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Anorectal malignant melanoma (AMM) is a rare malignant tumor. Surgery remains the gold standard but new adjuvant treatments to allow local sphincter-saving are warranted. Electrochemotherapy (ECT) is an alternative to surgery in selected cohorts of patients. To evaluate safety and efficacy of ECT in a retrospective series of patients with primary or recurrent AMM in terms of local disease control, local progression free and overall survival. Seven primary and one recurrent AMM underwent ECT. Patients were followed at 1 and 2 months and at the longest available follow-up with clinical examination and/or ultrasound. One month after ECT 6/8 (75%) patients showed complete response, 1/8 partial response (12.5%) and 1/8 stable disease (12.5%), confirmed at 2 months. Bleeding stopped in all patients, and pain was absent or mild/moderate in all patients. No serious adverse events were observed. At 1 year of follow-up seven out of eight patients were alive (87.5%), four were disease-free and three were alive with disease. At the longest available follow-up (mean 4.9 ± 2.0 years) five out of eight (62.5%) of patients were still alive. Our study showed that ECT is well tolerated and effective in the treatment of patients with anal melanoma with good local control of disease.

Background Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years. Methods A total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12–48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification. Results All KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10−7 to 6.9 × 10−4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response. Conclusions ECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus.

Background Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Methods Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Results Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Conclusions Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

To assess the incidence of nonmajor lymphatic basin sentinel nodes in patients with cutaneous melanoma in order to propose a correct nomenclature and inform appropriate surgical management.This was a retrospective review of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site. Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic basin along the lymphatic drainage to a major classical nodal basin) or interval (located anywhere along the lymphatics between the primary tumor site and the nearest lymphatic basin) sentinel nodes.Nonclassical sentinel nodes were identified in 32 patients (3.0 %). Uncommon sentinel nodes were identified in 3.2 % (n = 17) of trunk melanoma primary disease and in 1.5 % (n = 7) of upper and lower extremity sites. Interval sentinel nodes were identified in 1.3 % (n = 7) of trunk primary lesions, with none from upper and lower extremities melanomas. The incidence of tumor-positive sentinel nodes was 24.1 % (245 of 1,013) in classical sites and 12.5 % (4 of 32) in uncommon/interval sites.The definition of uncommon and interval sentinel nodes allows the identification of different lymphatic pathways and inform appropriate surgical treatment. Wider experience with uncommon/interval sentinel nodes will better clarify the clinical implications and surgical management to be adopted in the management of uncommon and interval sentinel node sites.

Nasal tip reconstruction can be very challenging. It requires close attention to skin texture, colour and thickness matching, with the respect of the nasal aesthetic units and symmetry. Flaps are usually preferred to skin grafts where possible. Based on different donor areas, various flaps have been described for reconstruction of this region. Here we present a new V–Y myocutaneous island flap based on the levator alae nasi muscle (LAN muscle) blood supply. This flap may represent an alternative to the nasalis myocutaneous sliding V–Y flap previously described by Rybka. As its pivot point it is located more cranially than the nasalis flap, and it can advance more medially than the Rybka flap, with the possibility of covering larger defects of the nasal tip area, up to 1.8 cm in diameter. Over the past 5 years, 24 patients received nasal tip reconstruction with this flap following the resection of basal cell carcinomas. Good tip projection was maintained, and the aesthetic outcome was satisfactory, with well healed scars. We recommend this technique as an alternative to other flaps for nasal tip defects, especially if paramedian.

Healing tissues by first intention after abdominoperineal resection (APR) for rectal cancer (RC) is difficult to achieve due to the large tissue deficit and the anatomical and functional complexity of the pelvic region. APR in RC removes a much tissue that connects the abdominal cavity with the exterior of the body, with the risk of severe complications. APR must therefore be well planned out in a synchronous approach by an expert multidisciplinary team.

