Non-bacterial thrombotic endocarditis manifested by ventricular fibrillation in a patient with low grade ovarian carcinoma: case report and literature review.

BACKGROUND: Non-bacterial thrombotic endocarditis (NBTE) is a rare form of endocarditis notably described in patients with advanced malignancy and auto-immune diseases. It is characterized by the formation of sterile, fibrin-containing vegetations on cardiac endothelium, in the absence of positive blood cultures. It is predominantly located on the mitral- and aortic valve (AV). Vegetations in NBTE are prone to embolize. Trousseau syndrome (TS) is defined as unexplained thrombotic events that precede the diagnosis of malignancy. CASE SUMMARY: A 49-year-old pre-menopausal woman with a history of visual disturbances, recurrent deep vein thrombosis (DVT) with concurrent pulmonary emboli (PE), and uterine myomas with dysfunctional uterine bleeding was resuscitated for ventricular fibrillation. While echocardiography revealed vegetations on the AV, blood cultures remained negative. Additional work-up for the aetiology of sterile vegetations revealed a low-grade ovarian carcinoma. Cardiac analysis showed evidence of myocardial infarction in the absence of coronary atherosclerosis as a cause for ventricular fibrillation. DISCUSSION: Unexplained thrombotic events (venous, arterial, or both) warrant further investigation, e.g., with regard to TS. NBTE is a potential source of thromboembolism in TS and a rare ante-mortem finding, which prompts additional investigation of the underlying cause. In our patient, a triad of (suspected) (i) arterial/systemic embolization (i.e. visual disturbances, splenic infarction, coronary embolism), (ii) peripheral thrombophlebitis/hypercoagulability (i.e. DVT and PE), and (iii) malignancy (i.e. gynaecological abnormalities) raised suspicion of NBTE in the setting of TS. Early diagnosis and treatment of NBTE is of importance due to the high incidence of embolization, with possible fatal outcome.

Breast malignancy in female-to-male transsexuals: systematic review, case report, and recommendations for screening.

BACKGROUND: Female-to-male (FtM) transsexuals may use testosterone therapy for masculinization, which potentially influences the risk of breast cancer development. Guided by our case report, we aimed to investigate the evidence regarding the risk of testosterone therapy on breast malignancy in female-to-male transsexuals and evaluate breast cancer screening in this subgroup. METHODS: We conducted a systematic literature search according to the PRISMA checklist in June 2020 in PubMed/MEDLINE and Ovid/EMBASE. Reference lists of included articles were screened to find additional articles that met the inclusion criteria. All cohort studies and case reports evaluating breast cancer in FtM transsexuals after testosterone therapy were included. RESULTS: We found 23 cases of FtM transsexuals who developed breast cancer after testosterone therapy, including our own case. Moreover, we evaluated ten retrospective cohort studies investigating breast malignancy in the transsexual population. The cohort studies showed no elevated risk in FtM transsexuals compared to natal women. Including our own case, nine cases were described in which breast malignancy was incidentally found during routine histological examination after mastectomy. High-level evidence for a correlation between testosterone therapy and breast malignancy is missing. CONCLUSION: Few cases are described of FtM transsexuals with breast malignancy. However, cases such as these make physicians aware of the possibility of breast cancer in FtM transsexuals. Radiological screening of FtM transsexuals for breast cancer prior to mastectomy and histological screening of the mammalian tissue after mastectomy should be considered; physicians should decide together with every individual FtM transsexual if screening is necessary.

Effects of controlled ovarian stimulation on toxicity of TAC chemotherapy in early breast cancer patients.

