Vol. 6, n. 1, 2010 Periodico quadrimestrale - Spedizione in abbonamento postale 45% - art. 2 comma 20/B legge 662/96 - Milano In caso di mancata consegna restituire al mittente che si impegna a pagare la relativa tassa. Program & Abstracts 4 th Meeting Matera, 17-19 Giugno 2010 Topical photodynamic therapy for the treatment of mild to moderate acne: results of a multicenter, prospective, 24-month follow up study Pietro Cappugi, Claudio Comacchi, Giovanni Menchini, Pier Luca Bencini, Michela Gianna Galimberti, Matteo Tretti Clementoni, Daniele Torchia A new device for breast self examination Stefano Verardi, Ludovico Palla, Lorenzo Brinci, Caterina Cerretani, Eleonora Tati, Massimiliano Petrocelli, Giampaolo Palla The use of cryotherapy in the management of cutaneous hemangiomas: a review of 12 cases Massimiliano Galeone, Elisa Cervadoro, Gregorio Cervadoro Oral intake of nanosilicium in telogen effluvium: a scanning electro microscope microanalysis study Renata Strumia, Federica Baldo Edematofibrosclerotic panniculitis and cutaneous laxity treated with a combined laser-radiofrequency-ultrasound device Federica Tamburi, Tiziano Zingoni, Leonardo Celleno A compound containing aluminium potassium bisulphite, 18ß-glycirretic acid and retinyl palmitate (Alukina ) in the treatment of seborrheic dermatitis Antonino Di Pietro Lycopene, photoprotection and skin care: the benefits of organic quality Leonardo Rescio, Antonio Di Maio, Pietro Cazzola Effectiveness of a topical gel containing onion extract and allantoin in improving postsurgical scars healing Francesco Borgia, Valentina Bevelacqua, Laura Maggio Savasta, Mauro Barone, Serafinella P. Cannavò Sun and children, risks and benefit Carlo Alfaro Merkel cells carcinoma: a case of rapid and fatal evolution Enrico Scaparro, Marco Repetto, Marco Cacciapuoti, Manuela Scaparro NUTRIDERMATOLOGY Applications of DNA biotechnology in aging Bruno Mandalari, Nicola Sorrentino, Mariuccia Bucci MEETING REPORT Scalp disorders Antonio Di Maio, Damiano Abeni, Gianfranco Altomare, Enzo Berardesca, Piergiacomo Calzavara Pinton, Clara De Simone, Alberto Giannetti, Paolo Gisondi, Torello Lotti, Stefano Piaserico, Rosita Saraceno, Gino Antonio Vena Indexed in: EMBASE, EMNursing, Compendex, GEOBASE
Foto di Bob Krieger Cari soci e amici, la Dermatologia potrà avere un grande futuro se si sapranno cogliere in tempo i bisogni e le aspettative dei pazienti. Il dermatologo che vive e opera sul territorio e svolge la sua professione liberamente o negli ambulatori pubblici si confronta quotidianamente con le problematiche più frequenti e deve cercare di offrire soluzioni valide e rapide. Negli ultimi anni il dermatologo non è più solo un prescrittore di pomate ma utilizza sempre più strumenti di alta tecnologia sia per la diagnostica che per le terapie: dermatoscopi, ecografi, microscopi confocali, laser, radiofrequenza, ecc. La figura del vecchio dermatologo a cui bastava solo una lente di ingrandimento e una penna per scrivere sta velocemente cambiando. Il giovane dermatologo ha capito che il suo compito non si limita a curare la pelle malata ma anche quando essa è sana, per mantenerla sana e giovane il più a lungo possibile. Per capire quanto questo processo evolutivo si stia sviluppando abbiamo svolto una indagine tra i dermatologi dell ISPLAD a cui abbiamo chiesto di rispondere via web ad un questionario. Sono stati evidenziati importanti dati statistici che rappresentano una prima fotografia dello stato dell arte nella nostra specialità. Un dato che si può sottolineare è il crescente ruolo della dermatologia plastica e rigenerativa e l uso di strumenti tecnologici sempre più indispensabili nella dermatologia pratica quotidiana. All interno di questo numero di JPD si potranno trovare tutti i risultati di questa interessante indagine. Dermatology will have a great future if we are able to understand the needs and expectations of our patients in time. Dermatologists who work in the field, be it as private practitioners or in public hospitals, confront the more frequent problems on a daily basis and must constantly strive to offer valid and rapid solutions. In the last few years, the dermatologist has become more than just a prescriber of creams. More and more, he utilises instruments of high technology for both diagnoses and therapies. Such instruments include dermatoscopes, echographs, confocal microscopes, lasers, and radio frequencies e.t.c. The traditional image of the dermatologist, for whom a magnifying glass and a pen for writing were sufficient, is rapidly changing. The modern dermatologist has clearly understood that his job is not limited to treating ill skin. Nowadays, he also treats healthy skin and does his best to keep it looking healthy and young for as long as possible. To better understand how this evolutionary process is developing, we decided to carry out a survey among the dermatologists of ISPLAD and kindly asked them to complete an online questionnaire. Significant statistical data that paint a first snapshot of the state of art in our specialization has been collected. One such data is the growing role of plastic and regenerative dermatology and use of technological instruments, which are becoming increasingly indispensable in daily practical dermatology. You will find all the results of this very interesting survey inside this volume of JPD. Antonino Di Pietro 1
Journal of Plastic Dermatology Editor Antonino Di Pietro (Italy) Editor in Chief Francesco Bruno (Italy) Co-Editors Bernd Rüdiger Balda (Austria) Salvador Gonzalez (USA) Pedro Jaen (Spain) Associate Editors Francesco Antonaccio (Italy) Mariuccia Bucci (Italy) Franco Buttafarro (Italy) Ornella De Pità (Italy) Giulio Ferranti (Italy) Andrea Giacomelli (Italy) Alda Malasoma (Italy) Steven Nisticò (Italy) Elisabetta Perosino (Italy) Andrea Romani (Italy) Nerys Roberts (UK) Editorial Board Fabio Ayala (Italy) Lucio Andreassi (Italy) Kenneth Arndt (USA) Nicola Balato (Italy) H.S. Black (USA) Lucia Brambilla (Italy) Günter Burg (Switzerland) Stefano Calvieri (Italy) Michele Carruba (Italy) Aldo Di Carlo (Italy) Robin Eady AJ (UK) Paolo Fabbri (Italy) Giuseppe Micali (Italy) Martin Charles Jr Mihm (USA) Giuseppe Monfrecola (Italy) Joe Pace (Malta) Lucio Pastore (Italy) Gerd Plewig (Germany) Patrizio Sedona (Italy) Riccarda Serri (Italy) Adele Sparavigna (Italy) Abel Torres (USA) Stefano Veraldi (Italy) Umberto Veronesi (Italy) Managing Editor Antonio Di Maio English editing Rewadee Anujapad Direttore Responsabile Direttore Generale Direttore Marketing Consulenza grafica Impaginazione Pietro Cazzola Armando Mazzù Antonio Di Maio Piero Merlini Stefania Cacciaglia Registr. Tribunale di Milano n. 102 del 14/02/2005 Scripta Manent s.n.c. Via Bassini, 41-20133 Milano Tel. 0270608091/0270608060 - Fax 0270606917 E-mail: scriman@tin.it Abbonamento annuale (3 numeri) Euro 39,00 Pagamento: conto corrente postale n. 20350682 intestato a: Edizioni Scripta Manent s.n.c., via Bassini 41-20133 Milano Stampa: Arti Grafiche Bazzi, Milano Sommario pag. 5 Topical photodynamic therapy for the treatment of mild to moderate acne: results of a multicenter, prospective, 24-month follow up study Pietro Cappugi, Claudio Comacchi, Giovanni Menchini, Pier Luca Bencini, Michela Gianna Galimberti, Matteo Tretti Clementoni, Daniele Torchia pag. 11 A new device for breast self examination Stefano Verardi, Ludovico Palla, Lorenzo Brinci, Caterina Cerretani, Eleonora Tati, Massimiliano Petrocelli, Giampaolo Palla pag. 17 The use of cryotherapy in the management of cutaneous hemangiomas: a review of 12 cases Massimiliano Galeone, Elisa Cervadoro, Gregorio Cervadoro pag. 21 Oral intake of nanosilicium in telogen effluvium: a scanning electro microscope microanalysis study Renata Strumia, Federica Baldo pag. 25 Efficacia e sicurezza di un sistema combinato laser, radiofrequenza ed ultrasuoni per il trattamento della pannicolopatia edemato fibro sclerotica e del rilassamento cutaneo Federica Tamburi, Tiziano Zingoni, Leonardo Celleno pag. 33 Prima valutazione dell efficacia di un composto contenente allume di potassio (Alukina ) nel trattamento della dermatite seborroica Antonino Di Pietro pag. 37 Licopene, fotoprotezione e cura della pelle: i vantaggi della