Molecular basis and therapeutic targets in prostate cancer: A comprehensive review.

Prostate cancer is one of the most significant causes of morbidity and mortality in male patients. The incidence increases with age, and it is higher among African Americans. The occurrence of prostate cancer is associated with many risk factors, including genetic and hereditary predisposition. The most common genetic syndromes associated with prostate cancer risk are BRCA-associated hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. Local-regional therapy, i.e., surgery is beneficial in early-stage prostate cancer management. Advanced and metastatic prostate cancers require systemic therapies, including hormonal inhibition, chemotherapy, and targeted agents. Most prostate cancers can be treated by targeting the androgen-receptor pathway and decreasing androgen production or binding to androgen receptors (AR). Castration-resistant prostate cancer (CRPC) usually involves the PI3K/AKT/mTOR pathway and requires targeted therapy. Specific molecular therapy can target mutated cell lines in which DNA defect repair is altered, caused by mutations of BRCA2, partner and localizer of BRCA2 (PALB2), and phosphatase and tensin homolog (PTEN) or the transmembrane protease serine 2-ERG (TMPRSS2-ERG) fusion. Most benefits were demonstrated in cyclin dependent-kinase 12 (CDK12) mutated cell lines when treated with anti-programmed cell death protein 1 (PD1) therapy. Therapies targeting p53 and AKT are the subject of ongoing clinical trials. Many genetic defects are listed as diagnostic, prognostic, and clinically actionable markers in prostate cancer. Androgen receptor splice variant 7 (AR-V7) is an important oncogenic driver and an early diagnostic and prognostic marker, as well as a therapeutic target in hormone-resistant CRPC. This review summarizes the pathophysiological mechanisms and available targeted therapies for prostate cancer.

Basic cardiovascular risk assessment in naïve patients with colon cancer.

Cardiovascular assessment of oncological patients suggests that cancer can lead to subclinical damage of the heart. The aim of the present study was to analyze the value of baseline cardiovascular biomarkers in patients with newly diagnosed colon cancer prior to treatment. Additionally, another aim was to establish baseline cut-off alert values for this low-intensity neoplastic damage. A total of 51 patients with newly diagnosed colon cancer, without history of cardiac disease, were enrolled in a prospective, cross-sectional study. All patients underwent clinical, biochemical and basic echocardiographic evaluation before starting treatment. Patients were assessed for myocardial damage using high-sensitivity troponin T (hs-TnT), creatine kinase-MB (CK-MB) and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A group of 28 healthy controls was included for comparison. Cardiac ultrasound revealed similar left ventricular (LV) ejection fraction but enlarged LV chambers compared with the control group (LV at end systole, 29.50 vs. 26.00 mm; LV at end diastole, 44.50 vs. 38.00 mm; P<0.001 in both cases). The levels of cardiovascular biomarkers of myocardial damage were higher in the patients than in the control group (CK-MB, 17.00 vs. 11.00 IU/l, P<0.001; hs-TnT, 8.20 vs. 3.00 ng/l, P<0.001; NT-proBNP, 155.40 vs. 48.50 pg/ml, P=0.001). In multivariate analysis, CK-MB and hs-TnT retained statistical significance (P=0.004 and P=0.045, respectively). Moreover, it was demonstrated that new cut-offs for hs-TnT (8.00 ng/l) and NT-proBNP (220.00 pg/ml) can identify cardiac damage in patients ≥65 years old. Thus, the present study confirmed the hypothesis that a basic cardiovascular assessment of treatment-naïve patients with colon cancer can identify important pre-treatment myocardial impact. Adapted cut-off values should be set for cardiovascular biomarkers in the cancer population, different from those currently accepted for acute coronary syndromes or heart failure.

Gastrointestinal Manifestations and Treatment Options in Fabry Disease Patients. A Systematic Review.

BACKGROUND AND AIMS: Fabry disease (FD) is a rare chronic genetic disorder that presents under a paucity of symptoms. Gastrointestinal (GI) involvement is a common event and can sometimes be debilitating, but relatively often it is overlooked. We aimed to provide a systematic review of main GI symptoms in FD patients and treatment possibilities. METHODS: We completed a systematic review of literature, using the MeSH terms: "Fabry disease", "gastrointestinal", "gastrointestinal", "digestive", "manifestations", "symptoms", "clinical", "treatment", "therapy" and the supplementary concepts "enzyme replacement", "chaperone", "Migalastat", in different combinations, with defined inclusion and exclusion criteria. RESULTS: From 221 initial studies identified, through our selection process we included a final date base of 51 articles on GI signs and symptoms and their treatment. The primary GI manifestations of the disease consist of abdominal pain, bowel movement disorders or nausea and vomiting. Less frequent manifestations such as diverticular bowel disease, gastroesophageal reflux or achalasia have also been described. Main treatment options in FD are represented by enzyme replacement therapy and chaperone treatment. Patients presenting with GI symptoms unfortunately do not always respond to enzyme replacement, necessitating symptomatic relief. CONCLUSION: Fabry disease is a rare disease that often involves the GI tract, affecting patients' quality of life and burdening the healthcare system. Physicians must be aware of the multitude of manifestations in this category of patients, to promptly recognize and treat them.

Zinner syndrome - case report.

We present the case of a 51-year-old male with Zinner syndrome, which is a rare disease, resulting from an abnormal evolution of the mesonephric (Wolffian) duct. It consists in cystic dilations of one seminal vesicle and/or ejaculatory duct and ipsilateral renal agenesis. It leads to symptoms related to urination, ejaculation, even infertility, and to low-abdomen and perineal pain. The diagnosis is set by ultrasonography, CT scan and, mainly, MRI. Usually it is treated conservatively, but certain cases require surgery, nowadays minimally invasive.

Liver Injury and Elevated FIB-4 Define a High-Risk Group in Patients with COVID-19.

Liver involvement in Coronavirus Disease 2019 (COVID-19) has been widely documented. However, data regarding liver-related prognosis are scarce and heterogeneous. The current study aims to evaluate the role of abnormal liver tests and incidental elevations of non-invasive fibrosis estimators on the prognosis of hospitalized COVID-19 patients. We conducted a retrospective cohort study to investigate the impact of elevated liver tests, non-invasive fibrosis estimators (the Fibrosis-4 (FIB-4), Forns, APRI scores, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio), and the presence of computed tomography (CT)-documented liver steatosis on mortality in patients with moderate and severe COVID-19, with no prior liver disease history. A total of 370 consecutive patients were included, of which 289 patients (72.9%) had abnormal liver biochemistry on admission. Non-survivors had significantly higher FIB-4, Forns, APRI scores, and a higher AST/ALT ratio. On multivariate analysis, severe FIB-4 (exceeding 3.25) and elevated AST were independently associated with mortality. Severe FIB-4 had an area under the receiver operating characteristic (AUROC) of 0.73 for predicting survival. The presence of steatosis was not associated with a worse outcome. Patients with abnormal liver biochemistry on arrival might be susceptible to a worse disease outcome. An FIB-4 score above the threshold of 3.25, suggestive of the presence of fibrosis, is associated with higher mortality in hospitalized COVID-19 patients.

Spontaneous cholecystocutaneous fistula as a primary manifestation of gallbladder adenocarcinoma associated with gallbladder lithiasis - case report.

Spontaneous cholecystocutaneous fistula (SCF) is a rare complication of neglected calculous biliary disease and also an extremely rare complication of gallbladder neoplasm. This pathology has become even rarer because of prompt diagnosis and expedient surgical intervention for gallstones. So far, there is one published report of a SCF due to gallbladder adenocarcinoma. We present the case of a woman aged 87 years, admitted to the Vth Department of Surgery, Clinical Municipal Hospital of Cluj-Napoca (Romania) for a tumoral mass located in the epigastrium. In the epigastrium, the patient had three skin orifices of about 1-2 mm each, through which purulent secretion occurred. The abdominal ultrasound highlighted a cholecystocutaneous fistula with the presence of a subcutaneous gallstone. Intraoperatively, we found a cholecystocutaneous fistula, a 1 cm subcutaneous gallstone, gallbladder with thickened walls containing a cylinder-shaped gallstone of 5÷3 cm. Fistulectomy, gallstones extraction and cholecystectomy were performed. The histopathological examination highlighted gallbladder adenocarcinoma. In conclusion, SCF can be the first significant manifestation of gallbladder cancer associated with neglected calculous biliary disease.

Abdominal aortic aneurysm--online methods of patient education.

The authors present some of the most important online methods of patient education on diagnosis and treatment of abdominal aortic aneurysm (easy-to-read articles, medical journal with patient pages, patient guides, brochures, illustrations, animations, and frequently asked questions).