orthotopic model. ResultsMebendazole inhibited growth of ovarian cancer cell cultures at nanomolar concentrations and PDXs at doses up to 50 mg/kg, and reduced orthotopic tumor establishment at 50 mg/kg. The mechanism of mebendazole was associated with p53-independent induction of p21 and tubule depolymerization. PRIMA-1MET also inhibited tumor establishment and worked synergistically with mebendazole in cell culture to inhibit growth and induce intrinsic apoptosis through a p53- and tubule destabilization-independent mechanism. ConclusionThis work demonstrates the therapeutic potential of repurposing mebendazole and supports clinical development of mebendazole for ovarian cancer therapy and maintenance.

Ovarian Blood Sampling Identifies Junction Plakoglobin as a Novel Biomarker of Early Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy. Early detection would improve survival, but an effective diagnostic test does not exist. Novel biomarkers for early ovarian cancer diagnosis are therefore warranted. We performed intraoperative blood sampling from ovarian veins of stage I epithelial ovarian carcinomas and analyzed the serum proteome. Junction plakoglobin (JUP) was found to be elevated in venous blood from ovaries with malignancies when compared to those with benign disease. Peripheral plasma JUP levels were validated by ELISA in a multicenter international patient cohort. JUP was significantly increased in FIGO serous stage IA+B (1.97-fold increase; p < 0.001; n = 20), serous stage I (2.09-fold increase; p < 0.0001; n = 40), serous stage II (1.81-fold increase, p < 0.001, n = 23) and serous stage III ovarian carcinomas (1.98-fold increase; p < 0.0001; n = 34) vs. normal controls (n = 109). JUP plasma levels were not increased in early stage breast cancer (p = 0.122; n = 12). In serous ovarian cancer patients, JUP had a sensitivity of 85% in stage IA+B and 60% in stage IA-C, with specificities of 76 and 94%, respectively. A logistic regression model of JUP and Cancer Antigen 125 (CA125) revealed a sensitivity of 70% for stage IA+B and 75% for stage IA-C serous carcinomas at 100% specificity. Our novel ovarian blood sampling – proteomics approach identified JUP as a promising new biomarker for epithelial ovarian cancer, which in combination with CA125 might fulfill the test criteria for ovarian cancer screening.

Ascites IL-10 Promotes Ovarian Cancer Cell Migration

Ovarian cancer (OC) ascites is an inflammatory and immunosuppressive tumor environment characterized by the presence of various cytokines, chemokines and growth factors. The presence of high concentrations of these cytokines/chemokines in ascites is associated with a more aggressive tumor phenotype. IL-10 is an immunosuppressive cytokine for which high expression has been associated with poor prognosis in some cancers. However, its role on OC tumor cells has not been explored. Therefore, the aim of the current study was to elucidate the role of ascites IL-10 on the proliferation, migration and survival of OC cell lines. Here, we show that IL-10 levels are markedly increased in patients with advanced serous OC ascites relative to serous stage I/II ascites and peritoneal effusions from women with benign conditions. Ascites and IL-10 dose-dependently enhanced the proliferation and migration of OC cell lines CaOV3 and OVCAR3 but had no effect on cell survival. IL-10 levels in ascites positively correlated with the ability of ascites to promote cell migration but not proliferation. Depletion of IL-10 from ascites markedly inhibited ascites-induced OC cell migration but was not crucial for ascites-mediated cell proliferation. Taken together, our findings establish an important role for IL-10, as a component of ascites, in the migration of tumor cells.

Lymph node metastases as only qualifier for stage IV serous ovarian cancer confers longer survival than other sites of distant disease – a Swedish Gynecologic Cancer Group (SweGCG) study

Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer.Method: This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009–2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations.Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n = 51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n = 195) or other/multiple (n = 187) distant metastases (p = .0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p = .001) or other/multiple distant sites (HR 2.67, p = .007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p = .245).Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.

Gene Expression Analysis of Early Stage Endometrial Cancers Reveals Unique Transcripts Associated with Grade and Histology but Not Depth of Invasion

Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis.

Specificity and prognostic validation of a polyclonal antibody to detect Six1 homeoprotein in ovarian cancer

ObjectiveThe presence of Six1 mRNA gene portends a poor prognosis in ovarian cancer. We describe validation of a Six1 specific antibody and evaluate its association with tumorigenicity and prognosis in ovarian cancer. MethodsA Six1 antibody (Six1cTerm) was raised to residues downstream of the Six1 homeodomain, representing its unique C-terminus as compared to other Six family members. Cells were transfected with Six1–Six6 and Western blot was performed to demonstrate Six1 specificity. Ovarian cancer cell lines were analyzed for Six1 mRNA and Six1cTerm and tumorigenicity was evaluated. Ovarian cancer tissue microarrays (OTMA) were analyzed for Six1cTerm by immunohistochemistry and scored by two blinded observers. The metastatic tumors of 15 stage IIIC high grade serous ovarian cancers were analyzed with Six1 mRNA and Six1cTerm and expression was compared to clinical factors and survival. ResultsThe Six1cTerm antibody is specific for Six1. Cell line tumorigenicity in SCID mice correlates with Six1 levels both by mRNA(p=0.001, Mann–Whitney U test) and by protein (presence vs. absence, p=0.05 Fischer's Exact test). Six1 protein was present in up to 54% of OTMA specimens. Six1 protein expression in omental/peritoneal metastases correlated with worsened survival in a sample (n=15) of high grade serous stage IIIC ovarian cancers (p=0.001). ConclusionsThe Six1cTerm antibody is specific and able to detect Six1 in cell lines and tumor tissue. Six1 protein detection is common in ovarian cancer and is associated with tumorigenicity and poor prognosis in this group of patient samples. Six1cTerm antibody should be further validated as prognostic tool.

Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes

Background:The aim of this study was to investigate the prognostic effect of tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to determine TIL clonality and to correlate this to Her2/neu expression.Methods:Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-, CD3-, CD4- and CD8-positive lymphocytes (n=100), and for Her2/neu-positive tumour cells (n=55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor γ (TCRγ) gene rearrangements (n=93/100). Statistical analyses included experimental and clinico-pathological variables, as well as disease-free (DFS) and overall (OS) survival.Results:CD20-positive B lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3-positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with improved DFS in optimally debulked patients (P=0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P=0.0201) and in those undergoing paclitaxel/carboplatin therapy (P=0.0092). Finally, rarified and clonal TCRγ gene rearrangements were detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively. This was marginally associated with improved DFS (P=0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P=0.0264), this was non-directional (R=−0.257; P=0.0626).Conclusion:Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.

XIV. Tympanogenous Labyrinthitis Resulting from an Acute Otitis Media in its Early Stages, or in its Serous Stage: Report of Two Cases

XIV. Tympanogenous Labyrinthitis Resulting from an Acute Otitis Media in its Early Stages, or in its Serous Stage: Report of Two Cases