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.

Penile cancer: prognostic and predictive factors in clinical decision-making.

Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC.

Caloric restriction followed by high fat feeding predisposes to oxidative stress in skeletal muscle mitochondria.

The purpose of the present study was to assess the impact of previous period of caloric restriction on energy balance and skeletal muscle mitochondrial energetics in response to high-fat (HF) diet. To this end, 1 group of rats was subjected to 2 weeks of caloric restriction with nonpurified diet and then fed HF diet (430 kJ metabolizable energy/day) for 1 week, while the second group was fed ad libitum with nonpurified diet for 2 weeks and then fed HF diet (430 kJ metabolizable energy/day) for 1 week. Body composition, energy balance, and glucose homeostasis were measured. Mitochondrial mass, oxidative capacity and efficiency, parameters of oxidative stress, and antioxidant defense were evaluated in subsarcolemmal and intermyofibrillar mitochondria from skeletal muscle. Body energy and lipid content, plasma insulin, and metabolic efficiency were significantly higher, while energy expenditure significantly decreased, in food-restricted rats fed HF diet compared to controls. Mitochondrial efficiency and oxidative damage in skeletal muscle were significantly increased, while antioxidant defence was significantly lower in food-restricted rats fed HF diet, compared with controls. Finally, food-restricted rats fed HF diet exhibited significant reduction in subsarcolemmal mitochondrial mass. In conclusion, caloric restriction elicits higher mitochondrial efficiency and predisposes skeletal muscle to high fat-induced oxidative damage, which in turn could lead to impaired glucose homeostasis in food-restricted rats fed HF diet.

Radical retropubic prostatectomy using endoscopic gastrointestinal anastomosis staplers.

OBJECTIVE: To investigate whether the use of the endoscopic gastrointestinal anastomosis (GIA) stapler for hemostasis of the dorsal vein complex during radical retropubic prostatectomy saves operation time and blood loss together with therapeutic efficacy. MATERIALS AND METHODS: From April 1990 to December 1998, a total of 296 patients underwent radical retropubic prostatectomy for prostate cancer in clinical stages T1, T2 and T3. In 157 patients we evaluated the efficacy of the endoscopic GIA stapler in order to minimize blood loss from the dorsal vein complex and to reduce mean operative time. RESULTS: The mean total operative time decreased an average of 35 min and the mean blood loss fell from 850 to 400 cm(3) using the stapling technique. Although complications are seen with traditional methods, we noted a net increase in anastomotic strictures with this new technique. CONCLUSIONS: Even if this technical trick is effective in reducing blood loss, a higher incidence of anastomotic strictures has to be taken into account when using staplers close to the anastomotic site.

Emergency department evaluation and treatment of pelvic fractures.

Pelvic fractures are associated with a high morbidity and mortality rate. This article reviews the anatomy of the pelvis, discusses fracture patterns commonly seen in patients with an injured pelvis, and proposes a new method of classifying pelvic fractures based on potential associated injuries. Finally, algorithms for the management of hemodynamically stable and unstable patients with pelvic fractures are presented.

Evaluation of an enforcement program to reduce tobacco sales to minors.

OBJECTIVES: This study evaluated an active enforcement program to increase retailers' compliance with the law prohibiting tobacco sales to minors. METHODS: Tobacco sales to minors were monitored in 319 outlets in 6 pairs of communities in Erie County, New York. One community in each pair was randomly assigned to an enforcement intervention. RESULTS: Retailers' compliance with the law increased from 35% in 1994 to 73% in 1995. However, the change in compliance rates was roughly the same for stores in the enforcement and nonenforcement communities. CONCLUSIONS: Active compliance checking of retail outlets as a strategy to reduce illegal tobacco sales to minors may only be necessary insofar as it contributes to an increase in retailers' perception that the threat of enforcement is real.

[Diverticuli of the female urethra. Our experience and long-term clinico-instrumental evaluation]. / Diverticoli dell'uretra femminile. Nostra esperienza e valutazione clinico-strumentale a distanza.

Since 1978, in our Division, we treated for this pathology 11 patients aged between 18 and 60 (average 45). We always performed a transvaginal diverticulectomy, in one case with intradiverticular stone removal: while in no case did we associate a colposuspension because we never found concomitant stress incontinence, nor we discovered the presence of neoplasm in the diverticulum as reported by other authors. We did not report any complication in the postoperative period: the clinical results proved quite satisfactory; in the late follow-up, also including radiologic and profilometric investigation, no relapses occurred and no morphological or manometric alterations were observed.

[Priapism: our experience in 9 cases]. / Priapismo: nostra esperienza in 9 casi.

We report our experience with 9 cases of priapism treated with decompressive puncture of the corpora cavernosa or with spongiosum-cavernosum shunt. No significant difference in result between these two surgical approaches was found: we conclude that early treatment is decisive for the preservation of potency.

Reducing costs with formulary limitation of H2-receptor antagonists in a community hospital.

Cost containment has become a major issue for all hospital pharmacies. At Carney Hospital, a 366-bed community hospital, where H2-receptor antagonists accounted for 10% of a $1.5 million total drug budget, the search for cost savings led to a move from an open to a limited formulary for the H2-receptor antagonists. Cimetidine and ranitidine, the two most widely used agents of this class, are considered equivalent in terms of safety and efficacy. Prior to formulary limitations, however, most H2-receptor antagonist orders were written for ranitidine, the more expensive agent. Carney Hospital, a member of the Daughters of Charity hospital purchasing group, was able to participate in an advantageous H2-receptor antagonist cost agreement by limiting its formulary to cimetidine. After the first 9 months of the closed formulary program, Carney had realized cost savings of $33,220. At that time, cimetidine accounted for 96% of all parenteral H2-receptor antagonist orders, testifying to physician satisfaction with this agent. Finally, 85% of the parenteral cimetidine orders were written q8h, which was essential to the success of the cost savings program.

