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BACKGROUND: Hereditary ovarian cancers (HOC) represent about 23% of ovarian cancer (OC) cases: they are most frequently related to germline mutations in the BRCA genes. OBJECTIVE: We aimed to compare CA125/HE4 serum levels and Computed Tomography (CT) features at time of ovarian cancer (OC) diagnosis in two populations: BRCA mutant and BRCA wild-type (WT) OC, and to investigate the relationship between this laboratory and radiological biomarker and BRCA mutation status. METHODS: This retrospective study included 60 newly diagnosed OC patients with FIGO stage IIIC-IV disease, tested for BRCA1/2 germline mutation status of which preoperative CT scan and serum tumor marker assay were available. RESULTS: The median level of CA125 (708 U/mL) was significantly higher (p 2 cm (p = 0.000099), increased frequency of lymphadenopathies (p = 0.019), and metastasis (p = 0.052) compared to patients with BRCA WT. CONCLUSIONS: Tumor markers and CT patterns may help in identifying BRCA mutation status in OC directing patients towards a personalized treatment.

Currently, ovarian cancer (OC) is a target of intense biomarkers research because of its frequent late diagnosis and poor prognosis. Serum determination of Human epididymis protein 4 (HE4) is a very important early detection test. Most interestingly, HE4 plays a unique role in OC as it has been implicated not only in OC diagnosis but also in the prognosis and recurrence of this lethal neoplasm, actually acting as a clinical biomarker. There are several evidence about the predictive power of HE4 clinically, conversely less has been described concerning its role in OC oncogenesis. Based on these considerations, the main goal of this review is to clarify the role of HE4 in OC proliferation, angiogenesis, metastatization, immune response and also in the development of targeted therapy. Through a deeper understanding of its functions as a key molecule in the oncogenetic processes underlying OC, HE4 could be possibly considered as an essential resource not only for diagnosis but also for prognosis and therapy choice.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represents one of the most threatening viral infections in the last decade. Amongst susceptible individuals, infected pregnant women might be predisposed to severe complications. Despite the extensive interest in SARS-CoV-2 research, the clinical course of maternal infection, the vertical transmission and the neonatal outcomes have not been completely understood yet. The aim of our study was to investigate the association between SARS-CoV-2 infection, obstetric outcomes and vertical transmission. Methods: A prospective observational study was performed, enrolling unvaccinated pregnant patients positive for SARS-CoV-2 (cases) and matched with uninfected pregnant women (controls). Maternal and neonatal nasopharyngeal swabs, maternal and cord blood, amniotic fluid and placenta tissue samples were collected; blood samples were tested for anti-S and anti-N antibodies, and histologic examination of placental tissues was performed. Results: The cases showed a significant association with the development of some obstetric complications, such as intrauterine growth restriction and pregnancy-associated hypothyroidism and diabetes, as compared to controls; their newborns were more likely to have a low birth weight and an arterial umbilical pH less than 7. The viral genome was detected in maternal and cord blood and placental samples in six cases. Conclusions: Pregnant women positive for SARS-CoV-2 infection are more likely to develop severe obstetric outcomes; their newborns could have a low birth weight and arterial pH. Vertical transmission seems a rare event, and further investigation is strongly needed.

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 < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 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.

Purpose To correlate in COVID-19 pneumonia CT-based semi-quantitative score of pulmonary involvement with high serum levels of KL-6, a biomarker of disease severity. Methods Between March 28 to May 21, 2020, 196 patients with strong suspicion of SARS-CoV-2 were evaluated with RT-PCR for SARS-CoV-2, chest CT scan and blood test, including KL-6 serum protein, in our Emergency Unit. The final population included only patients who underwent blood sampling for KL-6 within 5 days from CT scan (n = 63), including n = 37 COVID-19-positive patients and n = 26 with negative RT-PCR testing for SARS-CoV-2 (control group). A semi-quantitative CT score was calculated based on the extent of lobar involvement (0:0%; 1, < 5%; 2:5–25%; 3:26–50%; 4:51–75%; 5, > 75%; range 0–5; global score 0–25). Results CT score was significantly correlated with serum value of KL-6 (r = 27, p = 0.035). This correlation was also present in COVID-19 positive patients (r = 0.423, p = 0.009) and CT score median value was significantly higher in patients with high KL-6 value (> 400 U/mL; 12.00, IQR 5.00-18.00, p-value 0.027). In control group, no statistically significant correlation was found between CT score and KL-6 value and CT score was higher in patients with high KL-6, although this difference was not statistically significant (5.00, IQR:1.75–8.00 versus 3.50, IQR:2.00–6.50). "Crazy paving" at the right upper (n = 8; 61.5%) and middle lobe (n = 4; 30.8%) and "consolidation" at the middle lobe (n=5; 38.5%) were observed in COVID-19 group with a significant difference between patients with high KL-6 value. Conclusion CT score is highly correlated with KL-6 value in COVID-19 patients and might be beneficial to speed-up diagnostic workflow in symptomatic cases.

Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach to harmonize HE4 values obtained with different laboratory resources. To this regard, six highly qualified Italian laboratories, using different analytical platforms (Abbott Alinity I, Fujirebio Lumipulse G1200 and G600, Roche Cobas 601 and Abbott Architett), have joined this project. In the first step of our study, a common reference calibration curve (designed through progressive HE4 dilutions) was tested by all members attending the workshop. This first evaluation underlined the presence of analytical bias in different devices. Next, following bias correction, we started to analyze biomarkers values collected in a common database (1509 patients). A two-sided p-value < 0.05 was considered statistically significant. In post-menopausal women stratified between those with malignant gynecological diseases vs. non-malignant gynecological diseases and healthy women, dichotomous HE4 showed a significantly better accuracy than dichotomous Ca125 (AUC 0.81 vs. 0.74, p = 0.001 for age ≤ 60; AUC 0.78 vs. 0.72, p = 0.024 for age > 60). Still, in post-menopausal status, similar results were confirmed in patients with malignant gynecological diseases vs. patients with benign gynecological diseases, both under and over 60 years (AUC 0.79 vs. 0.73, p = 0.006; AUC 0.76 vs. 0.71, p = 0.036, respectively). Interestingly, in pre-menopausal status women over 40 years, HE4 showed a higher accuracy than Ca125 (AUC 0.73 vs. 0.66, p = 0.027), thus opening new perspective for the clinical management of fertile patients with malignant neoplasms, such as ovarian cancer. In summary, this model hinted at a new approach for identifying the optimal cut-off to align data detected with different HE4 diagnostic tools.

One of the most urgent needs worldwide is to vaccinate against SARS-CoV-2 as many people as possible. We evaluated humoral response to Comirnaty vaccine in Thalassemia Major patients (TM). We measured SARS-CoV-2-specific antibodies against Spike protein in 57 TM patients and 58 healthy blood donors (HBD). TM and HBD subjects revealed a homogeneous serological response to the Comirnaty (Mean ± SD; TM = 1917,21 ± 1384,49; HBD = 2039,81 ± 1064,44; p = 0,5884). No statistically significant differences were observed among two groups. Interestingly, we observed in 73.3% of asplenic patients Ab-S titres above 800 BAU, whereas only in 26% of non splenectomized patients showed Ab-S titres above 800 BAU). This differences were statistically significant p 0.039. Further measurement on other Ab types was needed for better understanding humoral response to Comirnaty.

