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.

Detection of Merkel cell polyomavirus in Merkel cell carcinomas and small cell carcinomas by PCR and immunohistochemistry.

Recently, the clonal integration of a new human polyomavirus (Merkel cell polyomavirus or MCPyV) has been reported in Merkel cell carcinoma (MCC). In order to investigate the presence of MCPyV in small cell carcinomas (SCCs) and small round cell tumors (SRCTs), we collected formalin-fixed paraffin-embedded tissue specimens including 14 MCCs, 24 SCCs, 7 Ewing sarcoma/primitive neuroectodermal tumors (ES/PNETs) and 5 neuroblastomas. We also collected specimens of other cancers including 12 malignant melanomas, 10 breast, 10 ovarian and 20 gastric cancers. We used 3 primer sets for which the sequences were previously published (LT1, LT3, and VP1) and 3 newly designed primer sets (LT1-1, LT1-1a, and LT3a). Quantitative real-time PCR was also performed with the LTq primer set. Nested PCR using the LT3a primer set detected more cases of MCPyV infection in MCC. In total, 12 of 14 (85.7%) MCC cases were positive for MCPyV by PCR, which was consistent with published data. Some SCC specimens were also positive for MCPyV (37.5%) by PCR. PCR products from MCC and SCC cases showed premature truncation and frameshift mutation. Furthermore, one case of ES/PNET and one gastric carcinoma showed MCPyV DNA. However, MCPyV DNA and transcript were only detected in MCCs with quantitative real-time PCR analysis. In addition, 11 of 13 (84.6%) MCC cases and 6 of 23 (26.1%) SCC cases showed immunoreactivity with monoclonal antibodies against MCPyV large T-antigen. Considering both PCR and IHC results, MCPyV was detected in all MCCs tested. The presence of MCPyV in all MCC cases tested and in some SCC cases suggests that MCPyV may be involved in the malignant transformation.

Expression of RUNX3 in skin cancers.

BACKGROUND: Expression of Runt-related transcription factor 3 (RUNX3) is reduced in a large number of cancers. However, a few studies have reported higher expression of RUNX3 in several cancers, including basal cell carcinoma (BCC). In light of this, we explored the expression of RUNX3 in skin cancers generally, to determine whether it acts as an oncogene or a tumour-suppressor gene in skin tumours. AIM: To investigate the expression of RUNX3 in normal skin and malignant skin tumours. METHODS: RUNX3 expression was evaluated by western blotting in 24 specimens, comprising 6 malignant melanoma (MM), 6 squamous cell carcinoma (SCC), 6 BCC and 6 normal skin specimens. Immunohistochemical staining was carried out to analyse RUNX3 expression in 16 MM, 16 SCC and 16 BCC specimens. To identify where the protein was expressed, the cytoplasmic and nuclear protein expression of RUNX3 in skin cancer tissues was determined. A cell-proliferation study was performed on an MM line (G361) by small interfering (si)RNA transfection. RESULTS: The western blotting experiments showed that RUNX3 was not expressed in normal skin tissues, but it was overexpressed in all MM and SCC samples, and in five of the six BCC samples. Using immunochemistry, RUNX3 was found to be overexpressed in all cancer tissues analysed. Subcellular fraction analysis revealed that RUNX3 was expressed in the nuclei but not the cytoplasm of all the skin cancer tissues analysed, and RUNX3 silencing by siRNA in G361 cells resulted in a decrease in proliferation. CONCLUSIONS: Based on these results, we suggest that RUNX3 has an oncogenic potential and does not act as a tumour suppressor in skin cancers.

Localization of cytoskeletal proteins in Pneumocystis carinii by immuno-electron microscopy.

Pneumocystis carinii causes serious pulmonary infection in immunosuppressed patients. This study was undertaken to observe the cytoskeletal proteins of P. carinii by immuno-electron microscopy. P. carinii infection was experimentally induced by immunosuppression of Sprague-Dawley rats for seven weeks, and their lungs were used for the observations of this study. The gold particles localized actin, tropomyosin, and tubulin. The actin was irregularly scattered in the cytoplasm of the trophic forms but was much more concentrated in the inner space of the cell wall of the cystic forms called the inner electron-lucent layer. No significant amount of tropomyosin was observed in either trophic forms or cystic forms. The tubulin was distributed along the peripheral cytoplasm and filopodia of both the trophic and cystic forms rather than in the inner side of the cytoplasm. Particularly, in the cystic forms, the amount of tubulin was increased and located mainly in the inner electron-lucent layer of the cell wall where the actin was concentrated as well. The results of this study showed that the cell wall of P. carinii cystic forms is a structure whose inner side is rich in actin and tubulin. The location of the actin and tubulin in P. carinii suggests that the main role of these proteins is an involvement in the protection of cystic forms from the outside environment by maintaining rigidity of the cystic forms.