Sexuality in premature ovarian insufficiency.

Sexuality in women with spontaneous premature ovarian insufficiency (POI) deserves attention because of the young age and the distressing impact of such a life-changing diagnosis. Biomedical and psychosocial factors work in concert to determine significant changes of sexual function. Early hormonal deprivation gives origin to symptomatic vulvovaginal atrophy and contributes to hypoactive sexual desire disorder modulating central and peripheral circuitries, which regulate sexual response. Emotional and cognitive adjustment to the short-term and long-term consequences of POI may further determine negative attitudes toward sexuality. It is essential to counsel POI women on every aspect of their life, from menopausal symptoms to fertility concerns, from health risks to potential therapeutic solutions. The biopsychosocial perspective is the best approach to manage sexual symptoms, including tailored hormone therapy and focused counseling. Pharmacotherapies specifically investigated in spontaneous POI conditions are lacking and clinical judgment has to guide the choice of treatment, which must be continued at least until the average age at natural menopause according to the most recent guidelines. Further studies are needed to better characterize POI women and to understand the effective role of novel therapeutic strategies, including androgens and cognitive-behavioral and sexual interventions.

Monurelle Biogel® vaginal gel in the treatment of vaginal dryness in postmenopausal women.

OBJECTIVES: To evaluate efficacy, tolerability and safety of Monurelle Biogel® vaginal gel for treatment of vaginal dryness. METHODS: Multicenter, national, randomized, controlled vs. no-treatment, open-label study. Ninety-five postmenopausal women were randomized (48 to Monurelle Biogel® and 47 to no treatment). Primary endpoint was the change of Verbal Rating Scale (VRS) total score of vaginal atrophy (VA) symptoms after 8-week treatment. The main secondary endpoints were VRS single-item score, Vaginal Health Index (VHI) score, Maturation Index (MI), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale-Revised (FSDS-R). RESULTS: The VRS total score was statistically significant in favor of the treatment group on day 28 (p = 0.001) but not on day 56 (p = 0.064). By excluding women who were not sexually active, the total VRS scores reached the criteria for clinical success in 27/43 subjects (62.8%) in the control arm and in 38/46 subjects (82.6%) in the treatment arm (p = 0.035) on day 56. The VHI score significantly changed in the active arm (4.71 ± 4.85 vs. 0.28 ± 1.71) (p < 0.001) on day 56. Even the MI significantly improved, with an increase in the percentage of superficial cells (p = 0.01). The improvements in both VHI and MI were still present at the follow-up visit after the discontinuation of the treatment (day 84). Sexual function and distress showed a statistical significant difference on day 56. CONCLUSIONS: Monurelle Biogel® vaginal gel applied twice daily for 8 weeks is effective in relieving vaginal dryness and other VA symptoms. Such a clinical meaningful effect persists at least 4 weeks and is supported by an improvement in the vaginal environment. Trial Registration clinicaltrials.gov Identifier: NCT02994342.

Exhaled breath temperature in children: reproducibility and influencing factors.

OBJECTIVE: This study will investigate the reproducibility and influencing factors of exhaled breath temperature measured with the tidal breathing technique in asthmatic patients and healthy children. METHODS: Exhaled breath temperature, fractional exhaled nitric oxide, and spirometry were assessed in 124 children (63 healthy and 61 asthmatic), aged 11.2 ± 2.5 year, M/F 73/51. A modified version of the American Thoracic Society questionnaire on the child's present and past respiratory history was obtained from parents. Parents were also asked to provide detailed information on their child's medication use during the previous 4 weeks. Ear temperature, ambient temperature, and relative-ambient humidity were also recorded. RESULTS: Exhaled breath temperature measurements were highly reproducible; the second measurement was higher than the first measurement, consistent with a test-retest situation. In 13 subjects, between-session within-day reproducibility of exhaled breath temperature was still high. Exhaled breath temperature increased with age and relative-ambient humidity. Exhaled breath temperature was comparable in healthy and asthmatic children; when adjusted for potential confounders (i.e. ambient conditions and subject characteristics), thermal values of asthmatic patients exceeded those of the healthy children by 1.1 °C. Normalized exhaled breath temperature, by subtracting ambient temperature, was lower in asthmatic patients treated with inhaled corticosteroids than in those who were corticosteroid-naive. CONCLUSION: Measurements of exhaled breath temperature are highly reproducible, yet influenced by several factors. Corrected values, i.e. normalized exhaled breath temperature, could help us to assess the effect of therapy with inhaled corticosteroids. More studies are needed to improve the usefulness of the exhaled breath temperature measured with the tidal breathing technique in children.

