Early stage breast cancer follow-up in real-world clinical practice: the added value of cell free circulating tumor DNA.

PURPOSE: Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center. PATIENTS AND METHODS: Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA. RESULTS: Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1-5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed. CONCLUSIONS: Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.

Biologic therapies for plaque type psoriasis in patients with previous malignant cancer: long-term safety in a single- center real-life population.

INTRODUCTION: This is an Italian single-center retrospective study evaluating safety and efficacy of biologic agents in psoriatic patients with a previous diagnosis of malignant cancer. AIM: Management of moderate and severe psoriasis patients with a past medical history of malignancies could be difficult because biologic agents are historically associated with a presumptive increased risk of neoplastic reactivation or of a new incoming cancer. The aim of this study is to assess the safety of biologics in patients with a previous cancer diagnosis. MATERIAL AND METHODS: The study analyzed 16 moderate to severe psoriasis patients with a diagnosis of malignant cancer in the previous 10 years treated with biologic agents for up to at least 96 weeks. In five of these patients, cancer was diagnosed in the previous 5 years. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 90% improvement in 100% of patients. Oncologic follow up did not show any worsening or reactivation of cancer during the entire observation period. No new malignancies were observed in the analyzed sample. CONCLUSIONS: Biologic agents in our experience have demonstrated to be safe and effective in psoriatic patients with a past medical history of malignant cancer.

Has time come for a re-assessment of spa therapy? The NAIADE survey in Italy.

Goal of this study was to investigate whether appropriately applied spa therapy in several indications could be associated with a subsequent fall in the need for costly health services and missed working days due to sick-leave. The Naiade project was a multicenter observational, longitudinal, questionnaire-based study comparing an "entry" inquiry addressed to patients before an entry thermal cycle, and a "return" inquiry after 1 year. Routine statistical methods were used for comparisons. The study was carried out in 297 of the 340 certified Italian spa centers. Inquiries were managed by the spa doctor(s), with the collaboration of family doctors, and when necessary, hospitals, other health services, labour offices and employers. After exclusion of regular customers and of patients with acute disease phases or severe health conditions, 39,943 patients divided into eight diseases subgroups (rheumatic, respiratory, dermatologic, gynaecologic, otorhynologic, urinary, vascular and gastroenteric) underwent entry inquiry and appropriate spa treatment. Patients who returned for treatment after 1 year ("index year") were 23,680 (59.2%) and received return inquiry. Outcomes considered were: frequency and duration of hospitalisation periods; missed working days; regular use of disease-specific drugs; and resort to "non-spa" rehabilitation therapies. The data collected at return inquiry were compared with those of entry inquiry. All the considered outcomes appeared to be significantly reduced in the index year in seven of the eight disease subgroups in comparison with the previous year. In conclusion, disease-appropriate spa treatments were followed by a reduction in the need of subsequent health interventions in most disease subgroups. The health promoting value of spa treatments should therefore undergo more rigorous assessment with randomised controlled studies.

The endocannabinoid system in the brain of Carassius auratus and its possible role in the control of food intake.

Cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoylglycerol have been suggested to regulate food intake in several animal phyla. Orthologs of the mammalian cannabinoid CB(1) and CB(2) receptors have been identified in fish. We investigated the presence of this endocannabinoid system in the brain of the goldfish Carassius auratus and its role in food consumption. CB(1)-like immunoreactivity was distributed throughout the goldfish brain. The prosencephalon showed strong CB(1)-like immunoreactivity in the telencephalon and the inferior lobes of the posterior hypothalamus. Endocannabinoids were detected in all brain regions of C. auratus and an anandamide-hydrolysing enzymatic activity with features similar to those of mammalian fatty acid amide hydrolase was found. Food deprivation for 24 h was accompanied by a significant increase of anandamide, but not 2-arachidonoylglycerol, levels only in the telencephalon. Anandamide caused a dose-dependent effect on food intake within 2 h of intraperitoneal administration to satiated fish and significantly enhanced or reduced food intake at low (1 pg/g body weight) or intermediate (10 pg/g) doses, respectively, the highest dose tested (100 pg/g) being inactive. We suggest that endocannabinoids might variously contribute to adaptive responses to food shortage in fish.

Capillary gas chromatographic determination of spermidine in diet integrators.

Biogenic polyamines, among which is spermidine (SPD, NH2-(CH2)4-NH-(CH2)3-NH2), are ubiquitous polycationic molecules that have a definitive role in many biological processes, such as nucleic acid metabolism, protein synthesis and cell growth. SPD is present in diet integrators because it seems to favour the hair growth. This work describes a capillary gas chromatographic (CGC) method for the quantitative determination of SPD in diet integrators using cadaverine internal standard (IS), a methyl siliconic capillary column and flame-ionization detector (FID). Diet tablets, containing SPD, are pulverized; an aliquot of powder is treated with an alkaline aqueous solution and added with IS. The suspension is extracted with diethyl ether containing ethyl chloroformate (ECF). The ether extracts, evaporated to dryness and reconstituted in ethyl acetate were analyzed in CGC/FID. Derivatives of polyamines with ECF were characterized in CGC/MS too. Validation has considered specificity, linearity, precision and accuracy of analytical method; this parameters are valid for the quantitative determination of SPD in diet integrators.

Clinical efficacy and cost-effectiveness evidence of spa therapy in osteoarthritis. The results of "Naiade" Italian Project.

