Danazol for the Treatment of Myelodysplastic Syndromes: A Systematic Review.

Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.

External Beam Radiation and Brachytherapy for Prostate Cancer: Is It a Possible Trigger of Large Cell Neuroendocrine Carcinoma of the Urinary Bladder?

Neuroendocrine tumors commonly involve the respiratory and gastrointestinal systems. Primary genitourinary neuroendocrine tumors are rare, accounting for less than 1% of all bladder carcinomas. Four histopathologic subtypes have been described. Among those, large cell neuroendocrine carcinoma (LCNEC) is the least common, is more aggressive, and generally presents in an advanced stage with poor prognosis compared to transitional cell bladder carcinoma. There is no standardized treatment regimen because of the rarity of the disease. Herein, we present a case of 72-year-old male patient with previously treated prostate cancer, who received external beam radiation therapy and high dose brachytherapy, presenting with intermittent hematuria. Cystoscopy and transurethral resection of bladder tumor (TURBT) were performed. The histopathology and immunohistochemistry were consistent with large cell neuroendocrine carcinoma (LCNEC). Further studies are required to proof the higher risk of neuroendocrine carcinoma of the bladder in patients treated with external beam radiation therapy and brachytherapy for prostate cancer.

Association between various anthropometric measures of obesity and markers of subclinical atherosclerosis.

Central obesity is a known cardiovascular risk factor and measures of visceral obesity are known to predict atherosclerosis. This study sought to explore the association between various anthropometric measures and markers of subclinical atherosclerosis (MoSCA) among low risk healthy individuals. Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of Caucasian (38%), Afro-American (28%), Chinese (22%) and Hispanic (12%) subjects, aged 45-84 years, free from clinical cardiovascular disease. We performed a post hoc analysis of the limited access dataset of MESA subjects to evaluate the association between carotid intima media thickness and coronary artery calcium score (CACS), as MoSCA and various measures of obesity. Multivariable regression analyses adjusted for traditional cardiovascular risk factors, ethnicity and C-reactive protein were performed. Each unit increase in waist-hip ratio was strongly associated with increase in both common and internal carotid intima media thickness (beta: 0.12, 95% confidence interval (CI): 0.06 to 0.18, p < 0.001 and beta: 0.23, 95% CI: 0.03 to 0.43, p = 0.021, respectively). Measures of central obesity were superior to body mass index as demonstrated by their consistent association with each category of CACS when compared to the reference category (CACS = 0). Compared to body mass index, measures of visceral obesity were significantly associated with MoSCA in this multiethnic healthy population. Waist-hip ratio seems to be more consistent in its association with various MoSCA compared to other anthropometric measures.

PET scans as a predictive marker of survival in advanced colorectal cancer.

BACKGROUND: The clinical utility of fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan in predicting the outcome of patients with metastatic colorectal cancer (mCRC) has not been well studied. We hypothesized that standardized uptake value (SUV) in FDG-PET scans after treatment predicts outcomes among patients with mCRC. PATIENTS AND METHODS: We retrospectively reviewed mCRC patients who had FDG-PET scans before their treatment and measured their SUV on follow-up imaging at the Karmanos Cancer Institute. Primary end points of time to progression (TTP) and overall survival (OS) were compared in 2 groups: follow-up (posttreatment) SUV of 0 versus > 0. RESULTS: The study population consisted of 44 patients (median age of 58.1 years). Forty (91%) of the patients were treated first-line, 34 (77%) received an oxaliplatin-based regimen, and 7 (16%) received an irinotecan-based regimen. Thirty-four (77%) patients received concurrent bevacizumab. Median pretreatment SUV was 9.2 (range, 1.7-46.3), and median posttreatment SUV (in n = 41) was 4.0 (range, 0-14). The median percent change in SUV was -68.5% (range, -9.2% to -100%). The median time interval between scans was 2.6 months. There was no statistically significant difference noted between metabolic responders and nonresponders with regard to TTP and OS. However, patients with a posttreatment SUV of 0 had significantly longer OS than those with posttreatment SUV of > 0 (median, 42 vs. 25.2 months, respectively), and slightly longer TTP (median, 8.2 vs. 6.9 months, respectively). CONCLUSION: Systemic therapy significantly decreased SUV on follow-up PET scans in advanced colorectal cancer patients. Absence of FDG uptake on follow-up PET scans was associated with markedly longer OS and slightly longer TTP.

Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA.

Pancreatic cancer is the fourth leading cause of cancer related death in the US and exhibits aggressive features with short survival rate and high mortality. Therefore, it is important to understand the molecular mechanism(s) involved in the aggressive growth of pancreatic cancers, and further design novel targeted therapies for its treatment with better treatment outcome. In the present study, we found that the expression of miR-221 was significantly up-regulated in pancreatic cancer cell lines and tumor tissues compared to normal pancreatic duct epithelial cells and normal pancreas tissues. Moreover, we found that the pancreatic cancer patients with high miR-221 expression had a relatively shorter survival compared to those with lower expression, suggesting that miR-221 could be an oncogenic miRNA and a prognostic factor for poor survival of patients. Interestingly, transfection of miR-221 inhibitor suppressed the proliferative capacity of pancreatic cancer cells with concomitant up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA, which are the tumor suppressors and the predicted targets of miR-221. Most importantly, we found that the treatment of pancreatic cancer cells with isoflavone mixture (G2535), formulated 3,3'-diindolylmethane (BR-DIM), or synthetic curcumin analogue (CDF) could down-regulate the expression of miR-221 and consequently up-regulate the expression of PTEN, p27(kip1), p57(kip2), and PUMA, leading to the inhibition of cell proliferation and migration of MiaPaCa-2 and Panc-1 cells. These results provide experimental evidence in support of the oncogenic role of miR-221 and also demonstrate the role of isoflavone, BR-DIM, and CDF as potential non-toxic agents that are capable of down-regulation of miR-221. Therefore, these agents combined with conventional chemotherapeutics could be useful in designing novel targeted therapeutic strategy for the treatment of pancreatic cancer for which there is no curative therapy.

Azygos vein lead implantation for high defibrillation thresholds in implantable cardioverter defibrillator placement.

Evaluation of defibrillation threshold is a standard of care during implantation of implantable cardioverter defibrillator. High defibrillation thresholds are often encountered and pose a challenge to electrophysiologists to improve the defibrillation threshold. We describe a case series where defibrillation thresholds were improved after implanting a defibrillation lead in the azygos vein.

Eustachian valve endocarditis: a rare complication of automatic implantable cardioverter defibrillator placement.

Eustachian valve (EV) endocarditis is extremely rare and often difficult to diagnose. An extensive review of the English literature has shown no report of EV endocarditis as a complication of the automatic implantable cardioverter defibrillator (AICD). A rare case is reported following AICD placement that was diagnosed by clinical findings of sepsis and positive blood cultures, and supported (using transesophageal echocardiography) by the presence of vegetations attached to the EV. Previously reported cases of EV endocarditis are reviewed, and its significance discussed in the setting of an increased use of AICD.