A Case of Bullous Dermatitis Induced by Erlotinib

Herein, we report a case of bullous dermatitis that occurred in a 61‐year‐old woman 5 days after beginning therapy with erlotinib for the treatment of stage IV pulmonary adenocarcinoma with metastases at the hypophyseal level. Skin reactions are the most common adverse drug reactions (ADRs) associated with epidermal growth factor receptor tyrosine kinase (EGFR‐TK) inhibitors, and acneiform rash is the most frequently reported ADR in patients treated with erlotinib. To our knowledge, this is the first case of bullous dermatitis induced by erlotinib. This report highlights the need for additional research in the field of skin toxicity of EGFR‐TK inhibitors.     

Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development

Seven classes of mitogen-activated protein kinase (MAPK) intracellular signalling cascades exist, four of which are implicated in breast disease and function in mammary epithelial cells. These are the extracellular regulated kinase (ERK)1/2 pathway, the ERK5 pathway, the p38 pathway and the c-Jun N-terminal kinase (JNK) pathway. In some forms of human breast cancer and in many experimental models of breast cancer progression, signalling through the ERK1/2 pathway, in particular, has been implicated as being important. We review the influence of ERK1/2 activity on the organised three-dimensional association of mammary epithelial cells, and in models of breast cancer cell invasion. We assess the importance of epidermal growth factor receptor family signalling through ERK1/2 in models of breast cancer progression and the influence of ERK1/2 on its substrate, the oestrogen receptor, in this context. In parallel, we consider the importance of these MAPK-centred signalling cascades during the cycle of mammary gland development. Although less extensively studied, we highlight the instances of signalling through the p38, JNK and ERK5 pathways involved in breast cancer progression and mammary gland development.     

Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure

Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.     

Medial Displacement Calcaneal Osteotomy for Unilateral Adult Acquired Flatfoot: Effects of Minimally Invasive Surgery on Pain,Alignment, Functioning,and Quality of Life

We aimed to assess the effects of medial displacement calcaneal osteotomy (MDCO) through a minimal skin incision in terms of pain, function, and alignment in patients with unilateral adult acquired flatfoot. American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scale and Numeric Pain Rating Scale (NPRS) were assessed as outcomes at the baseline (T0), at 6 months (T1), and at 1 year (T2) from surgery. We analyzed data of 20 patients (7 male and 13 female), mean aged 46.6 ± 5.34 years, showed significant differences after 6 months in terms of AOFAS total score (44.30 ± 7.39 vs 96.50 ± 4.89; p = .0001), AOFAS subitems (p < .001), and pain (NPRS: 7.95 ± 1.36 vs 1.05 ± 1.05; p = .0001). At 1 year after surgery (T2), all outcome measures still significantly differ from baseline (p < 01). Therefore, percutaneous MDCO through a minimal skin incision seemed to be safe and effective in the middle and long term in reducing pain and improving function and alignment in patients with unilateral adult acquired flatfoot.     

Preliminary Experience with a New Sclerosing Foam in the Treatment of Varicose Veins

BACKGROUND: Recently a new method of using a foam sclerosing agent for the treatment of leg veins has been described. We present a pilot study of a new technique for producing the sclerosing foam (Tessari's method) (SFT) and its use in sclerotherapy of major and minor varicosities. OBJECTIVE: A preliminary multicenter experience of sclerotherapy performed by means of this new kind of sclerosing foam made of purified sodium tetradecylsulfate is described. The authors evaluated the safety and efficacy of different doses and concentrations of the drug as well as different methods of preparing the foam in addition, the results of this technique were evaluated. METHODS: Over a 6-week period the three authors performed sclerotherapy or duplex-guided sclerotherapy using SFT, treating 77 patients. The SFT was formed using a three-way stopcock and two syringes, mixing air with liquid sodium tetradecylsulfate to create a foam. Each author used different concentrations (0.1-3%) and doses (2-8 ml) of SFT according to the size and number of the veins. Alternate methods of preparing the foam were examined as well. Seventy percent of the sclerotherapy sessions were performed on either the long or short saphenous veins, recurrent varices, or collaterals. Thirty percent of the treatments were for reticular varices and telangiectases. RESULTS: At 1-month follow-up, the vast majority of treated larger veins were either obliterated or showed a normal state of cephalad blood flow. Results for minor varicosities were good, but with related complications of hyperpigmentation and small areas of cutaneous necrosis. Two patients experienced transient scotomas and one patient developed segmental phlebitis of a collateral vein. The best foam was obtained by mixing one part liquid sodium tetradecylsulfate and four to five parts air, but the duration of the foam product was also related to several other factors. CONCLUSION: This preliminary pilot study demonstrates that the technique of producing sclerosing foam according to Tessari's method (three-way stopcock device) is very promising, especially for larger veins. No serious complications were reported, and further standardization of the method may improve the results and feasibility of this technique. Further studies are needed to validate this new technique.     

N- and K-Ras Oncogenes in Plasma Cell Dyscrasias

N- and K-ras oncogene mutations represent the most frequent molecular lesions in plasma cell dyscrasias. They are not randomly distributed since they are detectable in multiple myeloma (MM) (9-31%) and plasma cell leukemia (PCL) (30%), and not in monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma (SP). Codons 12, 13 and 61 of N- and K-ras genes have been found mutated. Mutations affecting codon 61 of N-ras gene are the most frequent finding. A heterogeneous pattern of mutations is described with a prevalence of purine-pyrimidine trans versions. Ras gene mutations have been predominantly detected in myelomas characterized by an advanced stage disease, and adverse prognostic parameters. These findings suggest that ras mutations represent a late molecular lesion and may be implicated in tumor progression rather than tumor initiation.     

Determination of platinum in plasma of patients affected by inoperable lung carcinoma treated with radiotherapy and concurrent low-dose continuous infusion ofcis-dichlorodiammine platinum(II)

Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion ofcis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m² daily for 100h/week for 5 weeks, and the infusions were separated by 68h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5-day continuous infusions at much higher daily doses. Never-theless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule.