Pathological validation and significance of micrometastasis in sentinel nodes in primary breast cancer

In embracing a multidisciplinary approach to the management of patients with sentinel node biopsy in breast cancer, the pathologist task is to screen sentinel nodes for possible metastasis. The consequences of missing sentinel node micrometastasis can directly influence treatment strategies, and this screening therefore has to be performed with more attention than usual. There is presently great diversity in the histopathological work-up of sentinel nodes, with many centres employing additional techniques such as immunohistochemistry, reverse transcription polymerase chain reaction or flow cytometry in addition to routine haematoxylin and eosin staining. In this review, we address the pathological validation and significance of micrometastasis in sentinel node biopsy in primary breast cancer

Incidence of unilateral arm lymphoedema after breast cancer : a systematic review and meta-analysis

Background The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. Methods We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between January 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings. Findings 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16·6% (95% CI 13·6–20·2). Our estimate was 21·4% (14·9–29·8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to <24 months; 18·9%, 14·2–24·7), was highest when assessed by more than one diagnostic method (nine studies; 28·2%, 11·8–53·5), and was about four times higher in women who had an axillary-lymph-node dissection (18 studies; 19·9%, 13·5–28·2) than it was in those who had sentinel-node biopsy (18 studies; 5·6%, 6·1–7·9). 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese. Interpretation Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder.

Immediate Breast Reconstructions in the Treatment of Breast Cancer

Breast cancer is the most common form of potentially fatal cancer in women in the Western world. Better understanding of the breast cancer disease process together with developments in treatments have led to improved survival and reduced risk of recurrence, significantly influencing the acceptance of breast reconstructions as part of breast cancer treatment. Skin-sparing mastectomy followed by immediate breast reconstruction has proved superior to other forms of breast reconstruction in terms of aesthetic outcome. However, due to the relatively recent introduction of skin-sparing mastectomy concerns on the surgical and oncological safety of the operation persist. The aim of the present study is to evaluate the surgical and oncological safety of skin-sparing mastectomy and immediate breast reconstruction in a consecutive patient series with ensuing follow-up. Subsequent aims of the study are to examine possibilities of reducing surgical complications of the operation and to assess the feasibility of sentinel node biopsy together with immediate breast reconstruction. The study population comprises a consecutive series of patients having undergone skin-sparing mastectomy followed by immediate breast reconstruction at the Helsinki University Central Hospital between 1992 and 2006. In Study I, the hospital records of 207 patients, operated between 1992 and 2001, were analyzed for surgical complications and recurrences of breast cancer during follow-up. In Study II, 60 consecutive patients were randomized into either conventional diathermy or radiofrequency coagulation groups to examine possibilities of reducing skin-flap complications. Study III consists of 62 consecutive breast cancer patients evaluated for the feasibility of sentinel node biopsy simultaneously with immediate breast reconstruction. In Study IV, hospital records were analyzed to examine local recurrence of breast cancer in a consecutive series of 146 patients with Stage I or II disease. Post-operative complications in Study I included native skin-flap necrosis (10.1%), hematoma (10.1%), anastomose thrombosis (5.3%), infection (3.4%), hernia (2.6%) and loss of one microvascular flap (0.7%). The Stage I and II patients in Study IV had a local recurrence rate of 2.7%, an isolated regional lymph node recurrence rate of 2.1% and a systemic recurrence rate of 2.7%, during a mean follow-up time of 51 months. The Stage III patients in study I had a locoregional recurrence rate of 31.3% during follow-up. Radiofrequency coagulation in Study II did not decrease skin-flap complications when compared with conventional diathermy. An increased skin-flap complication rate in Study II was associated with smoking and the type of skin incision used. In Study III, eleven patients had tumor positive sentinel nodes, nine of which were detected intraoperatively. Skin-sparing mastectomy followed by immediate breast reconstruction is a safe procedure both surgically and oncologically, especially for early stage breast cancer. Tennis racket type incision is associated with an increased skin-flap complication rate. Sentinel node biopsy with intraoperative assessment of sentinel node metastases is feasible in patients undergoing immediate breast reconstruction.

