A Botanical Compound for the Treatment of Alopecia Areata and Chemotherapy-Induced Alopecia.

Legacy Healthcare has developed and patented a topical botanical with a unique mechanism of action, an extensive clinical data package, and excellent safety from the 2.2 million units already sold, all of which has enabled it to enter late-stage clinical development for alopecia areata (AA), chemotherapy-induced alopecia, and soon female androgenetic alopecia. As this drug candidate is very safe, the European Medicines Agency agreed to Legacy Healthcare's request to initiate late-stage clinical trial first in children, the neediest population suffering from AA. The initial trend from the phase II/III trial conducted to assess the efficacy and safety of the drug candidate in pediatric AA (RAAINBOW trial) looks promising, although no conclusions can be made. This drug candidate seems to offer several potential safety and economic advantages over other investigational synthetic and biologic compounds currently being investigated in populations with AA overall and especially for children.

Opioid use in gynecologic oncology in the age of the opioid epidemic: Part II - Balancing safety & accessibility.

As the only oncologists that provide both medical and surgical care, gynecologic oncologists encounter an exceptionally broad range of indications for prescribing opioids in clinical situations ranging from management of acute post-operative pain to chronic cancer-related pain to end-of-life care. While opioids are essential to the practice of gynecologic oncology, they can also have significant side effects and can be misused. Due to the explosive growth of opioid prescriptions and opioid-related overdoses and deaths during the first decade of the 21st century, there has been a recent concerted public health effort to prevent and treat opioid misuse through both legislation and education [1]. The first article in this two part series focused on appropriate use of opioids across clinical settings. This article addresses both the clinical and regulatory aspects of balancing opioid safety and accessibility for patients with gynecologic cancer.

Prognostic value of endocervical sampling following loop excision of high grade intraepithelial neoplasia.

OBJECTIVE: To assess the role of additional biopsies performed with loop electrosurgical excisional procedure (LEEP) in predicting the likelihood of persistent high grade intraepithelial neoplasia. METHODS: Clinicopathologic data were abstracted from women who underwent excision of high grade intraepithelial lesions between 2001 and 2014. Persistent disease was defined as uninterrupted high grade intraepithelial neoplasia, whereas recurrent disease was defined as disease diagnosed ≥1year after treatment with intervening normal evaluation. Chi-square and Fisher's exact tests were used to examine associations between demographic and histologic parameters and clinical outcomes. RESULTS: A total of 606 women underwent LEEP for high grade intraepithelial neoplasia (HSIL), of whom, 178 (29%) were additionally evaluated by endocervical curettage, 80 (13%), top hat and 99 (16%), both procedures. With mean follow-up of 1.9±1.5years, persistent disease was identified in 87 women (14%) while recurrent disease was diagnosed in 20 (3%). After adjusting for age, HIV status and histologic grade of disease, the presence of disease at the endocervical margin (aOR=2.2, 95% CL 1.8-5.5, p<0.0001), with endocervical curettage (aOR=2.39, 95% CL 1.2-9.9, p=0.025) or on top hat (aOR=4.0, 95% CL 1.1-16.2, p=0.04) correlated with the likelihood of persistent but not recurrent disease. Only endocervical margin status remained predictive (p=0.03) of outcome after controlling for pre-procedure likelihood of endocervical disease. Sensitivity of endocervical margin status for persistent disease was 56.9% with specificity of 72.2%. Positive predictive value (PPV) was 24.9% and negative predictive value (NPV) 90.9%. CONCLUSIONS: Despite frequent use of additional procedures to sample the endocervix, these strategies do not improve the ability of endocervical margin status to predict persistent or recurrent dysplasia.

Predictive value of preoperative serum CA-125 levels in patients with uterine cancer: The Asian experience 2000 to 2012.