qualità biologica Leonardo Rescio, Antonio Di Maio, Pietro Cazzola pag. 49 Efficacia e tollerabilità di un gel a base di Allium cepa ed allantoina nei processi di cicatrizzazione di ferite chirurgiche Francesco Borgia, Valentina Bevelacqua, Laura Maggio Savasta, Mauro Barone, Serafinella P. Cannavò pag. 57 Sole e bambini, rischi e benefici Carlo Alfaro pag. 61 Carcinoma e cellule di Merkel: un caso a rapida e fatale evoluzione Enrico Scaparro, Marco Repetto, Marco Cacciapuoti, Manuela Scaparro NUTRIDERMATOLOGY pag. 65 Biotecnologia del DNA nell invecchiamento Bruno Mandalari, Nicola Sorrentino, Mariuccia Bucci MEETING REPORT pag. 71 Patologie del cuoio cappelluto Antonio Di Maio, Damiano Abeni, Gianfranco Altomare, Enzo Berardesca, Piergiacomo Calzavara Pinton, Clara De Simone, Alberto Giannetti, Paolo Gisondi, Torello Lotti, Stefano Piaserico, Rosita Saraceno, Gino Antonio Vena pag. 85 Program & Abstracts 4 th Meeting Matera, 17-19 Giugno 2010 È vietata la riproduzione totale o parziale, con qualsiasi mezzo, di articoli, illustrazioni e fotografie senza l autorizzazione scritta dell Editore. L Editore non risponde dell opinione espressa dagli Autori degli articoli. Ai sensi della legge 675/96 è possibile in qualsiasi momento opporsi all invio della rivista comunicando per iscritto la propria decisione a: Edizioni Scripta Manent s.n.c. Via Bassini, 41-20133 Milano Journal of Plastic Dermatology 2009; 5, 2 3
Topical photodynamic therapy for the treatment of mild to moderate acne: results of a multicenter, prospective, 24-month follow up study Pietro Cappugi 1,2 Claudio Comacchi 1-3 Giovanni Menchini 1,2 Pier Luca Bencini 3,4 Michela Gianna Galimberti 3,4 Matteo Tretti Clementoni 3,5 Daniele Torchia 2 Summary Topical photodynamic therapy for the treatment of mild to moderate acne: results of a multicenter, prospective, 24-month follow up study Photodynamic therapy (PDT) has been attempted for a wide range of dermatologic entities other than the commonly utilized indications of actinic keratoses, basal cell carcinoma and squamous cell carcinoma. Acne vulgaris is often a chronic-relapsing disease and therefore requires long-term and/or repeated treatment courses. Recent data suggest that light-based treatments, including visible light, specific narrowband light, intense pulsed light, pulsed dye laser, and PDT with or without photosensitizing agents, are useful in acne and offer greatest utility when used as an adjunct to medical therapy or for patients who refuse or cannot tolerate medical therapy. The purpose of this study was to evaluate the efficacy and tolerability of topical PDT in the treatment of acne. PDT treatment can lead to the eradication of etiological bacteria to acne and the suppression of new papulopustular lesions for about 24 months. KEY WORDS: Topical photodynamic therapy, Acne, ALA-PDT Piero Cappugi 1 International-Italian Society of Plastic- Regenerative and Oncologic Dermatology (ISPLAD), Milan, Italy 2 Italian Group of Radiofrequencies and Photodynamic Therapy (GIRTeF), Florence, Italy 3 Italian High-Tech Network in Dermatologic Sciences, Milan, Italy 4 Institute of Surgery and Laser Surgery in Dermatology (ICLID), Milan, Italy 5 European Dermatologic Institute (IDE), Milan, Italy I ntroduction Acne vulgaris is often a chronic-relapsing disease and therefore requires long-term and/or repeated treatment courses 1. Various combination of topical benzoyl peroxide, topical/oral antibiotics, and topical/oral retinoids have shown to be highly effective in treating acne at different levels of severity 1. Nevertheless, the need of months sometimes years of treatment, the high frequency of side effects, and increasing microbial resistance limit the clinical effectiveness and patients compliance to drug-based treatments. Recent data suggest that light-based treatments, including visible light, specific narrowband light, intense pulsed light, pulsed dye laser, and photodynamic therapy (PDT) with or without photosensitizing agents, are useful in acne and offer greatest utility when used as an adjunct to medical therapy or for patients who refuse or cannot tolerate medical therapy 1-4. PDT using 5-aminolevulinic acid (ALA) or me - thylaminolevulinate (MAL) is a safe and effective option for the treatment of several premalignant, malignant and noncancerous skin disorders, including acne. After topical application, ALA and MAL are taken up mainly by cells of epithelial origin and are converted by haem biosynthesis into photosensitizing porphyrins, mainly protoporphyrin IX. Following activation to the photosensitizer with light of the appropriate wavelength (405-635 nm), reactive oxygen species, in particular singlet oxygen, are generated and finally lead to cell death via necrosis or apoptosis 5, 6. Although demonstrated mainly in vitro, at least two mechanisms are thought to be important in acne: 1) destruction of Propionibacterium acnes, which normally produces porphyrins that absorb visible light at wavelengths between 400 and 700 nm; 2) damage of sebaceous gland cells with subsequent reduction of sebum excretion for prolonged periods of time 1, 4, 7-10. A number of clinical trials have demonstrated the effectiveness and safety of PDT in acne 1-4. 5
P. Cappugi, C. Comacchi, G, Menchini, P.L. Bencini, M.G. Galimberti, M. Tretti Clementoni, D. Torchia However, the small sample size of the various series, the frequent lack of appropriate controls, widely differences in study designs (scoring of acne severity, type of prodrug and light sources, incubation time, number of sessions, outcome measures, short-term follow up) have prevented PDT from being rated with a high level of evidence in acne so far 1. We report herein the results of a study aimed at evaluating the maintenance of clinical results obtained with PDT in patients with mild to moderate acne over a 24-month follow up period. aterials and methods m This prospective, multicentric, open and uncontrolled study was performed according to the Declaration of Helsinki. Patients were enrolled consecutively according to the following inclusion criteria: 1) acne vulgaris stage I (only comedones) or II (comedones, papules and/or pustules); 2) written informed consent. Exclusion criteria included: 1) acne vulgaris stage III-IV (presence of cysts and/or nodules); 2) personal history of hypertrophic scars and/or keloids, severe local skin infections, endocrine disorders, and photo-mediated/photo-aggravated diseases; 3) no systemic drug (retinoids, antibiotics, hormones) and/or physical therapy aimed to the treatment of acne during the previous 4 weeks; 4) abnor mal serum levels of follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, te stosterone, 17-ß estra diol, progesterone, de hydroepiandro - sterone sulfate, cortisol; 5) ab normal ultrasono - gra phy of the genital ap paratus. After enrollment, pa tients were asked to apply a salycilic acid plus glycolic acid cream on the areas to be treated starting from 10 days before the treatment session. A gel containing 10% 5-ALA was then applied topically and covered with a po - lyethy lene dressing. After 3 hours, the ap - plication sites were ir - ra diated with 100 joule of red light with a peak emission at 630 nm. Patients were then prescribed emollients *: all with stage II acne. and sunscreens for home management during the following week. The same procedure was repeated every other week for 4 times (acne stage I) or 6 times (acne stage II). Follow-up visits were performed 3, 6, 12, 18, and 24 months after the last PDT session. Patients were also invited not to undergo any other pharmacologic or physical treatment for acne till the end of follow-up. Digital pictures were taken before the first treatment session and during each follow-up visit. Clinical improvement was globally assessed by two independent dermatologists, who graded changes in acne from a small set of fixed-magnification clinical photographs. If a patient failed to respond even to the initial PDT cycle, he/she would be eventually addressed to other treatment modalities. In case of acne relapse after an initial improvement induced by PDT, other PDT sessions followed at the investigator s discretion. Either case, the patient s outcome was considered negative for the purpose of this study. A 90% or greater improvement from pretreatment images plus no further need of pharmacologic (topical and/or oral antibiotics and/or retinoids) or physical therapy (also taking into consideration the patients opinion) was set as the positive outcome at 12-, 18-, and 24-month followup visits. The percentage of positive responders was than calculated. Student s t test was used for statistical comparison; a result of 0.05 or less was considered as statistically significant. results One-hundred forty-eight subjects were considered for entering the study. Thirtyfour females affected by polycystic ovary syndrome and 6 males with acne stage III-IV were excluded. Fifty-nine females (age range 16-35 Table 1. Demographic data of our case series. Skin type Stage of acne Localization of lesions Gender Number II III IV I II Face Trunk Females 59 21 38 1 38 21 59 15* Males 47 14 31 2 25 22 47 16* Total 106 35 68 3 63 43 106 31* 6