Merkel cell carcinoma : Epidemiological study with special reference to polyomavirus and vascular factors in pathogenesis

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy that occurs predominantly on sun exposed skin areas. A new polyomavirus (MCPyV) was identified in MCC tumor tissues in 2008 suggesting that a viral infection might be an etiological factor. A typical MCC is a rapidly growing painless purple nodule. In its early stage it can be misjudged by its appearance as a cyst or abscess. Recurrences are common and approximately half of the patients will develop lymph node metastases and third of the patents will have distant metastases. It affects mostly elderly persons at an average age of 70 at the time of diagnosis. MCC was first described in 1972 and the first MCC patient in Finland was identified in 1983. MCC has been poorly recognized, but increased awareness and better diagnostic accuracy has increased the incidence since the early years. In this study, all cases with a notation of MCC during 1979 2008 were obtained from the Finnish Cancer Registry. Based on this data, the incidence is 0.11 for men and 0.12 for women. It is similar than that of other Nordic countries, but lower than in the USA. For clinical series, the files of patients diagnosed with MCC during 1983 2004 were reviewed, and the tissue samples were re-evaluated, if available (n=181). Third of the patients were men, and the most common site of the primary tumor was the head and neck (53%). The majority of the patients (86%) presented with a clinically node-negative (Stage I or II) disease, but the disease recurred in 38% of them. The treatment schemes were heterogeneous. No additional benefit from a wide margin (≥2 cm) was found compared to a margin of 0.1-1.9 cm, but intralesional excision was more often associated with local recurrence. None of the patients with Stage I-II disease who had received postoperative radiotherapy had local recurrence during the follow-up period. The 5-year relative survival ratio for Stage I disease was 68%, for Stage II 67%, for Stage III 16%, and for Stage IV 0%. The relative excess risk of death was significantly lower among women than among men. Some of these tissue samples were further analyzed for vascular invasion (n=126) by immunohistochemistry using vascular endothelial markers CD-31 and D2-40. Vascular invasion was seen in 93% of the samples and it was observed already in very small, <5mm tumors. The tissue samples were also analyzed for the presence of MCPyV by using a polymerase chain reaction (PCR) and quantitative PCR. MCPyV DNA was present in 80% of 114 samples studied. The patients with virus-positive tumors had better overall survival than patients with virus-negative tumors. Immunohistochemical analyses were performed for the expression of VEGFR-2 (n=21) and endostatin (n=19), but they had no prognostic value. Our results support the concept of treating MCC with margin-negative excision and radiotherapy to the tumor bed to reduce local recurrence. The finding of a high frequency of lymphovascular invasion reduces its value as a prognostic factor, but emphasizes the role of sentinel node biopsy even in very small primary MCC.

Impacto de dos técnicas quirúrgicas sobre la recaída local de carcinoma de mama en pacientes de una clínica de Bogotá D.C.

Introducción: El carcinoma de mama es el tumor maligno más frecuente entre las mujeres y representa una significativa mortalidad en los países en vías de desarrollo. Según datos del Instituto Nacional de Cancerología en el 2010 se reportaron 672 nuevos casos de cáncer de mama, lo que representó el 18% de todos los tumores malignos en mujeres. Durante las últimas 3 décadas las técnicas quirúrgicas para el tratamiento del cáncer de mama han presentado un cambio significativo y proponen disminución de procedimientos agresivos y radicales, intervenciones como: mastectomía radical modificada, cirugía conservadora y la disección de ganglio centinela son ejemplos claros de esta evolución asociado al incremento de la reconstrucción mamaria inmediata. Metodología: Estudio observacional tipo cohorte retrospectivo en el cual se revisó una base de datos de pacientes con cáncer de mama de las cuales 632 fueron sometidas a mastectomía radical con preservación de piel y complejo areola-pezón y mastectomía radical con preservación de piel sin preservación del complejo areola-pezón, los dos procedimientos asociados a reconstrucción mamaria inmediata y se comparó la frecuencia de recaída local entre los dos grupos. Resultados: De las 632 pacientes estudiadas al 30.5% se les realizo preservación del complejo areola pezón. Las mujeres a quienes se les realizó preservación del complejo areola pezón presentaron menor sobrevida a la recaída local a 10 años (80.51%) comparado con las mujeres a quienes no se les preservó el complejo areola pezón (87.40%), sin embargo no se encontró diferencia estadísticamente significativa para determinar que las probabilidades de sobrevida sean diferentes. Discusión: No se evidenció diferencia estadísticamente significativa entre los 2 procedimientos quirúrgicos (con y sin preservación del complejo areola pezón) en relación a la recaída local, estudios retrospectivos no han evidenciado una mayor tasa de recaídas locales en pacientes a quienes se les preserva el complejo areola-pezón, sin embargo hacen falta estudios prospectivos y aleatorizados que puedan otorgar un mayor sustento científico que garantice la seguridad de la preservación del complejo areola-pezón.

