SEOM guide to primary and secondary prevention of cancer: 2014

PURPOSE: The current incidence of cancer in the world is 14 million cases in 2012, with a mortality rate of 8.2 million in that year. The incidence of cancer in Spain exceeds 215,000 cases a year, and survival rates are the highest when compared to those of our neighbouring countries. Among the reasons for the steady decrease in cancer mortality rates in Spain, two causes must be highlighted: the increasing efficacy of treatment and prevention measures. It is important evaluate the opportunity of early detection and prevention in these tumors. METHODS: We have reviewed the evidence published in the most prevalent tumors. The evidence levels described in this paper are based on the GRADE system. RESULTS: We show the recommendations about primary and secondary prevention in breast cancer, cervical cancer, colorectal cancer, prostate cancer and lung cancer. CONCLUSION: The diffusion of these preventive tools can reduce the incidence of cancer and increase the number of early diagnostics in the most prevalent tumors.(AU)

SEOM guide to primary and secondary prevention of cancer: 2014.

PURPOSE: The current incidence of cancer in the world is 14 million cases in 2012, with a mortality rate of 8.2 million in that year. The incidence of cancer in Spain exceeds 215,000 cases a year, and survival rates are the highest when compared to those of our neighbouring countries. Among the reasons for the steady decrease in cancer mortality rates in Spain, two causes must be highlighted: the increasing efficacy of treatment and prevention measures. It is important evaluate the opportunity of early detection and prevention in these tumors. METHODS: We have reviewed the evidence published in the most prevalent tumors. The evidence levels described in this paper are based on the GRADE system. RESULTS: We show the recommendations about primary and secondary prevention in breast cancer, cervical cancer, colorectal cancer, prostate cancer and lung cancer. CONCLUSION: The diffusion of these preventive tools can reduce the incidence of cancer and increase the number of early diagnostics in the most prevalent tumors.

Phase II study of pegylated liposomal doxorubicin HCl (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small cell lung cancer.

BACKGROUND: Despite chemotherapy and radiotherapy for small cell lung cancer (SCLC), most patients die within 2 years. Response rates for second-line chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated liposomal formulation of doxorubicin, may be better tolerated and has activity in SCLC. PATIENTS AND METHODS: Thirty-two patients were enrolled in a phase II study of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles. RESULTS: Thirty patients were evaluable for response, with a response rate of 10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2 cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis, plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required transfusions. All patients on study have now expired, with a median survival of 28 weeks (7 months). For patients with SD or partial response, median time to progression was 15 weeks. CONCLUSION: The combination of Caelyx, cyclophosphamide and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest activity in relapsed SCLC with acceptable toxicity.

Characterization of the muscarinic receptor mediating contraction of the dog prostate.

1. We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2. Acetylcholine and carbachol induced contraction of prostate strips from the peripheral zone, ('the capsule'). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3. Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractile response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibited it in a competitive manner. 5. The muscarinic M1 (pirenzepine), M2 [AF-DX 116, himbacine (M2/M4) and methoctramine], M3 (HHSID and f-F-HHSID), and putative M4 (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC50 values were: atropine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6. The antagonist profile indicates that an predominant M2 receptor subtype could mediate the muscarinic contraction in the canine prostate.

Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP.

The involvement of nitric oxide (NO) and the mechanisms mediating neurogenic relaxation were investigated in the horse corpus cavernosum. NADPH-diaphorase activity was expressed in nerve fibres around arteries and muscular bundles in the horse trabecular tissue. Relaxations in response to electrical field stimulation were tetrodotoxin (10(-6) M)-sensitive, indicating their neurogenic origin. The NO synthase inhibitor, L-NO-arginine (L-NO-Arg, 3 x 10(-5) M), abolished the electrically induced relaxations, which were significantly reversed by L-arginine (3 x 10(-3) M). Exogenous NO (10(-6)-10(-3) M) evoked relaxations which were unaffected by L-NO-Arg. 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 5 x 10(-6) M), an inhibitor of guanylate cyclase activation by NO, reduced the relaxations in response to electrical stimulation and exogenous NO. Iberiotoxin (3 x 10(-8) M) or apamin (5 x 10(-7) M), inhibitors of large and small conductance Ca2+-activated K+ channels, respectively, and glibenclamide (3 x 10(-6) M), a blocker of ATP-sensitive K+ channels, failed to modify the relaxations with NO. It is suggested that NO is present in nerve fibres of the horse corpus cavernosum and relaxes smooth muscle through a guanylate cyclase-dependent mechanism. Neither Ca2+-activated nor ATP-sensitive K+ channels seem to be involved in these relaxations.

