Linking type 2 diabetes and gynecological cancer: An introductory overview

Type 2 diabetes (T2D) is a chronic disease with a growing prevalence and a leading cause of death in many countries. Several epidemiological studies observed an association between T2D and increased risk of many types of cancer, such as gynecologic neoplasms (endometrial, cervical, ovarian and vulvar cancer). Insulin resistance, chronic inflammation and high free ovarian steroid hormones are considered the possible mechanisms behind this complex relationship. A higher risk of endometrial cancer was observed in T2D, even though this association largely attenuated after adjusting for obesity. A clear relationship between the incidence of cervical cancer (CC) and T2D has still not be determined; however T2D might have an impact on prognosis in patients with CC. To date, studies on the association between T2D and ovarian cancer (OC) are limited. The effect of pre-existing diabetes on cancer-specific mortality has been evaluated in several studies, with less clear results. Other epidemiological and experimental studies focused on the potential role of diabetes medications, mainly metformin, in cancer development in women. The correct understanding of the link between T2D and gynecologic cancer risk and mortality is currently imperative to possibly modify screening and diagnostic-therapeutic protocols in the future

HE4 in the differential diagnosis of ovarian masses

Ovarian masses, a common finding among pre- and post-menopausal women, can be benign or malignant. Ovarian cancer is the leading cause of death from gynecologic malignancy among women living in industrialized countries. According to the current guidelines, measurement of CA125 tumor marker remains the gold standard in the management of ovarian cancer. Recently, HE4 has been proposed as emerging biomarker in the differential diagnosis of adnexal masses and in the early diagnosis of ovarian cancer. Discrimination of benign and malignant ovarian tumors is very important for correct patient referral to institutions specializing in care and management of ovarian cancer. Tumor markers CA125 and HE4 are currently incorporated into the Risk of Ovarian Malignancy Algorithm” (ROMA) with menopausal status for discerning malignant from benign pelvic masses. The availability of a good biomarker such as HE4, closely associated with the differential and early diagnosis of ovarian cancer, could reduce medical costs related to more expensive diagnostic procedures. Finally, it is important to note that HE4 identifies platinum non-responders thus enabling a switch to second line chemotherapy and improved survival

Low 25-OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer.

The objective of this study was to evaluate the correlation between 25-OH vitamin D and ovarian cancer as a diagnostic marker or recurrence disease marker. We studied the following: (1) 61 women without gynecologic diseases, (2) 45 women affected by benign ovarian disease, (3) 46 women with recent diagnosis of ovarian cancer, (4) 26 follow-up women with recurrent ovarian cancer, and (5) 32 follow-up women with stable ovarian cancer. The 25-OH vitamin D was quantified with LUMIPULSE® G 25-OH vitamin D on LUMIPULSE® G 1200 (Fujirebio, Japan). As a threshold value, identified by ROC curve analysis, 20.2 ng/mL (sensitivity 73.3 %, specificity 84 %) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the WHO. Low 25-OH vitamin D levels were observed in 26 % of women without gynecologic diseases, in 80 % of women with recent diagnosis of ovarian cancer and in 24 % women affected by benign ovarian diseases (p < 0.001). The follow-up study showed an insufficient level of 25-OH vitamin D in 73 % women with recurrent ovarian cancer and in 47 % women with stable ovarian cancer (p < 0.0003). This study showed that patients with ovarian cancer are often insufficient in 25-OH vitamin D compared to women with benign ovarian diseases. The women with recurrent ovarian cancer presented more often low levels compared to women with stable ovarian cancer. This study suggests that 25-OH vitamin D, due to its antiproliferative properties, can be a good marker for ovarian cancer also

Magnetic resonance imaging tumor regression shrinkage patterns after neoadjuvant chemotherapy in patients with locally advanced breast cancer: correlation with tumor biological subtypes and pathological response after therapy

The objective of this study is to analyze magnetic resonance imaging shrinkage pattern of tumor regression after neoadjuvant chemotherapy and to evaluate its relationship with biological subtypes and pathological response. We reviewed the magnetic resonance imaging studies of 51 patients with single mass-enhancing lesions (performed at time 0 and at the II and last cycles of neoadjuvant chemotherapy). Tumors were classified as Luminal A, Luminal B, HER2+, and Triple Negative based on biological and immunohistochemical analysis after core needle biopsy. We classified shrinkage pattern, based on tumor regression morphology on magnetic resonance imaging at the II cycle, as concentric, nodular, and mixed. We assigned a numeric score (0: none; 1: low; 2: medium; 3: high) to the enhancement intensity decrease. Pathological response on the surgical specimen was classified as complete (grade 5), partial (grades 4-3), and non-response (grades 1-2) according to Miller and Payne system. Fisher test was used to relate shrinkage pattern with biological subtypes and final pathological response. Seventeen patients achieved complete response, 25 partial response, and 9 non-response. A total of 13 lesions showed nodular pattern, 20 concentric, and 18 mixed. We found an association between concentric pattern and HER2+ (p &lt; 0.001) and mixed pattern and Luminal A lesions (p &lt; 0.001). We observed a statistical significant correlation between concentric pattern and complete response (p &lt; 0.001) and between mixed pattern and non-response (p = 0.005). Enhancement intensity decrease 3 was associated with complete response (p &lt; 0.001). Shrinkage pattern and enhancement intensity decrease may serve as early response indicators after neoadjuvant chemotherapy. Shrinkage pattern correlates with tumor biological subtypes