Objectives: Women of childbearing age may be affected by psoriatic arthritis (PsA) and ankylosing spondylitis (AS). The aim was to assess the impact of biological agents (bDMARDs) on the fertility of women with PsA and AS by evaluating the serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and luteinising hormone (LH). Methods: Consecutive female patients (18-45 years) affected by PsA or AS starting a bDMARD were retrospectively evaluated at baseline (T0) and after 8 months (T8) of treatment. At both visits, demographic and clinical data were obtained. AMH, LH, and FSH serum levels were measured. A population of fertile women matched for age, body mass index and smoking habit was included as healthy controls (HCs). Results: Twenty-four patients with PsA, 20 with AS, and 44 HCs were included. The median (25th-75th percentile) levels of AMH in patients were 0.74 ng/ml (0.29-2) at baseline and 0.71 ng/ml (0.19-1.9) (p=n.s.) at T8. The median levels of AMH in HCs were 1.56 ng/ml (0.37-2.90), with no difference compared to patients. No correlation was found between the serum AMH levels and the indexes of disease activity for both PsA and AS. No differences were found in the serum levels of FSH and LH before and after treatment with bDMARDs. Conclusions: Our results support the use of bDMARDs in female patients with SpA. AMH levels were not influenced by bDMARDs nor by disease activity. AMH could be useful to assess the quantitative aspect of ovarian reserve in female SpA patients.

We read with great interest the paper by Gaudio and colleagues on vitamin D and on the state of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the time of admission [...]

An unusual clonal gammopathy was reported in COVID-19 patient but whether this anomaly is related or not to the disease has not yet been clarified. To this aim, we selected a cohort of 35 COVID-19 patients swab positive and investigated serological levels of IL-6, immune response to major viral antigens and electrophoretic profile. Elevated levels of IL-6 were accompanied by a significative humoral response to viral Spike protein, revealing an altered electrophoretic profile in the gamma region. We can conclude that elevated levels of IL-6 triggers humoral response inducing a transient plasma cell dyscrasia in severe COVID-19 patients.

In December 2019 a novel coronavirus strain disease called COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in China and fast spread around the word [1]. In t...

Background To compare predictive value of MCM5 to urinary cytology (UC) for the primary diagnosis of bladder cancer (BCa). Methods We prospectively enrolled 91 patients who presented macroscopic hematuria or persistent lower urinary tract symptoms at our institution. Single voided mid-stream urine specimens were collected for UC and MCM5 (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, United Kingdom) assessment. Cystoscopy was used as confirmatory test, and positive cases underwent transurethral resection of bladder tumor with histopathological evaluation. Results Forty cases (43.9%) showed a positive cystoscopy for BCa. Histology was obtained in 37 cases: 16 (43.2%) high-grade (HG) and 21 (56.8%) low-grade (LG) transitional cell carcinoma (TCC). UC had a sensitivity of 62.5%, specificity of 86.3%, PPV of 78.1% and NPV of 74.6%. Sensitivity, specificity, PPV and NPV of MCM5 were 60.0%, 88.2%, 80.0% and 73.8%, respectively. According to tumor grade, MCM5 and UC showed a sensitivity of 47.6% and 52.4% in LG, and 87.5% and 75.0%, respectively, in HG TCC. False-positive rates were 11.8% and 13.7% of negative cases for BCa with MCM5 and UC test, whereas false-negative results were found in 40.0% and 37.5% of BCa cases, respectively. The combination of the two tests showed a sensitivity of 71.4% in LG, and 93.8% in HG TCC. Conclusion In the present analysis, MCM5 showed lower sensitivity than UC in predicting BCa primary diagnosis. According to tumor grade, MCM5 showed a higher sensitivity in the detection of HG BCa compared to UC, although values were not significantly different.

Ovarian cancer is one of the most aggressive gynaecologic malignancies in women worldwide. The lack of proper screening programs and the characteristic abdominal spreading with minimal clinical symptoms give rise of its high lethality. Most patients show advanced disease at diagnosis and have a poor prognosis. The surveillance of ovarian cancer patients after initial treatment is a challenging question in clinical practice and there is no consensus in literature about the most appropriate follow-up strategy for these women. The role of Imaging has become increasingly important, allowing to properly monitor patients, distinguishing the different relapse patterns, thus guiding the correct management and therapy. In this review, we report and analyze the scientific evidence about the role of the different imaging modalities now available in the follow-up strategy and management of Epithelial Ovarian Cancer patients with recurrent disease.