Tidal-breathing measurement of exhaled breath temperature (EBT) in schoolchildren.

BACKGROUND: Non-invasive assessment of airway inflammation is particularly useful in children. The exhaled breath temperature (EBT) may reflect inflammatory vasodilation and serve to assess respiratory symptoms and therapy with inhaled corticosteroids (ICs). AIMS: To compare EBT with other non-invasive measurements in unselected schoolchildren in relation to respiratory symptoms and IC-therapy, as well as to assess reproducibility, and potentially influencing factors. METHODS: In 298 Italian schoolchildren, we assessed tidal-EBT, FE(NO), spirometry, skin-prick tests, questionnaires on chronic respiratory symptoms, and medication. Subjects were divided as follows: reported wheeze, respiratory symptoms other than wheeze, and without symptoms. RESULTS: Subjects with reported wheeze (n = 30) more frequently presented atopy, respiratory symptoms, higher FE(NO), lower lung function than subjects with symptoms other than wheeze (n = 141) and those without symptoms (n = 127), but had a similar EBT. IC-treated children (5 wheeze, 9 respiratory symptoms other than wheeze, 4 without chronic symptoms) had lower median (interquartile range) EBT levels than IC-untreated children (n = 280) [EBT: 31.7 (30.1-32.5) vs. 32.6 (31.4-33.4), P = 0.027]. Duplicate EBT measurements were highly reproducible (ICC = 0.94). In a multiple linear-regression model, EBT was explained by age, weight, duration of EBT measurement, FE(NO), and ambient temperature (r = 0.63, P < 0.001). CONCLUSION: Tidal-EBT measurements are easy to perform, reproducible, though symptom misclassification may affect the results obtained regarding the effect of IC therapy. Factors influencing EBT should be addressed in further epidemiological studies.

Evaluation of fat grafting safety in patients with intraepithelial neoplasia: a matched-cohort study.

BACKGROUND: Fat grafting is widely carried out in breast cancer patients to improve quality in breast reconstruction. Recently, in vitro and animal studies have questioned the role of adipose tissues in cancer development. DESIGNS: Matched-cohort study. We analysed: (i) 59 intraepithelial neoplasia patients who had undergone lipofilling, with no recurrence between primary surgery and lipofilling. (ii) A control group of 118 matched patients (two controls per lipofilling patient) with the corresponding recurrence-free intervals. Both groups were also matched for main cancer criteria. A local event (LE) was the primary end point, with follow-up starting from the baseline. RESULTS: Median follow-up was 63 and 66 months from surgery, and 38 and 42 from baseline, for the lipofilling and control groups, respectively; the 5-year cumulative incidence of LE was 18% and 3% (P = 0.02). Ki-67 was the significant factor in univariate survival analysis. A subgroup analysis showed that lipofilling increased the risk of LE in women <50 years, with high grade neoplasia, Ki-67 ≥ 14 or who had undergone quadrantectomy. CONCLUSION: Higher risk of LE was observed in intraepithelial neoplasia patients following lipofilling. Although further studies are required to validate our conclusions, patients belonging to this subgroup should be informed of these results and the potential risks.

Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction.