OBJECTIVE: Much of the early investigative work on the usefulness of preoperative serum CA-125 levels in identifying patients with early-stage endometrial carcinoma who have occult metastases were carried out in Europe and the United States. This article reviews CA-125 as a possible index for determining the need for full surgical staging, from the results of large medical centers in Asia, particularly Taiwan and Korea. METHODS: A Medline search was performed using CA-125 and endometrial cancer as index words from 1981 to 2012. Those publications felt to be the most important especially from institutions from Asia since 2000 were identified in this review. RESULTS: Most articles that analyzed the utility of serum CA-125 levels as predictive marker for disease extent or prognosis in uterine cancer used univariate and multivariable logistic regression analysis, and performed receiver operative curves to find the best cut-off values. The main factor of interest was whether clinicians can stratify patients that need lymphadenectomy in early stage disease. Suggested optimal cut-off value ranged from 20 to 210 U/mL. Not only preoperative CA-125 level, but myometrial invasion status by magnetic resonance imaging was the most significant combined parameter for predicting disease extent. CONCLUSION: Elevated CA-125 in patients with apparent early-stage disease is clearly a risk factor for the presence of extra-uterine disease although the optimal cut-off levels vary. The evolution of clinical investigations over the past decade, particularly in Asia, suggests employment of the test in a more focused manner to identify high risk patients preoperatively.

Clinical implications of human papillomavirus genotype in cervical adeno-adenosquamous carcinoma.

BACKGROUND: Our aims were to evaluate the genotype distribution of human papillomavirus (HPV) and the correlation between HPV parameters and clinicopathological/treatment variables with prognosis in cervical adeno-adenosquamous carcinoma (AD/ASC). PATIENTS AND METHODS: Consecutive patients who received primary treatment for cervical AD/ASC International Federation of Gynecology and Obstetrics (FIGO) stages I-IV between 1993 and 2008 were retrospectively reviewed. Prognostic models were constructed and followed by internal validation with bootstrap resampling. RESULTS: A total of 456 AD/ASC patients were eligible for HPV genotyping, while 452 were eligible for survival analysis. HPV18 was detected in 51.5% and HPV16 in 36.2% of the samples. Age >50 years old, FIGO stages III-IV and HPV16-negativity were significantly related to cancer relapse, and age >50, FIGO stages III-IV, HPV16-negativity and HPV58-positivity were significant predictors for cancer-specific survival (CSS) by multivariate analyses. HPV16-positivity was also significantly associated with good prognosis in those receiving primary radiotherapy or concurrent chemoradiation (RT/CCRT) (CSS: hazard ratio 0.41, 95% confidence interval 0.21-0.78). Patients with FIGO stages I-II and HPV16-negative AD/ASC treated with primary RH-PLND had significantly better CSS (p<0.0001) than those treated with RT/CCRT. CONCLUSIONS: Age >50 years old, FIGO stages III-IV and HPV16-negativity were significant poor prognostic factors in cervical AD/ASC. Patients with HPV16-negative tumour might better be treated with primary surgery (e.g. radical hysterectomy for stages I-II and pelvic exenteration for stage IVA). Those with unresectable HPV16-negative tumour (stage IIIB) should undergo CCRT in combination with novel drugs. The inferences of a single-institutional retrospective study require prospective studies to confirm.

Problems associated with direct-to-consumer advertising (DTCA) of restricted, implantable medical devices: should the current regulatory approach be changed?

Advertising and promotion of Food and Drug Administration (FDA)-approved medical products has been one of the most controversial and bitterly litigated areas in food and drug law in the U.S. for more than a decade. Hundreds of newspaper articles and dozens of law review articles have been written on the subject of the risks and benefits of direct to consumer advertising (DTCA) of medical products, but until very recently virtually all of this literature and commentary has focused exclusively on prescription and over-the-counter drugs. Even when FDA has sponsored public hearings to address the issue of DTCA of all medical products, as it did in 2005, review of the content of the speakers' presentations reveals that almost all of the subject matter, nearly all of the data, and the majority of comments concerned DTCA of drugs. Not a single law review article has ever been devoted exclusively to the subject of advertising and promotion of medical devices to consumers--until now.

Riegel v. Medtronic, Inc.: revisiting pre-emption for medical devices.

The recent United States Supreme Court decision in Riegel v. Medtronic, Inc. affirmed the doctrine of pre-emption protection only for those medical devices reaching U.S. markets via the PMA (premarketing approval) process and preserved the previous Lohr v. Medtronic decision's lack of preemption protection for those medical devices marketed via the generally more abbreviated 510(k) clearance mechanism. This paper reviews the logic and faults of the Riegel decision and discusses the implications of the Riegel decision for pre-emption protection for other classes of FDA-approved medical products.