Electrochemotherapy with cisplatin enhances local control after surgical ablation of fibrosarcoma in cats: an approach to improve the therapeutic index of highly toxic chemotherapy drugs.

BACKGROUND: Cancer is one of the most difficult current health challenges, being responsible for millions of deaths yearly. Systemic chemotherapy is the most common therapeutic approach, and the prevailing orientation calls for the administration of the maximum tolerated dose; however, considerable limitations exist including toxicities to healthy tissues and low achievable drug concentrations at tumor sites. Electrochemotherapy (ECT) is a tumor treatment that combines the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses. In this article we evaluate the capability of ECT to allow the use of cisplatin despite its high toxicity in a spontaneous feline model of soft tissue sarcoma. METHODS: A cohort of sixty-four cats with incompletely excised sarcomas were treated with cisplatin-based adjuvant ECT and monitored for side effects. Their response was compared to that of fourteen cats treated with surgery alone. RESULTS: The toxicities were minimal and mostly treated symptomatically. ECT resulted in increased local control (median not reached at the time of writing) with a mean time to recurrence of 666 days versus 180 of controls. CONCLUSIONS: We conclude that ECT is a safe and efficacious therapy for solid tumors; its use may be considered as part of strategies for the reintroduction of drugs with a narrow therapeutic index in the clinical protocols.

Definition of an automated Content-Based Image Retrieval (CBIR) system for the comparison of dermoscopic images of pigmented skin lesions.

BACKGROUND: New generations of image-based diagnostic machines are based on digital technologies for data acquisition; consequently, the diffusion of digital archiving systems for diagnostic exams preservation and cataloguing is rapidly increasing. To overcome the limits of current state of art text-based access methods, we have developed a novel content-based search engine for dermoscopic images to support clinical decision making. METHODS: To this end, we have enrolled, from 2004 to 2008, 3415 caucasian patients and collected 24804 dermoscopic images corresponding to 20491 pigmented lesions with known pathology. The images were acquired with a well defined dermoscopy system and stored to disk in 24-bit per pixel TIFF format using interactive software developed in C++, in order to create a digital archive. RESULTS: The analysis system of the images consists in the extraction of the low-level representative features which permits the retrieval of similar images in terms of colour and texture from the archive, by using a hierarchical multi-scale computation of the Bhattacharyya distance of all the database images representation with respect to the representation of user submitted (query). CONCLUSION: The system is able to locate, retrieve and display dermoscopic images similar in appearance to one that is given as a query, using a set of primitive features not related to any specific diagnostic method able to visually characterize the image. Similar search engine could find possible usage in all sectors of diagnostic imaging, or digital signals, which could be supported by the information available in medical archives.

Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

Spontaneous intestinal melanoma in dogs.

Primary melanoma of the gastrointestinal tract is a rare, highly malignant neoplasm that is associated with an unfavorable long-term prognosis. Animal studies are needed to further characterize this tumor and to develop new and more effective protocols. A spontaneous canine intestinal melanoma is described which, because of its local aggressive behavior and advanced stage, was not treatable with conventional strategies, thus being a potential candidate for investigational trials.

Cutaneus pseudolymphoma: a case report.

The authors report on a case of pseudolymphoma cutis in a 48-year-old man. The clinical and histopathological characteristics of this benign skin disorder, especially regarding the differential diagnosis with cutaneous B or T cell lymphomas, are reviewed. Finally, the use of hydroxychloroquine sulfate is suggested for the therapy of pseudolymphoma cutis, especially when the causal factor is unknown.

Skin phototype and local trauma in the onset of balanitis xerotica obliterans (BXO) in circumcised patients.

