Melanoma in the very elderly, management in patients 85years of age and over.

OBJECTIVES: Melanoma treatment in the elderly can entail complex decision making. This study characterizes the presentation, management, and outcome of melanoma in the very elderly. METHOD: Retrospective review of all patients in their 85th year or older presenting to a tertiary referral cancer centre between 2000 and 2012 with American Joint Committee on Cancer stages 0-II cutaneous melanoma. RESULTS: 127 patients, 26 with in-situ disease and 101 with stages I-II disease, were included. For invasive primary disease, the median age was 87years (IRQ=86-89). Most patients had melanomas with poor prognoses at diagnosis: 49.5% were ulcerated, 68.3% mitotically active (mitotic rate≥1), and the median tumor thickness was 3.7mm (IQR=1.7-5.8). Nodular melanomas were the most frequent subtype (31.7%, 32/101). Only 66.3% received an excision margin≥10mm. Suboptimal excision margins were associated with increased risk of local recurrence (HR=6.87, 95% CI=5.53-8.20, p=0.0045) but not poorer disease specific survival (DSS, p=0.37) or overall survival (OS, p=0.19). Sentinel node biopsy (SNB) did not influence survival (DSS, p=0.39, OS, p=0.78). Median OS was 33months. Overall, one-third (34.7%) of patients died from causes other than melanoma during the follow up period. In patients aged ≥90 only 1 patient (4.3%) died from melanoma, while 10 patients (43.5%) died of other causes. CONCLUSIONS: Older patients have thick, mitotically active and frequently ulcerated melanomas. An excision margin≥10mm should be considered to reduce risk of local recurrence. SNB did not impact on survival. With increasing age, patients will more commonly die of causes other than melanoma regardless of the extent of surgical care.

CD271 Expression on Patient Melanoma Cells Is Unstable and Unlinked to Tumorigenicity.

The stability of markers that identify cancer cells that propagate disease is important to the outcomes of targeted therapy strategies. In human melanoma, conflicting data exist as to whether hierarchical expression of CD271/p75/NGFR (nerve growth factor receptor) marks cells with enriched tumorigenicity, which would compel their specific targeting in therapy. To test whether these discrepancies relate to differences among groups in assay approaches, we undertook side-by-side testing of published methods of patient-derived melanoma xenografting (PDX), including comparisons of tissue digestion procedures or coinjected Matrigel formulations. We found that CD271(-) and CD271(+) melanoma cells from each of seven patients were similarly tumorigenic, regardless of assay variations. Surprisingly variable CD271 expression patterns were observed in the analyses of sibling PDX tumors (n = 68) grown in the same experiments from either CD271(-) or CD271(+) cells obtained from patients. This indicates unstable intratumoral lineage relationships between CD271(-) and CD271(+) melanoma cells that are inconsistent with classical, epigenetically based theories of disease progression, such as the cancer stem cell and plasticity models. SNP genotyping of pairs of sibling PDX tumors grown from phenotypically identical CD271(-) or CD271(+) cells showed large pairwise differences in copy number (28%-48%). Differences were also apparent in the copy number profiles of CD271(-) and CD271(+) cells purified directly from each of the four melanomas (1.4%-23%). Thus, CD271 expression in patient melanomas is unstable, not consistently linked to increased tumorigenicity and associated with genetic heterogeneity, undermining its use as a marker in clinical studies. Cancer Res; 76(13); 3965-77. ©2016 AACR.

Excision margins and sentinel lymph node status as prognostic factors in thick melanoma of the head and neck: A retrospective analysis.

BACKGROUND: Recommended margins for thick cutaneous melanoma (Breslow thickness >4 mm; T4) have decreased over recent decades. Optimal margins and the role of sentinel node biopsy (SNB) in thick head and neck melanoma remain controversial. METHODS: A single-center review was conducted of patients treated between 2002 and 2012 assessing the impact of excision margins and sentinel lymph node status on locoregional recurrence and melanoma-specific survival (MSS). RESULTS: One hundred eight patients were identified. Median age was 71.1 years and median Breslow thickness was 6.0 mm. Median follow-up was 40 months. Locoregional recurrence occurred in 27% and there was no significant reduction in recurrence with margins ≥2 cm (p = .17). Increasing margins did not improve survival (p = .58). Fifty-nine patients (55%) underwent SNB, of which 27% were positive. There was a trend toward longer survival for patients who were sentinel lymph node-negative (p = .097). CONCLUSION: Wider margins do not significantly improve locoregional recurrence or MSS. Sentinel lymph node involvement reflects a poor prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1373-1379, 2016.