Topical photodynamic therapy for the treatment of mild to moderate acne: results of a multicenter, prospective, 24-month follow up study FU (mo) Table 2. Number and percentage of patients with positive results over various follow up visits. Stage I acne Patients with positive results Stage II acne F M Total F M Total Grand total N % N % N % N % N % N % N % PT 38 0 25 0 63 0 21 0 22 0 43 0 106 0 12 37 97.37 25 100 62 98.41 16 76.19 13 59.09 29 67.44 91 85.85 18 36 94.74 23 92.0 59 93.65 14 66.67 10 45.45 24 55.81 83 78.3 24 35 92.11 23 92.0 58 92.06 13 61.90 9 40.9 22 51.16 80 75.47 FU: follow-up; mo: months; F: females; M: males; N: number; PT: pre-treatment. years) and 47 males (age range 15-29 years) affected by acne stage I-II (grand total of 106) were enrolled in the study (Table 1). Ten females and 6 males had used topical antibiotics during the previous months. All patients showed an initial clinical improvement (mainly reduction of open comedones and inflammation) many of whom already after the first PDT session and disappearance of most lesions by the end of the treatment cycle (Figures 1-4). The skin texture also showed an evident improvement. As detailed in Table 2, almost 85% of all 106 patients maintained the positive results achieved after the PDT cycle for at least 12 months, and about 75% of them for at least 24 months. Nonetheless, important differences were detected among several subgroups. While over 90% of patients with stage I acne did not experience any relapse as detected at follow-up visits, the response of patients with stage II acne was significantly poorer (p < 0.0001 at all times), with about half of patient still in remission phase at 24 months. Worse results, albeit non statistically significant, were obtained in stage-ii males when compared to females. However, involvement of the trunk did not imply a different outcome (data not shown). Two additional PDT sessions were performed with satisfying results on those 26 patients who relapsed at different times before the 24-month follow up. All patients complained of erythema and edema during the days immediately following PDT applications. A few of them developed also scales, crusts or pustules, which eventually disappeared within 7-10 days. No long-term side effects were registered. Figure 1. a. An acne patient with some papulopustular lesions. The view just before the first PDT. b. Three months after one PDT series (four PDT treatments). a b 7
P. Cappugi, C. Comacchi, G, Menchini, P.L. Bencini, M.G. Galimberti, M. Tretti Clementoni, D. Torchia Figure 2. a. An acne patient with many papulopustular lesions and several large cystic lesions. b. One year after one PDT series (six treatments). a b Figure 3. a. An acne patient with many papulopustular lesions and several large cystic lesions. The view just before the first PDT. b. One year after one PDT series (six treatments) a b Figure 4. a. An acne patient with some cystic lesions. The view just before the first PDT. b. Three months after one PDT series (four PDT treatments). a b D iscussion PDT is an emerging technique for treating acne vulgaris. The majority of PDT trials for acne reported to date showed a bene- fit from using PDT compared with light therapy alone 2. Multiple treatments appeared to be superior to single treatments, especially at longer follow-up periods. The major disadvantage of PDT was that some participants experienced 8
Topical photodynamic therapy for the treatment of mild to moderate acne: results of a multicenter, prospective, 24-month follow up study side-effects (pain, erythema, desquamation) severe enough for them to discontinue the treatment. However, those trials which looked at patient satisfaction score for PDT showed that most patients felt their acne had improved significantly 2. A major limitation of all studies was a short follow up, ranging from a few weeks to a maximum of 6 months 1. Our multicentric prospective study, aimed at assessing the long-term maintenance of PDT results in 106 patients affected by mild-tomoderate acne, showed that ALA-PDT manages to achieve a long-lasting remission (till 24 months) in more than 90% of stage I (comedonic) acne and in about half of stage II (papulopustular) acne patients. Results were better in females than in males, albeit without reaching statistical significance; this finding may possibly reflect a higher severity of lesions in male individuals, but the lack of quantitative assessment of acne severity prevents from confirming this hypothesis. We also point out that the patients who relapsed earlier than the last follow up visit actually improved with two additional sessions, thus suggesting the possible effectiveness of recall sessions whenever needed. Nonetheless, our study was affected by several limitations, including lack of controls and randomization, lack of quantitative outcome measures as well as of subjective scales aimed to evaluate patients satisfaction and compliance. On the basis of previous studies and the data presented here, the main advantages of the use of PDT in acne over pharmacologic treatments include: 1) unlimited number of treatment sessions without risk of tachyphylaxis or onset of bacterial resistance; 2) good safety profile without long-term sequelae; 3) quick improvement and mainteinance of results over time without any need to take daily medications; 4) cosmetic effect on skin texture. Hence, more evidence-based studies aimed to assess the best treatment protocol, effectiveness, patients compliance, and cost/benefit ratio, as well as to make a comparison of PDT versus other acne treatments, are warranted. r eferences 1. Thiboutot D, Gollnick H, Bettoli V, et al. Global Alliance to Improve Outcomes in Acne. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol 2009; 60(5 Suppl):S1-50. 2. Hamilton FL, Car J, Lyons C, et al. Laser and other light therapies for the treatment of acne vulgaris: systematic review. Br J Dermatol 2009; 160:1273-85. 3. Haedersdal M, Togsverd-Bo K, Wulf HC. Evidencebased review of lasers, light sources and photodynamic therapy in the treatment of acne vulgaris. J Eur Acad Dermatol Venereol 2008; 22:267-78. 4. Hongcharu W, Taylor CR, Chang Y, et al. Topical ALAphotodynamic therapy for the treatment of acne vulgaris. J Invest Dermatol 2000; 115:183-92. 5. Comacchi C, Cappugi P. Terapia Fotodinamica in Dermatologia. Un trattamento non invasivo di patologie cutanee tumorali e non. Hi.techdermo, anno III, 2008; 4:11-24. 6. Comacchi C, Cappugi P. guidelines for topical photodynamic therapy. Journal of Plastic Dermatology 2009; 5,2:1-8. 7. Zelickson BD. Mechanism of action of topical aminolevulinic acid. In: Photodynamic Therapy. Goldman MP ed. Elsevier Saunders, 2005; 1-11. 8. Pollock B. Topical ALA-PDT for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action. British Journal of Dermatology 2004; 151:616-622. 9. Ross EV. Optical treatment for acne. Dermatologic Therapy 2005; 18:253-266. 10. Itoh Y. Treatment of acne. In: Photodynamic Therapy. Goldman MP ed. Elsevier Saunders 2005; 13-31. 9