The association between balanitis xerotica obliterans (BXO) and skin disorders is long established, however, the role of skin phototype and local trauma in its onset has never been investigated in detail. Medical records of all Caucasian children circumcised over a 6-year period were reviewed. The excised skin underwent histological examination for BXO. Children with histological diagnosis of BXO were classified as group A, whereas children without histological diagnosis of BXO were classified as group B. The Fitzpatrick phototype (FT) was obtained in all children performing a personal or family interview with regards to their sunburn and suntan experience. According to their FT, both group A and B patients were divided into two subgroups: FT 1-2, with a higher tendency to sunburn due to their low skin melanin content; and FT 3-4 with a higher tendency to tan due to their higher skin melanin content. Maneuvers of mechanical reduction of the foreskin (MRF) performed at least 5-10 times per month during the year preceding circumcision was also considered. Statistical analysis was performed using univariate and multivariate analysis. A total of 297 patients met the inclusion criteria of our study: 78 patients were classified as group A and 219 as group B. The risk of developing BXO was significantly greater in FT 1-2 patients (n=76) (odd ratio=0.232, 95% confidence interval=0.124-0.435, p<0.0001). Furthermore, those undergoing MRF (n=131) had a significantly higher risk of developing BXO (odds ratio= 5.344, 95% confidence interval=2.860-9.987, p<0.0001). Although the foreskin is not directly exposed to sunlight, this study emphasizes the role of skin phototype on the onset of BXO in circumcised individuals. Moreover, the data produced suggest should the advantages of repeated MRF be weighed against the increased risk of developing BXO, which in turn may increase complication rate of circumcision surgery.

Automated dermoscopy image analysis of pigmented skin lesions.

Dermoscopy (dermatoscopy, epiluminescence microscopy) is a non-invasive diagnostic technique for the in vivo observation of pigmented skin lesions (PSLs), allowing a better visualization of surface and subsurface structures (from the epidermis to the papillary dermis). This diagnostic tool permits the recognition of morphologic structures not visible by the naked eye, thus opening a new dimension in the analysis of the clinical morphologic features of PSLs. In order to reduce the learning-curve of non-expert clinicians and to mitigate problems inherent in the reliability and reproducibility of the diagnostic criteria used in pattern analysis, several indicative methods based on diagnostic algorithms have been introduced in the last few years. Recently, numerous systems designed to provide computer-aided analysis of digital images obtained by dermoscopy have been reported in the literature. The goal of this article is to review these systems, focusing on the most recent approaches based on content-based image retrieval systems (CBIR).

Malignant melanoma associated with a blue naevus: a case report.

INTRODUCTION: Combined malignant naevi are characterised pathologically by the association of a melanoma with one or more different types of benign melanocytic naevi in a single lesion. CASE PRESENTATION: We show here a case of malignant combined naevus made up of a blue naevus and a melanoma, presenting as a slowly progressing and asymptomatic pigmented lesion on the trunk of a 35-year-old man. Dermoscopic examination was not conclusive for a malignant lesion, showing only an atypical brown pigment network. The definitive diagnosis was reached only at the hystopathological examination. CONCLUSION: This finding suggests that combined naevi should be always excised and histologically examined to achieve a correct diagnosis and avoid risk of misclassification.

Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistance.

Apoptosis protease-activating factor-1 (Apaf-1) is a key regulator of the mitochondrial apoptotic pathway, being the central element of the multimeric apoptosome formed by procaspase 9, cytochrome c, and Apaf-1 itself. In this review, the principal aspects about Apaf-1 gene structure and function, and its role in the apoptotic machinery, are described. Moreover, the most recent findings about the involvement of this molecule in melanoma progression and chemoresistance, as well as the clinico-pathological relevance of these findings in the treatment of this deadly disease, are reported.

Analysis of APAF-1 expression in human cutaneous melanoma progression.

APAF-1 plays a pivotal role in mitochondria-dependent apoptosis, binding to cytochrome c and favoring activation of caspase-9. It has been shown that epigenetic silencing of the APAF-1 gene is a common event in several metastatic melanoma cells in vitro. We determined, by Western blot, variation in the level of expression of APAF-1 in several human melanoma cell lines and, by immunohistochemistry, in a group of 106 histological samples including benign and malignant melanocytic lesions. We observed APAF-1 down-regulation or loss of expression in two metastatic melanoma cell lines, compared to primary melanoma cell lines. The immunohistochemical analysis revealed a significant difference in APAF-1 staining between nevi and melanomas. In addition, we found a significant negative correlation between APAF-1 expression level and tumor thickness and between primary melanomas and metastases. We conclude that loss of APAF-1 expression can be considered as an indicator of malignant transformation in melanoma.