Background Treatment of early and multiple cutaneous unresectable recurrences is a major therapeutic problem with around 80% of patients relapsing within 5 years. For lesions refractory to elective treatments, electrochemotherapy (ECT) involving electroporation combined with antineoplastic drug treatment appears to be a new potential option. This study was undertaken to analyze the short- and long-term responses of lesions treated with ECT with intravenous injection of bleomycin in melanoma patients with in-transit disease or distant cutaneous metastases. Methods Between June 2007 and September 2012, 60 patients with relapsed and refractory cutaneous melanoma metastases or in-transit disease underwent 100 courses of ECT with intravenous injection of bleomycin. Response to treatment was evaluated three months after ECT. A long-lasting response was defined as no cutaneous or in-transit relapse after a minimum of six months. Results Three months after ECT, a complete response was observed in 29 patients (48.4%), a partial response in 23 patients (38.3%) and no change or progressive disease in 8 patients (13.3%). The objective response rate of all treated lesions was 86.6%. Thirteen patients (44.8% of complete responders) experienced a long-lasting response after one ECT session and were disease-free after a mean duration of follow-up of 27.5 months. Conclusions The favorable outcome obtained in the present study demonstrates that ECT is a reliable, and effective procedure that provides long-term benefit in terms of curative and palliative treatment for unresectable cutaneous lesions without adversely impacting the quality of life of patients.

Background Seroma formation is a frequent complication following radical lymph node dissection (RLND) in patients with metastatic melanoma. Several strategies have been used to prevent fluid accumulation and thereby reduce the duration of postoperative drainage, including fibrin sealants. Methods This was a prospective, single-center study in which consecutive patients undergoing surgical treatment of stage III metastatic melanoma by axillary or ilio-inguinal RLND were randomized to receive standard treatment plus fibrinogen/thrombin-coated collagen sealant patch (CSP) or standard treatment alone. The primary endpoint of the study was postoperative duration of drainage. Results A total of 70 patients underwent axillary (n = 47) or ilio-inguinal (n = 23) RLND and received CSP plus standard treatment (n = 37) or standard treatment alone (n = 33). Mean duration of drainage was significantly reduced in the CSP group compared with standard treatment (ITT analysis: 20.1 ± 5.1 versus 23.3 ± 5.1 days; p = 0.010). The percentage of patients drainage-free on day 21 was significantly higher in the CSP group compared with the standard treatment group (86% versus 67%; p = 0.049). Conclusions Use of the tissue sealant resulted in a significant reduction in duration of drainage. Further studies are warranted to confirm these results in different and selected types of lymphadenectomy.

Background Approximately 200,000 new cases of melanoma are diagnosed worldwide each year. Skin metastases are a frequent event, occurring in 18.2% of cases. This can be distressing for the patient, as the number and size of cutaneous lesions increases, often worsened by ulceration, bleeding and pain. Electrochemotherapy (ECT) is a local modality for the treatment of cutaneous or subcutaneous tumors that allows delivery of low- and non-permeant drugs into cells. ECT has been used in palliative management of metastatic melanoma to improve patients’ quality of life. This is, to our knowledge, the first application of ECT as neoadjuvant treatment of metastatic subcutaneous melanoma. Methods and results A 44-year-old Caucasian woman underwent extensive surgical resection of a melanoma, with a Breslow thickness of 1.5 mm, located on the right side of her scalp. No further treatment was given and the woman remained well until she came to our attention with a large nodule in her right cheek. Whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) was performed for staging and treatment monitoring. Baseline FDG PET/CT showed the lesion in the cheek to have a maximal standardized uptake value (SUVmax) of 19.5 with no evidence of further disease spread. Fine needle aspiration cytology confirmed the presence of metastatic melanoma. The patient underwent two sessions of ECT with intravenous injections of bleomycin using a CliniporatorTM as neoadjuvant treatment permitting conservative surgery three months later. Follow-up PET/CT three months after the first ECT treatment showed a marked decrease in SUVmax to 5. Further monitoring was performed through monthly PET/CT studies. Multiple cytology examinations showed necrotic tissue. Conservative surgery was carried out three months after the second ECT. Reconstruction was easily achieved through a rotation flap. Pathological examination of the specimen showed necrotic tissue without residual melanoma. One year after the last ECT treatment, the patient was disease-free as determined by contrast-enhanced CT and PET/-CT scans with a good functional and aesthetic result. Conclusions ECT represents a safe and effective therapeutic approach that is associated with clear benefits in terms of quality of life (minimal discomfort, mild post-treatment pain and short duration of hospital stay) and may, in the neoadjuvant setting as reported here, offer the option of more conservative surgery and an improved cosmetic effect with complete local tumor control.

