Health promotion in Local Health Unit 4 Chiavarese--Liguria Region, Italy. "Unplugged" project: needs, methodology and implementation.

AIM: The aim of this paper was to use and evaluate the unplugged project, a school-based program of proven effectiveness aimed at the prevention of substance abuse based on social influence. METHODS: This project was conducted during the school-year 2011/2012; it involved the Local Health Unit (LHU)'s personnel specifically and adequately formed and was addressed to teachers working in the three districts of the LHU4 Chiavarese. The courses involved teachers in three consecutive days and provided both theoretical inputs and practical exercises designed to enpower skills and to make the same effective. As a whole, 25 teachers of the secondary schools (public and private) of first and second level were trained. Following the training, 14 curricular courses have been launched and 286 students have been involved. RESULTS: The teachers have mainly worked on personal and social components of their students, stimulating their critical assessment of standards and skills potentially transferable in everyday life. The benefits for students have been: establishment of the classroom, positive relationship with the teacher, empathy, decrease of conflicts, increased self-awareness and self-esteem, better school results. Besides, teachers benefit from increased respect, self-reliance and confidence, as well as acquisition of new skills. CONCLUSION: Both the interest shown by teachers and the results achieved in classrooms have stimulated school leadership and personnel belonging to LHU4 Chiavarese to plan a new edition of the program the next autumn.

A systemic approach to cancer treatment: tumor cell reprogramming focused on endocrine-related cancers.

The term "cancer cell reprogramming" is used to define any kind of intervention aimed at transforming cancer cells into terminally differentiated cells. Using this approach, new technologies have been applied with different methods for a more systemic approach to cancer treatment. This review reports on advances of these technologies, including our personal contributions, mainly carried out on endocrine-related cancers. Some of the interventions, aimed at reverting cancer cells into a normal phenotype, are based on the evidence that tumor development is suppressed by the embryonic microenvironment. On the basis of this rationale, experiments have been conducted using stem cell differentiation stage factors (SCDSFs) taken at different stages of development of Zebrafish embryos, oocyte extracts, or naïve human umbilical cord matrix derived stem cells (UMDSCs). SCDSFs induce significant growth inhibition on different tumor cell lines in vitro, likely because of increases in cell cycle regulatory molecules, such as p53 and pRb. Treatment with these factors activates apoptosis and differentiation related to caspase-3. This is achieved via p73 apoptotic-dependent pathway activation with a concurrent normalization of the E-cadherin and beta-catenin ratio. Extracts from prophase amphibian oocytes could reprogram relevant epigenetic alterations in MCF-7 and HCC1954 breast cancer cell lines, while un-engineered (naïve) human UMDSCs attenuated growth of MDA-231 human breast carcinoma cells. A product prepared for human treatments, containing SCDSFs at very low doses, yielded favorable results in breast cancer and in intermediate-advanced hepatocellular carcinoma. Other reprogramming interventions used in the models of breast, prostate and ovarian cancer cell lines are described. Finally, current and future perspectives of this novel technology are discussed and a new hallmark of cancer is suggested: the loss of differentiation of cancer cells.

Interlinking of hypoxia and estrogen in thyroid cancer progression.

Estrogen aids in neo-vascularization of various tumors during hypoxic conditions, however the role of estrogen within the hypoxic environment of thyroid cancer is not known. In a series of experimentations, using human thyroid cancer cells, we observed that estrogen and hypoxia modulate the hypoxia inducible factor-1 (HIF-1) signaling which is abrogated by the anti-estrogen fulvestrant and the HIF-1 inhibitor YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole). Furthermore, we found that the conditioned medium from estrogen treated thyroid cancer cells lead to enhanced migration and tubulogenesis of human umbilical vein endothelial cells (HUVECs) which is abrogated by HIF-1 inhibitor. These findings, in addition to our previous and other scientific literature data, lead us to conclude that estrogen and hypoxia are interlinked in thyroid cancer and can equally modulate epithelial-endothelial cell interactions by mediating key cellular, metabolic and molecular processes of thyroid cancer progression. We believe that the hormonal component and cellular adaptation to oxygen tension of cancer cells are functionally equivalent with a cellular transition that can be exploited clinically for a combinational approach for thyroid cancer treatment involving antiestrogens as well as anti-hypoxic agents.

Changing the endocrine dependence of breast cancer: data and hypotheses.