Introduction: Protein induced by vitamin K absence II (PIVKA-II) is an abnormal prothrombin increased in gastrointestinal malignancy. We aimed to evaluate PIVKA-II in comparison to established pancreatic cancer (PC) biomarkers (CA 19-9, carcinoembryonic antigen (CEA) and CA 242) measured in PC patients and in patients with benign pancreatic diseases. Materials and methods: We studied 26 PC patients (Group 1) and 20 patients with benign pancreatic diseases (Group 2). PIVKA-II and CEA were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Gent, Belgium), CA 19-9 and CA 242 were measured by ELSA (CisBio Bioassays, Codolet, France) and EIA (Fujirebio Diagnostics AB, Göteborg, Sweden), respectively. Receiver operating characteristic (ROC) analysis was performed to assess biomarkers’ diagnostic characteristics in both groups. Results: Median and interquartile range (IQR) in Group 1 and Group 2 were: 1749.0 (320.2 – 3921.0) vs. 31.0 (23.0 – 43.0) mAU/mL (P < 0.001) for PIVKA-II, 260.0 (158.7 – 272.0) vs. 45.2 (9.0 – 58.0) U/mL (P = 0.034) for CA 19-9, 104.0 (30.2 – 150.0) vs. 7.2 (4.8 – 26.0) U/mL (P < 0.050) for CA 242, 9.4 (5.3 – 37.5) vs. 4.5 (1.8 – 7.0) ng/mL (P = 0.021) for CEA. Areas under the ROC curve of PIVKA-II, CA 19-9, CA 242, CEA were 0.86 (95% CI: 0.71 – 1.00), 0.58 (95% CI: 0.38 – 0.78), 0.73 (95% CI: 0.54 – 0.92), 0.64 (95% CI: 0.44 – 0.85), respectively. Conclusions: PIVKA-II is significantly higher in PC than in benign pancreatic diseases. PIVKA-II shows a rather good diagnostic performance compared to CA 19-9, CEA and CA242, thus its determination could help PC management.

Background Pancreatic adenocarcinoma (PDAC) is an incurable cancer without adequate tumor markers. Our previous study has showed a better diagnostic performance of Protein Induced by Vitamin K Absence II (PIVKA-II) compared to currently used PDAC biomarkers. To corroborate our previous data with a larger sample size and to assess a possible role of PIVKA-II in predicting surgical success. Additionally, to further evaluate the hypothesis of a direct PIVKA-II production by PDAC cells, we examined PIVKA-II tissue expression in a case of PDAC using immunofluorescence. Methods We enrolled 76 newly diagnosed PDAC patients and selected 11 patients to determine PIVKA-II levels also after surgical resection. An immunofluorescence (IF) study of PIVKA-II tissue expression was carried out in one of them. PIVKA-II serum values were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Belgium). Results PIVKA-II serum levels were above the cut-off at baseline in 71 patients (94%) with a median value of 464 mAU/Ml (range 27–40783 mAU/mL); the sensitivity and specificity were 78.67% and 90.67% respectively. Patients with pre-operative PIVKA-II positivity showed a significant decrease (P < 0.015) of median PIVKA-II serum concentrations after surgery: 820 (91–40783) mAU/mL at diagnosis vs 123 (31–4666) mAU/mL post-operatively. IF assay on PDAC sections demonstrated PIVKA-II expression in cancer cells. Conclusion These data are the first showing a decreased PIVKA-II serum levels after surgery in PDAC patients and reporting PIVKA-II expression in PDAC tissue. Further studies are needed to confirm these findings and to determine PIVKA-II usefulness in diagnosing and monitoring PDAC patients.

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.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.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.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.

