Mechanisms of anorexia-cachexia syndrome and rational for treatment with selective ghrelin receptor agonist.

Cancer cachexia is a multi-organ, multifactorial and often irreversible syndrome affecting many patients with cancer. Cancer cachexia is invariably associated with weight loss, mainly from loss of skeletal muscle and body fat, conditioning a reduced quality of life due to asthenia, anorexia, anaemia and fatigue. Treatment options for treating cancer cachexia are limited. The approach is multimodal and may include: treatment of secondary gastrointestinal symptoms, nutritional treatments, drug, and non-drug treatments. Nutritional counselling and physical training may be beneficial in delaying or preventing the development of anorexia-cachexia. However, these interventions are limited in their effect, and no definitive pharmacological treatment is available to address the relevant components of the syndrome. Anamorelin is a first-in-class, orally active ghrelin receptor agonist that binds and stimulates the growth hormone secretagogue receptor centrally, thereby mimicking the appetite-enhancing and anabolic effects of ghrelin. It represents a new class of drug and an additional treatment option for this patient group, whose therapeutic options are currently limited. In this review we examine the mechanisms of anamorelin by which it contrasts catabolic states, its role in regulation of metabolism and energy homeostasis, the data of recent trials in the setting of cancer cachexia and its safety profile.

What is the price of functional surgical organ preservation in local-regionally advanced supraglottic cancer? Long-term outcome for partial laryngectomy followed by radiotherapy in 32 patients.

AIMS AND BACKGROUND: To achieve the goal of organ preservation, both a chemoradiotherapy and a conservative surgical approach can be proposed. The aim of the study was to review all patients treated in our Institute with conservative surgery and postoperative radiotherapy for locally advanced supraglottic tumor. METHODS AND STUDY DESIGN: A retrospective analysis of 32 patients treated between 2000 and 2010 was performed. Overall survival, disease-free survival and late laryngeal toxicity were evaluated. The impact of surgical procedures, radiotherapy characteristics and addition of chemotherapy on late laryngeal toxicity was studied. RESULTS: The median follow-up was 38 months. Overall survival and disease-free survival at 5 years were 73% and 66%, respectively. Three (9%) patients experienced local recurrence (after 22, 25 and 40 months, respectively) and were treated with total laryngectomy. The larynx preservation rate was 93%. Severe treatment-related late laryngeal toxicity (grade 3 and 4 laryngeal edema, laryngeal stenosis, presence of tracheotomy at last follow-up because of treatment-related toxicity, and the need for enteral nutrition) was experienced by 34% of patients. The functional larynx preservation rate was 81%. The statistically significant risk factors for severe late toxicity were: female gender, extension of the surgical procedure, removal of one arytenoid and association with concomitant chemotherapy. CONCLUSIONS: We confirmed literature data on the feasibility and efficacy of a surgical organ preservation strategy. However, the high incidence of severe late toxicity requires further studies to improve patient selection and to reduce side effects.

Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study.

BACKGROUND: This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women. STUDY DESIGN: On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION: Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.

Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study.

OBJECTIVE: To compare the effects of bovine lactoferrin with ferrous sulfate on iron nutritional status and to evaluate their tolerability in 100 pregnant women with iron deficiency anemia. DESIGN: Prospective, randomized, controlled, double blind trial. SETTING: Obstetrics clinic of a University Department of Obstetrics and Gynecology. POPULATION: One-hundred pregnant, healthy women to be treated either with one capsule of 100 mg bovine lactoferrin twice a day (Group A; n=49) and 520 mg ferrous sulfate once a day (Group B; n=48). METHODS: After 30 days, we evaluated hemoglobin (Hb), serum ferritin, serum iron and total iron- binding capacity (TIBC) values. All women were asked to keep a diary of five potential gastrointestinal side effects (abdominal pain, nausea, vomiting, diarrhea and constipation). For each symptom, patients had to rate its severity according to a scale ranging from 0 (absent) to 3 (severe). MAIN OUTCOME MEASURES: Hb level before and after treatment. Secondary outcomes were serum ferritin, serum iron and TIBC levels and the difference in symptom scores between groups. RESULTS: In Groups A and B, Hb, serum ferritin and iron were significantly increased while TIBC was significantly reduced in comparison with basal values. No significant differences were observed between Groups A and B. The median scores of abdominal pain and constipation were significantly higher in patients treated with ferrous sulfate in comparison with those treated with bovine lactoferrin. CONCLUSIONS: The results show that bovine lactoferrin has the same efficacy as ferrous sulfate in restoring iron deposits with significantly fewer gastrointestinal side effects.

Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study.

BACKGROUND: The effects of a 21-day combined oral contraceptive containing 30 mcg ethinyl estradiol plus 3 mg drospirenone with a 21-day preparation containing 20 mcg ethinyl estradiol plus 3 mg drospirenone on bone turnover and bone mineral density (BMD) in young fertile women were compared. METHODS: A randomized, controlled trial was conducted on healthy fertile women treated with 30 mcg ethinyl estradiol plus 3 mg drospirenone (Group A; n=21), 20 mcg ethinyl estradiol plus 3 mg drospirenone (Group B; n=23) and healthy controls (Group C; n=21). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin (BGP), urinary pyridinoline and deoxypyridinoline were measured. At baseline and after 12 months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary pyridinoline and deoxypyridinoline at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Groups A and B in urinary levels of pyridinoline and deoxypyridinoline, in calcium levels and in BGP levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION: Both combined oral contraceptives exert a similar positive influence on bone turnover in young postadolescent women.