Implications of systemic adjuvant melanoma treatments for U.K. melanoma services: Results of the U.K. Melanoma Adjuvant Pathway Survey.

OBJECTIVE: To understand current U.K. management pathways for patients with resected stage III melanoma and changes expected with the routine availability of systemic adjuvant melanoma treatments. METHODS: In April-May 2018 (pre-National Institute for Health and Care Excellence approval of adjuvant therapy), 49 structured interviews were conducted with U.K. health professionals involved in melanoma management (28 oncology, 12 dermatology and 9 surgery) from 34 geographically dispersed National Health Service Trusts (1-6 respondents/Trust). RESULTS: Respondents expect to see a median of 5 (range 1-35) patients/month eligible for adjuvant therapy. Currently, 31 (63%) respondents include standardised BRAFV600 mutation testing for primary melanoma in their local guidelines; 30 (61%) respondents are from centres offering sentinel lymph node biopsy (SLNB) on-site after excision of melanoma from the trunk/limbs; 21 (43%) after excision of head/neck melanoma. Referral for SLNB (if not performed on site) is not always offered. With systemic adjuvant treatments becoming routinely available, respondents expect oncology involvement in patient care to increase considerably. Significant impacts are predicted on staffing, training, commissioning, service structure, local guidelines and patient psychological support requirements. CONCLUSION: The routine availability of systemic adjuvant melanoma treatments is expected to have wide-ranging implications for the commissioning, organisation and delivery of melanoma services.

Correction to: 1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study.

In the original article John F. Thompson was inadvertently omitted as an author. The author list is updated as shown in this correction.

1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study.

BACKGROUND: There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma > 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma > 1 mm in BT. METHODS: This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma > 1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients' QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation. RESULTS: Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p < 0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p = 0.036). After 12 months' follow-up, no differences were noted in QoL between groups. DISCUSSION: This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.

Closure of the radial forearm donor site using a local hatchet flap: analysis of 45 consecutive cases.

BACKGROUND: The radial forearm free flap (RFFF) is widely used in reconstructive surgery. Traditional donor-site closure by grafting may be associated with significant aesthetic and functional morbidity. We report our experience with primary closure using a local hatchet flap. METHODS: In all, 45 consecutive patients who underwent RFFF reconstruction in the head and neck during an 8-year period were retrospectively assessed with regards to their donor-site morbidity. RESULTS: The mean age of the patients was 54, with 23 being female. The mean RFFF area harvested was 37.7 cm; mean width, 7.6 cm (5.5-11 cm); and mean length, 4.7 cm (3.5-6.5 cm). All patients had their donor site closed primarily utilizing a local hatchet flap. At the time of follow-up, there were 33 surviving patients, of which 31 patients were available for assessment. CONCLUSIONS: We recommend this technique of primary closure of the RFFF donor site: it is well tolerated by the patient, with good cosmesis and is associated with no discernable functional morbidity.

Cartilage-sparing surgery for melanoma of the external ear.

BACKGROUND: The excision of melanoma of the external ear poses a challenge to surgeons, who must achieve adequate oncological control while minimising impact on form and function. Cartilage-preserving surgery is an attractive option, as it leaves behind a scaffold for immediate reconstruction with a variety of techniques including full-thickness skin grafts (FTSGs) and local flaps. This manuscript will review the literature comparing cartilage-sparing surgery with composite excision of the skin and the cartilage for the treatment of auricular melanoma. We report the results of a 17 year experience of using both techniques, together with sentinel node biopsy at our centre. METHODS: A structured review of MEDLINE and EMBASE was conducted to evaluate all studies reporting local recurrence or survival rates for melanoma of the external ear treated with cartilage-preserving surgery. A retrospective review of all patients undergoing wide local excision (WLE) and sentinel lymph node biopsy (SLNB) for auricular melanoma at our centre between 2000 and 2017 was performed. RESULTS: Of 40 patients identified, 29 underwent cartilage-preserving surgery with no local recurrences or evidence of perichondral involvement. There was one local recurrence out of 11 patients who had their cartilage excised. There were no significant differences in recurrence rates or melanoma-specific survival rates when comparing cartilage-preserving and cartilage-sparing surgery. Our results are supported by the literature review, which suggests that cartilage-sparing surgery is gaining acceptance as a safe practice.

Sentinel node biopsy status is strongly predictive of survival in cutaneous melanoma: Extended follow-up of Oxford patients from 1998 to 2014.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is widely used as a key investigatory tool for cutaneous melanoma, with results incorporated into the latest AJCC staging guidelines. We present the results of our extended follow-up of sentinel lymph node biopsy for melanoma over a sixteen-year period. METHODS: Data were collected prospectively from June 1998 to December 2014 from a single tertiary skin cancer referral centre. Chi-squared analysis was used to analyse patient demographics and primary tumour pathology. Survival analysis was conducted using Cox regression models and Kaplan-Meier survival curves. RESULTS: Over a sixteen-year period 1527 patients underwent SLNB in 1609 basins, with 2876 nodes harvested. 347 patients (23%) had a positive biopsy. The most common primary tumour sites for males was the back (32%); women had a significantly higher number of melanomas occurring on the lower and upper limbs (45% and 26% respectively) [all p < 0.0001, Chi-squared]. Mean follow-up time was 4.9 years. Patients with a positive SLNB at diagnosis were significantly more likely to die from melanoma (subhazard ratio 5.59, p = 0.000, 95% CI 3.59-8.69). Breslow thickness and ulceration were also significant predictors of melanoma-specific mortality. For patients with a primary Breslow >4.0 mm ten-year disease free survival was 52% for SLNB negative and 26% for SLNB positive patients. For Breslow thicknesses of 2.01-4 mm these values were 66% and 32% respectively. CONCLUSIONS: Sentinel lymph node biopsy status is strongly predictive of survival across all thicknesses of primary cutaneous melanoma.

Neuropathic pain and quality of life after wide local excision and sentinel lymph node biopsy for melanoma: a multicentre study.

Wide local excision and sentinel lymph node biopsy is the mainstay of treatment for patients with melanoma. As survival outcomes improve, longer term quality of life questions become more pertinent and this study aims to assess the factors which may play a role following surgery. A total of, 221 patients who underwent wide local excision and sentinel lymph node biopsy for melanoma (AJCC stage I and II) were recruited from three UK centres. These patients completed a patient outcome questionnaire, which included demographic and treatment data as well as quality of life and pain questionnaires. Pain was the only significant factor influencing the quality of life with a negative correlation seen between pain and quality of life scores (P<0.001). In total, 34% of patients reported pain at their surgical site and four (1.8%) patients scored as high risk for neuropathic pain. Patients experiencing pain were significantly younger that those not reporting pain (median 55.0 vs. 63.5 years, P<0.001). Length of time since surgery did not correlate with pain nor quality of life scores. Our results suggest that following this common procedure a sizeable proportion of patients experience pain and poorer quality of life which does not improve with time. The level of pain experienced is clinically significant and merits evaluation and treatment in this group of patients who are increasingly surviving their melanoma diagnosis. Further investigation into potential prophylactic measures is suggested.

Generation of a vascularized organoid using skeletal muscle as the inductive source.

The technology required for creating an in vivo microenvironment and a neovasculature that can grow with and service new tissue is lacking, precluding the possibility of engineering complex three-dimensional organs. We have shown that when an arterio-venous (AV) loop is constructed in vivo in the rat groin, and placed inside a semisealed chamber, an extensive functional vasculature is generated. To test whether this unusually angiogenic environment supports the survival and growth of implanted tissue or cells, we inserted various preparations of rat and human skeletal muscle. We show that after 6 weeks incubation of muscle tissue, the chamber filled with predominantly well-vascularized recipient-derived adipose tissue, but some new donor-derived skeletal muscle and connective tissue were also evident. When primary cultured myoblasts were inserted into the chamber with the AV loop, they converted to mature striated muscle fibers. Furthermore, we identify novel adipogenesis-inducing properties of skeletal muscle. This represents the first report of a specific three-dimensional tissue grown on its own vascular supply.

Sentinel lymph node biopsy in melanoma: The Oxford ten year clinical experience.

Sentinel lymph node biopsy (SLNB) has become an established investigation for assessing microscopic nodal metastasis in melanoma. The American Joint Committee on Cancer (AJCC) incorporates the sentinel node status in its staging criteria for melanoma. We present our clinical evaluation of performing SLNB in a single UK centre between 1998 and 2008. There were 697 patients with a mean age 53 years (range 13-92). We were able to surgically harvest at least one sentinel node in 694 patients of which 532 (76%) were negative. Of the 162 positive patients, 129 underwent further completion lymphadenectomy with 29 showing further pathologically positive nodes. At median follow up of 46 months, mortality from melanoma for SLN positive and negative patients was 32% and 4%, respectively. Disease recurrence was noted in 10% of the SLN negative group. Survival curves showed significant difference (p<0.001) in outcomes for patients grouped by Breslow thickness. Postoperative complications were noted in 6% of patients. No life-threatening complications were noted. Our results are comparable to other national and international studies. We await the outcomes of ongoing trials to assess the therapeutic value of SLNB for melanoma.

The Cook-Swartz venous Doppler probe for the post-operative monitoring of free tissue transfers in the United Kingdom: a preliminary report.

Accurate assessment of the perfusion of free tissue transfers has always been a challenge for surgeons undertaking microvascular reconstructive procedures. The complexities of flap microcirculation are often difficult to assess despite all the subjective and objective examination techniques available today, particularly when the free tissue transfer is buried, and not visible for monitoring. The Cook-Swartz venous Doppler system is a technique for monitoring venous flow in free tissue transfer consisting of an implantable, removable, 20 MHz ultrasonic probe around the venous pedicle and a battery operated portable monitor. We perceive it as a quick and easy to use system, which in our study was well received by both medical and nursing staff. It can be used in conjunction with other monitoring techniques and we found it of value following revascularisation, during inset and in post-operative monitoring of free flaps particularly when operating outside our base hospital. We believe our initial experiences, on 24 patients, with the device, supports the use of a Cook-Swartz probe as an adjunct to traditional clinical monitoring techniques. We have had no technical difficulties with its application, use and removal, so far and we plan to continue with its use when it becomes available outside of a clinical trial.

Treatment of nevoid hyperkeratosis of the nipple and areola by shave excision.

The case is presented of a 29-year-old female who, at the age of 13 years, developed bilateral verrucous thickening of her areolae. Despite the condition causing her significant psychosocial morbidity, a specialist referral was initially denied on the grounds that no treatment was apparently available. The condition progressively deteriorated over the subsequent 14 years. She was eventually referred for a dermatology opinion, and the diagnosis of nevoid hyperkeratosis was made. Topical therapy with keratolytics was unsuccessful, and she was referred for a plastic surgery review. Bilateral shave excision of the lesion was performed under general anesthesia, with a satisfactory outcome and no evidence of recurrence at 10 months.