Reducing waste: a significant cost containment measure in an i.v. additive program.

The need to reduce IV minibag waste was reported during a management study of pharmacy services. Outlined is the method of operation in effect at the time. The period of study indicated a 19.98% waste factor, which was equivalent to 3,000 minibags. The problems were identified and methods were developed and implemented to reduce this percentage. Various studies have reported IV minibag waste to be in the 7% range. A follow-up study after the new policies and procedures were implemented indicated a current waste factor of 2.26%. This improvement had a significant impact in the operation of the IV additive program and in the cost-containment goals of the department.

Effects of almitrine bismesylate on nocturnal hypoxemia in patients with chronic bronchitis and obesity.

In a double-blind placebo controlled randomised study, the effects of almitrine bismesylate on the sleep induced Hb desaturations, associated or not with disorders of breathing, were tested. Patients (37-75 yrs, 8M and 2F) were affected by chronic bronchitis (out of any exacerbation) and obesity (weight excess at least 20%). They were known to have at least one nocturnal episode of hypoxemia (SaO2 fall higher or equal to 10%) with respect to the wakefulness level. Patients received either placebo or almitrine (1.5 mg/Kg/day) for 18 days and nocturnal polysomnography was performed both before and the last day of treatment. Almitrine induced an increase in PaO2 during wakefulness (p less than .05), an increase in mean SaO2 during sleep (p less than .01) and a decrease in the quantity of desaturation (Qd) during sleep, defined as the product of the mean desaturation by the duration of the episodes of desaturation (p less than .025). No clear effect could be observed either on the mean duration of the sleep disordered breathing (SDB) events or on their frequency whereas the desaturations due to them had a decrease.

Variability of peak expiratory flow rate as a prognostic index in asymptomatic asthma.

The prognostic relevance of an enhanced variability of peak expiratory flow rate (PEFR) throughout the day was evaluated in asthmatics in remission: it was expressed as the coefficient of variation (CV) of values recorded 4 times daily for 2 weeks. Outcome at 3, 6, and 12 months was assessed in 2 groups of 16 patients each, differing because of a CV respectively higher (group A) and lower (group B) than 8%. A significantly higher frequency of abnormal PEFR values during the subsequent 3 months was recorded in patients of group A, and found as correlated to the magnitude of CV; in the same group a significantly worse clinical status--scored on the basis of response to treatment--was pointed out. Therefore, a high CV of PEFR may be assumed as a reliable indicator of the risk of exacerbation--not otherwise predictable--both in a short and a longer term; on this basis home monitoring of PEFR may be recommended as a useful tool in the evaluation of all the cases of asthma in remission.

Teratogenic effects of excess glucose on head-fold rat embryos in culture.

Rat embryos explanted at nine and one-half days of gestation (early head-fold stages) were cultured for 48 hours in rotating bottles containing rat serum and a gas phase. Addition of 12-15 mg/ml of D-glucose to the culture medium resulted in severe abnormalities and retarded development in a high proportion of embryos, whether or not the osmolarity increase brought about by the addition of glucose was corrected. The raised osmolarity, however, increased the frequency and severity of malformations observed. L-glucose produced no abnormalities, though embryonic development was retarded.

Development of a placental blood circulation in rat embryos in vitro.

Rat embryos explanted with their membranes at head-fold stage (9 1/2 days gestation) formed an allantoic placenta which enlarged in culture and developed a foetal blood circulation. Embryos explanted at early somite stages (10 1/2 days) also formed a growing allantoic placenta but only after removal of most of the ectoplacental trophoblast. Assays of total protein in the embryo and placenta suggested that, in the absence of a maternal blood circulation to the placenta, embryo and placenta compete for the respiratory and nutritional resources obtained through the yolk-sac.

Comparison of growth in vitro and in vivo of post-implantation rat embryos.

Rat embryos explanted at early head-fold stage and grown in vitro by improved culture methods were compared with littermates in vivo. Very similar rates of growth and differentiation were obtained over a period of 48 h, while the embryos developed to around the 25-somite stage.

Secretory component and sudden-infant-death syndrome.

Post-mortem specimens of blood, respiratory-tract washings, bronchopulmonary tissue, spleen, and thymus were examined for respiratory viruses, immunoglobulins, and secretory component (S.C.) in eight infants with sudden-infant-death syndrome (S.I.D.S) and in eight other (control) infants with an identifiable cause of death. Serum-immunoglobulin levels were similar in infants with S.I.D.S. and in control infants. In some S.I.D.S. cases serum-IgM was slightly raised. Respiratory syncytial virus was found in the pulmonary tissues of five S.I.D.S. patients but no viruses were isolated from other subjects. However, in one control subject parainfluenza type-3 viral antigen was detected in the bronchial tissue. In all patients with S.I.D.S., immunological reactions and fluorescent antibody staining for S.C. in the broncho-pulmonary epithelium were absent or grossly reduced. The levels of IgG and IgM in bronchial washings were unremarkable. These observations suggest a possible defect in respiratory mucosal defence in patients with S.I.D.S.