A phase ll trial assessing the safety and efficacy of sorafenib in combination with yttrium90 radioembolization in patients with advanced hepatocellular carcinoma

In a phase II trial we investigated the safety, tolerability and efficacy of sorafenib in combination with ytrium90 radioembolization in advanced hepatocellular carcinoma (HCC). 26 patients with advanced HCC were recruited and were treated with sorafenib continuously and ytrium90 radioembolization 6 to 8 weeks after the beginning of sorafenib. The most common adverse events were constitutional symptoms such as fatigue (23.1%), and weight loss (23.1%) as well hand‐foot skin reaction (19.2%), and abdominal pain (23.1%). When looking at grade 3 and 4 events, diarrhea (11.5%), hand‐foot skin reaction (15.4%) and abdominal pain (15.4%) were the most frequent. Overall, the type and rate of adverse events observed in our study did not differ widely from those seen with sorafenib or Y90 radioembolization alone.Overall median survival was 395 days (12.97 months) and survival rate at 1 years was 65.4%. Alcoholic cirrhosis, the absence of macroscopic vascular invasion or extrahepatic disease, and decrease in AFP with sorafenib were associated with prolonged survival.The proposed regimen was associated with a 21% increase in survival when compared to sorafenib alone and may also confer a survival advantage when compared to yttrium90 radioembolization.Dans cette étude de phase II, la sécurité, la tolerabilité et l'efficacité de sorafenib combiné avec la radioembolization yttrium90 sont investiguées. 26 patients avec un carcinome hépatocellulaire avancé ont été recrutés et ont reçu sorafenib en continue ainsi que la radioembolization ytrium90 entre 6 à 8 semaines après le de but du sorafenib.Les effets secondaires les plus fréquents sont des symptômes systémiques tels que la fatigue (23.1%), la perte de poids (23.1%), le syndrome pieds‐main (19.2%) ainsi que la douleur abdominale (23.1%). La diarrhée (11.5%), le syndrome pieds‐mains (15.4%) et la douleur abdominale sont les effets secondaires de grade 3 ou 4 les plusfréquents (15.4%). De manière générale, le type et la fréquence des effets secondaires observés dans cette étude ne diffèrent pas grandement de ceux obtenus avec un traitement par sorafenib ou radioembolization seul. La survie médiane est de 395 jours (12.97 mois) et le taux de survie à 1 an est de 65.4%. La cirrhose d'origine alcoolique, l'absence d'invasion vasculaire macroscopique ainsi que la baisse de l'AFP avec sorafenib sont associés avec une prolongation de la survie. Le régime de traitement proposé dans cette étude est associé avec une augmentation de la survie de 21%

Vaginal CO2 laser use for the management of genitourinary syndrome of menopause in gynecological cancer survivors

Genitourinary syndrome of menopause (GSM) may arise from the destruction of ovarian function resulting in hypoestrogenism caused by various forms of gynecological cancer treatment including surgery, chemotherapy, radiation, and anti-estrogen therapy. Historically, patients with a hormone dependent gynecological cancer and physicians have been less comfortable introducing vaginal estrogen due to risk of recurrence. Published data indicate that low-dose vaginal estrogens cause a minimal, if any significant, time limited, increase in plasma estradiol and do not rise significantly enough to cause recurrence. Often physicians and patients are reluctant to treat GSM with local estrogen. CO2 vaginal laser therapies have demonstrated efficacy as an effective, nonhormonal alternative for the treatment of GSM in healthy menopausal patients. Our objective is to evaluate the published data on the effect of CO2 vaginal laser for the management of GSM in gynecological cancer patients. Well-controlled clinical trials in gynecological cancer patients are needed to further elucidate both the safety and efficacy of this nonhormone therapy. More data is needed about the longevity of effect and cost-effectiveness of the CO2 vaginal lasers use in gynecological cancer survivors before this can be implemented in clinical practice

Decreased PCSK9 expression in human hepatocellular carcinoma

BACKGROUND: The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. METHODS: Thirty-nine patients undergoing partial hepatectomy or liver transplantation for HCC were consented for use of HCC tissue to construct a tissue microarray (TMA). The TMA was immunostained for PCSK9. Imagescope software was used to objectively determine staining, and assess for pathological and clinical correlations. PCSK9 and LDL receptor mRNA levels in flash-frozen HCC and adjacent liver tissue were determined by quantitative RT-PCR. Serum PCSK9 levels were determined by ELISA. RESULTS: By immunohistochemistry, there was significantly lower expression of PCSK9 in HCC as compared to adjacent cirrhosis (p-value < 0.0001, wilcoxon signed-rank test). Significantly greater staining of PCSK9 was present in cirrhosis compared to HCC (p value <0.0001), and positivity (percentage of positive cells) was significantly greater in cirrhosis compared to HCC (p-value < 0.0001). Conversely, significantly higher expression of LDL-R was present in HCC as compared to the adjacent cirrhosis (p-value < 0.0001). There was no significant correlation of PCSK9 staining with grade of tumor, but there were significant correlations between PCSK9 staining and stage of fibrosis, according to spearman correlation test. PCSK9 mRNA levels were relatively less abundant within HCC compared to adjacent liver tissue (p-value =0.08) and normal control tissue (p-value =0.02). In contrast, serum PCSK9 levels were significantly increased among patients with HCC compared to those with chronic liver disease without HCC (p-value =0.029). LDL receptor mRNA was consistantly greater in HCC when compared to normal control tissue (p-value = 0.06) and, in general, was significantly greater in HCC when compared to adjacent liver (p-value = 0.04). CONCLUSIONS: The decreased expression of PCSK9 and conversely increased LDL-R expression in HCC suggests that HCC modulates its local microenvironment to enable a constant energy supply. Larger-scale studies should be conducted to determine whether PCSK9 could be a therapeutic target for HCC