Background Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis. Materials and methods Consecutive sera from obese patients, 444 with NGT, 322 with T2D, and 212 controls were analysed by radioimmunoassay or enzyme-linked immunosorbent assay for glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen-2 (IA-2)IC and IA-2(256-760) , islet beta-cell zinc cation transporter (ZnT8), thyroid peroxidase, and anti-parietal cell autoantibodies. Results Altogether the presence of organ-specific autoantibodies was significantly more frequent in obese patients with NGT (128/444, 28.5%) and obese with T2D (79/322, 24.5%) than in controls (36/212, 17%; P = 0.002). Thyroid peroxidase immunoreactivity was prevalent in all groups of subjects investigated. The frequencies of diabetes-specific autoantibodies were slightly higher in obese patients with NGT (20/444, 4.5%) than in obese with T2D (12/322, 3.7%) and controls (4/212, 1.9%). The anti IA-2(256-760) was the most frequent islet autoantibody in obese subjects with NGT (14/20, 70%). Conclusions We observed significant evidence of immunoreactivity specific to diabetes, thyroid, and gastric-parietal cells in obese patients with NGT. The relatively higher frequency of the diabetes-related IA-2(256-760) autoantibodies in obese patients with NGT may suggest that this autoantibody could be associated with obesity the presence of obesity itself.

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.

Prostate cancer is the most common tumor in men. To the best of our knowledge a systematic assessment of bone and mineral abnormalities has not been performed in prostatic cancer patients consecutively enrolled. This study was therefore carried out to investigate changes of skeletal and mineral metabolism in patients with prostate cancer (n = 69). A population of patients with cancer of various origin was also investigated as a control group (n = 53), since a comparison with non-prostate cancer patients has not been previously reported. In the prostatic cancer group, one patient had extremely high values of C-terminal Fibroblast Growth Factor 23, low values of tubular reabsorption of phosphate and very high values of bone alkaline phosphatase, suggesting the diagnosis of oncogenic osteomalacia. We found nine patients with primary hyperparathyroidism in the group of prostate cancer vs. only one in cancer patients group (p

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

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 specialized 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.

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.

Objectives To evaluate the sacral nerve root features by the means of magnetic resonance imaging–diffusion tensor imaging (MRI-DTI) tractography in women with endometriosis and/or adenomyosis, and to analyze the correlations among DTI abnormalities, pain symptoms, and endometriotic lesions found at surgery. Design A cross-sectional, observational study (Canadian Task Force classification II-2). Setting University hospital. Patients Women (n = 76) with clinical suspicion of endometriosis. Interventions Before surgery, dysmenorrhea, deep dyspareunia, and noncyclic pelvic pain (NCPP) were assessed using a 10-point visual analog scale. MRI enabled a 3-dimensional reconstruction of S1, S2, and S3. Fractional anisotropy was calculated for each root. Laparoscopic treatment of endometriosis was performed in 56 patients. Measurements and Main Results Our findings revealed correlations among sacral root reconstruction by MRI-DTI, pain symptoms, and laparoscopic findings. DTI of sacral roots revealed a regular and homogeneous appearance in 17 patients (25.8%) and abnormalities in microstructure reconstruction, with fiber irregularities and disorganization and loss of the simple unidirectional course, in 44 patients (66.7%). At laparoscopy, ovarian endometriomas were found in 82.1% of the patients, and deeply infiltrating endometriosis (DIE) were found in 57.1%. Endometriosis was staged according to the revised American Society for Reproductive Medicine classification. Pathological DTI findings were significantly associated with the severity of dysmenorrhea and NCPP, pain duration, presence of tubo-ovarian and cul-de-sac adhesions, and DIE. Conclusion The presence of pathological DTI findings of the sacral nerve roots correlates with the type of pain, adhesions, and DIE. At present, DTI can be useful for providing a better understanding of pain; however, DTI could become a useful tool in therapeutic planning for patients with endometriosis.

As the knowledge on cancer genetic alterations progresses, it fosters the need for more personalized therapeutic intervention in modern cancer management. Recently, mutations in KRAS, BRAF, and PIK3CA genes have emerged as important mechanisms of resistance to EGFR-targeted therapy in metastatic colorectal cancer (mCRC). Here we report the first case of a mCRC patient whose disease had progressed on standard lines of treatment and for which we devised a personalized therapeutic approach consisting of vemurafenib (ZelborafTM) and panitumumab (VectibixTM), based on the following molecular profile: BRAFV600E-mutant, amplified EGFR (double positive) and WT KRAS, WT PIK3CA, not-amplified HER2 (triple negative). This new combination therapy was well tolerated and resulted in a strong control of the disease. In particular, the vemurafenib-panitumumab combination appears to limit the typical toxicity of single agents, since no cutaneous toxic effects typically associated with vemurafenib were observed. Here we report the first clinical evidence that the combination of an anti-EGFR (panitumumab) and an inhibitor of BRAFV600E (vemurafenib) is well tolerated and results in a strong disease control in an extensively pretreated mCRC patient.

Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer.Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer.Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) ().Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels.

Tumor markers are commonly used to detect a relapse of disease in oncologic patients during follow-up. It is important to evaluate new assay systems for a better and more precise assessment, as a standardized method is currently lacking. The aim of this study was to assess the concordance between an automated chemiluminescent enzyme immunoassay system (LUMIPULSE® G1200) and our reference methods using seven tumor markers. Serum samples from 787 subjects representing a variety of diagnoses, including oncologic, were analyzed using LUMIPULSE® G1200 and our reference methods. Serum values were measured for the following analytes: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 19 fragment (CYFRA 21-1). For the determination of CEA, AFP, and PSA, an automatic analyzer based on chemiluminescence was applied as reference method. To assess CYFRA 21-1, CA125, CA19-9, and CA15-3, an immunoradiometric manual system was employed. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 0.9728 to 1.9089 and correlation coefficients from 0.9977 to 0.9335. The precision of each assay was assessed by testing six serum samples. Each sample was analyzed for all tumor biomarkers in duplicate and in three different runs. The coefficients of variation were less than 6.3 and 6.2 % for within-run and between-run variation, respectively. Our data suggest an overall good interassay agreement for all markers. The comparison with our reference methods showed good precision and reliability, highlighting its usefulness in clinical laboratory's routine.

AIM To evaluate whether obesity represents a risk factor for the onset of ovarian cancer. PATIENTS AND METHODS One hundred and sixty-three patients with a body mass index (BMI) >30 kg/m2 (group 1) and 130 women with a BMI of 13%) was found in 24.5% of group 1 patients, whereas a high ROMA score was identified in 5.3% of group 2 women. During the study, 13 out of 40 group 1 patients with ROMA >13% were deemed eligible for bariatric surgery. After bariatric surgery and decrease of BMI, eight out of these 13 obese women had a ROMA index

Aim To compare analytical characteristics between two different methods, a automated chemiluminescent immunoassay (CLIA) versus a radioimmunometric assay (RIA), for the determination of carbohydrate antigen 19-9 (CA19-9). Materials and methods One hundred and eighty-five blood samples from consecutively enrolled individuals (87 males and 98 females, aged 22-89 and 29-89 years, respectively) were evaluated. For both assays, a cut-off of 37 U/ml was used. Results Comparison between assays was analyzed using Passing-Bablok regression, which showed a high inter-assay correlation (r=0.926). The mean intra-assay coefficient of variation was 17.6% (range=6.1-50.7%) for the RIA (n=10 samples) and 5.2% (range=0.4-17.0%) for the CLIA assay (n=26 samples). Conclusion This study showed that CLIA for CA19-9 has a good reliability on all samples analyzed and should be preferred to RIA with the aim of reducing costs, greater standardization and more harmonized results.

Type 2 diabetes is characterized by peripheral insulin resistance, pancreatic beta-cells dysfunction, and decreased beta-cell mass with increased rate of apoptosis. Chronic exposure to high levels of free fatty acids (FFAs) has detrimental effects on beta-cell function and survival. FFAs have adverse effects on mitochondrial function, with a consequent increase in the production of reactive oxygen species. Hepatocyte growth factor (HGF) plays a critical role in promoting beta-cell survival. In the present study, we investigated whether HGF was capable of protecting beta-cells from death induced by prolonged exposure to FFAs. RINm5F cell line was cultured in the presence of FFAs (oleate:palmitate 2:1) for 72 h in order to induce apoptosis. Simultaneous administration of HGF and FFAs significantly suppressed the impaired insulin secretion and FFA-induced apoptosis. Specifically, HGF exerted its protective effect by counteracting: (i) the overproduction of either hydrogen peroxide and superoxide anion, (ii) the reduction of intracellular gamma-glutamylcysteinylglycine level, and (iii) the depolarization of mitochondrial membrane, induced by prolonged FFAs exposure. These effects appear to be mediated by bcl-2 and phosphatidylinositol 3 kinase (PI3K)/Akt pathways. Indeed, HGF increased mRNA and protein expression of bcl-2 downregulated by FFAs-treatment; moreover, pre-treatment with the specific PI3-kinase inhibitor LY294002, significantly abolished the protective effect of HGF. In conclusion, in rat insulin-producing RINm5F cells, HGF exerts its prosurvival effect by counteracting the increased intracellular oxidative stress and, consequently, by inhibiting apoptosis induced by chronic exposure to FFAs.