Among the most common human cancers, often only breast and prostate cancers have advantage of hormone dependence. For a long time, this advantage permitted breast cancer to be efficaciously managed in the adjuvant and metastatic settings with low side effects by endocrine therapy. Unfortunately, soon or afterward hormone dependence is lost in most patients. In breast cancer, de novo or acquired hormone resistance is an hot issue and the focus of endless debate. Although a lack of oestrogen receptors (ERs) is considered to be the main reason for de novo hormone resistance, many studies have been conducted and many different mechanisms have been hypothesised to account for acquired hormone resistance. Thus far, hormone resistance appears to be occasionally delayed or avoided in "in vivo" experiments. However, this finding did not have a significant benefit in current clinical practice. The principal aim of this review article is to sum up and update the issue of changing the endocrine dependence of breast cancer. Recent molecular insights extensively elucidating and shedding new light on this very controversial issue are considered. Moreover, based on our recent reports, a new mechanistic interpretation of and a therapeutic approach for overcome hormone resistance are proposed.

Reprogramming cancer cells in endocrine-related tumors: open issues.

Reprogramming technologies have been developed to revert somatic differentiated cells into pluripotent stem cells that can be differentiated into different lineages potentially useful in stem cell therapy. Reprogramming methods have been progressively refined to increase their efficiency, to obtain a cell population suitable for differentiation, and to eliminate viral plasmid which could be responsible for many unwanted side-effects when used in personalized medicine. All these methods are aimed to introduce into the cell genes or mRNAs encoding a set of four transcription factors (OCT- 4, SOX-2, KLF-4 and c-MYC) or a set of three lincRNAs (large intragenic non-coding RNAs) acting downstream of the reprogramming transcription factors OCT-4, SOX-2 and NANOG. Translational clinical applications in human pathologies and in developmental, repair and cancer biology have been numerous. Cancer cells can be, at least in principle, reprogrammed into a normal phenotype. This is a recently raised issue, rapidly advancing in many human tumors, especially endocrine-related cancers, such as breast, prostate and ovarian ca. The present review aims to describe basic phenomena observed in reprogramming tumor cells and solid tumors and to discuss their meaning in human hormone-related cancers. We will also discuss the fact that some of the targeted transcription factors are "normally" activated in a number of physiological processes, such as morphogenesis, hypoxia and wound healing, suggesting an in vivo role of reprogramming for development and homeostasis. Finally, we will review concerns and warnings raised for in vivo reprogramming of human tumors and for the use of induced pluripotent stem cells (iPSCs) in human therapy.

Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids.

BACKGROUND: Limited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization. OBJECTIVES: To evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids. METHODS: Nineteen patients were treated with thalidomide for 24 months starting with 200 mg/d for first 2 weeks, followed by 100 mg/d for 11 weeks and a maintenance dose of 100mg on alternate days for 35 weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28). RESULTS: Skin score significantly decreased (P<0.001). Lower skin scores occurred after 3 and 6 months (P<0.05). s-ACE levels decreased over time at the third month (P<0.001). CXR assessed by radiological stage significantly improved during the first 6 months (P<0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment. CONCLUSIONS: Thalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids.

Cancer stem cells: perspectives of new therapeutical approaches for breast cancer.

Currently stem cells are hypothesized to play a central role in the origin, spread and resistance to treatment of breast cancer. Common anticancer therapy is effective but transient, with tumor relapse and metastatic disease often occurring. For therapy to be more effective, debulking of differentiated tumors must occur followed by targeting of the remaining surviving often quiescent tumor stem cells. New therapeutics aimed at cancer stem cells are achieved through non immunological and immunological methods. The former include elective ABC drug transporters or the heat shock protein 90 inhibition, targeting the self-renewal signalling pathways or the EMT program, differentiation therapy, or other interventions to eliminate BrCSCs. The latter include targeting specific antigens expressed on BrCSCs, dendritic cells (DCs) based vaccination and blockers of the extrinsic signals at CSC niche. Here all these novel approaches related to breast cancer stem cells are described.

Stem cells: their role in breast cancer development and resistance to treatment.

About 20% of the total cells from primary breast tumors could generate palpable tumors in non-obese diabetic severe combined immunodeficient (NOD/SCID) immunocompromised mice. All the tumorigenic cells originate from a normal mammary stem cell. Human mammary stem cells are sensitive to oncogenic mutations and in mouse models they share similarities with breast cancer stem cells (BrCSCs). Tumorigenicity, invasion, progression and metastasization are further BrCSCs properties likely depending on their CD44+/CD24- phenotype. Local invasion and tumor metastasization seem to be facilitated by the epithelial to mesenchymal transition (EMT) program. This program may be reactivated from stable genetic alterations or through exposure of cancer cells to factors present in the surrounding micro-environment, or by an up-regulation of EMT-inducing transcription factors. One main explanation for resistance to treatment by cancer cells is that a rare subpopulation of cells in residual tumors with tumorigenic potential is intrinsically resistant to therapy. Consistent with this hypothesis, in human breast tumors, the subpopulation of tumor-initiating cancer cells with CD44(high)/CD24(low) cell surface-marker profile was found more resistant to cancer therapies (chemo, hormone and radiotherapy) than is the major population of more differentiated breast cancer cells. The reasons for CSC resistance to chemotherapy, hormone therapy and radiotherapy also have been examined and they opened new scenarios for cancer therapy.

Changes in autonomic regulation and ventricular repolarization induced by subclinical hyperthyroidism.

UNLABELLED: The aim of the present study was to evaluate the effect of subclinical hyperthyroidism (SHT) on cardiovascular autonomic function and ventricular repolarization. METHODS: Thirty subjects (25 females; mean age 49.6 ± 9.8 years) with SHT, as judged by reduced TSH serum levels and normal free T4 and T3 serum levels, and 30 age and sex-matched control subjects underwent standard 12-lead ECG, and 24h ambulatory ECG monitoring. The dispersion of the QT interval, an index of inhomogeneity of repolarization, and the heart rate variability (HRV), a measure of cardiac autonomic modulation, were studied. RESULTS: Patients with SHT showed higher QT dispersion (p<0.001) and lower HRV measures (0.01>p<0.001) than controls. In SHT patients, QT dispersion was inversely related to HRV (r=-0.47, p<0.01). CONCLUSION: The results of the present study demonstrated that SHT is associated with a sympathovagal imbalance, characterized by increased sympathetic activity in the presence of diminished vagal tone, and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with SHT may represent a useful tool in monitoring the cardiovascular risk of this condition.

Total parathyroidectomy without autotransplantation for the treatment of secondary hyperparathyroidism associated with chronic kidney disease: clinical and laboratory long-term follow-up.

Forty-six consecutive patients who underwent total parathyroidectomy (tPTX) for hyperparathyroidism associated with end-stage kidney disease (CKD5) in a University Hospital from 1990 to 1999 were included in a long-term observational study. Outcome parameters included symptoms (bone pain, pruritus and muscle weakness evaluated by visual analog scales [VAS]) and laboratory data (intact parathyroid hormone [iPTH], total calcium, and alkaline phosphatase) assessed before, shortly postoperatively and then at a later time point: 40 patients were on maintenance hemodialysis and six on conservative medical therapy. Forty-four patients had four glands removed, while only three glands were found in the remaining two. Perioperative complications consisted of acute symptomatic hypocalcemia in 10 (22%) patients and non-specific complaints in three (7%). No laryngeal nerve palsies occurred. After a median follow-up of eight years, 43 subjects were evaluated: 37 (86%) were cured, three (7%) had persistent and three (7%) recurrent disease. Eleven patients underwent successful renal transplantation and 23 died during the period of observation. iPTH decreased from a mean of 1084+/-505 pg/ml to 120+/-381 pg/ml (p < 0.0001). No subsequent bone fractures, persistent bone pain or disability were reported; this includes patients who later received a functioning renal graft. tPTX was able to correct hyperparathyroidism in most of the patients and was associated with a low long-term relapse rate. iPTH levels remained low in 17 cases without symptoms and no clinically significant side effects. The beneficial effects of tPTX occurred in the majority of patients while renal transplantation was performed in a minority of patients. tPTX should be considered a safe and successful procedure for the treatment of severe secondary hyperparathyroidism associated with chronic kidney disease.

Cataract surgery in the United Kingdom: a postal survey.

PURPOSE: A postal questionnaire study to evaluate the current practice of cataract surgery delivery in the United Kingdom including strategies for postoperative review was performed. METHODS: A cataract questionnaire was sent to all hospital departments delivering ophthalmic services in the United Kingdom based on a list from the Royal College of Ophthalmologists. It included questions about the staffing level, number of cases operated on per list, and the different strategies employed postoperatively. The results were statistically analyzed. RESULTS: A total of 248 questionnaires were sent and 106 (43%) replies were received. The mean number of consultant teams was 11 (2-20). The average number of cases per list was 6-7 (range 4-9). In 65 hospitals, all patients are reviewed postoperatively in the hospital and some consultant teams review patients postoperatively in 18 hospitals. In 15 hospitals, patients were seen by the community optician. Most hospitals review their patients postoperatively within the first 3 weeks with more hospitals seeing them at 2-3 weeks. A wide variety of health professionals review the postoperative cases and they include doctors, nurses, and opticians (in house and community). CONCLUSIONS: There are varied practices for cataract surgery in the United Kingdom including the number of cases on the list and postoperative review protocols. There is room for better service organization in some hospitals in terms of patient flow and better use of medical staff time to improve output.

Relationship between triiodothyronine and proinflammatory cytokines in chronic heart failure.

UNLABELLED: Cytokines and thyroid hormones are involved in the biochemical changes associated to heart failure (HF). AIM: Aims of the study were to investigate: plasma circulating levels of the cytokines Interleukine-6 (IL-6) TNF alpha and C reactive protein (CRP) in patients with stable HF in relation to the severity of left ventricular dysfunction; the relationship between these inflammatory markers and thyroid hormones. METHODS: One-hundred and sixty-six patients (121 males, age 64+/-12), with non-ischemic cardiomyopathy, were admitted to the Institute of Clinical Physiology for progressive deterioration of symptoms. Forty-eight healthy subjects (30 males, age range 26-75 years) were also enrolled as control group (Group N). High sensitivity (hs)-IL-6 and hs-TNFalpha were quantified using solid phase sandwich ELISA kits. Hs-CRP was measured by Immulite System. RESULTS: In the whole population (HF and N), the association between inflammatory markers and age resulted statistically significant only for IL-6 serum concentration (p<0.001) but not for TNFalpha and CRP. IL-6 and TNFalpha were strongly higher in the HF in comparison with N (p<0.001) while CRP showed a less significant difference (p<0.05). Whole population showed a negative association between IL-6 and EF% and between CRP and EF% (respectively p<0.01, r=-0.23; p<0.05, r=0.19). Comparing normal subjects with two classes of patients, respectively with EF>35% and EF<35%, we clearly observed the progressive enhancement of the inflammatory markers. Considering normal subjects, patients without and with low T3 syndrome, IL-6 and TNFalpha increased progressively from normal to patients with fT3<2 pg/ml (p<0.01 and p<0.01) while CRP only respect to the group with low T3 syndrome (p<0.01). The inflammatory markers were all inversely correlated with FT3 levels. CONCLUSION: Because low FT3 serum concentration represents a negative prognostic index, it is likely that impairment of T3 production and enhanced inflammation represent pathogenic mechanisms linked to HF progression.

Cytokines in the management of high risk or advanced breast cancer: an update and expectation.

Some cytokines (interleukin (IL)-2, IL-11, transforming growth factor(TGF)beta) stimulate, while others (IL-12, IL-18, Interferons (IFNs)) inhibit breast cancer proliferation and/or invasion. So far IL-2, IFNalpha, IFNbeta and occasionally IFNgamma, IL-6, IL-12 have been used for the treatment of advanced breast cancer either to induce or increase hormone sensitivity and/or to stimulate cellular immunity. Only two long term pilot studies suggest that IL-2 and IFNbeta can improve clinical benefit and/or overall survival of metastatic breast cancer patients with minimal residual disease after chemotherapy or with disseminate disease non progressing during endocrine therapy. These results have been interpreted assuming that tumour microenvironment impairs the immune system of the host. Consequently, minimal disease or intense cytostatic effects following chemo or endocrine therapy, respectively, permit the patient's immune system to respond to the stimulatory effect of the cytokines. Therefore a prospective, phase III, randomised, simple blind trial has been planned. The aim is to assess whether the addition of IFNbeta and IL-2 to standard hormone therapy in postmenopausal patients with metastatic breast cancer and positive or unknown positive receptors prolongs the clinical benefit and survival since the metastatic diagnosis and the beginning of first line salvage antiestrogen therapy, compared with the results achieved with standard hormone therapy alone. If this immunotherapy prolongs survival of endocrine dependent metastatic breast cancer patients, IL-2 and IFNbeta can also be evaluated as adjuvant treatment of patients with positive estrogen receptors.

Thyroid hormones and the cardiovascular system: pathophysiology and interventions.