AIM: The "Naiade" Project was carried out in execution of the Decree of December 1994 by the Italian Ministry of Health, with the objective of defining the therapeutic role of spa therapy in the various sectors of medicine. In this study the authors refer to the results obtained in osteoarthritis (OA). METHODS: The OA study included the observation of patients for 2 consecutive years, with the compilation of a series of clinical and socio-economic data. The initial sample was of 11437 patients suffering from primary and secondary OA, and in the 2(nd) year the total number of assessable patients was 6111 (53.4%). All patients underwent 1 annual cycle of balneotherapy and mud packs therapy for 2 consecutive years. The thermal treatments were carried out in 98 Italian spas with sulphurous water, sodium chloride-bromide-iodide water, sulphate water, and bicarbonate water. Analysis of the data collected confirmed the clinical efficacy of spa treatments for OA, particularly for localisations in the cervical and lumbar spine. The benefits of these treatments and the persistence of the therapeutic effects over time were clearly demonstrated by the collection of some socio-economic indicators relative to the year before each cycle of thermal therapy. RESULTS: In fact, the analysis of these indicators showed a significant reduction in recourse to additional treatments (hospital admissions, physical and pharmacological therapies) and absence from work. CONCLUSION: The obtained data was particularly interesting for the number of samples examined, the follow-up over a period of 2 years, and the collection of clinical and, especially, socio-economic parameters. The results of the Naiade Project confirmed the value of spa therapies in the treatment of OA.

Changes in the use of health resources by patients with chronic phlebopathies after thermal hydrotherapy. Report from the Naiade project, a nation-wide survey on thermal therapies in Italy.

BACKGROUND: Chronic venous disorders carry lifelong medical and social burdens. Within conservative approaches, spa hydrotherapy is popular among patients with venous disorders in Europe, but whether the practice is associated with health or social benefits remains controversial. METHODS: The present work is a substudy of the nation-wide Italian Naiade Project, a large multicenter observational exercise on spa treatments in different disease groups. The "Chronic Phlebopathies" substudy included 2504 patients with primary or secondary varicosis or non-varicose venous insufficiency. After a first visit and administration of a detailed questionnaire, patients underwent a "thermal cycle" of 15-20 days consisting of underwater active and passive physical therapy with mineral waters. The same procedures were repeated after 1 year on the 1352 patients (54%) who spontaneously returned to the same spa. Primary endpoints of the study were some indicators of the use of health resources related to the year after the first thermal cycle, compared with the same indicators recorded at first visit using appropriate statistical methods. RESULTS: The occurrence of acute venous episodes, working days missed, number and duration of hospital admissions, consumption of drugs and physical therapies were all significantly reduced in the year after thermal therapy, thus indicating lesser use of health resources. CONCLUSIONS: The study suggests that thermal hydrotherapy in patients with chronic venous disorders is associated with health and social benefits.

The prediction of clinical outcome from transurethral microwave thermotherapy by pressure-flow analysis: a European multicenter study.

A total of 100 patients treated with a single session of microwave thermotherapy at 4 European centers was stratified according to 2 different types of obstruction (constrictive and compressive) and compared to clinical outcome at 6 months. Patients had a Madsen-Iversen score of 8 or more, maximum flow rate of 15 ml. per second or less and residual urine volume of 300 ml. or less at entry. The change in Madsen-Iversen score was the same in the 2 groups. Maximum flow rate increased from 8.71 +/- 2.62 to 14.73 +/- 4.04 ml. per second in the constrictive group, and from 8.54 +/- 2.26 to 10.41 +/- 4.52 in the compressive group (p < or = 0.0001). Residual urine decreased from 96.00 +/- 72.85 to 40.34 +/- 56.33 ml. in the constrictive group and from 109.86 +/- 67.09 to 84.65 +/- 81.45 ml. in the compressive group (p < or = 0.0001). Success, as defined by an increase of 50% or more in maximum flow rate and Madsen-Iversen score, was noted in 68% of the constrictive but only 15% of the compressive groups (p < or = 0.0001 chi-square test for trend). Selection by pressure-flow criteria for patients being considered for thermotherapy should improve the overall clinical results.

The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption. A case-control study. Provincial Group for the Study of Chronic Liver Disease.

In order to assess the interaction between alcohol intake, tobacco smoking and coffee consumption in determining the risk of liver cirrhosis we carried out a hospital-based case-control study involving 115 patients at their first diagnosis of cirrhosis and 167 control patients consecutively enrolled in the General Hospitals of the Province of L'Aquila (Central Italy). The mean life-time daily alcohol intake (as g ethanol consumed daily) was measured by direct patient interviews, whose reproducibility was > 0.80 and similar for cases and controls, as checked by interviewing the relatives of a sample of 50 cases and 73 controls. During the same patient's interview we also measured the mean consumption of coffee (daily number of cups of filtered coffee) and tobacco (life-time daily number of cigarettes smoked). A dose-effect relationship on the risk of cirrhosis was present both for alcohol intake--for which the risk was significantly increased above 100 g of daily intake--and for cigarette consumption. The latter did not however improve the goodness-of-fit of a logistic regression model including alcohol intake as covariate. By contrast, coffee consumption had a protective effect on the risk of cirrhosis and significantly improved the goodness-of-fit of such a model. Abstaining from coffee consumption determined both a significantly increased risk of cirrhosis, even for daily alcohol intake below 100 g, and a multiplicative effect with alcohol intake on this risk. In patients drinking > or = 101 g ethanol daily the relative risk increased from 5.5 (95% confidence interval: 1.4-22.0) for coffee consumers to 10.8 (95% confidence interval: 1.3-58.1) for coffee abstainers.(ABSTRACT TRUNCATED AT 250 WORDS)