Management of systemic prostate cancer: current algorithm from castration sensitive to castration resistant setting.

In recent years, the advanced knowledge of clinical, biological and molecular features of prostate cancer have led to the introduction of new drugs and have allowed the relocation of old drugs in different settings. In this way, the new concepts of systemic disease arise: high risk or high volume vs. low risk and low volume disease castration sensitive prostate cancer (CSPC), diversifying the use of previously approved drugs (CRPC) and opening new scenarios for sequence therapy. The aim of this review is to integrate new developments into the medical management of systemic prostate cancer.

Is there a role for FDG-PET for the assessment of treatment efficacy in Wilms' tumor? A case report and literature review.

BACKGROUND: The role of FDG-PET in Wilms' tumor has not been well established. The aim of this report is to describe the role of FDG-PET to assess chemotherapy efficacy and to show potential correlations between different Standardized Uptake Values (SUVs) and histopathological features in a patient with persisting metastatic disease. CASE DESCRIPTION: A 3-year-old boy was diagnosed with Wilms' tumor without anaplasia. The patient underwent treatment as according to the AIEOP-TW-2003 protocol, for stage III tumors. Therapy was discontinued with no evidence of disease, yet 9 months later thorax metastases were found. Although second and third line treatments were administered, conventional imaging demonstrated stable disease. Metronomic chemotherapy as well was employed for 44 months and FDG-PET was annually performed basing on responsible local physician choice trying to better describe the disease status. Four months after fourth line treatment was stopped, the patient manifested clinical symptoms; lesions began to increase their metabolic activity inhomogeneously. Therapy was hence restarted and SUVs decreased. Metastasectomies were then performed and histology revealed a correlation between viable disease shown by higher FDG-PET uptake and viable tumor areas. CONCLUSIONS: Our case discussion demonstrates that FDG-PET is potentially valuable in Wilms' tumor correlating SUV values and histological features of the tumor after chemotherapy. This case suggests that FDG-PET is a valid tool to assess chemotherapy response in relapsed Wilms' tumor even in case of no evidence of significant dimensional changes under conventional imaging.

Constitutive activity of cannabinoid-2 (CB2) receptors plays an essential role in the protean agonism of (+)AM1241 and L768242.

BACKGROUND AND PURPOSE: Cannabinoid-2 (CB(2)) receptor-selective agonists have shown anti-nociceptive activity in models of neuropathic and inflammatory pain, and the two agonists most widely used, (+/-)AM1241 [(2-iodo-5-nitrophenyl)-[1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl-methanone] and L768242 [(2,3-dichloro-phenyl)-[5-methoxy-2-methyl-3-(2-morpholin-4-yl-ethyl)-indol-1-yl]-methanone] (GW405833), have been suggested to be protean agonists. Here we investigated the role of the constitutive activity of CB(2) receptors in (+)AM1241 and L768242 protean agonism. EXPERIMENTAL APPROACH: Pharmacological profiles of CB(2) receptor ligands were evaluated in Chinese hamster ovary cells expressing recombinant human (hCB(2)) or rat (rCB(2)) receptors, by measuring modulation of cAMP. To assess the influence of constitutive activity on pharmacological profile, constitutive activity was abolished by pretreatment with AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)], followed by extensive washing. KEY RESULTS: In cell lines expressing either hCB(2) or rCB(2) receptors, (+)AM1241 did not reverse forskolin stimulation of cAMP levels. Conversely, L768242 was an inverse agonist at both hCB(2) and rCB(2) receptors. Abolition of constitutive activity disclosed (+)AM1241 and L768242 agonist activity, while activity of CP55940 [5-(1,1-dimethylheptyl)-2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxy-propyl)-cyclohexyl]-phenol] was unaffected and AM630 became a neutral antagonist. In presence of constitutively active CB(2) receptors, (+)AM1241 antagonized CP55940, but when constitutive activity was abolished, it acted as a partial agonist with additive or antagonistic behaviour, depending on concentration. CONCLUSIONS AND IMPLICATIONS: These results show that (+)AM1241 and L768242 are protean agonists at both hCB(2) and rCB(2) receptors. Abolition of constitutive activity reveals the agonist activity of these compounds. Thus, differences between in vivo and in vitro profiles of CB(2) receptor agonists could be due to different levels of constitutive activity in recombinant versus native CB(2) receptors.

Efficacy, safety and tolerability of sublingual monomeric allergoid in tablets given without up-dosing to pediatric patients with allergic rhinitis and/or asthma due to grass pollen.

The efficacy and safety of monomeric allergoid (Lofarma, Milan) have been demonstrated in adults but very few studies have examined it in children. This study therefore investigated the efficacy and safety of this sublingual immunotherapy (SLIT) at the dosage of 1000 AU five times a week without any up-dosing. Forty allergic children (17 M and 23 F, mean age 7 years, range 4-16 years), 16 with rhinitis and 24 with rhinitis and asthma, were randomized to SLIT or drug therapy. All the patients were sensitized to grass; some were also sensitized, though to a lesser extent, to Parietaria, Olea and Betulaceae. The patients were treated pre-/co-seasonally for two years. A visual analogue scale (VAS) was used at baseline and at the end of the first and second pollen seasons to rate the patients' well-being. The VAS score was significantly higher after both the first and the second year of treatment in the SLIT group than in the controls (p<0.05). It improved in comparison to baseline only in the active group. All 40 children tolerated the therapy very well. The monomeric allergoid at the dosage of 5000 AU/week thus appears to have a good efficacy and safety profile in children.

The safety of sublingual immunotherapy with one or multiple pollen allergens in children.