a new device for breast self examination Stefano Verardi 1 Ludovico Palla 1 Lorenzo Brinci 1 Caterina Cerretani 1 Eleonora Tati 1 Massimiliano Petrocelli 1 Giampaolo Palla 2 Summary a new device for breast self examination A cross-sectional study of 130 women presenting for screening mammography was conducted. All women were provided with a breast self administrated questionnaire and all women were invited to provide a breast self-examination (BSE). All patients under the study were split into two groups homogeneous for ages. In the first group the women which made the BSE wearing a special glove amplifying the hand sensibility were included, in the second group women made the same examination without any glove. The target of the study was to determine if an improved lump detection rate could be achieved. Collected data showed a significant difference for the identification of breast lumps between the group wearing the amplifying detection glove and the control group using the bare hand. Among the second group 28 women failed to detect any existing lumps which were instead detected in the first group. Patients found the glove easy to be used and stated that the fact of having it has greatly increased their awareness of the breast cancer prevention. By this it came out that the use of the amplifying glove increased the hand sensibility towards breast lumps and therefore their ability to make an early detection of breast lumps. KEY WORDS: Breast self-examination, Early cancer detection Stefano Verardi 1 Department of Plastic and Reconstructive Surgery, University of Tor Vergata Rome, Italy 2 Department of Gynecology and Obstetric, Central Hospital of Viterbo, Italy I ntroduction Recently several authors 1-3 reported studies in which them started to rise several questions about the fact that the Mammography screening might be a profit-driven technology posing risks compounded by unreliability. In striking contrast, annual clinical breast examination (CBE) by a trained health professional, together with monthly breast self-examination (BSE), is safe, at least as effective, and low in cost. International programs for training nurses how to perform CBE and teach BSE are critical and overdue. Contrary to popular belief and assurances by the U.S. media and the cancer establishment the National Cancer Institute (NCI) and American Cancer Society (ACS) mammography is not a technique for early diagnosis. In fact, a breast cancer has usually been present for about eight years before it can finally be detected. Furthermore, screening should be recognized as damage control, rather than misleadingly as secondary prevention. Mam - mography poses a wide range of risks of which women worldwide still remain uninformed. Those risks can be summarized in radiation risks 4-9, cancer risks from breast compression 10, 11, delays in diagnostic mammography 12. Beside mammography started to be also evaluated for its unreliability because falsely negative mammograms 13-15, interval cancers 5, 16, falsely positive mammograms 17, 18, over diagnosis 19-23 and quality control 24. Despite the long-standing claims, the evidence that routine mammography screening allows early detection and treatment of breast cancer, thereby reducing mortality, is at best highly questionable. In fact, the overwhelming majority of breast cancers are unaffected by early detection, either because they are aggressive or slow growing 24. There is supportive evidence that the major variable predicting survival is the so called biological determinism, a combination of the virulence of the individual tumor plus the host s immune response, rather than just early detection 25. Claims for the benefit of screening mammo- 11
S. Verardi, L. Palla, L. Brinci, C. Cerretani, E. Tati, M. Petrocelli, G. Palla graphy in reducing breast cancer mortality are based on eight international controlled trials involving about 500.000 women 26. However, recent meta-analysis of these trials revealed that only two, based on 66.000 postmenopausal women, were adequately randomized to allow statistically valid conclusions 26. Based on these two trials, the authors concluded that there is no reliable evidence that screening decreases breast cancer mortality- not even a tendency towards an effect. Accordingly, the authors concluded that there is no longer any justification for screening mammography; further evidence for this conclusion will be detailed at the May 6, 2001. Annual meeting of the National Breast Cancer Coalition in Washington, D.C., and published in the July report of the Nordic Cochrane Centre. Even assuming that high quality screening of a population of women between the ages of 50 and 69 would reduce breast cancer mortality by up to 25 percent, yielding a reduced relative risk of 0.75, the chances of any individual woman benefiting are remote 21, 27. For women in this age group, about 4 percent are likely to develop breast cancer annually, about one in four of whom, or 1 percent overall, will die from this disease. Thus, the 0.75 relative risks apply to this 1 percent, so 99.75 percent of the women screened are unlikely to benefit. The fact that most breast cancers are first recognized by women themselves was admitted in 1985 by the ACS, an aggressive advocate of routine mammography for all women over the age of 40: We must keep in mind the fact that at least 90 percent of the women who develop breast carcinoma discover the tumors themselves 28. Furthermore, as previously shown, training increases reported breast self-examination frequency, confidence, and the number of small tumors found 29. A pooled analysis of several 1993 studies showed that women who regularly performed BSE detected their cancers much earlier and with fewer positives nodes and smaller tumors than women failing to examine themselves 30 ; BSE would also enhance earlier detection of missed or interval cancers, especially in pre-menopausal women 31. There is a strong consensus that the effectiveness of BSE critically depends on careful training by skilled professionals, and that confidence in BSE is enhanced with annual CBEs by an experienced professional using structured individual training 32. The tactile sensitivity of BSE Figura 1. Donna Glove, medical device created to improve the detection of breast lumps. can be increased by the use of Mammacare techniques to enhance lump detection skills 33, 34, and by the use of FDA-approved and non-prescription thin and pliable lubricant-filled sensor pads 35, 36. To determinate the relation between different methods of BSE and actual existence of breast lumps, the authors studied 130 patients at the University of Rome Tor Vergata and at the Central Hospital of Viterbo, Italy from October 1st 2006 to September 30 th 2009. All patients were trained by professional nurses to do a good BSE using structured individual training conformed to Italian Health Service suggestions. The idea was to test if a medical device called Donna Glove (Figure 1) created to improve the detection of breast lumps was effectively functioning. An external layer of a Polyurethane- Membrane makes the glove. Inside this membrane a light mineral oil NF 18 is contained. All components of the device are conformed to EC Directives and FDA requirements as for 21 CFR 172.878 and 21 CFR 178.3620A. aterials and methods m Our 130 women suspecting and/or actually having detected breast lumps composed the panel of the study. The patients under the study were split into two equal groups (Table 1): Group 1: the 65 patients of this group weared 12