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients

OBJECTIVE: As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies. MATERIALS AND METHODS: Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE(®) G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects. RESULTS: The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases. CONCLUSIONS: The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice

Monitoring the infection of SARS-CoV-2 and the development of diagnostic tools

Several issues are still unclear about the COVID-19 pandemic infection. The spreading of the infection throughout the world shows striking differences. In the present survey is described the prevalence of SARS-CoV-2 infection as reported in internationally updated online registers, comparing reported cases and deaths per million of inhabitants. Analysis of the data reflects a wide range among the continents and within each geographic area there are important differences among different countries. A focus on the Italian regions describes significant differences in terms of cases between North and South Italy in August 2020, a situation that reflects the diffusion of the SARS-CoV-2 infection in the period of February-April 2020. The scenario becomes completely different in October; indeed the number of cases and hospitalized patients shows an increase of 20-fold with respect to August 2020. Tools for the diagnosis of SARS-CoV-2 infection have become pivotal in the efforts to control the infection and monitor infected subjects. In the present report the different tests currently available are described as well as their usefulness in the present situation and their potential usage once the campaign for mass vaccination is effective

Role of galectin-3 combined with multi-detector contrast enhanced computed tomography in predicting disease recurrence in patients with ovarian cancer

Galectin-3 (Gal-3) is an endogenous β-galactoside-binding lectin, playing an important role in the pathogenesis of multiple malignancies. Aim of the study was to evaluate in a group of patients treated for ovarian cancer (EOC), the role of Gal-3 combined with multi-detector contrast-enhanced computed tomography (MDCT), as predictor of recurrence disease. Seventeen follow-up patients with recurrent ovarian cancer and 13 follow-up patients with stable ovarian disease, who performed MDCT at one-year follow-up after cytoreductive treatment, were enrolled. Serum Gal-3 concentrations were determined by using ELISA method. Twenty healthy controls were included in the analysis. Two radiologist blinded to patients status, reviewed MDCT exams, recording the following signs of disease recurrence: local tumor spread, enlarged lymph-nodes, carcinomatosis implants and metastases. We calculated the respective threshold values of Gal- 3 identified by ROC curve analysis for each imaging findings related to disease recurrence : lymphoadenopathies 92.45 ng/ml (AUC: 0.81, Se=91% Spe=73%), carcinomatosis 85.95 ng/ml (AUC:0.93 Se= 93.7%, Spe=92.8%), local tumor spread 99.05 (AUC:0.90, Se=100%, Spe=73% ) and metastasis 99.05ng/ml (AUC :0,78, Se=100% , Spe=70%). A significant correlation between high Gal-3 serum levels and presence of local tumor spread (n=11/17, p:0.001), carcinomatosis (n=16/17, p:0.00), lymphoadenopathies (n=15/17, p:0.00) and metastasis (n=11/17, p:0.003) related with recurrence disease was observed. Patients with recurrence of ovarian cancer presents higher Gal-3 values compared to women with stable diseases. Gal-3 combined to CECT should be used to improve the monitoring of EOC patients

Endometriosis: 10 keys points for MRI

Endometriosis is a chronic disease and a clinical problem in women of fertile age, with a high impact on quality of life, work productivity and health care management. Two imaging modalities are employed in the diagnosis and evaluation of extent of disease: ultrasound examination with endovaginal approach and magnetic resonance imaging (MRI). MRI, thanks to its high contrast and resolution characteristics, offers a high level of accuracy in the study of endometriosis and adenomyosis. We illustrate here 10 key MRI points for the detection and diagnosis of endometriosis

Anti-N SARS-CoV-2 assays for evaluation of natural viral infection

Background: The 2019 coronavirus (COVID-19) epidemic, required the development of different diagnostic tests. While reverse transcriptase real-time PCR (RT-PCR) remains the first-line test of choice in acute infection diagnosis, anti-N antibodies serological assays provide a valuable tool to differentiate natural SARS-CoV-2 immunological response from that induced by vaccination, thus the goal of our study was to evaluate three serological tests agreement for these antibodies detection. Methods: Three anti-N different tests were examined in 74 sera from patients referred or not COVID infection: immunochromatographic rapid test (Panbio™ COVID-19 IgG/IgM Rapid Test Device Abbott, Germany), ELISA kit (NovaLisa® SARS-CoV-2 IgG and IgM NovaTech Immunodiagnostic GmbH, Germany) and ECLIA immunoassay (Elecsys® Anti-SARS-CoV-2 Roche Diagnostics, Manheim, Germany). Results: Qualitative comparison of the three analytical methods revealed a moderate agreement between ECLIA immunoassay and immunochromatographic rapid test (Cohen kappa coefficient κ = 0.564). Correlation analysis indicated weak positive correlation between total Ig (IgT) detected by ECLIA immunoassay and IgG by ELISA test (p &lt; 0.0001), the analysis of ECLIA IgT and IgM ELISA detected, showed no statistical correlation. Conclusion: Comparison between of three analytical systems available for anti-N SARS-CoV-2 IgG and IgM antibodies showed a general agreement when compared to detect total and G class immunoglobulins, while doubtful or discordant results have been highlighted for IgT and IgM class. Anyway, all the tests examined provide reliable results to assess the serological status of SARS-CoV-2 infected patients

Efficacy of n-acetylcysteine on endometriosis-related pain, size reduction of ovarian endometriomas, and fertility outcomes

Abstract: Background: Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels. Methods: Patients aged between 18–45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated. Results: One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p &lt; 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p &lt; 0.0001) and the serum levels of Ca125 (p &lt; 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001). Conclusions: Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis