University Hospital Waterford: 5-year experience of cutaneous melanoma.

INTRODUCTION: The incidence of cutaneous melanoma (CM) continues to rise in Ireland. Despite significant advances in melanoma molecular therapy, surgery remains the mainstay of treatment for CM. The University Hospital Waterford (UHW) prospectively maintained CM registry was established in 2010. AIM: To summarize 5-year experience (2010-2015) of primary CM presenting to UHW. METHODS: Data were retrospectively obtained from a central electronic pathology and radiology repository augmented by HIPE data and theatre logs. Data collected included patient demographics and clinico-pathological characteristics, specimen number, size, anatomical location, melanoma subtype, Breslow thickness, Clark's level, ulceration, and mitosis. RESULTS: 592 CMs were managed in UHW during the study period. Overall, females comprised the majority of cases with mean age at presentation 60.78 ± 18.29 years. The most commonly affected anatomical location was the lower limb (26.7%) followed by the back (15.1%), upper limb (15.07%), and face (14.40%). Superficial spreading and lentigo maligna were the most common histological subtype accounting for 19.8 and 20%, respectively. Overall, the mean Breslow depth was 2.4 ± 3.7 mm with corresponding Clark's Level III. Sentinel lymph node positivity was 39/103 (37.89%) most commonly located in the axilla (53.8%) and groin (30.7%). CONCLUSION: There has been a steady increase in the number of cutaneous melanoma presentations over the past 5-years to the South East Cancer Centre. Patients are managed best by prompt surgical excision and multidisciplinary management. Our results are in keeping with international standards and work continues in determining overall 5-year survival and recurrence rates.

Management of the axilla: has Z0011 had an impact?

BACKGROUND: Management of axillary disease in breast cancer has evolved significantly over the last two decades with the introduction of SLNB and a trend towards less radical surgery. Data from the American College of Surgeons Oncology Group Z0011 trial proposes that not all patients with positive axillary lymph nodes require completion axillary dissection. AIMS: The aim of this study was to determine whether there has been a change in practice patterns for axillary management in Ireland since the publication of this 'practice-changing' trial. METHODS: A review of breast cancers managed in the 12 months prior to publication of Z0011 (pre-Z0011) and comparison with those managed in the following 12 months (post-Z0011) was undertaken in three tertiary referral breast cancer centres. Patients with a positive SLNB were identified, and clinicopathologic data and subsequent management was compared between the two cohorts. RESULTS: There were 708 SLNB performed during the study period; 326 pre-Z0011 and 382 post-Z0011. There was no difference in the rate of SLN positivity between the two cohorts: 29.1 % had a positive SLN pre-Z0011 and 29.3 % were positive post-Z0011. There were a significantly lower number of axillary clearances performed in SLN-positive patients in the post-Z0011 period (71.4 %) compared to the pre-Z011 period (93.7 %, p = 0.0022 Chi-square). Of the patients with tumour characteristics meeting the Z0011 inclusion criteria in the initial 12 months of the study, 92.3 % underwent ALND compared with 65.6 % in the final 12 months of the study (p = 0.0006 Chi-square). CONCLUSIONS: There has been a change in clinical practice since the publication of the Z0011 trial, illustrated by a decrease in the rate of axillary clearance in node-positive breast cancers.

Questioning the role of axillary node dissection in sentinel node positive early stage breast cancer in the South Eastern Cancer Centre.

INTRODUCTION: Axillary node status is a predictor of breast cancer survival. Axillary node dissection (ALND) following positive sentinel node biopsy (SLNB) is challenged by the American College of Surgeons Z0011 trial, where clinically/radiologically node-negative, SLNB positive early stage patients failed to derive therapeutic benefit from ALND at 6 years. AIMS: To quantify the rates of non-sentinel lymph node positivity after ALND in all breast cancer stages. To assess Z0011 trial result application to an Irish patient population. METHODS: Retrospective review of a prospectively maintained database of clinically node-negative patients undergoing breast conserving surgery and ALND for a positive SLNB from January 2011 to January 2012. RESULTS: Of 174 new breast cancers diagnosed, 144 underwent surgery of which 127 patients were clinically/radiologically node-negative; 46 patients were SLNB positive; 34 (73.9 %) proceeded to ALND. Of 9 T1 tumours, 3 (33.3 %) had further positive nodes on ALND. Of 24 T2 tumours, 11 (45.8 %) had further positive nodes on ALND. All 3 (100 %) T3/T4 tumours had further positive nodes on ALND. Mean numbers of sentinel and axillary nodes harvested were 2.3 and 15.2, respectively. In the SLNB positive, ALND negative group, 12 of 18 (66.7 %) patients were <60 years versus 14 of 17 (82.4 %) in the SLNB positive, ALND positive group. This may be indicative that younger women have a trend toward node positivity following ALND for a positive SLNB. CONCLUSION: These data suggest that a significant proportion (41.9 %) of T1/T2 tumours undergoing ALND following positive SLNB have further positive nodes. It may be premature to exclude ALND in patients with T1/T2 tumours following a positive SLNB.

Recombinant bactericidal permeability increasing protein (rBPI21) inhibits surgery-induced tumour growth in a murine model of metastatic disease.

BACKGROUND: Endotoxin (LPS), a cell wall constituent of gram-negative bacteria, is a potent inflammatory stimulus. We demonstrated that laparotomy increases primary tumour growth and experimental lung metastases, implicating endotoxin as a causative factor. We hypothesised that the anti-endotoxin agent, rBPI(21) would block surgery-induced tumour growth. METHODS: Mammary adenocarcinoma cells were injected into female BALB/c mice to establish lung metastases. Mice were randomised into three groups receiving anaesthesia, laparotomy or laparotomy and rBPI(21) treatment on day 14. Animals were killed on day 19, lungs harvested and blood obtained. Number and size of lung metastases were recorded. Apoptosis, mitosis and microvessel density within metastases were assessed and VEGF measured. CONCLUSIONS: Laparotomy increased metastatic growth, decreased tumour cell apoptosis, increased tumour cell proliferation, increased microvessel density and circulating VEGF. LPS blockade by rBPI(21) attenuated this increased growth and decreased proliferation, increased apoptosis, decreased micro-vessel density and circulating VEGF. This suggests that rBPI(21), has clinical potential in attenuating surgery enhanced tumour growth, especially in patients with a history of cancer undergoing laparotomy.