A new device for breast self examination Table 1. Subdivision by groups of the patients under the study. Groups System Used Number of patients Group 1 Donna Glove 65 Group 2 BSE with the bare hands 65 Total of patients 130 the Donna Glove, the medical device under detection, a special glove designed to enhance sensitivity of palpation. Group 2: the 65 patients of this group continued to make breast self-examinations (BSE) with the bare hand. The target of the study was to determinate if an improved lump detection rate could be achieved. r esults At a medium follow-up time of 18 months 83% of all patients had a re-occurrence of lumps detected by mammography. These were equally present in both groups (Table 2), 54 patients in each group had a recurrence of lumps. Table 2. Re-occurence of lumps detected by mammography. Groups Recurrence of lumps Detection Rate Failed to Detect Group 1 54/65 patients 100% 0% Group 2 54/65 patients 48% 52% Group 1, had a 100% detection rate, all 54 positives were detected. Group 2, had a 48% detection rate and only 26 positives were detected while 28 failed to detect any existing lump. Since lumps can grow within a week, is highly recommended that the women in such highrisk groups have a BSE at least weekly. The significant difference persisted after adjustment for any combination of age, method of detection and family history of breast cancer. The subsequent mammography confirmed these percentages. The best reason for performing monthly breast self-examinations is the fact that 90% of all lumps and just under half of all breast cancers are actually discovered by women or by their partners. As with all tumors early detection may lead to an early treatment and it is the most important factor to reach a successful lumpectomy with preservation of the breast. It is statistically estimated that one over nine Italian women will probably develops a breast cancer. Breast cancer is the most common malignancy cancer among Italian women and their survival rates is strictly connected with early detection. We adopted an easy to follow modern breast self-examination education and training using a 3 layers plastic glove containing a light mineral oil, brand name Donna Glove, manufactured and supplied by the Italian company Poggio Fiorito srl. This device may increase from 3 to 5 times the fingers sensitivity of the user 37. A BSE (Figures 2, 3) should be performed on each breast in a routine fashion to be sure that no area is missed. To perform a BSE, a woman should lie down and place her right arm behind her head to begin examining her right breast. It is not recommended to perform a BSE standing up because the position does not allow the breast tissue to spread evenly over the chest wall. By lying down instead the tissue is spread thinner and thus makes it easier to detect any possible change. After the breast has been examined, it is important for a woman to also examine each underarm for any lumps or signs of enlarged lymph nodes. This part of the exam can be done while sitting or standing. Each arm should be raised only slightly so that the tissue is not tightened. For women who choose to perform monthly breast self-examinations, it is important to do the procedure regularly and become familiar with their breasts. A woman who detects a change or lump in the breast should contact her physician if any of the following signs or symptoms develops: development of a lump in the breast or underarm area; irregular thickening of the breast tissue; swelling; dimpling or puckering; nipple pain; nipple retraction (turning inward); redness or scaliness of the nipple or breast; discharge from the nipple (other than breast milk). Breast self-exam is an important part of a threesteps procedure to screen for breast cancer. 13
S. Verardi, L. Palla, L. Brinci, C. Cerretani, E. Tati, M. Petrocelli, G. Palla This three steps procedure includes: BSE; CBE; mammography and/or sonography (according with the age of the patients). Figura 2. Breast self examination (BSE) performed with Donna Glove. At the end for the woman the most important target is to report any changes in her breasts to a physician. C onclusion A cross-sectional study of 130 women presenting for screening mammography was conducted. All women were provided with a self-administrated questionnaire. Data were collected regarding socio-demographic information, health care provider information, and breast self-examination practices. We found a significant difference between the group 1, wearing the detection glove and the group 2 using the bare hand, were 28 women failed to detect any existing lump. The authors conclude that in a population of potential breast cancer patients the BSE wearing the detection glove (Donna Glove ) is related to a greater number of earlier detected lumps. In case of a malignant lump the detection glove may improve the survival chances more than the BSE using bare hands. Figura 3. Breast self examination (BSE) performed with Donna Glove. D iscussion For some women, has been helpful to be trained in the skill of BSE by health care professionals, but for the majority of women, the teaching aids produced by a self-explaining brochure proved to be sufficient. They found the glove easy to be used and stated that the fact of having it has greatly increased their awareness of the breast cancer prevention. It should also be noted that the CBE performance by trained nurses had been shown to be as good as, if not better than, that of the study surgeons 38, a finding of particular interest in view of the growing perception among women that professional women are more sensitive than men to women s health issues 39, 40. The results of this study provide clear evidence on the reliability of CBE, in association with BSE 41, 42 : In women age 50-59 years, the addition of annual mammography screening to physical examination has no impact on breast cancer mortality. In other words, the mammographic detection of no palpable cancers failed to improve survival rates, as the majority of the small cancers detected by mammography represent pseudodisease or over diagnosis 40, 43, 44 ; confirmation of this explanation awaits a trial, a protocol of which is available, comparing mammography alone with physical examination alone. It should further be noted that the mammogram group had a three-fold increase in the number of false positives compared with the CBE and BSE group, resulting in unnecessary biopsies. The effectiveness of CBE is further supported by the results of a new Japanese mass screening study 41, 45, 46. Breast cancer mortality was compared in municipalities with or without high coverage by CBE. The age-adjusted breast cancer mortality between 1986-1990 and 1991-1995 was reduced by over 40 percent in high coverage municipalities, in contrast to only 3 percent 14
A new device for breast self examination in controls. In spite of such evidence, the ACS and radiologists persist in their dismissiveness of CBE and BSE, particularly as a substitute for screening practices that have a proven benefit such as mammograms 36,47-49. The NCI no longer prints a BSE guide in its breast cancer booklet, claiming no studies have clearly shown a benefit of using BSE ; similarly, the ACS no longer distributes information on BSE, such as showerhanger cards. There are immediate needs for a large-scale crash program for training nurses in how to perform annual CBE and how to teach BSE. This need is critical for underinsured and uninsured low-socioeconomic and ethnic women in the United States, and even more so for developing countries. Once well trained, women of all social and cultural classes could perform monthly BSE, at no cost or risk apart from false positives, which decrease with increasing practice, along with annual CBE screening. Clinics offering CBE and training in BSE could be established nationwide, and eventually worldwide, in a network of clinics, community hospitals, churches, synagogues, and mosques. These clinics could also act as a comprehensive source of reliable information on how to reduce the risks of breast cancer, about which women still remain largely uninformed by the cancer establishment 8, 50. Besides lifestyle and reproductive risk factors, emphasis should be directed to the massive over prescription of carcinogenic hormonal drugs and the avoidable and involuntary exposures to petrochemical and radio nuclear carcinogens in the totality of the environment 42, 44. r eferences 1. Zografos GC, Sergentanis TN, Zagouri F, et al. Breast self-examination and adherence to mammographic follow-up: an intriguing diptych after benign breast biopsy. Eur J Cancer Prev 2010; 9:71. 2. Lyman GH. Breast cancer screening: science, society and common sense. Cancer Invest 2010; 28:1. 3. Kearney AJ, Murray M. Breast cancer screening reccomendations: is mammography the only answer? Womens Healt 2009; 54:393. 4. Gofman JW. Preventing Breast Cancer: The Story of a Major Proven Preventable Cause of this Disease. Committee for Nuclear Responsibility, San Francisco, 1995. 5. Epstein SS, Steinman D, LeVert S. The Breast Cancer Prevention Program, Ed. 2. Macmillan, New York, 1998. 