Background Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate to low-grade malignancy. Although metastasis rarely occurs, DFSP has a locally aggressive behavior with a high recurrence rate. In the head and neck area, resection involving a wide margin of healthy tissue can be difficult because of functional and cosmetic considerations. We describe a novel reconstructive method for half forehead defects with an innovative single local wide scalp flap following excision of DFSP with a 3 cm margin of healthy tissue. Methods Two patients underwent wide resection of forehead DFSP and reconstruction with a single rotational scalp flap. The scalp flap blood supply was provided from three main vessels: the superficial temporal artery, occipital artery and posterior auricular artery. Results No early or late complications were observed in either patient with no local recurrence after 18 months of follow-up. The donor area could be closed primarily in both cases and the flaps survived completely. Conclusion This innovative technique allowed a radical excision of forehead DFSP with sufficient healthy margins, thus potentially decreasing tumor recurrence rate. Reconstruction was achieved avoiding microsurgery, skin expanders and large skin grafts. Moreover, all main reconstructive criteria, such as functional and cosmetic tissue characteristics, were completely fulfilled.

Sentinel lymph node biopsy is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node. In rare cases, lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site. These peculiar sentinel nodes, so-called “uncommon/interval” nodes, must be surgically removed because they may contain micrometastatic disease and may be the only site of nodal involvement.

Melanoma is responsible for most skin cancer-related deaths and is one of the most common cancers diagnosed in young adults. In melanoma, tumors can become established by activation of the negative regulator of cytotoxic T lymphocytes (CTLs), CTL antigen-4 (CTLA-4). Ipilimumab blocks the interaction of CTLA-4 with CD80/CD86 and augments T-cell activation and proliferation. In electrochemotherapy (ECT), local application of short high-voltage pulses renders cell membranes transiently permeable to chemotherapeutic drugs. The combination of ipilimumab and ECT may be beneficial for the treatment of metastatic melanoma; however, no prospective data are available to date. Here, we report the retrospective analysis of patients treated with ipilimumab in an expanded access program (EAP) who also received ECT. Fifteen patients with previously treated metastatic melanoma who received ipilimumab 3 mg/kg every three weeks for four cycles and underwent ECT for local disease control and/or palliation of cutaneous lesions with bleomycin 15 mg/m2 after the first ipilimumab infusion were included in the analysis. Over the study period, a local objective response was observed in 67% of patients (27% complete response [CR] and 40% partial response [PR]). According to immune-related response criteria, a systemic response was observed in nine patients (five PR and four stable disease [SD]), resulting in a disease control rate of 60%. Evaluation of circulating T-regulatory (T-reg) cells demonstrated significant differences between responders and non-responders. Overall, treatment was well-tolerated and without notable toxicity. In conclusion, the combination of ipilimumab and ECT appears to be beneficial to patients with advanced melanoma, warranting further investigation in prospective trials.

Background: Approximately 200,000 new cases of melanoma are diagnosed worldwide each year. Skin metastases are a frequent event, occurring in 18.2% of cases. This can be distressing for the patient, as the number and size of cutaneous lesions increases, often worsened by ulceration, bleeding and pain. Electrochemotherapy (ECT) is a local modality for the treatment of cutaneous or subcutaneous tumors that allows delivery of low- and non-permeant drugs into cells. ECT has been used in palliative management of metastatic melanoma to improve patients’ quality of life. This is, to our knowledge, the first application of ECT as neoadjuvant treatment of metastatic subcutaneous melanoma. Methods and results: A 44-year-old Caucasian woman underwent extensive surgical resection of a melanoma, with a Breslow thickness of 1.5 mm, located on the right side of her scalp. No further treatment was given and the woman remained well until she came to our attention with a large nodule in her right cheek. Whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) was performed for staging and treatment monitoring. Baseline FDG PET/CT showed the lesion in the cheek to have a maximal standardized uptake value (SUVmax) of 19.5 with no evidence of further disease spread. Fine needle aspiration cytology confirmed the presence of metastatic melanoma. The patient underwent two sessions of ECT with intravenous injections of bleomycin using a Cliniporator TM as neoadjuvant treatment permitting conservative surgery three months later. Follow-up PET/CT three months after the first ECT treatment showed a marked decrease in SUVmax to 5. Further monitoring was performed through monthly PET/CT studies. Multiple cytology examinations showed necrotic tissue. Conservative surgery was carried out three months after the second ECT. Reconstruction was easily achieved through a rotation flap. Pathological examination of the specimen showed necrotic tissue without residual melanoma. One year after the last ECT treatment, the patient was disease-free as determined by contrast-enhanced CT and PET/-CT scans with a good functional and aesthetic result. Conclusions: ECT represents a safe and effective therapeutic approach that is associated with clear benefits in terms of quality of life (minimal discomfort, mild post-treatment pain and short duration of hospital stay) and may, in the neoadjuvant setting as reported here, offer the option of more conservative surgery and an improved cosmetic effect with complete local tumor control.

Background Treatment of early and multiple cutaneous unresectable recurrences is a major therapeutic problem with around 80% of patients relapsing within 5 years [1]. For lesions refractory to elective treatments, electrochemotherapy (ECT) involving electroporation combined with antineoplastic drug treatment appears to be a new potential option [2]. This study was undertaken to analyze the shortand long-term responses of lesions treated with ECT with intravenous injection of bleomycin in melanoma patients with in-transit disease or distant cutaneous metastases.

Background Ipilimumab is the first agent approved for the treatment of advanced melanoma that showed a survival benefit in randomized phase 3 trials. Despite the survival benefit, due to its mechanism of action it is associated with a slow onset and low rate of responses and, in many cases, responses occur after other therapies, like chemotherapy, targeted therapy and radiotherapy. Electrochemotherapy (ECT) has been shown to be effective and well tolerated for local control of metastatic melanoma with superficial lesions. The current challenge is to improve ipilimumab efficacy by combination/sequence with other therapies. We performed a pilot study of combination with ipilimumab and ECT in order to verify the possible increase of response rate. Furthermore, due to the lack of predictive markers, we evaluated the possible predictive role of circulating T-regulatory cells (T-Reg) variations in peripheral blood mononuclear cells (PBMC) of treated patients. Methods

Background The aims of this retrospective analysis were to evaluate the effect of combined superficial and deep groin dissection on disease-free and melanoma-specific survival, and to identify the most important factors for predicting the involvement of deep nodes according to clinically or microscopically detected nodal metastases. Methods Between January 1996 and December 2005, 133 consecutive patients with groin lymph node metastases underwent superficial and deep dissection at the National Cancer Institute, Naples. Lymph node involvement was clinically evident in 84 patients and detected by sentinel node biopsy in 49 cases. Results The 5-year disease-free survival was significantly better for patients with superficial lymph node metastases than for patients with involvement of both superficial and deep lymph nodes (34.9% vs. 19.0%; P = 0.001). The 5-year melanoma-specific survival was also significantly better for patients with superficial node metastases only (55.6% vs. 33.3%; P = 0.001). Conclusions Metastasis in the deep nodes is the strongest predictor of both disease-free and melanoma-specific survival. Deep groin dissection should be considered for all patients with groin clinical nodal involvement, but might be spared in patients with a positive sentinel node. Prospective studies will clarify the issue further.

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported. We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT). EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread.

bleomycin-A5 injection for head and neck lymphangioma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:139e44. 17. Shou BQ, Shou WD, Yang Z, et al. Intralesional injection of pingyangmycin for treatment of venous-venular malformation in the maxillofacial regions of children: report of 306 cases. Shanghai Kou Qiang Yi Xue 2006;15:136e9. 18. Roggiani M, Stoehr JA, Leonard BA, et al. Analysis of toxicity of streptococcal pyrogenic exotoxin A mutants. Infect Immun 1997;65:2868e75. 19. Kullendorff CM. Efficacy of bleomycin treatment for symptomatic hemangiomas in children. Pediatr Surg Int 1997;12:526e8. 20. Tai KW, Lii CK, Chou MY, et al. Relationship between intracellular glutathione level and the mode of cell death induced by pingyangmycin. Oral Oncol 2003;39:13e8. 21. Puig S, Casati B, Staudenherz A, et al. Vascular low-flow malformations in children: current concepts for classification, diagnosis and therapy. Eur J Radiol 2005;53:35e45. 22. Green D. Mechanism of action of sclerotherapy. Semin Dermatol 1993;12:88e97.

e20031 Background: Ipilimumab is the first agent approved for the treatment of advanced melanoma that showed a survival benefit in randomized phase 3 trials. Despite the survival benefit, due to its mechanism of action it is associated with a slow onset and low rate of responses and, in many cases, responses occur after other therapies, like chemotherapy, targeted therapy and radiotherapy. Electrochemotherapy (ECT) has been shown to be effective and well tolerated for local control of metastatic melanoma with superficial lesions. The current challenge is to improve ipilimumab efficacy by combination/sequence with other therapies. We performed a pilot study of combination with ipilimumab and ECT in order to verify the possible increase of response rate. Furthermore, due to the lack of predictive markers, we evaluated the possible predictive role of circulating T-regulatory cells (T-Reg) variations in peripheral blood mononuclear cells (PBMC) of treated patients. Methods: We collected data from 10 patients (pts) with advanced melanoma (6 stage IIIc and 4 stage IV M1c) treated with ipilimumab at 3 mg/kg every 3 weeks for 4 cycles (day 1) and ECT with bleomycine at 15 mg/m2 (day 2) on superficial lesions. Blood draws were collected on day 0, 1 and 2, then on day 15 and 30 from ECT, at each cycle of ipilimumab and at every tumor evaluation (every 12 weeks). PBMC were thawed and labeled with anti-CD4-Pe-Cy-5, CD25-Pe and anti-FoxP3-AlexaFlour488 for T-Reg. Results: 10/10 (100%) pts showed local objective responses (4 CR and 6 PR). 7/10 (70%) pts showed local response (6 PR and 1 CR) after the second ipilimumab dose and 3/10 showed response (3 CR) at week 12. Two pts with PR (28%) out of the group of 7 showed response on distant lesions at week 24 (abscopal effect). All pts are still alive with a median follow up of 11 months (range 6-18). We found in all pts a decrease of T-Reg of 0.10% (range 0.50-2.6%) per cycle and no variation of CD4+ and CD25+ lymphocytes. Conclusions: Our preliminary results show that a combination approach with ipilimumab and ECT may increase responses to ipilimumab. T-Reg decrease in PBMC could be associated with response to treatment. Further studies about this combination are warranted.

Background Primary umbilical melanoma is an uncommon tumor that is poorly described in the medical literature. The umbilical region is a particular anatomic site owing to the presence of embryonal remnants, which can be a potential metastatic pathway, as well as the braided lymphatic network drainage. Hence, primary malignant neoplasms affecting the umbilicus require a different and more radical surgical approach compared with other melanomas. Case presentation In this report, we describe a series of three patients of Caucasian ethnicity who presented with primary umbilical melanoma at the National Cancer Institute of Naples, Italy. All patients underwent wide excision of the tumor including the underlying peritoneum. No surgical complications, either immediate or delayed, were observed in any of the patients. Sentinel lymph node biopsy was negative in two cases. Two of the patients developed metastatic disease and died after systemic medical therapy. The other patient is currently in follow-up, and remains disease-free after 21 months. Conclusions The umbilicus has vascular and embryological connections with the underlying peritoneum, so that early visceral involvement is more likely to occur with primary umbilical melanomas. As such, tumor resection including the underlying peritoneum is required to avoid local relapse, whilst sentinel lymph node biopsy appears to be of poor diagnostic value.

Meeting abstracts Identifying molecular biomarkers in melanoma may provide useful diagnostic and therapeutic tools. Melanoma delivers immune suppressive stimuli through the pathway PDL-1/PD-1. Recent data suggest tumour-cell expression of PD-L1 in melanoma may be driven by constitutive oncogenic