Amelia Insa

Antineoplastic Therapy-Induced Palmar Plantar Erythrodysesthesia ('Hand-Foot') Syndrome Incidence, Recognition and Management

Palmar plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, and fluorouracil are the most frequently implicated agents. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence.PPE presents as a painful erythema, often preceded by paresthesia, located on the palms and soles in the context of treatment with chemotherapy. Histologically, PPE shows few specific findings. Mild spongiosis, scattered necrotic and dyskeratotic keratinocytes and vacuolar degeneration of the basal layer is seen. Dermal changes in most cases include dilated blood vessels, papillary edema, and a sparse superficial perivascular lymphohistiocytic infiltrate can be found in varying degrees in the epidermis.Withdrawal or dose reduction of the implicated drug usually gives rise to amelioration of the symptoms. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve the pain. Use of systemic corticosteroids, pyridoxine (vitamin B6), blood flow reduction, and, recently, topical 99% dimethyl-sulfoxide have been used with variable outcomes. It could be of interest to consider them as preventive measures when drugs with a strong association with PPE are going to be administered.

Prognostic factors predicting survival from first recurrence in patients with metastatic breast cancer: analysis of 439 patients

We have analyzed retrospectively 439 women with recurrent breast cancer, followed at a single institution, in order to define potential prognostic factors for survival at the time of first recurrence. Median age at the time of first recurrence was 58 and the median disease free interval (DFI) from initial diagnoses to recurrence was 33 months. Thirteen percent of the patients did not receive any adjuvant therapy while 87% received different combinations of chemotherapy, radiotherapy and hormone therapy as adjuvant treatment. With a median follow‐up of 44 months from the time of recurrence the median survival (MSR) was 24 months (SE 1.24) and five‐year overall survival was 18% (SE 2.02). On the univariate analysis, pathological tumor size (pT) at diagnosis (p<0.0006), axillary lymph node status at diagnosis (p<0.00001), negative estrogen receptor (ER) status (p<0.0001), negative progesterone receptor (PgR) status (p<0.0001), adjuvant chemotherapy (p<0.001), disease free interval (p<0.00001), location of recurrence (p<0.0002) and number of metastatic sites (≥3: p, ≤ 0.0003), were significantly associated with shorter survival from first relapse. On the multivariate analysis, only the site of recurrence, axillary lymph node status at diagnosis, ER status and DFI remained independently associated with decreased MSR after first relapse.

Prognostic factors in localized invasive cutaneous melanoma: high value of mitotic rate, vascular invasion and microscopic satellitosis.

The aim of this study was to determine independent clinical and pathological prognostic factors for overall and disease-free survival in Spanish melanoma patients. Eight hundred and twenty-three patients with localized melanoma and complete clinical and pathological information were evaluated. The age at diagnosis, gender, location, tumour thickness, invasion level, ulceration, histological subtype, inflammatory infiltrate, mitotic rate, vascular invasion, microscopic satellitosis, regression and cell type were all included. Univariate and multivariate Cox regression analyses were performed for overall and disease-free survival. Gender, histological subtype, tumour thickness, invasion level, ulceration, inflammatory infiltrate, microscopic satellitosis, vascular invasion and mitotic rate were related to overall and disease-free survival in univariate analysis. Age and location were only related to disease-free survival. Only tumour thickness, vascular invasion and gender exhibited independent significance for overall survival in multivariate analysis. For disease-free survival, tumour thickness, location, mitotic rate, vascular invasion and microscopic satellitosis were the sole independent factors. It can be concluded that the Breslow thickness remains the most significant prognostic factor for the survival of patients with localized cutaneous melanoma. Our results support the inclusion of microscopic satellitosis and vascular invasion in the current American Joint Committee on Cancer (AJCC) staging system, although further studies evaluating their separate influence are needed. Mitotic rate is confirmed as an objective and independent predictor of disease-free survival for melanoma patients that should be considered in further revisions of the mentioned staging system.

Tratamiento neoadyuvante del cáncer de mama operable

Preoperative or neoadjuvant systemic treatment refers to either the first postdiagnosis systemic treatment that a patient receives or indicates that additional subsequent therapy is intended. Randomized controlled clinical trials have shown that preoperative systemic treatment offers the same disease free survival and overall survival benefits as does adjuvant systemic treatment. Neoadjuvant therapy has been found to increase the breast-conserving surgery rate. This therapy also allows to evaluate the primary tumor response to chemotherapy. Additionally, on the basis of the biologic characteristics of a tumor and differences in the response to systemic treatment, primary systemic treatment should be regarded as a tool that can be used to individualize systemic treatment for patients with breast cancer. However, some issues remain to be resolved, such as the markers that should be assessed before this therapy, as well as the optimal surgical and radiotherapy treatment.

Molecular genetic analysis of HLA-DR and -DQ alleles in Spanish patients with melanoma.

Controversial data have been reported about HLA alleles and susceptibility to melanoma. The relationship between distribution of HLA alleles in patients with melanoma and susceptibility to tumour was analysed, to study the possible correlation between HLA class II DQA1, DQB1 and DRBI genes and melanoma in a Spanish population. Genomic DNA from 82 patients with melanoma and 367 random healthy donors, from the same geographic area, were typed by PCR-SSP (sequence specific primers). The patients were also divided into different groups according to the age and presence of cancer relatives, and compared with the controls. None of these HLA class II alleles showed significant positive or negative associations with either the overall population of patients with melanoma or the considered subgroups. Moreover, values for relative risk of DQB1*0301, DQB1*0302, DQB1*0303, DQB*05, DQA1*0401, DQA1*0101/0104 and DRB*08, which have been reported to be increased or decreased in patients with melanoma, were very low and of no statistical significance. Our results indicate that HLA class II alleles may not contribute to a strong susceptibility to melanoma in the Spanish population, although further studies on larger series are needed to corroborate this. Key words:

Germline mutations in CDKN2A are infrequent in female patients with melanoma and breast cancer.

Carriers of mutations in the melanoma susceptibility gene, CDKN2A, exhibit a higher than expected risk of breast cancer. In this study, we aimed to determine mutations in the CDKN2A gene in patients with melanoma and additional breast cancer. Thirty-one women with histologically confirmed melanoma and breast cancer were studied for CDKN2A/ARF gene mutations by direct sequencing analysis. We identified four CDKN2A germline mutations. Two patients harbored the A148T polymorphism, one of them with family history of breast cancer. Another patient, with a melanoma diagnosed at 77 years, a breast cancer diagnosed at 66 and a family history of melanoma, had the V59G mutation. The fourth patient had a melanoma diagnosed at 54 years, a breast cancer at 46, and a strong family history of breast cancer (mother and grandmother), and presented the A85T mutation. The epidemiologic link between cutaneous melanoma and breast cancer is not mainly related to CDKN2A mutations. However, some mutations might have a role in this association or even in familial breast cancer, as it could be inferred from the patient with the A85T mutation.