BACKGROUND: Oocyte and embryo cryopreservation, using controlled ovarian stimulation (COS), are common fertility preservation methodologies in breast cancer patients receiving gonadotoxic neo (adjuvant) chemotherapy (CT). The effects of COS and peak estradiol levels on CT-induced side effects are unknown. PATIENTS AND METHODS: Eighteen patients with stage II and III breast cancer underwent oocyte or embryo cryopreservation at Leiden University Medical Center before receiving docetaxel, adriamycin, and cyclophosphamide (TAC) CT (COS group). A control group (N=18) was retrospectively selected from breast cancer patients, aged between 18 and 40, who underwent TAC CT without fertility preservation. CT -induced toxicity in the 2 groups was compared using χ2 analysis. Associations between peak estradiol levels and distinct stimulation protocols and side effects in the COS group were investigated by using regression analysis. RESULTS: Patient characteristics between both groups were similar, except for a lower age in the COS group vs the control group (30.5 vs 35.2 years, P=0.005). No differences were seen in grade III/IV side effects between both groups. In the COS group, an increase in thrombopenia grade I/II was seen, while grade I/II stomatitis and constipation were significantly lower in the COS group as compared with the control group (P=0.006 and P=0.008, respectively). In the COS group, no association was found between the peak estradiol levels and distinct stimulation protocols and side effects of CT. CONCLUSION: COS prior to TAC CT was not associated with an increase in grade III/IV side effects. Interestingly, COS may have a protective effect on mucositis and constipation. Moreover, the peak estradiol levels and distinct stimulation protocols had no effect on grade III/IV side effects in our study.

Lactic Acidosis in Prostate Cancer: Consider the Warburg Effect.

Lactic acidosis is a commonly observed clinical condition that is associated with a poor prognosis, especially in malignancies. We describe a case of an 81-year-old patient who presented with symptoms of tachypnea and general discomfort. Arterial blood gas analysis showed a high anion gap acidosis with a lactate level of 9.5 mmol/L with respiratory compensation. CT scanning showed no signs of pulmonary embolism or other causes of impaired tissue oxygenation. Despite treatment with sodium bicarbonate, the patient developed an adrenalin-resistant cardiac arrest, most likely caused by the acidosis. Autopsy revealed Gleason score 5 + 5 metastatic prostate cancer as the most probable cause of the lactic acidosis. Next-generation sequencing indicated a nonsense mutation in the TP53 gene (887delA) and an activating mutation in the PIK3CA gene (1634A>G) as candidate molecular drivers. This case demonstrates the prevalence and clinical relevance of metabolic reprogramming, frequently referred to as "the Warburg effect," in patients with prostate cancer.

Levels of natural IgM antibodies against phosphorylcholine in healthy individuals and in patients undergoing isolated limb perfusion.

Natural IgM antibodies against phosphorylcholine (anti-Pc IgM) resemble C-reactive protein (CRP) regarding specificity and have gained increasing attention because of their supposed role in clearance of damaged cells and in cardiovascular disease. In order to quantify these antibodies in human plasma, we have developed an ELISA system, in which p-aminophenylphosphorylcholine (PCH) coupled to human serum albumin (HSA) was coated on microtiters plates. Human plasma or serum samples were incubated in the plates, after which bound anti-Pc IgM was detected with mouse anti-human IgM-HRP. Pre-incubation of plasma with competitors such as phosphorylcholine, phosphorylethanolamine, phosphorylserine or glycine-HSA, confirmed that the ELISA was specific for anti PC IgM. Levels of anti Pc IgM in a cohort of healthy donors differed by more than 100-fold, whereas the fluctuation of anti-Pc IgM levels in individuals over time was small (coefficient of variation between 6% to 25%). Furthermore, there was no correlation between CRP and anti-Pc IgM in this cohort. Levels of anti-Pc IgM in the normal donors correlated significantly with IgM binding to apoptotic cells. To test the hypothesis that anti-Pc IgM can bind to neo-antigens expressed on necrotic or apoptotic cells, anti-Pc IgM was also quantified in patients with tumors undergoing isolated limb perfusion with tumor necrosis factor-alpha (TNF-alpha). Following this procedure, a significant decrease of circulating anti-Pc IgM relative to total IgM was found in all five patients tested. In conclusion, we have developed a specific and reproducible ELISA for anti Pc IgM quantification. Fluctuation of levels of these natural antibodies over time in healthy individuals was limited, although the variation among individuals was large. Significant decreases of levels of anti-Pc IgM were found to occur during tissue damage.