Marco Pignatti

Keratinocytes enriched for stem cells are protected from anoikis via an integrin signaling pathway in a Bcl-2 dependent manner.

Because inhibition of integrin signaling induces apoptosis, we investigated whether keratinocytes expressing β1 and α6β4 integrins (enriched for stem cells) are protected from cell death. Keratinocytes rapidly adhering to type IV collagen expressed highest levels of β1 and α6β4 and of the anti‐apoptotic stem cell marker p63. Apoptotic cells were significantly higher in slowly adhering than in rapidly adhering keratinocytes. Anti‐β1 integrin caused a significant increase in apoptotic cells, while it decreased Bcl‐2 levels in stem keratinocytes. Bax and Bad proteins were higher in slowly adhering than in rapidly adhering cells. By contrast, Bcl‐2, Bcl‐x and Mcl‐1 proteins were highest in rapidly adhering keratinocytes and nearly absent in slowly adhering cells. After addition of anti‐β1 integrin, the apoptotic rate was significantly higher in HaCaT cells not expressing Bcl‐2 than in controls. These results indicate that keratinocytes enriched for stem cells are protected from apoptosis via β1 integrin, in a Bcl‐2 dependent manner.

The "Tokyo" consensus on propeller flaps

Background: Over the past few years, the use of propeller flaps, which base their blood supply on subcutaneous tissue or isolated perforators, has become increasingly popular. Because no consensus has yet been reached on terminology and nomenclature of the propeller flap, different and confusing uses of the term can be found in the literature. Methods: In this article, the authors report the consensus on the definition and classification of propeller flaps reached by the authors that gathered at the First Tokyo Meeting on Perforator and Propeller Flaps in June of 2009. Some peculiar aspects of the surgical technique are discussed. Results: A propeller flap can be defined as an “island flap that reaches the recipient site through an axial rotation.” The classification is based on the nourishing pedicle (subcutaneous pedicled propeller flap, perforator pedicled propeller flap, supercharged propeller flap), the degrees of skin island rotation (90 to 180 degrees) and, when possible, the artery of origin of the perforator. Conclusions: The propeller flap is a useful reconstructive tool that can achieve good cosmetic and functional results. A flap should be called a propeller flap only if it fulfils the definition above. The type of nourishing pedicle, the source vessel (when known), and the degree of skin island rotation should be specified for each flap.

A rapid genetic counselling and testing in newly diagnosed breast cancer is associated with high rate of risk-reducing mastectomy in BRCA1/2-positive Italian women

BACKGROUND Risk-reducing mastectomy (RRM) decreases breast cancer (BC) risk in BRCA1/2 mutation carriers by up to 95%, but the Italian attitude towards this procedure is reluctant. PATIENTS AND METHODS This is an observational study with retrospective design, using quantitative and qualitative research methods, aimed at evaluating the attitude towards RRM by rapid genetic counselling and testing (RGCT), at the time of BC diagnosis, compared with traditional genetic counselling and testing (TGCT), after previous BC surgery. Secondary aims were to investigate patient satisfaction after RRM and the rate of occult tumour in healthy breasts. A total of 1168 patients were evaluated: 1058 received TGCT, whereas 110 underwent RGCT. RESULTS In TGCT, among 1058 patients, 209 (19.7%) mutation carriers were identified, with the rate of RRM being 4.7% (10 of 209). Conversely in RGCT, among 110 patients, 36 resulted positive, of which, 15 (41.7%) underwent bilateral mastectomy at the BC surgery time, showing an overall good satisfaction, measured by interpretative phenomenological analysis 12 months after the intervention. CONCLUSIONS Our study shows that RGCT in patients with a hereditary profile is associated with a high rate of RRM at the BC surgery time, this being the pathway offered within a multidisciplinary organization.

Pharmacogenomics in dermatology: from susceptibility genes to personalized therapy

Abstract:  A significant proportion of patients with skin disease do not respond to treatment and adverse drug reactions are a common problem. Genetic factors are important determinants for both drug efficacy and toxicity. The fields of pharmacogenetics and pharmacogenomics examine inter‐individual variations in the DNA sequence that are related to drug efficacy and toxicity. Here, we present pharmacogenomic data relevant to dermatology and explore the role of dermatologists in identifying patients who may respond to treatment or experience adverse drug reactions.

Management of Complications Caused by Permanent Fillers in the Face: A Treatment Algorithm.

