Hidradenitis suppurativa is a chronic and recurrent inflammatory disease of the apocrine glands characterized by recurrent abscesses, draining sinus tracts, and scarring that can be located in the groin, axilla, perineal, and perianal areas and less frequently in the scalp area. The chronic and relapsing nature of hidradenitis suppurativa leads to physical and psychological damage because it frequently causes disabling pain, diminished range of motion, and social isolation. Surgical removal of all apocrine glands in the affected region is the definitive treatment because conservative treatment usually does not prevent recurrence of hidradenitis suppurativa. The resultant defect can be either left to heal secondarily or closed primarily. Secondary healing in the axilla may cause contractures and stiffening of the shoulder. Primary healing requires direct closure, split-skin grafting, or locoregional flap transposition. The majority of the listed surgical procedures cause long hospital stays and leave contour defects in both the axilla and the arm. This report presents a series of 16 cases managed between March 2006 and June 2008. All the patients had endured a long period of medical treatment and subsequently required surgery for long-term relief of symptoms. The functional and aesthetic outcomes were very satisfactory in all cases despite the final scar. The initial reconstructive aims were achieved for these patients. The authors consider the thoracodorsal artery perforator flap a useful option for the surgical treatment of axillary hidradenitis suppurativa.

No abstract

ResumenLas pérdidas de sustancia en la pierna y fundamentalmente en su tercio inferior, siguen siendo un reto en Cirugía Reconstructiva puesto que los tejidos de vecindad, dañados por el traumatismo o por el edema concomitante, son inadecuados para cubrir hueso, tendones o material de osteosíntesis expuesto.El colgajo propeller o colgajo en hélice es un método elegante y versátil para la cubrir estas pérdidas de sustancia de la extremidad inferior con tejido locorregional no comprometido vascularmente por el traumatismo y/o lesión causante. A diferencia de los colgajos convencionales de rotación o transposición, es posible el cierre directo de la zona donante, lo que ofrece un resultado estético óptimo. Además, la presencia de perforantes más proximales permite usar pastillas musculares y tendinosas en el mismo colgajo para resolver defectos más complejos, convirtiéndose en algo más que una alternativa a los colgajos libres.Presentamos una serie de 43 pacientes para describir las posibilidades reconstructivas que ofrece el colgajo de perforante de arteria tibial posterior en su forma en hélice, en cuanto a la variabilidad del diseño y a su uso como colgajo compuesto, con el fin de minimizar aun más la morbilidad de la zona donante sin el uso de injertos. AbstractLower extremity defects, specially lower third defects, keep being a true challenge in Reconstructive Surgery, since nearness damaged tissues, due to the traumatism or to the concomitant edema, are not suitable for the coverage of bone, tendons or exposed osteosynthesis material.Propeller flap has become an elegant and mobile method for the coverage of this type of lower extremity defects. It provides us with locorregional tissue with not vascular involvement in the traumatism and/or subsequent injury. Unlike conventional rotation or transposition flaps, direct closure of the donor site is possible, offering an optimum aesthetic result. Moreover, the presence of more proximal perforators allows the use of muscular and tendinous cuffs in the same flap to solve more complex defects, becoming something more than a free flap alternative.We present a serie of 43 patients to describe the reconstructive possibilities of the tibialis posterior perforator flap in its propeller form, as for design variability and composed flap use, with the aim of minimizing donor site morbility even more without the use of grafts.

Breast cancer is a leading cause of cancer mortality in women due to the high frequency of metastatic disease, which, despite advances in therapeutic options, is still essentially incurable. The role of Myc in promoting tumorigenesis is beyond doubt, but there are contradictory reports in the literature on its role in the metastatic process. Using a Myc dominant negative termed Omomyc, we have demonstrated in various mouse models that Myc inhibition is a safe and effective therapeutic approach against several types of cancer, regardless of the tissue of origin or the driver oncogenic lesion. So far, Omomyc has only been tested in primary tumors. However, since many steps of the metastatic cascade have been reported to depend on Myc, we hypothesized that Omomyc could be extremely effective in both the prevention and treatment of metastasis too. Here we show that Omomyc expression has a dramatic effect on colony formation capacity in human breast cancer cell lines representative of all the molecular subtypes of the disease. In MDA-MB-231 cells, not only did it impair their proliferation but also migration, invasion and their capacity to induce angiogenesis, key aspects of the metastatic process. We demonstrate that, in vivo, Omomyc reduces the growth of orthotopically-implanted human breast cancer cells in immunocompromised mice, induces regression of established metastases after primary tumor resection and impairs the development of lung metastases after tail vein injection. In the immunocompetent MMTV-PyMT transgenic model, Omomyc expression dramatically delays the formation and growth of mammary fat pad tumors, thereby preventing the appearance of lung metastases. When the purified Omomyc mini-protein is administered exogenously, we observe remarkable growth inhibition in vitro that recapitulates transgenic expression of Omomyc. Intravenous administration of the mini-protein reduces lung colonization and tumor growth in vivo. We have demonstrated for the first time the applicability of Omomyc against metastasis, challenging the pre-established notion that Myc inhibition could potentiate, rather than inhibit, invasion. Finally, we have validated the use of the purified Omomyc mini-protein as the first directly-deliverable Omomyc-based drug for the treatment of metastatic breast cancer, providing a new therapeutic opportunity for patients suffering from this dreadful and incurable disease. Citation Format: Daniel Massó-Vallés, Marie-Eve Beaulieu, Toni Jauset, Erika Serrano, Sandra Martínez-Martín, Laia Foradada, Virginia Castillo, Francisco Castillo, Génesis Martín, Sílvia Casacuberta-Serra, Mariano F. Zacarias-Fluck, Antonio Luque-García, Marta Escorihuela, Jonathan R. Whitfield, Joaquín Arribas, Laura Soucek. Translating Myc inhibition to the clinic in metastatic breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1823.

Introduction and Hypothesis: Breast cancer is a leading cause of cancer mortality in women due to the high frequency of metastatic disease, which, despite advances in therapeutic options, is still essentially incurable. The role of Myc in promoting tumorigenesis is beyond doubt, but there are contradictory reports in the literature on its role in the metastatic process. Using a Myc dominant negative termed Omomyc, we have demonstrated in various mouse models that Myc inhibition is a safe and effective therapeutic approach against several types of cancer, regardless of the tissue of origin or the driver oncogenic lesion. So far, Omomyc has only been tested in primary tumors. However, since many steps of the metastatic cascade have been reported to depend on Myc, we hypothesized that Omomyc could be extremely effective in both the prevention and treatment of metastasis too. Methods: We induced transgenic expression of Omomyc in a panel of 11 breast cancer cell lines and analyzed its effect on clonogenic capacity, proliferation, cell cycle progression, angiogenesis, migration, and invasion. To characterize the effect of Omomyc expression in vivo, we performed prevention and intervention studies in several mouse models of metastatic breast cancer: an orthotopic human cell line-derived model with surgical resection, a human cell line-derived lung colonization model, and the MMTV-PyMT transgenic model. Omomyc expression was induced at different stages of the disease, and tumor burden and metastatic spread were compared between groups at different time points. In parallel to this systemic modeling of Myc inhibition by transgenic expression of Omomyc, we are also validating the therapeutic utility of Omomyc-derived peptides as a pharmacologic approach. To this aim, we assessed the cell-penetrating capacity of the peptides in MDA-MB-231 cells by confocal microscopy and flow cytometry. To enhance its activity and to target metastases in vivo, Omomyc was conjugated with a metastasis-targeting sequence, and its efficacy compared with the one exerted by Omomyc alone in vitro. We selected the fusion peptide for in vivo studies and treated the orthotopic and lung colonization mouse models by several routes of administration. Results: Here we show that Omomyc expression has a dramatic effect on colony formation capacity in human breast cancer cell lines representative of all the molecular subtypes of the disease. In MDA-MB-231 cells, not only did it impair their proliferation but also migration, invasion, and their capacity to induce angiogenesis, key aspects of the metastatic process. We demonstrate that, in vivo, Omomyc reduces the growth of orthotopically implanted human breast cancer cells in immunocompromised mice, induces regression of established metastases after primary tumor resection, and impairs the development of lung metastases after tail vein injection. In the immunocompetent MMTV-PyMT transgenic model, Omomyc expression dramatically delays the formation and growth of mammary fat pad tumors, thereby preventing the appearance of lung metastases. When the Omomyc peptide is administered exogenously, we observe remarkable growth inhibition that recapitulates transgenic expression of Omomyc. When conjugated with a metastasis-targeting sequence, its cell-penetrating capacity is increased and causes abundant cell death in vitro. In vivo, treatment with the fusion peptide reduces growth of mammary primary tumors and lung metastases. Conclusions: We have demonstrated for the first time the applicability of Omomyc against metastasis, challenging the pre-established notion that Myc inhibition could potentiate, rather than inhibit, invasion. Finally, we have validated a metastasis-targeting fusion peptide as the first directly deliverable Omomyc-based drug for the treatment of metastatic breast cancer, providing a new therapeutic opportunity for patients suffering from this dreadful and incurable disease. Citation Format: Daniel Massó-Vallés, Marie-Eve Beaulieu, Toni Jauset, Erika Serrano, Sandra Martínez-Martín, Laia Foradada, Virginia Castillo, Sílvia Casacuberta-Serra, Mariano F. Zacarias-Fluck, Génesis Martín, Antonio Luque-García, Marta Escorihuela, Jonathan R. Whitfield, Joaquín Arribas, Laura Soucek. Targeting Myc in metastatic breast cancer by Omomyc: From proof of principle to pharmacologic approach [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B16.