BACKGROUND: Since the majority of allergic patients are polysensitized, it is often necessary to prescribe immunotherapy with multiple allergens. It is crucial to know if the administration of multiple allergens with sublingual immunotherapy (SLIT) increases the risk of side-effects in children. METHODS: Consecutive children with respiratory allergy because of pollens, receiving SLIT for multiple or single allergens were followed-up in a postmarketing survey. Inclusion criteria were those for prescribing SLIT according to guidelines. Parents recorded in a diary card the side-effects (eye symptoms, rhinitis/ear itching, asthma, oral itching/swelling, nausea, vomiting, abdominal pain, diarrhoea, urticaria, angioedema and anaphylaxis). The side-effects were graded as mild, moderate and severe. RESULTS: Four hundred and thirty-three children (285 male, age range 3-18 years) receiving SLIT were surveyed. Of them, 179 received a single extract, and 254 multiple allergens. The total number of doses given was 40 169 (17 143 with single allergen). Overall, 178 episodes were reported. Of them, 76 occurred with the single allergen (42.46% patients, 4.43/1000 doses) and 102 (40.3% patients, 4.42/1000 doses) with multiple allergens (P = NS). 165 episodes (92.5%) were mild and self-resolving and were equally distributed in the two groups. In 13 cases, the events were judged of moderate severity and medical advice was required. Three patients discontinued SLIT, despite the local side-effects being mild. No emergency treatment was required at all. CONCLUSION: The use of multiple allergens for SLIT does not increase the rate of side-effects in children.

Robotically assisted small intestinal strictureplasty in dogs: a survival study involving 16 Heineke-Mikulicz strictureplasties.

BACKGROUND: Robotically assisted surgery offers the advantages of improved dexterity and elimination of tremor over conventional laparoscopic surgery. There have been few studies to date, however, examining the role of robotics in intestinal surgery. This study was undertaken to determine the feasibility and safety of using a robotic surgical system in the performance of intracorporeal small bowel strictureplasties in dogs. METHODS: Using a robotic surgical system, a total of 16 strictureplasties were performed in the small bowel of eight dogs (two strictureplasties per dog). Using only intracorporeal robotic surgery, a 2.5 cm enterotomy was made longitudinally in the small bowel, and then closed in a Heineke-Mikulicz configuration with a one-layer running 3-0 braided absorbable suture (strictureplasty). All animals were allowed to survive for 7 days with prospective monitoring of bowel movements, level of activity, oral intake, and abdominal examination. After 7 days, necropsy was performed, examining all strictureplasty sites for signs of sepsis. The endpoints of the study were recovery of normal intestinal function (bowel movements), intraoperative and postoperative complications, and the appearance of the anastomoses at necropsy. RESULTS: There was no intraoperative morbidity or mortality. All eight dogs survived 7 days and recovered well. All dogs had a bowel movement on the first postoperative day, and appeared healthy throughout the study period. Necropsy revealed that all 16 strictureplasty sites were healing without signs of sepsis. The median time per strictureplasty was 65 min (range, 45-110 min). One dog developed a superficial wound infection at a trocar site. CONCLUSIONS: A robotic surgical system can successfully be employed in the performance of intestinal strictureplasties in dogs. This study supports further investigation into the role of robotics in intestinal surgery in humans.

Laparoscopic total colectomy: hand-assisted vs standard technique.

BACKGROUND: Although hand-assisted laparoscopic surgery (HALS) has been proposed as an alternative to laparoscopically assisted surgery (LAP), little is known about its role in total colectomy. The objectives of the study were to compare the outcomes in patients undergoing total colectomy via either HALS or LAP and to determine what benefits HALS might have in extensive colorectal procedures. METHODS: We reviewed the data for 23 patients who underwent total proctocolectomy (TPC) or total abdominal colectomy (TAC) using either a HALS or LAP technique. RESULTS: There were 12 HALS (five TPC, seven TAC) and 11 LAP (seven TPC, four TAC) for ulcerative colitis (n = 17), familial polyposis (n = 5), and colonic inertia (n = 1). One LAP was converted (9.1%). The operative time was shorter for HALS than for LAP (210 vs 273 min; p = 0.03). Blood loss and incision length were similar. Postoperative recovery and morbidity rates were comparable. CONCLUSION: HALS reduces the operative time but patient morbidity rates and recovery are similar to LAP. HALS may be preferable for extensive colorectal procedures such as TPC and TAC.

Hand-assisted laparoscopic colorectal surgery using GelPort.

BACKGROUND: An easily usable hand access device will optimize success in hand-assisted laparoscopic surgery (HALS). The authors describe their initial series of HALS colorectal resections using GelPort to evaluate their current technique and results with this new device. METHODS: A retrospective study investigated 33 HALS colorectal procedures including total colectomy ( n = 16) and low anterior resection ( n = 10). All operative data, including intraoperative GelPort performance, were prospectively recorded and retrospectively analyzed. RESULTS: In this study, 3 (9.1%) of 33 HALS procedures were converted to open surgery, and 4 (13.3%) of 30 HALS procedures required minimal enlargement of incisions to facilitate extracorporeal procedures. The operative time was 263 +/- 85 min, and the blood loss was 282 +/- 148 ml. There were no device malfunctions. Three major complications (9.1%) and 7 minor wound infections (21%) were noted postoperatively. The mean hospital stay was 7.9 +/- 3.8 days. CONCLUSION: When performed with GelPort, HALS is safely and reliably applicable for various colorectal procedures.

Caregiving and Parkinson's disease.

Relatively little has been published in the international literature concerning the caregiving-related problems associated with Parkinson's disease. We therefore undertook two exploratory studies that have allowed us to identify the needs and specific problems perceived by such caregivers in both qualitative and quantitative terms.