Thyroid dysfunction, however mild, can significantly affect the cardiovascular (CV) system. The effects of thyroid hormones may be viewed as genomic and non-genomic, with the former occurring over a longer time scale and both affecting structural and functional proteins in CV tissue. As the interplay between thyroid function and the CV system becomes elucidated, particularly in the context of a system biology approach, the heart failure phenotype is better understood. Symptomatology is related to disturbance in inotropic and chronotropic function. Moreover, biochemical changes reflected by thyroid function testing with the non-thyroidal illness syndrome can prognosticate and guide therapy in heart failure. In addition, empiric treatment with thyroid hormone analogues or T3 represent emergent and highly controversial interventions.

Study of skin vasomotion during phollicular and luteal phase in young healthy women.

The aim of this study was to evaluate if changes in female sex hormones associated to follicular phase (FP) and luteal phase (LP) may affect skin vasomotion in women with evidence of ovulatory cycle. Nine healthy non-smoker women aged 25+/-4 years, with regular menstrual cycle of 28+/-2 days and evidence of ovulation (indicated by a mid-luteal serum progesterone concentration > 5 ng/ml) (group-1) and six healthy non-smoker healthy women aged 24+/-2 years with evidence of an-ovulatory cycle (group-2) were enrolled in the study. At the times 1 (7th-10th day from the beginning of the last menstrual cycle) and at the time 2 (18th-22th day from the beginning of the last menstrual cycle) forearm skin vasomotion was investigated by means of spectral Fourier analysis of the skin laser Doppler flowmetry (LDF) tracing registered under basal conditions and following acetylcholine (ACh) iontophoresis. The power spectral density (PSD) of the 0.01-0.02, 0.02-0.06 and 0.06-0.2 Hz LDF tracing frequency intervals (related to endothelial-, sympathetic- and myogenic-dependent vasomotion, respectively) was measured in PU2 (LDF perfusion unit)/Hz (1 PU = 10 mV). At the same times skin blood flux response (percentage change from baseline) to ACh and to sodium nitroprusside (SNP) iontophoresis was also investigated. Basal and ACh-stimulated skin vasomotion did not significantly differ between time 1 and time 2 in PSD of the three frequency intervals investigated in both groups, as well as between the two groups at each time of investigation. Similarly, no significant changes were observed in skin vasodilator response to ACh and SNP iontophoresis between time 1 and 2 in each group. These results suggest that the female sex hormone changes associated to the FP and LP in young women with ovulatory cycle do not affect basal and ACh stimulated skin vasomotion as well as the endothelial- and non-endothelial-dependent skin vasoreactivity.

Skin blood flowmotion and microvascular reactivity investigation in hypercholesterolemic patients without clinically manifest arterial diseases.

Fourier spectral analysis of forearm skin laser Doppler flowmetry (LDF) signal was performed in fifteen hypercholesterolemic patients (HP), without clinically manifest arterial diseases, and in fifteen age-matched healthy control subjects (CS), in order to investigate skin blood flowmotion (SBF). The LDF frequency intervals studied were: 0.01-1.6 Hz total spectrum, as well as 0.01-0.02 Hz (endothelial), 0.02-0.06 Hz (sympathetic), 0.06-0.2 Hz (myogenic), 0.2-0.6 Hz (respiratory) and 0.6-1.6 Hz (cardiac). Skin microvascular reactivity (MVR) to acetylcholine (ACh) and to sodium nitroprusside (SNP) iontophoresis was also investigated. HP showed a lower post-ACh increase in power spectral density (PSD) of the 0.01-0.02 Hz SBF subinterval compared to CS (1.80+/-1.73 PU(2)/Hz vs 3.59+/-1.78 PU(2)/Hz, respectively; p<0.005), while they did not differ in MVR from CS. In eleven HP the 0.01-0.02 Hz SBF subinterval showed a higher post-ACh PSD increase near to the statistical significance after 10 weeks of rosuvastatin therapy (10 mg/day) compared to pretreatment test (3.04+/-2.95 PU(2)/Hz vs 1.91+/-1.94 PU(2)/Hz; p=0.07). The blunted post-ACh increase in PSD of the 0.01-0.02 Hz SBF subinterval in HP suggests a skin endothelial dysfunction in these patients. This SBF abnormality showed a tendency to improve after rosuvastatin therapy in eleven treated patients.

Skin vasomotion investigation: a useful tool for clinical evaluation of microvascular endothelial function?

Skin vasomotion is the rhythmic variation of skin microvessel diameter responsible for skin microcirculatory blood flow oscillation, the so called skin blood flowmotion. It can be easily investigated by means of the spectral analysis of skin laser Doppler flowmetry (LDF) signal. Experimental and clinical findings suggest that vasomotion is partially dependent on microvascular endothelial activity. Based on this, investigation of skin vasomotion, using spectral analysis of skin LDF signal has been recently proposed for the investigation of microvascular endothelial function in clinical setting. Clinical studies have demonstrated that the LDF technique coupled with spectral analysis of skin LDF tracing is a useful and accurate method for the measurement of skin microvascular endothelial-dependent vasomotion in patients with different pathological conditions. In these studies skin vasomotion investigation showed a higher sensitivity in the evaluation of skin microvascular endothelial function than tests based on the simple LDF measurement of skin blood flow response to different stimuli. Further studies are needed to evaluate whether the investigation of skin endothelial-dependent vasomotion can predict clinical and therapeutic outcomes of patients with vascular diseases.

Thyroid fine needle aspiration: how to improve clinicians' confidence and performance with the technique.

Studies from single institutions report an acceptable accuracy rate for thyroid fine needle aspiration (FNA). However, FNA accuracy is much lower in many other centers in Europe and the USA and large multicenter studies indicate that the clinicians' confidence in the FNA technique remains low. One explanation for this is that there is an excess of inadequate and indeterminate findings for a follicular nodule at FNA cytology. In a University Hospital with large and qualified experience on thyroid nodule diagnosis, a review of 320 slides with an FNA diagnosis of indeterminate follicular nodule from different minor Italian Hospitals led to a different diagnosis in 61%. Since ancillary thyroid imaging may be overutilized and only a few authors report a proportion of excised nodules lower than 10%, we suspect that use of the FNA procedure is suboptimal. Several techniques are reported to improve the performance of thyroid FNA. Among these are tumor markers and large needle aspiration biopsy (LNAB). Immunodetection of the tumor marker galectin-3 has been evaluated by large multinational studies. Analysis of LNAB specimens reduces the number of inadequate FNA findings, improves the diagnostic determination of indeterminate follicular FNA findings and represents a better substrate for the determination of galectin-3. Therefore, we propose that clinical practice guidelines reflect these adjuvant techniques to thyroid FNA in order to improve selection criteria for thyroid nodule surgery.

Immunotherapy prolongs the serum CEA-TPA-CA15.3 lead time at the metastatic progression in endocrine-dependent breast cancer patients: a retrospective longitudinal study.

In metastatic breast cancer tumour markers' increase predicts, by a few months (lead time) disease progression. In breast cancer patients with endocrine dependent metastatic disease, we reported a prolonged clinical benefit and overall survival when first line conventional antiestrogen hormone therapy was started at the lead time and also when an immunotherapy schedule was added to the same conventional hormone treatment. Thirty-two of these last patients were considered (group a). In 27 (group b) of these 32 patients who progressed during first line salvage hormone plus immunotherapy the lead time at the progression of metastatic disease during therapy was compared with that at the onset of metastases when the same patients were without treatment and with that of a control group (group c) who did not receive immunotherapy. At disease progression, CEA-TPA-CA15.3 sensitivity was 92.5% in the group b (studied patients) and 88.5% in the group c (controls). At the progression in the group b, CEA-TPA-CA15.3 lead time (m+/-sd, months) was significantly longer than in group c (12.1+/-12.9 vs 2.4+/-4.0) (P=0.000). Besides, in group b the lead time was significantly longer at the progression than at the metastatic onset (P=0.003) while in the group c the difference was near to significance (P=0.05). The CEA-TPA-CA15.3 tumour marker panel accurately predicted metastatic disease progression and immunotherapy significantly prolonged the CEA-TPA-CA15.3 lead time. This can be used for anticipating salvage treatment in these patients.

Percutaneous large-needle aspiration biopsy histology of palpable thyroid nodules: technical and diagnostic performance.

AIM: To report original and review existing data on safety and performance of large-needle aspiration biopsy (LNAB) histology in the preoperative selection of palpable thyroid nodule. METHODS AND RESULTS: The English literature and original data were reviewed or analysed. The literature on LNAB of thyroid nodules did not report any complications. A study on needle dimensions has explained why LNAB obtains more tissue than fine-needle aspiration (FNA) and is safe. LNAB histology has higher specificity than FNA cytology and markedly reduces the number of inadequate and indeterminate FNA findings. A comparison of 150 FNA-derived cell blocks with 200 LNAB-derived histological blocks after galectin-3 determination in a large nationwide (Italian) study has shown that one to two sections in 10% of the FNA cell blocks and at least five sections in 90% of the LNAB blocks were available for further determinations of thyroid tumour markers. CONCLUSION: LNAB merits further consideration for the preoperative selection of thyroid nodules.