6. Bertell R. Breast cancer and mammography. Mothering, Summer 1992, pp. 49-52. 7. National Academy of Sciences- National Research Council, Advisory Committee. Biological Effects of Ionizing Radiation (BEIR). Washington, D.C., 1972. 8. Swift M. Ionizing radiation, breast cancer, and ataxiatelangiectasia. J Natl Cancer Inst 1994; 86:1571. 9. Bridges, B. A., and Arlett, C. F. Risk of breast cancer in ataxia-telangiectasia. N Engl J Med 1992; 326:1357. 10. Quigley DT. Some neglected points in the pathology of breast cancer, and treatment of breast cancer. Radiology 1928; 338-346. 11. Watmough DJ. Quan, KM. X-ray mammography and breast compression. Lancet 1992; 340:122. 12. Martinez B. Mammography centers shut down as reimbursement feud rages on. Wall Street Journal, October 30, 2000; p. A-1. 13. Vogel VG. Screening younger women at risk for breast cancer. J Natl Cancer Inst Monogr 1994; 16:55. 14. Baines CJ, Dayan R. A tangled web: Factors likely to affect the efficacy of screening mammography. J Natl Cancer Inst 1999; 91:833. 15. Laya MB. Effect of estrogen replacement therapy on the specificity and sensitivity of screening mammography. J Natl Cancer Inst 1996; 88:643. 16. Spratt JS, Spratt SW. Legal perspectives on mammography and self-referral. Cancer 1992; 69:599. 17. Skrabanek P. Shadows over screening mammography. Clin Radiol 1989; 40:4. 18. Davis DL, Love SJ. Mammography screening. JAMA 1994; 271:152. 19. Christiansen CL, et al. Predicting the cumulative risk of false-positive mammograms. J. Natl. Cancer Inst 2000; 92:1657. 20. Napoli M. Overdiagnosis and overtreatment: The hidden pitfalls of cancer screening. Am J Nurs 2001, in press. 21. Baum M. Epidemiology versus scaremongering: The case for humane interpretation of statistics and breast cancer. Breast J 2000; 6:331. 22. Miller AB, et al. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years. J Natl Cancer Inst 2000; 92:1490. 23. Black WC. Overdiagnosis: An under-recognized cause of confusion and harm in cancer screening. J Natl Cancer Inst 2000; 92:1280. 24. Napoli M. What do women want to know. J Natl Cancer Inst Monogr. 25. Lerner BH. Public health then and now: Great expectations: Historical perspectives on genetic breast cancer testing. Am J Public Health 1999; 89:938. 26. Gotzsche PC, Olsen O. Is screening for breast cancer with mammography justifiable? Lancet 2000; 355:129. 15
S. Verardi, L. Palla, L. Brinci, C. Cerretani, E. Tati, M. Petrocelli, G. Palla 27. National Institutes of Health Consensus Development Conference Statement. Breast cancer screening for women ages 40-49, January 1997; 21-23. J Natl Cancer Inst Monogr 1997; 22:7-18. 28. Ross WS. Crusade: The Official History of the American Cancer Society, p. 96. Arbor House, New York, 1987. 29. Hall DC, et al. Improved detection of human breast lesions following experimental training. Cancer 1980; 46:408. 30. Smigel K. Perception of risk heightens stress of breast cancer. J Natl Cancer Inst 1993; 85:525. 31. Baines CJ. Efficacy and opinions about breast selfexamination. In Advanced Therapy of Breast Disease, edited by SE. Singletary and GL. Robb, pp. 9-14. BC Decker, Hamilton, Ont 2000. 32. Leight SB, et al. The effect of structured training on breast self-examination search behaviors as measured using biomedical instrumentation. Nurs Res 2000; 49:283-289. 33. Worden JK, et al. A community-wide program in breast self-examination. Prev Med 1990; 19:254. 34. Fletcher SW, et al. How best to teach women breast self-examination: A randomized control trial. Ann Intern Med 1990; 112:772 35. Associated Press. FDA approves use of pad in breast exam. New York Times, December 25, 1995; p. 9Y. 36. Gehrke, A. Breast self-examination: A mixed message. J Natl Cancer Inst 2000; 92:1120. 37. Leaflet aziendale con informazioni sul prodotto. 38. Baines CJ, Miller AB, Basset AA. Physical examination: Its role as a single screening modality in the Canadian National Breast Screening Study. Cancer 1989; 63:1816. 39. Lewis T. Women s health is no longer a man s world. New York Times, February 7, 2001; p. 1. 40. Miller AB, Baines CJ, and Wall C. Correspondence. J Natl Cancer Inst 2001; 93:396. 41. Kuroishi T, et al. Effectiveness of mass screening for breast cancer in Japan. Breast Cancer 2000; 7:1-8. 42. Epstein SS. American Cancer Society: The world s wealthiest non-profit institution. Int J Health Serv 1999; 29:565. 43. Epstein SS, Gross L. The high stakes of cancer prevention. Tikkun 2000; 15:33-39. 44. Epstein SS. The Politics of Cancer Revisited. East Ridge Press, Hankins, N.Y., 1998. 45. Ramirez A. Mammogram reimbursements. New York Times, February 19, 2001. 46. John L. Digital imaging: A marketing triumph. Breast Cancer Action Newsletter, No. 62, November-December 2000. 47. Tarkan L. An update that matters? Mammography s next step is assessed. New York Times, January 2, 2001; p. D5. 48. Miller AB. The role of screening in the fight against breast cancer. World Health Forum 1992; 13:277. 49. Mittra I. Breast screening: The case for physical examination without mammography. Lancet 1994; 343:342. 50. Greenlee RT. Cancer Statistics, 2001. CA Cancer J Clin 2001; 51:15. 16
The use of cryotherapy in the management of cutaneous hemangiomas: a review of 12 cases Massimiliano Galeone 1 Elisa Cervadoro 2 Gregorio Cervadoro 3 Summary The use of cryotherapy in the management of cutaneous hemangiomas: a review of 12 cases Cutaneous hemangiomas are common benign vascular tumors of childhood that in most cases use to involve spontaneously in few years. However often it may be necessary to stop their growth using several kind of treatment, in order to prevent eventual complications as bleedings, ulcerations and superinfections. The results of 12 cases of cutaneous hemangiomas are exposed in this article. They're treated with spray cryotherapy with liquid nitrogen, easy and cheap technique that causes necrosis of such lesions through direct cell damage (due to water crystallization) and vascular alterations against endothelium. For its good results, cryotherapy arises as valid alternative for more expensive and complex therapies. KEY WORDS: Cutaneous hemangioma, Cryotherapy Massimiliano Galeone 1 Medical Doctor 2 Dermatologist 3 Chief of Dermatology Unit, University of Pisa (Italy) I ntroduction Cutaneous hemangiomas are common benign vascular tumors of childhood due to localized anomalies of the development of cutaneous vascularization that appears mostly in the head area in the first months of life. They interest the 10% of infants (F/M = 3/1) and the 30% of low birth weight prematures 1. Clinically, they are characterized by a typical evolution profile, consisting of a rapid proliferation during the first year of life and slow involution that usually is completed by 3 to 9 years of age 2. However, when cutaneous hemangiomas are located in areas at risk for functional complications it is required a prompt and adequate treatment. The approaches include topical, intralesional, and systemic corticosteroids, interferon-alfa, laser therapy, surgical therapy, embolization, radiotherapy and cryotherapy 3. Cryotherapy is a surgical technique which consists in subjecting a skin lesion at deleterious effect of cooling and thawing cycles in order to cause the destruction; the spray technique with cryogen such as liquid nitrogen is probably the most commonly used method. In hemangiomas treatment the destructive effects of cryotherapy can be grouped into two major mechanism: a direct cellular injury (immediate effect) and a vascular injury (delayed effect) 4. The most important event of the whole process is water crystallization, which begins at temperatures below -20 C, firstly in the extracellular spaces (this causes the raise of osmotic pressure and the following cellular dehydration), then in the intracellular one; during thawing, ice crystals fuse to form larger crystals (a process called recrystallization ) which are disruptive to cell membranes and cause additional cell damage. So, the repetition of cycles of treatment during the same session is of primary importance because it associates to a more wide and certain disruption of the cells already weakened during the former cycle and to a major diffusion of the freezing laterally and deeply. Apoptosis phenomena happen in a peripheral area; they are detectable also many hours after the freezing 5. Vascular alterations are associated to the direct damage at endothelial cells; there alterations are caused by the progressive vasoconstriction of the microcirculation tributary of the treated 17