BACKGROUND: A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features. METHODS: We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥ 14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied. RESULTS: Median follow up time was 74 months (range 3-165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥ 25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR. CONCLUSION: Luminal B/HER2 positive, triple negative subtypes and BMI ≥ 25 are independent prognostic factors for risk of LRR after IBR.

Locoregional recurrence risk after lipofilling in breast cancer patients.

BACKGROUND: Lipofilling has been indicated for postmastectomy and postlumpectomy breast reconstruction. The clinical literatures underline its technical efficacy but experimental studies raise important questions about the potential detrimental effect of adipocytes on the stimulation of cancer growth and reappearance. DESIGN: We collected 321 consecutive patients operated for a primary breast cancer between 1997 and 2008 who subsequently underwent lipofilling for reconstructive purpose. For each patient, we selected two matched patients with similar characteristics who did not undergo a lipofilling. RESULTS: Eighty-nine percent of the tumors were invasive. Median follow-up was 56 months from the primary surgery and 26 months from the lipofilling. Eight and 19 patients had a local event in the lipofilling and control group, respectively, leading to comparable cumulative incidence curves [P = 0.792; Hazard Ratio(Lipo vs No lipo) = 1.11 (95% confidence interval 0.47-2.64)]. These results were confirmed when patients undergoing quadrantectomy and mastectomy were analyzed separately and when the analysis was limited to invasive tumors. Based on 37 cases, the lipofilling group resulted at higher risk of local events when the analysis was limited to intraepithelial neoplasia. CONCLUSIONS: Lipofilling seems to be a safe procedure in breast cancer patients. Longer follow-up and further experiences from oncological series are urgently required to confirm these findings.

Safety of fat grafting in secondary breast reconstruction after cancer.

BACKGROUND: Fat grafting is largely used to correct soft-tissue defects in any region of the human body. This study analysed its safety when the technique is used to correct defects after breast-cancer reconstruction. METHODS: A total of 158 patients who underwent 194 breast fat grafting procedures were analysed. Almost all patients (98%) had a personal history of breast cancer: conservative surgery or mastectomy with breast reconstruction. In all cases, fat grafting was performed according to the Coleman's technique by a single surgeon. RESULTS: Immediate complications included liponecrosis and infection in seven cases (3.6%) that required only daily dressings and oral antibiotics administration. In cases of fat grafting after conservative surgery, only four patients (5.9%) showed minor alterations in the postoperative mammograms, consisting of the appearance of benign images. CONCLUSION: Breast fat grafting can be a good solution to repair defects after breast-cancer treatment and reconstruction, and can reduce the indication for more extensive surgeries such as myocutaneous flaps. Postoperative complication rates are very low and there is little alteration in follow-up mammograms. Two points remain unclear--how much of the fat is absorbed after grafting and the potential risk of local 'dormant' tumour cells being stimulated to induce a local recurrence.

Acute radiation dermatitis in breast cancer: topical therapy with vitamin E acetate in lipophilic gel base.

BACKGROUND: Radiotherapy can cause adverse skin reactions over the course of their treatment. Currently, management is based on several tropical products although there is no gold-standard approach to prevention and management of radiation toxicity. METHOD: We report our experience of vitamin E acetate in the treatment of radiation dermatitis in breast cancer patients who experienced grade 4 side effects (according to Radiation Therapy Oncology Group criteria). RESULTS: Clinical management consisted of oral antibiotics and local application of vitamin E acetate and local escarectomy. All of the patients achieved complete re-epithelialization within 40 days. CONCLUSION: Skin ulceration and necrosis post-radiation may interrupt oncological treatment in breast cancer patients. In acute radiodermatitis with skin necrosis, we propose the use of oral antibiotics together with escarectomy and the application of vitamin E acetate to facilitate the healing process in order to minimize the interruption to the oncological treatment.

Nipple sparing mastectomy with nipple areola intraoperative radiotherapy: one thousand and one cases of a five years experience at the European institute of oncology of Milan (EIO).

