Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer

IntroductionDiabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones.Patients and MethodsOne hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d.ResultsNinety-six women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (?29%) and estradiol (?38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate.ConclusionMetformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance.     

HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.Subject terms: Diagnostic markers, Biliary tract cancer     

COVID-19 and Guillain-Barré syndrome: A single-center prospective case series with a 1-year follow-up

Single reports of Guillain-Barré syndrome (GBS) have been reported worldwide during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. While case reports are likely to be biased toward uncommon clinical presentations, systematic assessment of prospective series can highlight the true clinical features and spectrum. In this prospective, observational study, we included all consecutive patients who developed GBS. In patients with SARS-CoV-2 infection as antecedent, the time-gap between the infection and GBS onset had to be ≤30 days. The referral was a neurological University Research Hospital, in the Italian Region more severely involved by the pandemic, and hospitalizing both COVID+ and non-COVID neurological diseases. Clinical, laboratory, cerebrospinal fluid, and electromyographic features of GBS diagnosed between March 2020 and March 2021 were compared to a retrospective series of GBS diagnosed between February 2019 and February 2020 (control population). Nasopharyngeal swab was still positive at GBS onset in 50% of patients. Mild-to-moderate COVID-related pneumonia, as assessed by X-ray (6 patients) or X-ray plus computerized tomography (2 patients) co-occurred in 6 of 10 patients. GBS diagnosed during the pandemic period, including 10 COVID-GBS and 10 non–COVID-GBS, had higher disability on admission (P = .032) compared to the GBS diagnosed between February 2019 and 2020, possibly related to later hospital referral in the pandemic context. Compared to non–COVID-GBS (n = 10) prospectively diagnosed in the same period (March 2020–2021), post–COVID-GBS (n = 10) had a higher disability score on admission (P = .028), lower sum Medical Research Council score (P = .022) and lymphopenia (P = .025), while there were no differences in GBS subtype/variant, severity of peripheral involvement, prognosis and response to treatment. Cerebrospinal fluid search for SARS-CoV-2 RNA and antiganglioside antibodies were negative in all COVID+ patients. Temporal clustering of cases, coinciding with the waves of the pandemic, and concomitant reduction of the incidence of COVID-negative GBSs may indicate a role for SARS-CoV-2 infection in the development of GBS, although the association may simply be related to a bystander effect of systemic inflammation; lack of prevalence of specific GBS subtypes in post–COVID-GBS also support this view. GBS features and prognosis are not substantially different compared to non–COVID-GBS.     

Difficulties with CT-guided needle biopsy and VATS, as combined approach for the diagnosis and treatment of peripheral pulmonary nodules: a case report.

AIM: To re-evaluate the use of CT-guided needle biopsy and VATS, as our combined approach protocol for the diagnosis and treatment of peripheral pulmonary nodules. METHODS AND RESULTS: We describe the case of a male smoking patient, 50-year-old, who came to our service for the histological diagnosis of a right pulmonary lesion incidentally revealed. He was submitted to our diagnostic and therapeutic protocol for peripheral pulmonary nodules, that is a combined approach of CT-guided needle biopsy, anchorage of the lesion and VATS resection. Difficulties with this technique can raise when: 1. the cytological CT-guided needle biopsy is not diagnostic, 2. the anchorage is not successful, 3. the malignancy of the lesion cannot be surely determined by the extemporary histological examination. In this patient all these difficulties were encountered. CONCLUSIONS: We conclude that our diagnostic and therapeutic protocol for peripheral pulmonary nodules is not invalidated by this experience, even in consideration of the fact that we applied successfully the protocol in several previous cases.