Pharmacological characterization of adrenoceptors in horse corpus cavernosum penis.

1. The presence and types of alpha and beta-adrenoceptors in the corpus cavernosum of the horse were studied in vitro by using selected ligands of adrenoceptors and isometric tension recording. 2. Noradrenaline and phenylephrine induced concentration-dependent contractions in corpus cavernosum preparations. B-HT 920 had no effect. 3. Phentolamine and prazosin produced a shift to the right of the dose-response curve of noradrenaline, while the alpha(2)-antagonist, rauwolscine had no effect on the response to noradrenaline. Phenylephrine-evoked contractions of corporal strips were significantly inhibited by the alpha(1)-adrenoceptor antagonist, prazosin. 4. Isoprenaline and salbutamol each relaxed precontracted corpus cavernosum preparations in a concentration-dependent manner; the isoprenaline effect was blocked by propranolol, practolol and butoxamine. The salbutamol effect was blocked by butoxamine. 5. These results suggest that presence of postjunctional alpha(1)-adrenoceptors in horse corpus cavernosum. There is also a heterogenous population of beta-adrenoceptors in this tissue, belonging to the beta(1) and beta(2) subtypes.

A case of melanoma concurrent with progressive systemic sclerosis.

The association between progressive systemic sclerosis (PSS; scleroderma) and malignancy has been a controversial issue in the literature. The present report describes a rare case of concurrent malignant melanoma and PSS. A literature review suggests a possible connection between these two conditions.

Chemotherapy in stage IV (metastatic) non-small-cell lung cancer. Provincial Lung Disease Site Group.

GUIDELINE QUESTION: In patients with metastatic, stage IV non-small-cell lung cancer (NSCLC) does chemotherapy improve survival and quality of life? OBJECTIVE: To make recommendations about the role of chemotherapy in the treatment of metastatic (stage IV) NSCLC. OUTCOMES: Survival and quality of life are the primary endpoints of interest. Specifically, 1-year survival will be considered. PERSPECTIVE: Evidence was selected and reviewed by 3 medical oncologists and the project coordinator of the Ontario Cancer Treatment Practice Guidelines Initiative. Drafts of this document have been circulated and reviewed by the Provincial Lung Disease Site Group (Lung DSG). The Lung DSG comprises medical and radiation oncologists, pathologists, surgeons, epidemiologists, a psychologists and a medical sociologist. There was no consumer participation in the development of this guideline. QUALITY OF EVIDENCE: There were 3 meta-analyses available for review, but only 1 is discussed in detail. The largest and most comprehensive meta-analysis is based on 11 randomized controlled trials involving 1190 patients. The main comparisons were chemotherapy plus supportive care versus supportive care alone. The largest trial included in the meta-analysis involved randomization of 188 patients, and the smallest trial involved randomization of 32 patients. Only trials that had accrued patients between Jan. 1, 1965, and Dec. 31, 1991, were included in the analysis. BENEFITS: A survival benefit at 1 year was seen for the group of patients treated with chemotherapy (pooled hazard ratio 0.84; 95% confidence interval [CI], 0.74 to 0.95). Subgroup analyses suggested a benefit for patients receiving chemotherapy regimens containing cisplatin (pooled hazard ratio, 0.73; 95% CI, 0.63 to 0.85; relative risk reduction for death, 27%; absolute improvement in 1 year survival, 10%; 95% CI, 5% to 18%; gain in median survival 1.5 months; 95% CI, 1 to 2.5 months). No benefit for patients treated with chemotherapy was found beyond 1 year. None of the randomized trials successfully measured quality of life using QOL assessment instruments. No firm conclusions can be made about the potential benefits (as measured by quality of life) that chemotherapy has for patients with metastatic NSCLC, as there are no available data from randomized controlled trials. However, several trials have documented relief of cancer-related symptoms, such as pain, cough, hemoptysis or dyspnea in the majority (approximately 70%) of patients. HARMS: In a subgroup analysis of trials that used long-term alkylating agents other than cisplatin (an approach no longer used as therapy in NSCLC) as part of the chemotherapy regimen, the meta-analysis demonstrated a detrimental effect of chemotherapy on survival (pooled hazard ratio, 1.26; 95% CI, 0.96 to 1.66, p = 0.09). In general, myelosuppression, sepsis resulting in hospitalization, drug-specific toxicities and death are potential complications of chemotherapy.