In order to reduce mutilation, nipple-areola complex (NAC) conservation can be proposed for the treatment of breast cancer when mastectomy is indicated. To reduce the risk of retro areolar recurrence, a novel radiosurgical treatment combining subcutaneous mastectomy with intraoperative radiotherapy (ELIOT) is proposed. One thousand and one nipple sparing mastectomies (NSM) were performed from March 2002 to November 2007 at the European institute of oncology (EIO), for invasive carcinoma in 82% of the patients and in situ carcinoma in 18%. Clinical complications, aesthetic results, oncological and psychological results were recorded. A comparison was performed between the 800 patients who received ELIOT and the 201 who underwent delayed one-shot radiotherapy on the days following the operation. The median follow up time was 20 months (range 1-69) for a follow up performed in 83% of the patients. The NAC necrosed totally in 35 cases (3.5%) and partially in 55 (5.5%) and was removed in 50 (5%). Twenty infections (2%) were observed and 43 (4.3%) prostheses removed. The median rate of the patients for global cosmetic result on a scale ranging from 0 (worst) to 10 (excellent) was 8. Evaluation by the surgeon in charge of the follow-up gave a similar result. Only 15% of the patients reported a partial sensitivity of the NAC. Of the fourteen (1.4%) local recurrences, ten occurred close to the tumour site, all far from the NAC corresponding to the field of radiation. No recurrences were observed in the NAC. In a group of patients characterized by a very close free margin under the areola, no local recurrence was observed. Overall, 36 cases of metastases and 4 deaths were observed. No significant outcome difference was observed between the 800 patients receiving intraoperative radiotherapy (ELIOT) and the 201 patients receiving delayed irradiation.

Does nipple preservation in mastectomy improve satisfaction with cosmetic results, psychological adjustment, body image and sexuality?

We investigated the influence of nipple areolar complex (NAC) sparing in mastectomy, on patient satisfaction with cosmetic results, body-image, sexuality and psychological well-being. We developed a specific questionnaire and compared two groups of women who underwent radical mastectomy with immediate breast reconstruction (IBR). Between 2004 and 2006, 310 women with NAC preservation and 143 patients with successive NAC reconstruction were mailed the questionnaire at follow-up 1 year after definitive complete breast reconstruction surgery. 256 questionnaires was available. Our results showed significant differences in favour of the NAC sparing group regarding body image (difficulty in looking at themselves naked and being seen naked by their partners after surgery, P = 0.001 and P = 0.003, respectively); regarding satisfaction with the appearance of the nipple (P < .0001) and with the sensitivity of the nipple (P = 0.001); regarding the feeling of mutilation (P = 0.003). NAC sparing in mastectomy has a positive impact on patient satisfaction, body image and psychological adjustment.

Nipple-sparing mastectomy: risk of nipple-areolar recurrences in a series of 579 cases.

BACKGROUND: When the conservative treatment is not recommended, Nipple Sparing Mastectomy (NSM) is proposed more and more frequently for the surgical treatment of breast cancer. The risk of local recurrence behind the nipple areolar complex (NAC) is the main limiting factor of the NSM procedure. To minimize such risk, we proposed in 2002 a intraoperative radiotherapy of the preserved NAC. PATIENTS AND METHODS: From March 2002 to November 2006, 579 cases (in 570 patients) of NSM were performed for carcinoma. The median follow up time was 19 months (Range: 1-60). The subcutaneous mastectomy was performed through an incision removing a portion of the skin overlying the tumour. An extemporaneous histological examination was performed on the retroareolar glandular tissue. If the histology was positive the patient was not considered eligible. Then an intraoperative radiotherapy with electrons (ELIOT) of 16 Gy in one shot was delivered on the NAC area. An immediate breast reconstruction was done using implants in most cases and in several cases a musculocutaneous flaps, usually in large breast. The number of local recurrences was recorded and the correlation between their occurrence and the clinical and histological criteria were analysed using the Gray test statistical method in a competing framework. RESULTS: In 516 cases the negative retroareolar frozen section biopsy was confirmed by the final histology, while in 63 cases, the final histology showed foci of carcinoma. Seven out of these 63 cases underwent a secondary NAC removal. In the 56 cases which preserved areolas we did not observe any local recurrence after 19 months follow up. The probability of retro areola positive histology increases with the tumour size. and was not related to the nodal status. The rate of local relapses was 0.9% per year. We didn't find any significant difference in the local relapse rate according to different patient's and tumour's features. Most relapses were located close to the tumour bed but never in the NAC area. CONCLUSION: Our study confirms that the local recurrence rate in the NSM completed with local radiotherapy on the NAC is not higher than the usual rate observed in the literature and the preservation of the NAC does not increase the risk. The absence of local recurrence in the region where a portion of glandular tissue has been purposely preserved is a good argument in favour of ELIOT.

Severe skin necrosis after breast reconstruction with a transverse rectus abdominis musculocutaneous flap in methylenetetrahydrofolate reductase deficiency.

We report a case of unexpected severe skin necrosis after autologous transverse rectus abdominis musculocutaneous flap breast reconstruction in a patient with homozygosis for the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene. This genetic deficiency is hypothesised as the cause of this exceptional skin necrosis. A 46-year-old woman underwent a radical mastectomy and immediate rectus abdominis musculocutaneous flap breast reconstruction. At the end of surgery, the blood supply to the flap and the abdominal wall was excellent. On the 5th postoperative day, the patient developed an extensive abdominal skin necrosis and a partial flap necrosis on the reconstructed breast. The rectus abdominis musculocutaneous flap breast reconstruction can be proposed to patients without any haemostatic defect in order to avoid life-threatening complications and unaesthetic results. This procedure requires careful patient selection, detailed preoperative planning, and complete laboratory investigations: However, mutation of the 5,10- methylenetetrahydrofolate reductase gene is too exceptional to form part of the routine preoperative investigation and can be looked for in these cases of extensive necrosis.

Oncological results of immediate breast reconstruction: long term follow-up of a large series at a single institution.

BACKGROUND: Reconstruction of the breast after mastectomy is an integral part of the complete management of breast cancer. However, a delay in the reconstruction is usually proposed after the mastectomy in case of invasive cancer, while there is a general agreement for immediate breast reconstruction in case of in situ tumors. PATIENTS AND METHODS: Among a total of 677 patients having undergone a mastectomy between 1997 and 2001, 518 (76.5%) underwent an immediate breast reconstruction (IBR). All the patients had a Patey mastectomy for invasive cancer (T1-T3). An adjuvant medical treatment was given according to the biological characteristics of the tumor and lymph node status. No patient received any kind of radiotherapy. The median follow up was 70 months (range 13-114). RESULTS: The local recurrence rate was 5.2% for the group of IBR and 9.4% for the mastectomy group without IBR (NoIBR). The regional metastases rate was 1.4 vs. 1.3%. The rate of distant metastases was 13.9 vs. 16.4%. Contra-lateral breast tumor was observed in 1.5 vs. 1.3%. Death rate was 10.4 vs. 16.4%. No statistical difference was observed between the two groups in terme of overall survival (OS) and disease free survival (DFS) (HR(IBR vs. NoIBR): 1.03 and 0.99 for OS and DFS, respectively). CONCLUSION: At our institution we have compared a large series that have undergone IBR (518) with a control group (159) and followed over a prolonged period of time (70 months). This study provides the best available results to suggest that IBR is a safe and reliable treatment option for the managing invasive breast cancer.

Non-invasive assessment of airway inflammation in ship-engine workers.

Smoking is harmful for respiratory function. In young to middle-aged men the damage is insidious and difficult to demonstrate. The respiratory impairment could increase under specific stressful conditions in the professional environment. On the hypothesis that exhaled markers are useful for assessing airway susceptibility to inhaled irritants, we measured exhaled markers and lung function in smoking and non-smoking engine-driver military coastguards before and after a patrol at sea. Eighteen men, mean age 39 yrs (range 23-58 yrs), 8 smokers, underwent spirometry, exhaled and nasal nitric oxide (eNO, nNO), exhaled carbon monoxide (CO) and exhaled breath condensate (EBC) for measures of hydrogen peroxide (H2O2), leukotriene B4 (LTB4), proteins (Prots), 8-isoprostanes (8-IsoPs), nitrite (NO2-) and nitrosothiols (RS-NOs) at baseline and after an 8-hour patrol navigation on board small, high-speed diesel-powered ships. At baseline, the smokers showed higher middle flows and CO levels, lower eNO and nNO than non-smokers, but similar levels of EBC markers; geometric means (95% confidence interval), CO: 23.6 (14.5 to 38.3) vs. 3.5 (2.5 to 5.3) ppm; eNO: 7.9 (4.8 to 12.9) vs. 26.7 (15.7 to 45.5) ppb, p=0.000. After navigation, Prots, 8-IsoPs and RS-NOs (but not lung function variables or other markers) significantly increased only in smokers; baseline vs post-navigation RS-NOs: 0.27 (0.11 to 0.65) vs. 1.30 (0.58 to 2.89) micromol, p=0.012. The respiratory consequences of a stressing environment in engine-driver military coastguards who actively smoke are better assessed by measuring EBC markers than by eNO, nNO or lung function. By increasing airway inflammation from oxidative-stress, tobacco smoking appears to interact with other chemical or physical factors elicited during sea navigation. Precisely what these factors are deserves further investigation.

Evaluation of skin perfusion after nipple-sparing mastectomy by indocyanine green dye. Preliminary results.

The aim of the study was to investigate the blood supply of the normal nipple areola complex (NAC) and the spared areola complex after a nipple-sparing mastectomy using the analysis of the fluorescence from the indocianine green dye (ICG) injection. Between December 2002 and July 2003 we performed the ICG analysis in 10 cases of healthy breasts and in 9 patients after a nipple-sparing mastectomy and one patient after subcutaneous mastectomy. In all cases, the resulting fluorescence was measured in three different zones: nipple, areola, surrounding mammary skin. Three parameters of the fluorescence curve (slope, maximum intensity, time to achieve a maximum level) were recorded. On the healthy breast, the nipple showed a very high perfusion as compared to the other zones. On the contrary, after the mastectomy the fluorescent pattern was completely altered, being the perfusion of the nipple very low. In conclusion, these preliminary results confirm the applicability and the importance of the ICG technique for evaluating the perfusion of the healthy and spared areola after surgery. Because of the small number of patients further studies are needed.

When mastectomy becomes inevitable: the nipple-sparing approach.

The preservation of the nipple areola complex (NAC) could improve the quality of life in cases of mastectomy. A novel radiosurgical treatment combining subcutaneous mastectomy with intraoperative radiotherapy is proposed. Three hundred nipple-sparing mastectomies (NSM) were performed. Invasive (58%) and in situ (42%) carcinomas were included. Clinical complications, aesthetic results, oncological and psychological results were recorded. The NAC necrosed totally in 10 cases and partially in 29 and it was removed in 12. Nine infections (3%) were observed and 10 prostheses removed. Good results were rated by 82.3% of the patients and by 84.8% of the surgeons. In 7.5% a radiodystrophy was observed. The sensitivity of the NAC recovered partially in 48%. Two local recurrences occurred outside the radiated field. Overall, we observed three metastases and no deaths. Sixty-eight of the patients were satisfied with their reconstructed breast and 85.5% were satisfied having preserved the NAC.

Systemic effects of surgery: quantitative analysis of circulating basic fibroblast growth factor (bFGF), Vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) in patients with breast cancer who underwent limited or extended surgery.

