Skin lesions in patients treated with imatinib mesylate: a 5-year prospective study.

Imatinib mesylate (IM) represents the first-line treatment of patients with chronic myeloid leukemia (CLM) or gastrointestinal stromal tumor (GIST). It presents several side effects. However, less than 10% are nonhematologic including nausea, vomiting, diarrhea, muscle cramps, and cutaneous reactions. The aim of our study was to identify data regarding IM cutaneous adverse effects (AEs) to improve the clinical diagnosis and management of the more frequent side effects. Skin examination should be done before and during IM treatment so that AEs can be diagnosed and treated early with less impact on chemotherapy treatments and on the quality of life of the patient.

Cancer surveillance series: role of demographic aspects, altitude and latitude in the extracutaneous malignant melanoma in a residential study.

BACKGROUND: Extracutaneous melanoma (ECM) is a very rare malignancy and its biology differs from that of cutaneous melanoma. Residential studies can offer an important contribution to the study of this disease. METHODS: We characterized the distribution of ECM according to residential and demographic baseline characteristics. We computer-searched patients that removed an ECM, and we analyzed all demographic and residential parameters. Disease free survival (DFS), date of death or last follow-ups were evaluated. The same parameters were analyzed using hazards-regression. Finally, we used the multiple regressions between DFS and the predictors. RESULTS: A total of 44 ECM patients were included in our analysis. Median DFS was of 10 months; at Log-Rank Test and Cox-hazard regression, the variable age (P<0.01; P<0.004) and latitude (P<0.02; P<0.006) reached a statistical significance; at multiple logistic regression, the significance was instead maintained only for the variable age. General OS was of 42 months at Log-Rank Test age (P<0.001), as well as latitude (P<0.006) maintained its significance at hazard-regression. CONCLUSIONS: Demographic and residential aspects can play an important role in the study of this rare disease, supporting the assumption that ECM are generated by processes actually unknown, as demonstrated in our results compared with those of the literature.

Thin melanoma and late recurrences: it is never too thin and never too late.

In the absence of risk factors, thin melanomas (TM) present a long-term survival; however, recurrences may occur. We describe the predictive clinicopathological features of patients with metastatic TM. Kaplan-Meier product was performed for the survival analysis, while Cox proportional hazards regression was used to evaluate the effect of the clinicopathological features on disease-free survival (DFS) and overall survival (OS). Median DFS of the entire cohort was 26 months and three patients developed late metastases. Nine patients developed extra-nodal metastases as first recurrence, while cases of positive sentinel lymph node biopsy (SLNB) were not found. DFS and OS varied according to the clinicopathological features, but only ulceration remained the main statistical significance value. According to our results, a hypothetical use of SLNB in TM without other risk factors is not currently feasible. No consensus exists as to which patients with TM are at risk for metastases or late recurrences.

Appearance of malignant melanoma after a non-cutaneous cancer diagnosis.

BACKGROUND: The aim of this study is to find the associations between malignant melanoma (MM) and other non-cutaneous malignancies and to see whether there are possible correlations between them. METHODS: We analysed a sample of 1720 patients collected by our melanoma database, to identify patients with both MM and non-cutaneous primary cancer (NCC). The incidence rate (IR) included in our database was calculated as the ratio between the observed patients with NCC and those with MM. RESULTS: A total of 74 patients, with both NCC and MM, were included in our analysis, corresponding to 4.30% of patients with MM present in our melanoma database. After breast cancer (24.3%; IR = 1:4), the most common malignancies were lymphomas (14.8%; IR = 1:4), renal cell carcinoma (13.5%; IR = 1:7), thyroid cancer (9.4%; IR = 1:11), and prostatic carcinoma (8.1%; IR = 1:12), followed by other cancers. Among patients with lymphomas, most patients (72.7%) had a non-Hodgkin lymphoma. Our study shows a high coexistence of multiple malignancies in patients with MM. CONCLUSION: Although we cannot definitively confirm a true association between non-skin cancers and MM, we believe that there are sufficient links for further investigation in order to identify new aetiological factors and therapeutic targets for these cancers.

Predictors and survival in patients with melanoma brain metastases.

Brain metastases (BM) are one of the most frequent neurological complications of cancers. Melanoma is the third most common tumor to metastasize to the brain with a reported incidence of 10-40 %, and many patients have subclinical BM (>73 %). We computer-searched the clinical records of all our patients registered into a database to identify patients that presented or developed BM. A total of 49 patients with melanoma BM were included in our analysis. General time to brain metastases (TTBM) was 23 months. The nonparametric test between TTBM and the single variables showed an association between TTBM and Breslow thickness (p < 0.0076; Spearman's coefficient-0.411), ulceration (p = 0.0656; Spearman's coefficient-0.287) and positive sentinel lymph node (p < 0.0015; Spearman's coefficient-0.475). Performing multiple regression, positive SLN remained the only, statistically significant, predictive variable (p < 0.01). Regarding the first melanoma site, the axial sites were more likely to develop BM than peripheral ones (p < 0.001). The analysis of brain metastasis survival (BMS) with Kaplan-Meier curves has resulted in a median survival rate of 6 months (range 1-134 months) and was strongly related to response to treatment, number of parenchymal lesions, presence or absence of symptoms. The results of the current analysis revealed clinical and primary tumor characteristics associated with the development of BM, TTBM, and BMS. The SNL was found to be the strongest predictor for BM development.

Melanoma with unknown primary: report and analysis of 24 patients.

In the literature, there are some papers reporting on patients with metastatic melanoma from an unknown primary lesion (MUP). The pathogenesis of this phenomenon and the prognosis of these patients are still debatable. Therefore, we reviewed our casistics on MUP patients. We identified 24 MUP patients out of all patients registered into a melanoma database from June 1996 to June 2011. The incidence was 1.4%. We compared the survival rate of all patients with MUP stage III-IV with all patients with metastatic melanoma known primary (MMKP) stage III-IV observing a clear survival improvement for MUP patients in front of MMKP patients (p<0.01). In a second instance, we compared stage III MUP patients with only lymph nodal involvement with stage III MMKP patients with only lymph nodal involvement, and again we found statistically significant better survival for MUP patients (p<0.05). In this retrospective study, the number of lymph nodes involved (p=0.8), the sex (p=0.9), and S100 value (p=0.2) were not statistically relevant for prognosis. The better prognosis for these patients is very similar to better survival rate for metastatic melanoma patients and vitiligo. This correlation may be in accord with the hypothesis of a regression of primary lesion by immunological system of the host and also the median age of patients at the time of diagnosis, commonly older than melanoma patients, may correspond to a long period of immunological interferences between the host and the melanoma disease.

Imiquimod 5% cream use in dermatology, side effects and recent patents.

Imiquimod is an immune response modifier that stimulates the patient's own immune system to release various chemical substances, such as interferon and interleukin-12. Although, approved by the United States Food and Drug Administration since 1997 as a topical treatment for genital and perianal warts, investigators have found that this product may offer an alternative treatment for a wide variety of medical conditions, such as for actinic keratoses, molluscum contagiosum, genital herpes, and various skin tumours. Clinical trials are now demonstrating the beneficial effects that its administration may have in treating other immune-related, dermatologic disorders. Understanding the pharmacology of this kind of drug is another step to fully understanding the power of the human immune system. Local reactions occur most frequently and include itching, burning, pain, soreness, flaking, erosions, and crusting. Since, it is administered locally; only a small amount of drug should reach systemic circulation, if used correctly. However, uncommon systemic side effects have been reported including headache, flu-like symptoms, fatigue, nausea, and myalgia. This article reviews imiquimod use in dermatology including its off-label use, side effects, future developments, new molecules related to dermatology and relevant patents.

Predictive factors for false negative sentinel lymph node in melanoma patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) represents a useful tool for staging melanoma patients. However false-negative SLNB are reported in the literature. OBJECTIVE: The aim of our study is to identify predictive factors for false-negative SLNB in melanoma patients. MATERIALS AND METHODS: We conducted a retrospective analysis on 316 melanoma patients who underwent SLNB and were followed up at the Department of Dermatology and Plastic Surgery of University of Rome "Sapienza" from March 1994 to June 2008. RESULTS: In our patients, SLNB was positive in 35 cases (11.07%) whereas it was negative in 281 cases (88.93%); 12/316 patients (3.8%) had positive SLNB and positive therapeutic lymph node dissection (TLND); 23/316 (7.28%) patients had positive SLNB and negative TLND; 266/316 (84.18%) patients had negative SLNB but without subsequent metastases in the SLN site; 15/316 (4.74%) patients had negative SLNB, but with subsequent metastases in the same SLN site (false-negative patients). Among the different prognostic factors, only ulceration was the main predictive factor for false-negative SLNB, according to statistical analysis (p=.0420). CONCLUSION: Our data confirm that SLNB is a useful technique for staging melanoma patients. However, in patients with negative SLNB, a closer follow-up is recommended when ulceration is present. The authors have indicated no significant interest with commercial supporters.

Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency: a prospective intervention study.

CONTEXT: Effects of vitamin D repletion in young people with low vitamin D status have not been investigated so far. OBJECTIVE: We evaluated the effect of a single massive dose of cholecalciferol on calcium metabolism at 3, 15, and 30 d, compared to baseline. DESIGN AND SETTING: We conducted a prospective intervention study in an ambulatory care setting. PARTICIPANTS: Forty-eight young subjects with vitamin D deficiency participated in the study. INTERVENTION: A single oral dose of 600,000 IU of cholecalciferol was administered to each subject. MAIN OUTCOME MEASURES: We evaluated serum changes of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, calcium, and PTH induced by a single load of cholecalciferol. RESULTS: The 25(OH)D level was 15.8 ± 6.5 ng/ml at baseline and became 77.2 ± 30.5 ng/ml at 3 d (P < 0.001) and 62.4 ± 26.1 ng/ml at 30 d (P < 0.001). PTH levels concomitantly decreased from 53.0 ± 20.1 to 38.6 ± 17.2 pg/ml at 3 d and to 43.4 ± 14.0 pg/ml at 30 d (P < 0.001 for both). The trends were maintained in a subgroup followed up to 90 d (P < 0.001). Mean serum Ca and P significantly increased compared to baseline, whereas serum Mg decreased at 3 d. 1,25-Dihydroxyvitamin D significantly increased from 46.8 ± 18.9 to 97.8 ± 38.3 pg/ml at 3 d (P < 0.001) and to 59.5 ± 27.3 pg/ml at 60 d (P < 0.05). CONCLUSIONS: A single oral dose of 600,000 IU of cholecalciferol rapidly enhances 25(OH)D and reduces PTH in young people with vitamin D deficiency.

Cutaneous implantation metastasis of cholangiocarcinoma after percutaneous transhepatic biliary drainage.

Percutaneous transhepatic biliary decompression is a preoperative surgical adjunct in patients with obstructive jaundice that has been in use since 1973. It is recommended that this procedure be adopted for both palliative treatment in unresectable patients and as a preoperative means of lowering serum bilirubin in patients with potentially resectable malignancies of the pancreas or biliary tract. Metastatic tumor seeding along the transhepatic biliary catheter is an unusual complication resulting from this procedure but there have been a few cases reported in the literature. Below is a report on a 59-year-old woman in whom the percutaneous transhepatic catheter drainage of the biliary tree, performed before surgical resection of a cholangiocarcinoma, caused cutaneous tumor implantation at the catheter site 3 months later. The clinical aspect was morphea-like and histopathologic examination revealed typical features of a dermal metastasis of adenocarcinoma. Immunohistochemistry revealed cytoplasmic positivity for cytokeratin 7-19, specific for the biliary tract epithelium. A review of the literature available led us to conclude that port-site metastasis in patients with obstructive jaundice treated with percutaneous transhepatic biliary decompression was an unusual but possible complication. In fact, many catheter-tract metastatic deposits in the liver parenchyma, detected at autopsy or on operation, are mistakenly identified as hematogenous or lymphatic metastasis and are not attributed to a catheter-related process. We also report on this case because of the atypical morphea-like aspect of the skin metastasis.

Complete remission of brain metastases in three patients with stage IV melanoma treated with BOLD and G-CSF.

BACKGROUND: Brain metastases are the most life-threatening among the secondary localizations of melanoma for their unresponsiveness to the surgical, radiotherapeutic and/or chemotherapeutic treatments. METHODS: Accidentally, we observed a complete response (CR) in a patient undergoing chemotherapy with bleomycin, vincristine or Oncovin, CCNU or lomustine, dacarbazine (BOLD) regimen for metastatic melanoma including brain metastases, who was also treated with G-CSF to manage a concomitant leukopenia. After this observation, seven more patients with stage IV melanoma with brain metastases were treated with BOLD regimen repeated every 6 weeks with administration of G-CSF in the intervals. RESULTS: Three patients presented CR (37.5%). Two patients stopped the treatment after two courses for evident progressive disease (25%). The other three patients showed stable disease (SD: 37.5%). Median duration of SD was 24 weeks. Among the eight patients, six (75%) achieved clinical benefit. Median time to progression was 8.5 months (range 0-74+ months). Median survival was 12.5 months (range 4-74+ months). Two patients are still alive and disease-free after 74 and 57 months, respectively. CONCLUSION: We believe that the brilliant CR, the long duration of the disease-free intervals and the long survival in at least three of eight patients should encourage further research on BOLD with G-CSF for the treatment of advanced melanoma.