We present a case of a 58-year-old menopausal woman referred to our hospital for the presence of large pelvic masses diagnosed by clinical examination and pelvic ultrasound. MRI examination showed voluminous bilateral capsulated multilocular ovarian cysts slightly hyperintense on T1-weighted images with thick septa and small papillary projections. CT scan confirmed the MRI findings. Among the ovarian tumor markers analyzed (CA125, HE4, and CA72.4), only Ca125 was slightly increased (48 U/ml). These data were suggestive of mucinous ovarian tumor. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, appendectomy, and multiple peritoneal biopsies. Pathological examination revealed bilateral borderline mucinous ovarian tumor with superficial atypical implants. Nine months later, the patient complained of left coxofemoral pain and underwent a PET/TC total body that suggested pubic bone metastases. Ovarian tumor markers were analyzed, and a second PET/TC was performed. CA125 was 252 U/ml, HE4 62 pM/L, and CA72.4 > 100 U/Ml. PET/TC was suggestive of peritoneal carcinosis. The patient was readmitted to the hospital. Clinical examination revealed small vaginal nodules. All nodules were excised. Microscopic analysis of all specimens revealed metastatic mucinous adenocarcinoma of intestinal type.The case shows that even a slight CA125 increase in the presence of a borderline ovarian tumor should not be overlooked since it can be indicative of a progressive disease. This case also highlights its additional diagnostic value when serum CA125 analysis is used in conjunction with MRI and CT imaging for the prognosis of mucinous borderline ovarian tumors (mBOTs).

It is well known that a high number of celiac patients may develop autoantibodies against endocrine glands, but it has not yet been clarified if this increased autoimmune response and the impaired organ function that can develop may be related to the presence or absence of gluten in the diet. The aim of the present study was to evaluate the effect of gluten on the autoimmunity and function of the endocrine glands in adolescent celiac patients.To clarify this aspect we investigated 44 patients (28 females), aged 11-20 yr (15.21+/-2.7 yr): 25 (mean age, 15.1+/-2.2 yr) on a gluten-free diet (treated patients) and 19 (mean age 15.4+/-2.9 yr) with a diet containing gluten (untreated patients). Forty adolescent subjects, aged 14-19 yr (mean age, 14.9+/-2.7 yr), of whom 20 were females, were studied as controls. Antibodies against the thyroid, adrenal, and pancreas were evaluated. Thyroid-stimulating hormone FT3, FT4, T3, T4, dehydroepiandrosterone sulphate, 17-OH progesterone, and cortisol, analyzed basally and 60 min after intravenous ACTH stimulation, were assayed to evaluate thyroid and adrenal function. The fasting glycemia level was used to evaluate the endocrine pancreas function. An ultrasonogram of the thyroid gland was performed on all patients. HLA class II typing for DR3 and DQB1 was performed in 32 of 44 patients.Seven of 44 (15.9%) patients were positive for antibodies against peroxidase. Six of 44 (13.6%) were positive for antibodies against thyreoglobulin and four of them also showed positive antibodies against peroxidase. Therefore, in nine of 44 at least one antibody directed against thyroid tissue was positive. Seven of 44 (15.9%) were positive for antibodies against islet cell, one of 44 (2.3%) positive for antibodies against glutamic acid decarboxilase, one of 44 (2.3%) positive for antibodies against insulin, and none for antibodies against islet cell- 512bdc. In 15 of 44 (34%) at least one antibody against an endocrine tissue was positive. The genotype DR3 was found in 21 of 32 (65.6%) celiac patients (10 in the untreated and 11 in the treated group, respectively) and the genotype DQB1*02 (DQ2) was found in 30 of 32 (93.8%) patients (16 in the treated and 14 in the untreated group, respectively). DHA-S values were significantly lower in the untreated (30.5+/-28.5 microg/dl) than in the treated group (61.3+/-59.4 microg/dl, p0.05), and both showing significantly (p0.01) lower levels with respect to the controls (161+/-52 microg/dl). One patient showed diabetes, another one clinical hypothyroidism (thyroid-stimulating hormone6), and two patients showed preclinical hypothyroidism. Interestingly, at least one antibody was positive in 10 of 19 untreated patients (52.6%) but only in five of 25 treated patients (20%), with a significantly different distribution (p0.001) between the two groups and without differences in the HLA genotype. The ultrasonographic evaluation of the thyroid resulted in a pathological score in six patients of the 44 examined (13.6%), suggesting the presence of thyropathy.The main results of this study are the high incidence of thyroid and pancreatic antibodies, and the possible role of gluten in the induction of the antibodies as well as, in few cases, the consequent organ dysfunction.