Impacto de dos técnicas quirúrgicas sobre la recaída local de carcinoma de mama en pacientes de una clínica de Bogotá D.C.

Introducción: El carcinoma de mama es el tumor maligno más frecuente entre las mujeres y representa una significativa mortalidad en los países en vías de desarrollo. Según datos del Instituto Nacional de Cancerología en el 2010 se reportaron 672 nuevos casos de cáncer de mama, lo que representó el 18% de todos los tumores malignos en mujeres. Durante las últimas 3 décadas las técnicas quirúrgicas para el tratamiento del cáncer de mama han presentado un cambio significativo y proponen disminución de procedimientos agresivos y radicales, intervenciones como: mastectomía radical modificada, cirugía conservadora y la disección de ganglio centinela son ejemplos claros de esta evolución asociado al incremento de la reconstrucción mamaria inmediata. Metodología: Estudio observacional tipo cohorte retrospectivo en el cual se revisó una base de datos de pacientes con cáncer de mama de las cuales 632 fueron sometidas a mastectomía radical con preservación de piel y complejo areola- pezón y mastectomía radical con preservación de piel sin preservación del complejo areola-pezón, los dos procedimientos asociados a reconstrucción mamaria inmediata y se comparó la frecuencia de recaída local entre los dos grupos. Resultados: De las 632 pacientes estudiadas al 30.5% se les realizo preservación del complejo areola pezón. Las mujeres a quienes se les realizó preservación del complejo areola pezón presentaron menor sobrevida a la recaída local a 10 años (80.51%) comparado con las mujeres a quienes no se les preservó el complejo areola pezón (87.40%), sin embargo no se encontró diferencia estadísticamente significativa para determinar que las probabilidades de sobrevida sean diferentes. Discusión: No se evidenció diferencia estadísticamente significativa entre los 2 procedimientos quirúrgicos (con y sin preservación del complejo areola pezón) en relación a la recaída local, estudios retrospectivos no han evidenciado una mayor tasa de recaídas locales en pacientes a quienes se les preserva el complejo areola-pezón, sin embargo hacen falta estudios prospectivos y aleatorizados que puedan otorgar un mayor sustento científico que garantice la seguridad de la preservación del complejo areola-pezón.

Linfadenectomia laparoscópica em cadela com neoplasia mamária

A linfadenectomia laparoscópica é realizada de forma rotineira na medicina, contudo é pouco utilizada na veterinária. Neste relato, um canino fêmea apresentando tumores na cadeia mamária esquerda (M4 e M5), foi submetido à aplicação intradérmica do azul de metileno estéril, ao redor do maior tumor (M5), buscando-se demarcação dos vasos linfáticos e linfonodos regionais. Após 15 minutos, iniciou-se a linfadenectomia abdominal videolaparoscópica na região inguinal esquerda, seguida da ovário-histerectomia (OVH) lapararoscópica com três portais. Realizou-se ainda mastectomia total unilateral esquerda. Pela histologia, obtiveram-se dois linfonodos abdominais livres de células tumorais. A paciente não apresentou recidiva em 60 dias.

