Adriamycin extravasation: Surgical treatment and possible prevention of skin and soft-tissue injuries

In a material consisting of approximately 6,000 injections of Adriamycin during a 2-year period, eleven moderate and five severe extravasation injuries have been observed. Even a small leakage of the drug may cause a permanent lesion. The most serious injuries were caused by large doses and on the dorsum of the hand. Plastic surgical operations were successfully performed in the severe cases. An active surgical intervention after primary neutralization of the extravasated Adriamycin is recommended.     

Managing vesicant extravasations

Extravasation is an unusual but potentially severe complication of vesicant chemotherapy administration. Some extravasation injuries prompt litigation and the oncologist's actions, or lack of action, are scrutinized in the courtroom. This article presents advice and recommendations for treating patients who receive vesicants and includes a discussion of FDA-approved vesicant extravasation treatments and antidotes.     

Clinical outcome of 31 patients with primary malignant melanoma of the vagina

Objective

To investigate the clinical characteristics of and prognostic factors for primary malignant melanoma of the vagina.

Methods

Clinical data from 31 patients treated for primary malignant melanoma of the vagina at the Sun Yat-sen University Cancer Center between March 1970 and June 2005 were retrospectively analyzed.

Results

The median age was 58 years (range, 18 to 73 years), and the main symptoms reported were vaginal bleeding and vaginal discharge. Most tumors were of the nodular type and classified as stage I according to International Federation of Gynecology and Obstetrics staging criteria. Surgery was performed on 22 patients, chemotherapy was administered to 7 patients, and immunotherapy was administered to 19 patients. Recurrent tumors developed in 11 patients (35.5%) during a median follow-up period of 20.2 months (range, 1 month to 18 years). The 5-year overall survival rate was 32.3%. Univariate analysis revealed that macroscopic tumor growth and the treatment method significantly affected survival outcome (p=0.039 and p<0.001, respectively), whereas the radicality of surgery did not (p=0.296). Multivariate analysis revealed that macroscopic tumor growth (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.4 to 12.1; p=0.010) and treatment method (HR, 0.3; 95% CI, 0.1 to 0.9; p=0.025) were independent prognostic factors for overall survival.

Conclusion

Patients with primary vaginal melanoma have a poor prognosis. Macroscopic tumor growth and treatment method are prognostic factors for primary malignant melanoma of the vagina.     

Surgical treatment of extravasation injuries

The authors present their experience of treating anti-cancer drug extravasation by means of a composite surgical technique that consists of infiltration with physiological solution and hyaluronidase and subsequent manual aspiration of solutes alternated with profuse irrigation of the infiltrated area. In the immediate post-op we carry out a medical therapy that consists of calciparine and topic antibiotic and/or steroid creams. Since the year 2000 this technique has been used on 25 patients. We have had neither complications nor scars.     

Multiple primary melanoma.

From a series of 712 patients with melanoma, 38 patients (5.3%) had more than one primary melanoma. Twenty-four patients had two primaries, 11 patients had three, 2 patients had four, and 1 patient had eight. Twelve patients (32%) had one or more synchronous primaries. Forty-five percent of all multiple primaries were diagnosed within the first year. Microstaging by level and depth was determined prior to treatment and in patients with nonsynchronous primaries, 83% had a subsequent melanoma equal or less advanced than the original. Twenty-six patients with Stage I primaries were skin-tested with DNCB prior to therapy. No significant differences in delayed cutaneous hypersensitivity reactions were found between multiple primary and matched controls with only a single melanoma. Four of 10 patients with multiple primaries treated with adjuvant BCG or BCG-tumor cell vaccine developed subsequent melanomas suggesting that immunotherapy with BCG will not prevent the development of a new primary melanoma. Survival in patients with Stage I and II multiple primary melanomas was improved compared to Stage I and Stage II patients with a single primary. This study suggests that prognosis in multiple primary melanomas is better reflected by the most advanced primary based on microstaging and the presence or absence of regional lymph node metastases than by multiplicity.     

Multiple primary melanoma revisited

BACKGROUND: Incidence of cutaneous melanoma continues to increase in the Caucasian population worldwide. Approximately 5% of melanoma patients develop additional primary melanoma. This rate is significantly higher than the estimated lifetime risk of an individual for developing the disease (1.4%). These features suggest that a genetic predisposition may underlie multiple primary melanomas (MPMs). Prior studies had identified CDKN2A mutations in a few MPM individuals. The objectives of this study were to determine the frequency of family history of melanoma in MPM cases, to characterize other clinical features including history of other cancer, and to determine the association with functional CDKN2A mutations. METHODS: This study used a case series design. All living patients who had been seen in the Pigmented Lesion Clinic at the University of Pennsylvania and who had more than one primary invasive malignant melanoma or an invasive primary followed by an in situ melanoma were eligible for participation. RESULTS: Individuals with MPM frequently had a family history of melanoma, dysplastic nevi (DN), and/or another cancer including basal cell carcinoma (BCC), and squamous cell carcinoma breast cancer, and a personal history of DN, and basal cell carcinoma. Germline mutations in CDKN2A gene were identified in 8 of 96 MPM cases (8.3%, 95% confidence interval, 6.7-9.9%). CONCLUSIONS: These data indicate that the presence of MPM is associated with a modest incidence of a family history of melanoma, DN, or BCC and a small association with CDKN2A mutations. Therefore, in addition to the MPM index case, other family members can benefit from screening and regular surveillance for melanoma, DN, and BCC.     

Treatment of unknown primary melanoma

Sixty-four patients with unknown primary melanoma were identified among 1045 new patients with melanoma (6%) seen during an 11-year period. Their mean age was 44.5 years (median age, 42.7 years). Of these, 39 (59%) were men, and 25 (38%) were women. In 34, only one site was involved. Common single sites were the axilla (29%), groin (24%), and neck (32%). Most of the melanomas (88%) were melanotic. Patients with localized melanoma surgically treated (n = 34) had a median survival of 53 months, and a 5-year survival rate of 45%. The respective rates for disseminated melanoma were 7 months and 10% (P = 0.00001). Localized, unknown primary melanoma should be treated with radical excision because a substantial proportion of patients so treated survive 5 years.     

Surgical management of primary melanoma

A significant proportion of the general population is diagnosed with malignant melanoma each year, and more people die of melanoma now than at any time in the past. Consequently, treatment of melanoma at all stages of development is an important clinical issue. A variety of management options are discussed here, including biopsy techniques and treatment of the primary melanoma. The latter include lymphatic mapping and sentinel lymph node biopsy, hyperthermic isolated limb perfusion, and surgery for stage IV melanoma patients. Procedure-associated benefits and possible complications associated with each modality are also summarized.     

Treatment of primary intraocular melanoma

The treatment of intraocular melanoma has evolved recently. Enucleation has been superseded largely by brachytherapy, proton beam radiotherapy, stereotactic irradiation, trans-scleral local resection, transretinal resection and diode laser phototherapy. Many patients develop metastatic disease, which usually involves the liver and occurs hematogenously. Disseminated disease rarely responds to therapy, and is usually fatal within 1 year of the onset of symptoms. Uveal melanomas develop characteristic chromosomal abnormalities, such as loss of chromosome 3. This is associated with a reduction in the 5-year survival from approximately 95% to less than 50%.     

Neutrophils influence melanoma adhesion and migration under flow conditions

We have studied human melanoma cell (C8161) adhesion and migration in response to stimulation by soluble collagen IV (CIV) using a modified Boyden chamber. In this modified chamber, shear flow can be introduced over the cell-substrate interface, affecting tumor cell chemotactic migration through a microporous filter. A relatively high level of intercellular adhesion molecule-1 (ICAM-1) was found on C8161 cells. In contrast, levels of beta(2)-integrins (e.g., LFA-1 and Mac-1), the molecules that would be necessary for C8161 stable adhesion to the endothelium substrate, were found to be very low on these melanoma cells. As a result, C8161 transendothelial migration under a flow condition of 4 dyn/cm(2) decreased by 70% as compared to static migration. When human neutrophils (PMNs) were present in the tumor cell suspension, C8161 migration recovered by 85% over C8161 cells alone under the 4 dyn/cm(2) flow condition. Blocking ICAM-1 on C8161 cells or Mac-1 on PMNs significantly inhibited C8161-PMN adhesion and subsequent C8161 migration through the endothelium under flow conditions. In addition, increased interleukin-8 production and Mac-1 expression by PMNs were detected when they were co-cultured with C8161 melanoma cells. These results suggest that transmigration of C8161 cells under flow conditions can be influenced by PMNs, mediated by Mac-1/ICAM-1 adhesive interactions and enhanced by altered cytokine production.     

Malignant melanoma with unknown primary site

From 1955 to 1976, 129 patients were seen with metastatic malignant melanoma from an unknown primary site, comprising 8.1% of all the referred patients with malignant melanoma. Eighty-two percent of the patients presented with a history of mass or lump. Overall median survival and 5-year survival rates after onset of symptoms were 10 months and 13%, respectively. Patients with lesions of the head and neck area had 5-year disease-free survival of 25%, whereas those with lymph node disease had a survival of 18%. Twenty-nine patients with regional disease had wide excision (usually lymphadenectomy) and their 5-year disease-free survival was 58%. Regional disease in patients with malignant melanoma of unknown primary site should be treated with radical surgical excision, since the survival is comparable or better to that of patients with regional disease having known and excised primary site.     

Surgical management of primary melanoma.

The outline of the surgical treatment of a primary cutaneous malignant melanoma may be divided into the problems of biopsy, definitive excision and reconstruction of the defect. An excisional, in contrast to an incisional, biopsy provides the full scope of prognostic parameters and should be used whenever possible. General anesthesia is not necessary, and frozen-section examination is inaccurate. An immediate excision biopsy should therefore be performed under local anesthesia as an outpatient procedure. Whenever possible, a margin of 10 mm should be used, as this would mean an adequate and definitive treatment in melanomas up to 1 mm, and possibly 2 mm, in Breslow thickness. In melanomas more than 1-2 mm in thickness a 3-cm free margin instead of a 5-cm free margin is recommended. Many patients, especially those with trunk lesions with a 3-cm free margin may not need a complicated repair, such as a skin graft or a flap. The excision in depth is recommended to be carried perpendicular to the skin and inclusion of underlying fascia is optional, as no study has proved it to be beneficial. The defect after the excision should whenever possible be closed directly. If this is not possible the defect is covered with either a skin graft or a flap and the latter is recommended from both a cosmetic and a functional point of view. If a skin graft has been used, the secondary defect may be reconstructed with a skin expansion technique.     

Surgical approach to primary cutaneous melanoma

The surgical management of primary cutaneous melanoma, from the diagnostic biopsy through the wide local excision and nodal staging, must be carefully planned, and the biology of the melanoma, microstaging and primary tumor pathologic features of the melanoma, location on the body, patient preferences, and comorbidities must be considered. The treating surgeon must balance preservation of oncologic principles, with optimization of functional and aesthetic outcome. This article reviews the rationale behind the surgical approach in the patient with a primary melanoma.     

Palliative radiation therapy for primary gastric melanoma

Introduction

Primary gastric melanoma is an exceedingly rare cause of upper gastrointestinal bleeding (GI bleeding). Prior reports of primary gastric melanoma have mostly been treated with surgery with utilization of radiation therapy being unreported. Radiation therapy has been used to palliate bleeding of other cancers including lung, bladder, cervix, and more recently primary gastric cancers.

Case presentation

This case documents an 87-year-old male who presented with fatigue and melena, and was found to have severe anemia. Endoscopy with biopsy revealed an isolated focus of melanoma. After discharge, he presented two days later and was found to have continued bleeding. Because he was deemed a poor surgical candidate he elected to undergo palliative radiation therapy for bleeding control.

Discussion

The diagnosis of primary verses metastatic melanoma is a topic of debate. Case reports of patients with no known extra-gastric primary have undergone surgical treatment with varying outcomes. Patients with metastatic gastric melanoma have relied on chemotherapy and radiation in addition to surgery, with radiation being used in the palliative setting. The use of radiation to control bleeding in other cancers including primary gastric adenocarcinoma has been previously studied. This case documents the utilization of radiation therapy in bleeding due to primary gastric melanoma.

Conclusions

Radiation therapy can provide adequate bleeding palliation in patients with primary gastric melanoma.