OBJECTIVE: To evaluate the existence of beta-cell differentiation and proliferation in the low-dose streptozotocin (ld-STZ) mouse model of autoimmune diabetes. DESIGN: We studied the expression of Reg protein and cytokeratin 20 (CK20), the presence of proliferative phenomena (judged by the incorporation of bromodeoxyuridine (BrdU)), and the co-expression of Reg, CK20 or BrdU with insulin. MATERIALS AND METHODS: Diabetes was induced in male C57Bl6/J mice by administration of ld-STZ. The animals were killed at days 10 and 23 from the beginning of the induction of disease. Five animals were used at each time point and each group was evaluated for blood glucose concentrations, insulitis, expression of Reg and CK20 pancreatic proteins and BrdU incorporation, together with staining for insulin by immunohistochemistry and laser confocal microscopy. RESULTS: All mice treated with ld-STZ were hyperglycemic and histological investigation showed a mild or severe insulitis both at day 10 and at day 23. At day 10, immunochemistry revealed an intense expression of Reg and CK20 in pancreatic ducts in ld-STZ mice, but not in control mice. Reg and CK20 immunoreactive cells were also positive for insulin. In contrast, at day 23, pancreatic sections reacted weakly with anti-Reg and anti-CK20 antibody; co-localization with insulin was observed for both Reg and CK20. The incorporation of BrdU was observed only in insulin-positive cells in pancreatic sections from mice killed at day 10. CONCLUSIONS: These observations show an islet regeneration mechanism in response to an autoimmune attack, and that the ld-STZ mouse is a suitable model in which to evaluate intervention strategies.

To verify whether autoimmune markers related to nervous system structures and other autoimmunity indexes present in diabetes mellitus are associated with subclinical neuropathy, we examined 48 non-insulin-dependent diabetic patients with and without neuroelectrophysiological alterations. Nerve conduction velocity at the external sciatic-popliteal nerve, at the sural nerve, at the median and ulnar nerves level has been evaluated. Autoimmunity was investigated by evaluating glutamic acid decarboxylase (GAD-Ab), insulin (IAA), GM3, GD3 and GT1b gangliosides, pancreatic islet cell (IC-A) and anti-nervous-tissue autoantibody presence. Nerve conduction velocities were decreased in 72.9% of diabetic patients. Anti-insulin antibodies were detected in seven non-insulin created diabetic patients and in higher amount in subjects with (17.1%) than in those without (7.7%) asymptomatic neuropathy. Anti-GM3 antibodies were detected in four diabetic patients all of whom presented neurological complication. A significant correlation has been found between neurological damage and presence of anti-insulin antibodies (p