M. Galeone, E. Cervadoro, G. Cervadoro district, with the temporary and complete interruption of tissue perfusion 6. Through electronic microscopy it has been possible to notice that the endothelial damage results in increased permeability of the capillary walls, blood stasis, edema, platelet aggregation and microthrombus formation; many small blood vessels become completely thrombosed 3 to 4 hours after thawing. Together, all these effects culminate in ischemic damage and tissue necrosis, with following sclerosis of the treated vascular lesion 7. aterial and methods m In our study we valued the efficiency of cryotherapy in cutaneous hemangiomas treatment in a sample of 12 patients aged 0 to 10 years. Lesions have been found at head (in more than half of cases), at neck and at trunk. There isn t absolute contraindications to cryotherapy, except lesions near to the eyelid, because of the risk of ectropion and lachrymal canal alterations 8. Many Authors choose to avoid the treatment, because in most cases hemangiomas use to involve spontaneously in few years 9. However, in our opinion the use of cryotherapic treatment can be justified by the need of stop the growth of such vascular neoformations, and in the meanwhile accelerate the involution, in order to prevent eventual complications as post-traumatic bleedings, ulcerations and superinfections. Liquid nitrogen has been adopted for the treatment. This liquid, which through the very low temperatures reached (-196 C) is the coldest and efficient available cryogen, is sprayed with equipments with the possibility of interchange brass nozzles and adapt them to the dimensions of the different lesions, in order to avoid the damage to the healthy tissues around the lesion. According to the dimensions of the lesion, the cryogen has been applied from 10 to 30 seconds for each cycle of freezing-unfreezing, with a variable number of sessions, one every 2-3 weeks. In 4 cases of small hemangiomas in growth, cryotherapy accelerates the involution phase just after only one treatment. Anesthesia is notusually required because the pain is mitigated by the low temperatures. Immediately after the treatment, the area appears pallid, surrounded by a erythematosus halo which grows in the following 24 hours; in the meanwhile necrosis begins to appear, and it will Figura 1. Cutaneous hemangioma of the head before and immediately after treatment. Figura 2. Cutaneous hemangioma of the chest and control 5 years after treatment. become more evident in few days (Figu re 1). The indication to cryotherapy is represented by small and medium hemangiomas, but we reached very good results also in a particular case of giant haemangioma in the trunk area in a patient aged 5 months (Figure 2): in the control photo at the age of 5 years, the aesthetic result has been very good, with total involution of the lesion and only slight ipochromic alteration in the treated area. C onclusion Few complications has been noticed, anyway transitional: between these we remember alopecia, ipopigmentation of the treated area (due to high cryosensibility of hair follicle and melanocytes 10 ) and the pain, especially in case of lesions of bigger dimensions in which has been 18
The use of cryotherapy in the management of cutaneous hemangiomas: a review of 12 cases required to extend the time of application of the cryogen. Despite these rare complications, few significative from the clinic point of view, cryotherapy revealed itself as a useful methodic in cutaneous hemangiomas treatments, safe, easy and most of all cheap, representing so a valid alternative for more expensive and complex therapies. The aesthetic result has been satisfying in the most of cases, according to the fact that often we can t see a fibrotic scar and so the quality of the tissue repair results excellent. r eferences 1. Enjolras O, Gelbert F. Superficial hemangiomas: associations and management. Pediatr Dermatol 1997; 14:173-9. 2. Enjolras O, Richè MC, Merland JJ, Mulliken JB. Hemangiomes et malformations vasculaires superficielles. Parigi: MEDSI/McGraw-Hill, 1990. 3. Musumeci ML, Schlecht K, Perrotta R, wt al. Mana - gements of cutaneous hemangiomas in padiatric patients. Cutis 2008; 81:315-22. 4. Gage AA, Baust J. Mechanisms of tissue injury in cryo - surgery. Cryobiology 1998; 37:171-86. 5. Baust J, Chang Z. Mechanisms of damage and new concepts in cryosurgical instrumentation. In: Baust J, Chang Z, eds. Cryosurgery: Mechanism and Applications. Paris, France: Institut international de froid. 1995; 21-36. 6. Hoffrnann NE, Bischof Je. The cryobiology of cryosurgical injury. Urology 2002; 60 (2 suppl 1):40-9. 7. Whittaker DK. Ice crystals fonned in tissue during cryosurgery. Electron microscopy. Cryobiology 1974; Il:202-17. 8. Buschmann W. A reappraisal of cryosurgery for eyelid basai celi carcinomas. Br J Ophthalmol 2002; 86:453-7. 9. Reischle S, Schuller-Petrovic S. Treatment of capillary hemangiomas of early childhood with a new method of cryosurgery. J Am Acad Dermatol 2000; 42(5 Pt 1):809-13. 10. Ramsey K, Ragan C and Dheansa B. Adverse effects of over the counter cryotherapy. Burns 2007; 33:533-4. 19
Oral intake of nanosilicium in telogen effluvium: a scanning electron microscope microanalysis study Renata Strumia 1 Federica Baldo 2 Summary Oral intake of nanosilicium in telogen effluvium: a scanning electro microscope microanalysis study Micro-nutrients have an essential role also in hair health. Orthosilicic acid, the bioavailable form of silicon (Si), maintains hair health suggesting that this element could be useful as treatment for patients with hair loss. The aim of the present study was to evaluate Si concentration in the hair of patients with telegen effluvium (TE) before and after 3 months of oral intake of nanosilicium. 12 female patients (average age 47.25) with TE lasted from at least one year were enrolled in the study. 15,9 mg/day oral nanosilicium was subministred for a period of 3 months of treatment. 2 samples of scalp hair obtained by pull test were collected: at T 0 (baseline) and at T 2 (four months later). Each sample was analyzed using scanning electron microscope with microanalysis device. Over a half of the samples revealed the presence or the increase of Si in the hair after oral intake of nanosilicium for 3 months; these data suggest the absorption of nanosilicium and its incorporation in the hair matrix after oral intake. Clinically in almost all the patients there was a reduction of hair loss. Also the patients whose hair had not Si after therapy had a reduction of hair loss. KEY WORDS: Telogen effluvium, Nanosilicium, Oral intake Renata Strumia 1 Unit of Dermatology, Hospital University S. Anna, Ferrara, Italy 2 Section of Dermatology, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy I ntroduction Skin, connective tissue collagen, bone and cardiovascular apparatus need of adequate amounts of micro-nutrients 1, 2. Recent scientific literature reports some progress in the knowledge of the biological role of the essential micro-nutrients also in hair health. Hair composition has been studied by microanalysis performed with scanning electron microscope (EDX analysis) 3, but mechanism of uptake, incorporation and binding of trace elements in the hair matrix is still unclear 4, 5. Orthosilicic acid [Si(OH) 4 ], the bio-available form of silicon (Si), has been demonstrated to play a role in maintaining hair health suggesting that this element could be useful as treatment for patients with hair loss 6. Our previous work, about the trace elements in telogen effluvium (TE) in otherwise healthy subjects, demonstrated low levels of Si in these patients 7. There are few reports in the literature about uptake, incorporation and binding of Si in the hair matrix and about the effects of this therapy in TE 8-10. Possibly, Si accumulates in the cornified epidermis and in the epicuticle of hair 11, 12 as was demonstrated in older studies. Dietary Si deficiency in growing animals indicated growth retardation and marked defects of bone and connective tissue 13, most likely due to decreased collagen and glycosaminoglycan synthesis. Others have suggested a structural role of Si in the cross-linking of glycosaminoglycans in connective tissue 14. The aim of the present study was to evaluate Si concentration in the hair of patients with TE before and after 3 months of oral intake of nanosilicium *. A clinical evaluation by pull test was added before and after the treatment. 21