A unique deep inferior epigastric artery perforator and implications for a muscle and fascia sparing vertical rectus abdominis myocutaneous flap: a case report.

Despite the sacrifice of rectus abdominis muscle, the vertical rectus abdominis musculocutaneous (VRAM) flap is still a preferred option for perineal reconstruction. This journal has previously reported on the utility of preoperative computed tomographic angiography (CTA) in this setting to identify cases that are both suitable and unsuitable for rectus abdominis flaps after previous surgery. We report a case which highlights a unique example of the benefits of such imaging, with the largest deep inferior epigastric artery (DIEA) perforator described to date identified on imaging, and used to potentiate a donor-site sparing procedure. The use of this dominant perforator was able to limit donor site harvest to only a small cuff of anterior rectus sheath and a small segment of rectus abdominis, potentiating a muscle-sparing and fascia-sparing VRAM flap for perineal reconstruction. As such, preoperative CTA was found to be a useful tool in identifying a unique anatomical variant in the largest DIEA perforator described to date, and was used to potentiate a muscle-sparing and fascia-sparing VRAM flap for perineal reconstruction.

Why there are two rows of deep inferior epigastric artery perforators despite variability in the number of deep inferior epigastric artery trunks: An anatomical and embryological argument.

The deep inferior epigastric artery (DIEA) distributes musculocutaneous perforators in a uniform pattern that comprises "medial row" versus "lateral row" perforators, with these two rows having anatomical and functional differences. This pattern of two perforator rows is distributed from the DIEA regardless of the number of major DIEA trunks, with there variably being one to four major trunks. As such, a single DIEA trunk will still distribute two perforator rows, as will four major DIEA trunks. What remains to be answered is how such an anatomical fact may come to be? The answer probably lies in the anatomy and embryology of the rectus abdominis muscle itself. With two muscle heads to each hemiabdominal rectus abdominis muscle present from early in its development, it is highly likely that each head of rectus abdominis muscle draws its own blood supply from its source DIEA pedicle, one "perforator row" for each head, regardless of DIEA branching pattern from which these rows are drawn, thus providing an embryological and anatomical basis for the observation of two uniform perforator rows.

The profunda femoris artery "fourth perforator" island flap: a new perforator flap in lower-limb reconstruction.

Although the lateral thigh flap has been well described as a fasciocutaneous flap based on one or more of the four perforators of the profunda femoris artery, the role for these individual perforators as perforator flaps has not been described. These profunda femoris artery perforators offer a particularly useful option in lower-limb reconstruction. In fact, a perforator flap based on the profunda femoris artery fourth perforator (PFA-P4) has not been described to our knowledge. We describe the utility of the PFA-P4 flap, offering modes of preoperative imaging and a role for its use in lower-limb reconstruction. Computed tomographic angiography (CTA) was able to identify the location and course of a PFA-P4, and Doppler ultrasound confirmed the CTA findings. A FA-P4 flap was designed and harvested, with direct closure of the donor site achieved. There were no operative complications. Perforator flaps based on the perforating branches of the profunda femoris artery have not been widely described, largely due to individual variability in perforator anatomy. With the advent of CTA for perforator mapping, the "freestyle" nature of such flaps is eliminated, and perforator flaps such as the PFA-P4 flap can be planned and harvested safely and confidently.

Mycobacterium ulcerans ulcers: a proposed surgical management algorithm.

Mycobacterium ulcerans (MU) is the third common mycobacterial infection after tuberculosis and leprosy. In endemic areas, MU ulcers should be considered in the differential diagnosis of any unusual or nonhealing lesion or ulcer. Diagnosis and treatment should be instigated promptly. Delay may lead to disfiguring or disabling scars. Surgical management, therefore, should aim towards early excision, with clear margins of the ulcer. We present 4 consecutive patients treated by our department within a 6-month period for MU ulcers. The presentation, diagnosis and surgical management are described. Based on our experience and after reviewing the literature, we have developed a surgical algorithm for the management of MU ulcers.