Distinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers.

BACKGROUND: Nodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness. METHODS: Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided. RESULTS: In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P < .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis). CONCLUSIONS: T1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.

Keystone Perforator Island Flap as an Alternative Reconstructive Option for Partial Thickness Alar Defects Up to 1.5 Centimeters.

INTRODUCTION: The ala is a unique landmark of the nose disposing aesthetic and functional properties. The head and neck area is the main site of appearance of nonmelanoma skin cancer. One third of them are located in the nose with an alar preponderance compared with other nasal subunits. Correction of alar defects is a challenging reconstructive task. The keystone perforator island flap (KPIF) was introduced as an alternative in nasal reconstruction by senior authors. In the present case series, KPIFs' application is introduced into the alar subunit as an alternative, versatile, and reproducible reconstructive option, even for the novice plastic surgeon. MATERIALS AND METHODS: From April 2014 to September 2015, patients presenting with partial thickness alar defects (≤1.5 cm) secondary to tumor extirpation sustained reconstruction with different types of KPIF. RESULTS: A total of 31 patients (mean age of 72 years) were treated with various types of KPIF. The mean diameter of the defect was 1.14 cm. The vast majority of reconstructions concerned a type IV KPIF (18/31 or 58.1%). Sometimes an upward alar retraction was noted. A minimal rim wedge excision was performed (≤0.3 mm) using counterbalancing correcting sutures. All flaps survived without any sign of venous congestion, whereas the rim healed uneventfully. The mean follow-up period was 6.5 months. CONCLUSIONS: KPIF was introduced as a single-stage alternative reconstructive option for partial thickness alar defects, completing author's experience with this flap into such a challenging and aesthetically critical anatomic area.

Redefining Vascular Anatomy of Posterior Tibial Artery Perforators: A Cadaveric Study and Review of the Literature.

INTRODUCTION: Perforator flaps whether in a free or pedicled form are essential in leg reconstruction, requiring meticulous dissection based on a detailed understanding of vascular topographic anatomy. Numerous investigators have addressed this issue. However, the directionality of their fascial exit has not been greatly discussed in the literature. Subfascial course of the perforating vessel is a crucial determinant for optimal perforator selection especially when the propeller perforator flap option is considered, because an angulated fascial penetration would eventually result in perforator kinking which would additionally compromise vascular patency. The aim of the current study was to investigate the vascular anatomy of posterior tibial artery evaluating a wide range of parameters, including perforators' subfascial directionality, to precisely determine constant reliable perforator sites, in relation to surface landmarks on the medial aspect of the lower leg. MATERIAL AND METHODS: Dissections in 30 lower legs from 25 fresh cadavers were performed. The lower leg was divided into 3 equal vascular zones. Measurements were taken in reference to anatomical landmarks. Perforator clusters to 5-cm intervals from medial malleolus were recorded and analyzed. Vessels with external diameter less than 0.5 mm were excluded. Data regarding the number, distribution, type, external diameter, length from posterior tibial artery, distance, and subfascial directionality were collected and treated. RESULTS: A total of 155 perforators were identified (average number, 5 per leg; average diameter, 1.0 mm). Septocutaneous (127/155) perforators predominated, followed by musculocutaneous (19/155) and septomusculocutaneous (9/155). Most was concentrated in the middle (73/155) and distal (64/155) tertile. There were no septomusculocutaneous perforators at the distal third of the leg, whereas septocutaneous perforators were encountered into all vascular tertiles. An average of 2 comitant veins accompanied each perforator. Length and diameter related to the perforators' location. There was a significant association between perforator length and type. Cluster analysis revealed that reliable perforators were identified within the 21 to 25, 26 to 30, and 16 to 20 cm intervals. CONCLUSIONS: Clinically optimal perforators for the first time were precisely located in relation to subfascial directionality, vascular diameter, and length from the source artery. Continuous improving details of vascular anatomy will further evolve perforator flaps' applications.

The Keystone Perforator Island Flap in Nasal Reconstruction: An Alternative Reconstructive Option for Soft Tissue Defects up to 2 cm.

The aim of this study was to present our experience with the use of the Keystone Perforator Island Flap (KPIF) in a case series of patients with small size (diameter ≤ 2 cm) nasal defects which will be useful prospectively to assist plastic surgeons in planning a reconstructive strategy that will work. The KPIF was utilized in 30 patients with nasal defects post tumor extirpation. More than one type of KPIF (type I or type III) was used following the nasal subunit principle or a modified version of it. The mean follow-up period was 10.5 months. Overall good outcomes were achieved, with no major complications encountered, except minor wound dehiscence in 3 cases. It is the first time that the utilization of this flap is reported in nasal reconstruction. The versatility of the KPIF makes it a safe technique even in the hands of inexperienced surgeons under guidance for nasal defects up to 2 cm in diameter.

High-frequency p16(INK) (4A) promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma.