BACKGROUND: To assess if feature, extent and duration of surgery could influence levels of systemic proangiogenic cytokines vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta). PATIENTS AND METHODS: We collected blood samples from 82 consecutive breast cancer patients who underwent various types of surgery, classified according to the magnitude of tissue injury in: minimal (quadrantectomy), moderate (mastectomy without reconstruction), and heavy [mastectomy followed by reconstruction with transversus recto-abdominal muscle cutaneous flap (TRAM)]. Samples were collected one day before surgery (D(-1)), at the end of surgical tumor removal (D0), and on 1st (D(+1)), 2nd (D(+2)) and 5th (D(+5)) day after surgery. Serum VEGF, bFGF and TGF-beta levels were measured by the enzyme immunoassay method. RESULTS: On average a continuous decrease was observed for all growth factors from the day before operation to the 5th day after operation. On day (D(+5)) an increase was observed for patients who underwent extended respect to moderate surgery. These differences were found statistically significant for bFGF and VEGF (p = 0.05 and p = 0.025 respectively). A statistically different trend for type of operation was observed also for TGF-beta at 24-48 h: a minor reduction, compared to time of operation, was observed for minimal surgery, an intermediate reduction for moderate surgery and a higher decrease for extended surgery. CONCLUSIONS: Angiogenic cytokines perioperative levels could be increased on 5th day (D(+5)) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.

Immediate skin reactivity to histamine and to allergens in cohorts of 9-year-old schoolchildren studied 16 years apart.

BACKGROUND: Differing or increasing prevalence of positive allergen skin-prick tests observed in Europe could at least in part be explained by population changes in histamine skin reactivity. These changes would also alter the relationship between positive allergen skin-prick tests and serum IgE. OBJECTIVE: To assess changes in histamine reactivity, allergen skin-prick tests and serum IgE in our geographical setting. METHODS: We compared the outcome of two epidemiological surveys conducted 16 years apart in unselected 9-year-old schoolchildren (170 in 1983 and 176 in 1999) from a semi-rural region in central Italy. Outcome measures were skin-prick tests with two histamine concentrations (10 and 1 mg/mL) and 11 locally relevant allergens; serum total and specific IgE for positive allergens. RESULTS: The two histamine concentrations induced significantly larger mean weal diameters in 1999 than in 1983 (10 mg/mL: 5.28+/-0.82 mm vs. 3.25+/-0.97 mm; P<0.001). Whereas the prevalence of subjects with at least one positive allergen-induced weal reaction (>or=3 mm) increased over the 16 years (from 15.3% in 1983 to 25.6% in 1999), the prevalence of positive skin-prick tests, expressed as the allergen/ histamine weal ratio, remained almost unchanged. A given allergen weal diameter yielded less total (P<0.05 by Student's t-test for cumulative weals <8 mm) and specific (P<0.01 by Student's t-test for weals <3 mm, P<0.05 by Kruskal-Wallis test) serum IgE in 1999 than in 1983. CONCLUSIONS: Although the causes and mechanisms remain unclear, the increased histamine skin reactivity over time is associated with an increase in positive allergen skin-prick tests. In the presence of increased tissue and organ susceptibility to histamine, minute amounts of specific IgE could have important biological consequences.

Lectin histochemistry of epidermal glandular cells in the earthworm Lumbricus terrestris (Annelida Oligochaeta).

Carbohydrate residues were localized in the glandular cells of the epidermis of Lumbricus terrestris by lectin histochemistry. The following biotinylated lectins were used: ConA, PNA, WGA, UEA-I. Each lectin has a specific binding pattern in the epidermal glandular cells. The ConA binding is evident in the orthochromatic mucous cells; PNA in the metachromatic mucous cells; WGA in the neuroendocrine-like cells; UEA-I in the cuticle. The epidermal glandular cells possess specific sites for the different lectins in relation to their functional characteristics. Therefore, these sugar residues indicate different behaviours of the cells in epidermal functions related to ion transport, receptor-secretory processes and defence.