Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases.

Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.

[Electrochemotherapy for treatment of cutaneous metastases]. / Elektrokemoterapi til behandling af kutane metastaser.

Cutaneous metastases occur in up to 9% of all patients with cancer and may cause discomfort and stigmatization. Electrochemotherapy is a local treatment using electric pulses to permeabilize cell membranes, enabling chemotherapy, such as bleomycin, to enter the cells and increase the cytotoxic effect by at least 300-fold. Electrochemotherapy is an efficient, once only treatment for cutaneous metastases with an objective response of 62-99%. Electrochemotherapy can reduce discomfort such as ulceration, oozing, bleeding and pain. Adverse events depend on the size of treatment area, but are very limited.

Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma.

INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL AND METHODS: A total of 84 perfusions were performed (53 women, 31 men, median age 63 years) from 1993 to 2010. 95% of the perfusions were administered to the lower limbs and 5% to the upper limbs. The inclusion criteria were recurrent and/or clinically apparent cutaneous/subcutaneous extremity in-transit melanoma metastases. RESULTS: The response rate after ILP was 85%; 42% had complete response (CR), 43% partial response (PR), 12% no change (NC) and 3% progression. Two- and five-year survival rates were 57% and 31%, respectively, and they were higher for patients with than without lymph node metastases. Time from ILP to recurrence was a median of seven months (range 1-37 months) for patients with CR or PR. Survival was longer for patients with CR or PR than for patients showing NC or progression. Several patients had mild or moderate local toxicity reactions, two patients developed severe local toxicity. CONCLUSION: ILP induces tumour regression in the vast majority of patients. One patient, i.e. 1% of the group, died from surgical complications. Otherwise, ILP treatment had an acceptable morbidity in this group of very sick patients. We are convinced that the treatment should be offered to improve local disease control in patients with multiple and/or recurrent melanoma confined to an extremity if surgical excision is not possible. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Polyacrylamide gel treatment of antiretroviral therapy-induced facial lipoatrophy in HIV patients.

BACKGROUND: Today, highly active antiretroviral therapy is lifesaving for most HIV-infected patients, but the treatment can result in facial lipoatrophy, which changes the face so radically that patients may develop severe psychological and social problems. Since 2001 polyacrylamide gel (PAAG) has been used successfully in HIV patients abroad. This article describes the results of a Danish study. METHODS: Forty HIV patients recruited from two major referral hospitals in the capitol area of Copenhagen, Denmark, each received a series of PAAG gel injections (small deposits in several sessions) with a 14-day interval. Patient satisfaction, injector's evaluation, evaluation by an external specialist in plastic surgery, and long-term aesthetic effect and complications were registered with follow-up until 2 years. RESULTS: All patients were very satisfied or satisfied with the result. The injector found the result very satisfying in 33 cases and a slight irregularity in 7. The external specialist found improvement in all cases with a one-grade reduction of the lipoatrophy in 11 cases, a two-grade reduction in 20, and a three-grade reduction in 3 cases. No filler-associated complications were recorded. CONCLUSION: This study has shown that PAAG can normalize contours in patients suffering from facial lipoatrophy within 3-6 sessions, with a mean amount of gel per session of 1.8 ml and a mean total amount of 8.8 ml. The results are in accordance with those of other large studies, confirming a high degree of biocompatibility and safety.

Rising incidence of Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investigate the incidence. We suggest guidelines for treatment. First we reviewed the medical records of 51 patients diagnosed with MCC from 1995 until 2006 in eastern Denmark. The nation-wide incidence of MCC was extracted from the Danish Cancer Registry for the calculations for the period 1986-2003. We reviwed published papers about MCC based on a MEDLINE search. Fourteen of the 51 patients developed recurrence, and 37 (73%) died during the study period. Mean follow-up was 13 months (range 1-122). A total of 153 patients were identified in the Danish Cancer Registry, and showed that incidence rates had increased 5.4 fold over the 18 year period from 1986 until 2003. Rates were highest in people over the age of 65. Recommended treatment with curative intent includes excision of the primary tumour with wide margins, excision of the sentinel node, computed tomogram (CT) or positron emission tomography (PET) of the thorax and abdomen, and adjuvant radiotherapy to the surgical bed. In the case of advanced disease, systemic palliative chemotherapy remains a possibility. There is a need for prospective multicentre evaluation of staging investigations and treatment of MCC.

[Keystone flap for reconstruction of skin defects]. / Keystone ø-lap til rekonstruktion af huddefekter.

INTRODUCTION: The keystone design perforator island flap was first described in 2003. It is a local flap based on axial perforators from the underlying structures. It is designed as a curvilinear shaped trapezoidal design flap which is essentially two V-Y flaps end to end. Most reports are of the lower limbs, but it has been used successfully almost all over the body. MATERIAL AND METHODS: We report our experience in 21 patients, who underwent excision of skin malignancies and reconstruction of the defect with a keystone flap (24 flaps in total). RESULTS: Only few complications were seen. Two patients had signs of infection at the border of the flap and were treated with local and/or oral antibiotics. In two cases a small necrosis developed at the border of the flap. In both cases, it healed conservatively. CONCLUSION: The keystone flap has proven to be very reliable with only few reported flap losses. Furthermore, it is technically easy to perform and thus may be performed by trainee surgeons as well as senior surgeons. The cosmetic result is excellent and far superior to the alternative skin grafting with its color differences and contour defect. In addition, many patients may be treated as day-only surgery or discharged from the hospital after only one day.