R. Strumia, F. Baldo aterials and methods m 12 female patients (average age 47.25) with TE lasted from at least one year were enrolled in the study. Women, using Si supplements less than 3 months before the start of the trial or any food supplement other than the study medication during the trial were excluded. Chemical treatment of the hair such as perming, coloring or bleaching and intake of pharmaceuticals (i.e. vitamin supplements) was prohibited during the trial. Women were also asked to maintain their usual diet during the trial. 15,9 mg/day oral nanosilicium was subministred for a period of 3 months of treatment. The characteristics of nanosilicium were the following: silicium dioxide (SiO 2 ), content of Si0 2 : 99,8%, extremely pure monomer, no chemical solvents or vegetal raw materials, colloidal (monomeric) SiO 2 : disperses instantly in water. Patient visits were scheduled as: T 0 : baseline (before treatment), T 1 : after 3 months (treatment end), T 2 : 1 month after T1. A pull test was made at T 0 and T 2. 2 samples of scalp hair obtained by pull test were collected from the patients: the first one at T 0, the second one at T 2. Each sample included 2 different hair segments (length = 1 cm) cut from the proximal portion of each hair. The samples were mounted on aluminium stubs and coated with carbon in evaporator (Emitech K 950). Only the proximal part of the hair was analyzed to reduce environmental exposure and cosmetic contamination in the detected elements. Energy-dispersive X-ray microanalysis (EDX analysis) was performed using scanning electron microscope (Cambridge Stereoscan S 360) with microanalysis device (Oxford Instruments INCA 3000). 48 analysis total were performed. r esults The values of the amounts of Si at T 0 and T 2 are reported in Table 1. At T0 3/12 patients (5/24 samples) were positive for Si presence, at T 2 8/12 patients (15/24 samples) were positive for Si presence. Statistical analysis showed a significant result: Mac Nemar test - two-sided p-value: p = 0,025 At T 0 all the patients 12/12 were positive to pulltest, at the end of the study (T 2 ) only 2 out of 12 patients were positive to pull-test. Statistical analysis showed a very significant result: Mac Nemar test two-sided p-value: p = 0,002. C onclusions The major dietary sources of Si are cereal/ grain-based products and vegetables but modern food processing, including refining, is likely to reduce the dietary Si intake 15. The intake of 15,9 mg/day oral nanosilicium is safe as no adverse effects related to the study medication were reported. Over a half of the samples revealed the presence or the increase of Si in the hair after oral intake of nanosilicium for 3 months; these data suggest the absorption of nanosilicium Table 1. Energy-dispersive X-ray microanalysis: amounts of Si at T 0 and T 2 in hair samples. T 0 T 2 Patient Age Weight Atomic Pull test Weight Atomic Pull test years % % % % 1 49 Sample 1: 0 0 positive 0.11 0.05 negative Sample 2: 0 0 0.12 0.06 2 52 Sample 1: 0 0 positive 0.06 0.03 negative Sample 2: 0 0 0.20 0.10 3 58 Sample 1: 0.25 0 positive 0.05 0.02 negative Sample 2: 0.12 0 0 4 43 Sample 1: 0 0 positive 0.81 0.39 negative Sample 2: 0 0 0.26 0.13 5 51 Sample 1: 0 0 positive 0.07 0.04 negative Sample 2: 0 0 0.13 0.07 6 48 Sample 1: 0 0 positive 0.18 0.08 negative Sample 2: 0 0 0.28 0.13 7 41 Sample 1: 0.11 0.05 positive 0.08 0.05 negative Sample 2: 0.12 0.06 0.08 0.05 8 46 Sample 1: 0.28 0.13 positive 0.24 0.12 positive Sample 2: 0.34 0.16 0.22 0.11 9 33 Sample 1: 0 0 positive 0 0 negative Sample 2: 0 0 0 0 10 51 Sample 1: 0 0 positive 0 0 negative Sample 2: 0 0 0 0 11 45 Sample 1: 0 0 positive 0 0 negative Sample 2: 0 0 0 0 12 50 Sample 1: 0 0 positive 0 0 positive Sample 2: 0 0 0 0 22
Oral intake of nanosilicium in telogen effluvium: a scanning electron microscope microanalysis study and its incorporation in the hair matrix after oral intake. Clinically in almost all the patients there was a reduction of hair loss. Also the patients whose hair had not Si after therapy had a reduction of hair loss. An explanation may be that since the hair follicle is embedded in a collagen rich matrix, stimulation of collagen synthesis by oral Si intake might influence the flow of nutrients to the hair follicle resulting in an effect on keratin formation 15. The quantity of Si in hair samples might not be detected yet 4 months after the beginning of treatment, due to a slower rate of hair growth in some patients. The reduction in the quantity of Si in the samples with Si before oral intake might suggest a threshold in the absorption of Si in the hair. All the patients spontaneously referred an improving of the aspect of their hair and a reduction of their nail fragility as well. Wickett et al. 16 reported an increase of the cross sectional area significantly 9 months compared to baseline in choline-stabilized orthosilicic acid (ch-osa) supplemented subjects. The change in urinary Si excretion was significantly correlated with the change in cross sectional area. Oral intake of ch-osa had a positive effect on tensile strength including elasticity and break load and resulted in thicker hair. To our knowledge, the present study is the first trial that illustrates the appearance of Si in hair samples after oral mineral supplement, by energy-dispersive X-ray microanalysis. * Trade Mark: Nanosan (Biocure S.r.l.) r eferences 1. Lassus A. Colloidal silicic acid for oral and topical treatment of aged skin, fragile hair and brittle nails in females. J Int Med Res 1993; 21:209-15. 2. McNaughton SA, Bolton-Smith C, Mishra GD, et al. Dietary silicon intake in post-menopausal women. Br J Nutr 2005; 94:813-7. 3. Seta S, Sato H, Yoshino M, et al. SEM/EDX analysis of inorganic elements in human scalp hairs with special reference to the variation with different locations on the head. Scan Electron Microsc 1982; (Pt 1):127-40 4. Kempson IM, Skinner WM, Kirkbride PK. Calcium distribution in human hair by ToF-SIMS. Biochim Biophys Acta 2003; 1624:1-5. 5. Bos AJJ, Van der Stap CCAH, Valkovic V, et al. Incorporation routes of elements into human hair; implications for hair analysis used for monitoring. Sci Total Environ 1985; 42:157-69. 6. Wickett RR, Kossmann E, Barel A, et al. Effect of oral intake of choline-stabilized orthosilicic acid on hair tensile strength and morphology in women with fine hair. Arch Dermatol Res 2007; 299:499-505. 7. Strumia R, Lauriola MM. Silicon in hair loss: a preliminary SEM microanalysis study JADV 2007; (21):1120. 8. Rushton DH. Nutritional factors and hair loss. Clin Exp Dermatol 2002; 27:400. 9. Jugdaohsingh R, Anderson SHC, Tucker KL, et al. Dietary silicon intake and absorption. Am J Clin Nutr 2002; 75:887-93. 10. Sukumar A. Factors influencing levels of trace elements in human hair. Rev Environ Contam Toxicol 2002; 175:47-78. 11. Carlisle EM. Silicon: an essential element for the chick. Science1972; 178:619-621. 12. Fregert S. Studies on silicon in tissues with special reference to skin. J Invest Dermatol 1958; 31:95-96. 13. Carlisle EM. Silicon: a requirement in bone formation independent of vitamin D1. Calcif Tissue Int 1981; 33:27-34. 14. Schwarz K. A bound form of silicon in glycosaminoglycans and polyuronides. Proc Natl Acad Sci USA 1973; 70:1608-1612. 15. Sripanyakorn S, Jugdaohsingh R, Elliott H, et al. The silicon content of beer and its bioavailability in healthy volunteers. Br J Nutr 2004; 91:403-409. 16. Wickett RR, Kossmann E, Barel, Demeester AN, et al. Effect of oral intake of choline-stabilized orthosilicic acid on hair tensile strength and morphology in women with Wne hair. Arch Dermatol Res 2007; 299:499-505. 23