Influence of complications following total mastectomy and immediate reconstruction on breast cancer recurrence.

BACKGROUND: Immediate breast reconstruction is safe from an oncological perspective, but the relatively high rate of postoperative complications raises oncological concerns. The present study aimed to evaluate the potential influence of postoperative complications after immediate breast reconstruction on breast cancer recurrence and survival. METHODS: Patients with breast cancer who had total mastectomy and immediate reconstruction between 2008 and 2013 were followed for at least 5 years. The impact of postoperative complications on oncological outcomes was assessed using multivariable Cox regression analyses. RESULTS: In total, 438 patients with a median follow-up of 82 months were analysed. Five-year local recurrence-free, disease-free and overall survival rates were 95·4, 93·1 and 98·4 per cent respectively. Postoperative complications developed in the operated breast in 120 patients (27·4 per cent) and at other sites (flap donor) in 30 patients (6·8 per cent). Development of breast complications was associated with significantly increased rate of recurrence compared with no complications (16·7 versus 5·9 per cent; P = 0·002). In multivariable analysis, patients with breast complications had significantly worse disease-free survival than those with no complications (hazard ratio (HR) 2·25; P = 0·015). This remained significant in patients who received adjuvant therapy without delay (8 weeks or less after surgery) (HR 2·45; P = 0·034). CONCLUSION: Development of postoperative complications in the breast can have a negative impact on survival and recurrence after immediate reconstruction.

ANTECEDENTES: La reconstrucción mamaria inmediata es una técnica segura desde el punto de vista oncológico, pero con una tasa relativamente alta de complicaciones postoperatorias, lo que preocupa por si puede afectar a los resultados. Este estudio tuvo como objetivo evaluar la influencia potencial de las complicaciones postoperatorias tras la reconstrucción mamaria inmediata en la recidiva y la supervivencia del cáncer de mama. MÉTODOS: Se hizo un seguimiento de al menos 5 años de las pacientes a las que se realizó una mastectomía total por cáncer de mama y una reconstrucción mamaria inmediata entre 2008 y 2013. Se evaluó el impacto de las complicaciones postoperatorias en los resultados oncológicos mediante un análisis multivariables de regresión de Cox. RESULTADOS: Se analizaron 438 pacientes con una mediana de seguimiento de 82 meses. La supervivencia libre de recidiva local a 5 años, la supervivencia libre de enfermedad y la supervivencia global fueron del 95,4%, 93,1% y 98,4%, respectivamente. Hubo complicaciones postoperatorias en la mama en 120 (31,8%) pacientes y en otros lugares (zona donante de colgajo) en 30 (6,8%). La presentación de complicaciones mamarias se asoció con una tasa de recidiva significativamente mayor en comparación con el grupo de pacientes sin complicaciones (16,7% versus 5,9%, P < 0,01). En el análisis multivariable, las pacientes con complicaciones mamarias mostraron una supervivencia libre de enfermedad significativamente menor que aquellas que no padecieron complicaciones (cociente de riesgos instantáneos, hazard ratio, HR 2,25; P = 0,02). También fue significativo el porcentaje de pacientes que recibieron tratamiento adyuvantes sin demora (≤ 8 semanas después de la operación) (HR 2,45; P = 0,03). CONCLUSIÓN: El desarrollo de complicaciones postoperatorias en la mama puede impactar negativamente en la supervivencia y en la recidiva después de la reconstrucción inmediata.

Method of breast reconstruction and the development of lymphoedema.

BACKGROUND: Several studies have demonstrated an association between immediate autologous or implant-based breast reconstruction and a reduced incidence of lymphoedema. However, few of these have ocused specifically on whether the reconstruction method affects the development of lymphoedema. The study evaluated the potential impact of breast reconstruction modality on the incidence of lymphoedema. METHODS: Outcomes of women with breast cancer who underwent mastectomy and immediate reconstruction using an autologous flap or a tissue expander/implant between 2008 and 2013 were reviewed. Arm or hand swelling with pertinent clinical signs of lymphoedema and excess volume compared with those of the contralateral side was diagnosed as lymphoedema. The cumulative incidence of lymphoedema was estimated by the Kaplan-Meier method. Clinicopathological factors associated with the development of lymphoedema were investigated by Cox regression analysis. RESULTS: A total of 429 reconstructions (214 autologous and 215 tissue expander/implant) were analysed; the mean follow-up of patients was 45·3 months. The two groups had similar characteristics, except that women in the autologous group were older, had a higher BMI, and more often had preoperative radiotherapy than women in the tissue expander/implant group. Overall, the 2-year cumulative incidence of lymphoedema was 6·8 per cent (autologous 4·2 per cent, tissue expander/implant 9·3 per cent). Multivariable analysis demonstrated that autologous reconstruction was associated with a significantly reduced risk of lymphoedema compared with that for tissue expander/implant reconstruction. Axillary dissection, a greater number of dissected lymph nodes and postoperative chemotherapy were also independent risk factors for lymphoedema. CONCLUSION: The method of breast reconstruction may affect subsequent development of lymphoedema.

Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines.

Cell migration and angiogenesis are key steps in tumor metastasis. However, the mechanism of migration regulated by vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is not completely understood. This study examined the relationship between VEGF and migration, along with the mechanism involved in the VEGF-regulated migration of human gastric cancer cells. The level of cell migration was increased by recombinant human (rh)VEGF-165 in the VEGF receptor-2-expressing SNU-601 cells. Interleukin (IL)-18 is associated with the malignant progression of tumors. Accordingly, this study examined the effect of IL-18 on the migration of cancer cells in order to identify the factors involved in VEGF-enhanced migration. Inhibiting IL-18 markedly reduced the level of VEGF-enhanced migration, and IL-18 increased cell migration directly through filamentous-actin polymerization and tensin downregulation. It was confirmed that rhVEGF-165 increased IL-18 production significantly. An antioxidant and an extracellular signal-regulated kinase (ERK)1/2-specific inhibitor blocked rhVEGF-165-enhanced IL-18 production. Accordingly, rhVEGF-165 increased the generation of region of interest (ROI) and activated the ERK1/2 pathway. These results suggest that rhVEGF-165 enhances IL-18 production via the generation of ROI and ERK1/2 phosphorylation, which results in the increased migration of gastric cancer cells.

Cryopreserved human adipogenic-differentiated pre-adipocytes: a potential new source for adipose tissue regeneration.

BACKGROUND: Previously, we have shown that in vitro adipogenic differentiation of pre-adipocytes before implantation can enhance in vivo adipose tissue formation. For large-scale adipose tissue engineering or repeat procedures, cryopreservation of fat grafts has been commonly used in recent years. However, the feasibility of cryopreservation of adipogenic differentiated pre-adipocytes has not been investigated. METHODS: To examine the impact of cryopreservation on the adipogenic functions of adipogenic-differentiated pre-adipocytes, freeze-thawed adipocytes were compared with fresh differentiated adipocytes in vitro and in vivo. Adipogenic function was assessed by Oil red O staining, ELISA analysis of leptin secretion and RT-PCR of adipogenic-related genes. After transplantation, adipose tissue formation was assessed by histomorphologic and volumetric analysis. RESULTS: Freeze-thawed adipocytes constantly showed typical adipogenic functions in terms of lipid content, leptin secretion and adipogenic gene expression, as well as good viability. Importantly, implants derived from freeze-thawed adipocytes were successfully developed to adipose tissue and newly formed adipose tissues were similar to those developed from fresh differentiated adipocytes, based on histomorphologic and volumetric analysis. In addition, CD34-positive endothelial cells were detected in implants. These results demonstrate that the specific characters of adipogenic-differentiated pre-adipocytes are successfully conserved after cryopreservation without any significant alteration. DISCUSSION: Cryopreservation of adipogenic-differentiated pre-adipocytes is a feasible method and extends their clinical use in adipose tissue-engineering applications and transplantation.

The elevation of the constructed auricle with a temporoparietal fascial flap wrapping a resorbable plate.

During the second stage reconstruction of the auricle in patients with microtia, we modified Nagata's method and two technical improvements were possible. After the implanted auricle was separated from the bed, we harvested the temporoparietal fascial flap through helical rim incision instead of incising the temporal scalp. So the surgical scar over the temporal region was avoided. Thereafter, a costal cartilage wedge was carved and grafted to the posterior aspect of the conchal region to get a firm projection. But in cases of unavailable costal cartilage wedge graft, we used a resorbable plate composed of polylactic and polyglycolic acid as a substitute for the former so that we could create firm elevation and sufficient ear projection. Between June 2002 and May 2004, 28 patients underwent this operation with the temporoparietal fascial flap and resorbable plating system. There was no complication resulting from our technique. It was possible to create firm elevation and good frontal projection even if there was no available cartilage wedge. Additionally, by harvesting the temporoparietal fascia through helical rim incision, we avoid creating additional scars on the scalp.