[Long-term complications after injection of permanent tissue-fillers to the lips]. / Langtidskomplikationer efter injektion af permanent vaevsfylder i laeber.

We present two cases with signs of infection and granulomas seen years after injection of permanent fillers to the lips. These side effects are difficult to treat. They resemble an immunological foreign body response and late-onset infection as well as granuloma and scaring depending on the substance injected. Steroid injections are indicated in case of granuloma, and antibiotics should be used when infection occurs, but surgical excision can be required. It is important to emphasize this condition in order to give patients proper advice prior to treatment and to recognize symptoms.

[Primary mucinous carcinoma of the skin--a literature review]. / Primaert mucinøst karcinom i huden--en oversigt over litteraturen.

Primary mucinous carcinoma of the skin (PKMK) is a rare malignant tumour of the sweat glands. It is often misdiagnosed as it has an uncharacteristic gross appearance - and may microscopically resemble a cutaneous metastasis from a mucinous carcinoma of the breast, gastrointestinal tract, lungs, ovaries or prostate. The recurrence rate is high, but mortality is low. A MEDLINE literature search was performed for reports on PKMK. A total of 228 cases were identified. These are presented with regard to tumour characteristics and clinical features as well as histopathological and immunohistochemical findings.

[Primary mucinous carcinoma of the skin]. / Primaert mucinøst karcinom i huden.

Primary mucinous carcinoma of the skin is a rare malignant tumour originating from the sweat glands. It is often misdiagnosed clinically since it has an uncharacteristic and variable presentation, and microscopically because it resembles a cutaneous metastasis from the more frequent mucinous adenocarcinomas of the colon, mammae, lungs and ovaries. The tumour often recurs, but mortality is low. We present a case with regional lymph node metastases five years after excision of the primary tumour.

Primary mucinous carcinoma of the skin: a population-based study.

BACKGROUND: Primary mucinous carcinoma of the skin (PMCS) is a rare malignant tumor deriving from the sweat glands. It is typically located on the head and is often mistaken for a metastasis from a more common primary tumor of the breast or gastrointestinal tract. We present the first population-based study of PMCS. MATERIALS AND METHODS: Data on PMCS was obtained from the Danish Cancer Registry, which has recorded incident cases of cancer on a nationwide basis since 1943. We extracted all patients diagnosed 1978-2003 with PMCS. RESULTS: Fifteen cases of PMCS have been registered during the study period of 26 years, seven in men and eight in women. The patient was typically in his or her 60th or 70th decennium. Seven cases were found on the scalp or neck, five on the eyelids, two on the face, and one on the trunk. Only one recurred, and apart from one regional metastasis, no distant spread or PMCS related deaths were reported. CONCLUSION: PMCS is a rare, slow-growing tumor which rarely metastasizes and is associated with low mortality. The age-standardized incidence rate, based on data from a population-based cancer registry of high quality and validity, is less than 0.1 per million. However, the precise number may be higher, since PMCS is an indolent tumor, which may be mistaken for a benign tumor and thus not always examined histologically.

Survival after a psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study.

PURPOSE: The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate. PATIENTS AND METHODS: We randomly assigned 262 patients with primary malignant melanoma to a control or an intervention group. Patients in the intervention group were offered six weekly 2-hour sessions of psychoeducation. Participants and nonparticipants were followed up for vital status and recurrence 4 to 6 years after surgical treatment. Prognostic factors (thickness of the tumor and lymph node status), sex, and age were adjusted for in a Cox regression model (proportional hazards regression) to derive an adjusted survival rate ratio and an adjusted relapse-free survival rate ratio, with 95% CIs. RESULTS: The hazard ratio was 1.30 (95% CI, 0.5 to 3.5) for survival and 0.73 (95% CI, 0.3 to 1.9) for recurrence. Being a nonparticipant increased the risk for death by more than two-fold (hazard ratio, 2.26; 95% CI, 1.0 to 5.2) over that of participants. CONCLUSION: Psychoeducation did not increase survival or the recurrence-free interval among patients with malignant melanoma; however, nonparticipants had a statistically significantly greater risk for death than participants.

Psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study.

PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous malignant melanoma were randomly assigned to the control or intervention group. Patients in the intervention group were offered six weekly sessions of 2 hours of psychoeducation, consisting of health education, enhancement of problem-solving skills, stress management, and psychological support. The participants were assessed at baseline before random assignment and 6 and 12 months after surgery. The analyses of the main effects of the intervention were based on analyses of covariance. RESULTS: The patients in the intervention group showed significantly less fatigue, greater vigor, and lower total mood disturbance compared with the controls, and they used significantly more active-behavioral and active-cognitive coping than the patients in the control group. The improvements were only significant at first follow-up. CONCLUSION: The findings of this study support the results of an earlier intervention study among patients with malignant melanoma and indicate that a psychoeducational group intervention for such patients can decrease psychological distress and enhance effective coping. However, this effect is short term and the clinical relevance is not obvious.