A biópsia de linfonodo sentinela não deve ser recomendada para pacientes portadores de melanoma espesso

Objective: To ascertain whether there is any relationship between the state of the sentinel lymph node histopathology, recurrence and mortality from thick melanoma in patients undergoing SLNB over a long follow-up. Methods: Eighty-six patients with thick melanoma undergoing SLNB were selected from a prospective database. Lymphoscintigraphy, lymphatic mapping and intraoperative gamma probe detection were performed in all patients. The sentinel lymph node (SLN) was analyzed by HE and immunohistochemistry. Complete lymphadenectomy was indicated for patients with positive sentinel node. The histopathological SLN status was related to the rate of recurrence and mortality from melanoma. Results: One hundred and sixty-six SLNs were taken from the 86 patients. Ages ranged from 18 to 73 years. There were 47 women and 39 men. Micrometastases were found in 44 patients. Forty-two patients underwent complete lymphadenectomy. Seven other patients had positive lymph node. Among the 44 patients with positive sentinel node, there were 20 recurrences and 15 deaths. There were 18 recurrences and 12 deaths in the group with negative SLN. The Breslow thickness was not correlated with the histopathological SLN status. The histopathological SLN status did not affect the rates of recurrence and mortality (Fisher test, p = 1.00). The median follow-up was 69 months. Conclusion: Considering the lack of evidence of benefit, SLNB should not be indicated for patients with thick melanoma outside of clinical studies.

Detecção do lindonodo sentinela com 99m Tc-Fitato em pacientes com carcinoma invasor do colo uterino

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Analysis by MRI of Residual Tumor After Radiofrequency Ablation for Early Stage Breast Cancer

OBJECTIVE. The objective of our study was to evaluate the effectiveness of MRI in the detection of possible residual lesions after radiofrequency ablation (RFA) in the treatment of breast cancer. SUBJECTS AND METHODS. We prospectively evaluated 14 patients who had undergone ultrasound-guided core biopsies diagnostic of invasive ductal carcinoma (IDC; range of diameters, 1.0-3.0 cm) and then ultrasound-guided percutaneous RFA with sentinel node biopsy as the primary treatment. Breast MRI was performed 1 week before RFA to evaluate tumor extension and again 3 weeks after RFA to verify the presence of possible residual lesions. Conventional surgical resection of the tumors was performed 1 week after RFA. The MRI findings were compared with histopathologic analyses to confirm the presence or absence of residual tumor. RESULTS. There was no residual enhancement in seven lesions on the postablation breast MRI scans. These findings were confirmed by negative histopathologic findings in the surgical specimens. The MRI scans of five patients showed small areas of irregular enhancement that corresponded to residual lesions. In the two remaining patients, we observed enhancement of almost the entire lesion, indicating that RFA had failed. CONCLUSION. Breast MRI is effective in detecting residual lesions after RFA in patients with IDC.

Monte Carlo simulation of light transport in tissue for optimizing light delivery in photoacoustic imaging of the sentinel lymph node

Noninvasive or minimally invasive identification of sentinel lymph node (SLN) is essential to reduce the surgical effects of SLN biopsy. Photoacoustic (PA) imaging of SLN in animal models has shown its promise for clinical use in the future. Here, we present a Monte Carlo simulation for light transport in the SLN for various light delivery configurations with a clinical ultrasound probe. Our simulation assumes a realistic tissue layer model and also can handle the transmission/reflectance at SLN-tissue boundary due to the mismatch of refractive index. Various light incidence angles show that for deeply situated SLNs the maximum absorption of light in the SLN is for normal incidence. We also show that if a part of the diffused reflected photons is reflected back into the skin using a reflector, the absorption of light in the SLN can be increased significantly to enhance the PA signal. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)

Therapeutic implications of the sentinel lymph node in breast cancer

Immunohistochemistry of histologically negative axillary lymph nodes in breast-cancer patients resulted in upstaging of the sentinel lymph node in eight (14%) of 52 patients, The resulting information altered clinical management in six of these patients. Thus, this technique may affect clinical decision-making in breast-cancer patients.

Indocyanine green fluorescence-guided sentinel lymph node biopsy in dermato-oncology

Sentinel lymph node biopsy (SLNB) for cutaneous malignancies usually carried out with radioactive nanocolloids (Tc-99m). The SLNE is controversially discussed internationally. This is especially given to the high false-negative rate up to 44 %. An alternative could be the fluorescent dye indocyanine green (ICG).