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16(INK) (4A) promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation-specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki-67 index), p16(INK) (4A) and SETDB1 expression were evaluated by immunohistochemistry. High-frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16(INK) (4A) promoter methylation was higher in vertical growth-phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16(INK) (4A) methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1-30%) p16(INK) (4A) expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16(INK) (4A) methylation and p16(INK) (4A) expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0-5/mm(2) vs >5/mm(2) , P = 0.0869), advanced Clark level (III-V, P = 0.0380), epidermal involvement (P = 0.0331) and the non-chronic sun exposure-associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16(INK) (4A) promoter and several prognostic parameters in melanomas.

Use of the hemifrontal flap in reconstruction of the forehead.

The hemifrontal flap is an efficient way of reconstructing large unilateral defects that involve the hemiforehead. Six patients had their foreheads reconstructed after the excision of neglected tumours in the frontal region. The flap was designed to provide adequate repair of large defects including the periosteum. The width of the flap above the eyebrow is almost equal to the vertical height of the forehead in the midline. Efficient reconstruction of the primary defect including surface and depth was achieved in all patients. There were no complications with the viability of the flap. The hairline and the line of the eyebrows were preserved in their original sites, with no alteration in the aesthetic landmarks of the forehead in 3 cases, where there was no invasion of tumour.

Nonmelanoma skin tumors involving the craniofacial region: our 22 years of experience.

Skin tumors comprise the largest group of malignancies of the head. Despite the accessibility of such lesions, the treatment of neglected, far advanced cancers, many of which have extended deeply into the facial bones and skull, is often required. The key to the cure of malignant tumors of the head is an accurate diagnosis and evaluation of the margins of an excised tumor. Reconstructive surgery of the head after resection of tumors requires a complete understanding of the anatomy of this region. From January 1986 to December of 2005, 31 patients underwent reconstructive surgery for nonmelanoma skin tumors involving the craniofacial region. Preoperative evaluation of the patients was performed in all cases. The results were estimated from the oncologic and functional point of view. The reconstruction, which was performed, included local, regional, and free flaps. In our series, the 5-year disease-free survival rate was 87%. The primary goal of surgical treatment of skin tumors with invasion of craniofacial bone structure is three-dimensional tumor resection with histologically clear margins. This goal has to be balanced, however, with an acceptable functional and aesthetic result. Resections are planned according to pathologic considerations rather than according to the anatomy involved.

Divided naevus of the eyelid, seven cases.

Divided naevus of the upper and lower lids is an infrequent congenital naevus of the human eyelids. It is also known as kissing naevus or split ocular naevus. The histological types of divided naevi may be melanocytic, cellular or compound. Until now about 30 such cases have been reported in the literature. In our clinic, in the last 20 years we have seen seven patients with divided naevus, four female and three male. Three patients, two children of 10 and 11 years and a 77-year-old nun, did not accept any treatment. The remaining four patients, three female and one male, accepted surgical treatment. None of them had received any treatment in the past. Three of these divided naevi were cellular and one was melanocytic. Treatment included a two stage reconstruction in three cases and a single stage procedure in one case. The lower eyelid was usually treated first, and upper eyelid full thickness grafts were mostly used. Lid shortening was common, particularly in the cellular naevi. The results were aesthetically and functionally good. No major complications were observed.

Orbitopalpebral repair after 835 excisions of malignant tumours.

Repair of any defect in the eyelid depends on its size and position and the state of the surrounding tissues. Basal cell carcinoma (BCC) is the most common malignant tumour of the eyelids, and squamous cell carcinoma (SCC), mixed carcinomas or basosquamous cell carcinomas (BSC), and cutaneous melanomas (CM), also invade the eyelids and periocular zones. Reconstruction of the eyelids and associated orbital structures after resection requires a complete understanding of the anatomy. The adequacy of the reconstruction is judged by the quality of functional restoration and the aesthetic appearance. The purpose of this study was to document various, simple or complex reconstructive procedures that may be used after excision of malignant tumours of the eyelids and to assess the outcome of surgical treatment.

Vertical trapezius musculocutaneous flap: a retrospective study.

From 1986 to 2001, 17 patients (aged 26-77 years) were treated using the vertical trapezius musculocutaneous flap. A two-stage procedure was used in 7 and a single-stage island flap in 10. The donor site was closed directly in all patients. Mean length of hospital stay was 16 days (range 12-25). There was no operative mortality. Complications were one partial flap necrosis and two seromas of the donor site, complicated by infection. With a minimum follow-up of more than two years, our study confirms the usefulness of the vertical trapezius musculocutaneous flap in head and neck reconstructive surgery. It is a reliable, thin flap of uniform thickness, which carries hairless skin. The length and thickness of its pedicle allows excellent mobility. The main disadvantage of the flap is the complete sacrifice of the muscle necessary for total mobilisation of the flap, and the intraoperative repositioning of the patient.