Background: Nonresorbable substances are still injected to enhance soft-tissue volumes and fill subcutaneous defects. Inflammatory reactions (often termed granulomas) to these materials can be functionally and socially disabling. Most therapeutic options used until now are nonspecific antiinflammatory treatments, targeting an ill-defined immune reaction of undefined cause. The minimally invasive intralesional laser treatment can remove the foreign substance and the inflammatory reaction with an 808-nm diode laser. Methods: Two hundred nineteen consecutive patients referred from September of 2006 until June of 2013 for inflammatory reactions to permanent facial fillers and treated with this technique at the authors’ institution with a minimum 6-month follow-up were studied. All patients were screened with an ultrasound soft-tissue examination and the lesions were classified as either cystic (implants inserted by bolus injections) or infiltrating (as in microdeposit injection). The authors’ therapeutic approach is summarized in an algorithm: infiltrating patterns were treated with intralesional laser treatment alone, whereas cystic distribution cases were also drained through stab wound incisions. The mean patient age was 49 years (range, 23 to 72 years); 204 patients were women. Results: Partial improvement was obtained in 30 percent of patients, whereas 8 percent discontinued the treatment because of a lack of satisfaction. Lesions disappeared completely in 62 percent. Complications included transient swelling in all cases, hematoma in 2 percent, secondary sterile abscess in 9.5 percent, and minimal scarring in 10 percent. Conclusion: A problem-oriented systematic approach to inflammatory complications from permanent fillers is proposed, based on the comprehensive work from the past 7 years, with an overall improvement rate of 92 percent. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Thalassaemia intermedia: the role of erythroexchange in the treatment of an indolent wound.

Thalassaemia intermedia is a haemoglobinopathy in which, by definition, the patient maintains satisfactory levels of haemoglobin without needing transfusions. Indeed, the condition is also called non-transfusion-dependent thalassaemia. Nevertheless, at some time during the patient’s lifetime, transfusion therapy may become necessary to guarantee a level of haemoglobin adequate for the activities of normal life. Thalassaemia intermedia is most commonly associated with a homozygous or compound heterozygous state for two beta-thalassaemia alleles but the severity of the clinical picture is related to the patient’s genotype and the consequent degree of globin chain imbalance1. The level of foetal haemoglobin (HbF) is usually variably elevated. In addition, patients with thalassaemia intermedia can suffer from an atypical form of pseudoxanthoma elasticum (PXE), a multisystem disorder affecting, among others, the elastic tissues of the arteries and leading to degeneration and calcification of the elastic lamina of the arterial wall2. At the level of the ankle, low haemoglobin concentrations associated with abnormal red cell rheology and increased haemoglobin F cause tissue hypoxia that promotes thinning of the skin and subcutaneous fragility. As a consequence, trophic ulcers are a common finding in adult patients3. We report here the difficult healing of a surgical wound in a patient with thalassaemia intermedia and the beneficial effect obtained with erythroexchange that, decreasing the level of HbF in favour of HbA, improved the oxygen availability in the area and promoted healing.

Porcine Model for Gluteal Artery Perforator Flap: Anatomy and Technique

1 BACKGROUND Although flap anatomy is well studied on cadavers and microsurgical techniques are well practiced on rats, still there are few training models for learning the techniques of perforator flap harvesting. The cadaver has no bloodstream, so accuracy of dissection cannot be evaluated and flap viability cannot be verified. Training on humans carries a high risk of flap damage. A living model for perforator flap harvest is needed to learn the technique before starting with its clinical application. The aim of this study was to optimize the use of the porcine gluteal artery perforator flap as a living model in the training for the superior gluteal artery perforator flap harvest.

Axial propeller flaps: A proposal for update of the “Tokyo consensus on propeller flaps”

With this communication, we would like to propose an update to the classification of propeller flaps, since after its publication, new flaps have been described that need to be included. In 2009, the “Tokyo” consensus on propeller flaps defined a propeller flap as an “island flap that reaches the recipient site through an axial rotation”. In the actual classification, the type of nourishing pedicle, the degree of skin island rotation and, when possible, the artery of origin of the perforator vessel, need to be indicated. With regards to the type of nourishing vessel, propeller flaps have been classified into 3 types:

Effects of silicone expanders and implants on echocardiographic image quality after breast reconstruction

Background: Use of silicone expanders and implants is the most common breast reconstruction technique after mastectomy. Postmastectomy patients often need echocardiographic monitoring of potential cardiotoxicity induced by cancer chemotherapy. The impairment of the echocardiographic acoustic window caused by silicone implants for breast augmentation has been reported. This study investigates whether the echocardiographic image quality was impaired in women reconstructed with silicone expanders and implants. Methods: The records of 44 consecutive women who underwent echocardiographic follow-up after breast reconstruction with expanders and implants at the authors’ institution from January of 2000 to August of 2012 were reviewed. The population was divided into a study group (left or bilateral breast expanders/implants, n = 30) and a control group (right breast expanders/implants, n = 14). The impact of breast expanders/implants on echocardiographic image quality was tested (analysis of covariance model). Results: Patients with a breast expander/implant (left or bilateral and right breast expanders/implants) were included. The mean volume of the breast devices was 353.2 ± 125.5 cc. The quality of the echocardiographic images was good or sufficient in the control group; in the study group, it was judged as adequate in only 50 percent of cases (15 patients) and inadequate in the remaining 15 patients (p < 0.001). At multivariable analysis, a persistent relationship between device position (left versus right) and image quality (p = 0.001) was shown, independent from other factors. Conclusions: Silicone expanders and implants in postmastectomy left breast reconstruction considerably reduce the image quality of echocardiography. This may have important clinical implications, given the need for periodic echocardiographic surveillance before and during chemotherapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.