[Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes]. / La biopsia del ganglio centinela después de quimioterapia neoadyuvante en el cáncer de mama. Relación con los subtipos moleculares.

OBJECTIVE: To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). MATERIAL AND METHODS: A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. RESULTS: SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. CONCLUSIONS: Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC.

Intraoperative ultrasound in conservative surgery for non-palpable breast cancer after neoadjuvant chemotherapy.

AIMS: A complete clinical response after neoadjuvant chemotherapy (NACT) in breast cancer patients hinders the localization of the residual lesion and the removal of a minimum amount of breast tissue. The aim of the present work is to report our single-centre experience with intraoperative ultrasound-guided (IOUS) excision performed by surgeons in these patients. PATIENTS AND METHODS: From January 2008 to December 2012, IOUS excisions were performed on 58 patients with a previous intralesional ultrasound-detectable metallic marker and non-palpable breast cancer after NACT. The specimen margins were estimated by ultrasonography and macroscopic pathologic examination. Successful lesion removal, specimen weight, and analysis of the results as regards margins were evaluated, and the need for breast-conserving re-excision and mastectomy was considered. RESULTS: After NACT the average ultrasound/mammography and MRI diameters were 11.7 mm (0-30) and 9.1 mm (0-40) respectively. In all cases, the residual lesion or tissue around the marker was removed. The average weight of the specimens was 26.4 g (6-84), being lower in cases of complete response according to ultrasound (p < 0.05). In 4 patients (6.8%), breast-conserving re-excision was carried out, and in 3 patients (5.2%) a secondary mastectomy was performed, two of which had invasive lobular carcinoma. CONCLUSIONS: The emplacement of a readily echodetectable metal marker before NACT makes IOUS excision feasible in an increasing number of complete clinical responses, with the excision of small amounts of breast tissue and a high percentage of conservative breast surgery. This technique requires surgeons to be trained, but has the advantage of a reduced use of other hospital services, better planning of operating theatres, and less discomfort for patients, which means that it is attractive and indeed recommendable.

[Incidence of axillary recurrence after a negative sentinel lymph node result in early stages of breast cancer: a 5-year follow-up]. / Incidencia de recurrencia axilar tras un ganglio centinela negativo en cáncer de mama en estadios iniciales: seguimiento de 5 años.

UNLABELLED: The sentinel lymph node (SLN) biopsy is currently the procedure of choice for axillary node staging in initial stages of breast cancer. The purpose of this study is to establish our false negative rate within a 5-year follow-up period in 258 patients with breast cancer staged with this procedure. METHODS: A retrospective study on 258 consecutive T1-T2<3 cm pN0 staged breast carcinomas treated from January 1, 2001 to December 31, 2005 was performed. The combined technique of isotope plus blue dye was used for detection. The subjects underwent a minimum follow-up of 5 years, mean 81 months, with an end of follow-up at December 31, 2010. Evidence of axillary recurrence, tumor recurrence in the breast and signs of disease progression or death were the events collected and analyzed. RESULTS: Of the 258 patients, 3 false negatives (1.1%) with axillary recurrence were detected at 10, 11 and 29 months of the surgery. This did not have a significant repercussion in the survival analysis on the contrary to the existence of breast recurrence or the appearance of distant metastasis in 4.7% and 6.2% patients, respectively. Global survival related with the cancer was 93.0 (240/258) and disease free survival was 89.1% (230/258). CONCLUSION: The risk of developing axillary recurrence after a negative SLN without axillary node dissection is low enough to consider the SLN procedure to be the best approach for axilla staging in early breast cancer. This staging technique also makes it possible to achieve local disease control without diminishing the survival of the patients.

[Sentinel node biopsy in T2 breast cancers larger than 3 cm and clinically negative axilla compared with the T1-T2 <3 cm standard indication]. / La biopsia del ganglio centinela en cáncer de mama de más de 3 cm y axila clínicamente negativa frente a la indicación estándar T1-T2 < 3 cm.

OBJECTIVE: To present our experience in the application of sentinel node (SN) biopsy in patients with breast cancer T > 3 cm without clinical evidence of axillary metastasis. MATERIAL AND METHOD: Retrospective study of 393 cases in the period 2001--2006, divided into group (A) 47 patients with 3-5 cm T2N0 tumours and group (B) 346 patients T < 3 cm, N0. We employed the combined technique with 99mTc-colloidal rhenium sulphide and isosulfan blue dye. Preoperative lymphoscintigraphy was performed and the SN was located intraoperatively with a gamma ray detection probe and the blue dye. Axillary lymph node dissection was completed only when the SN was positive for metastasis in the histopathology analysis or not located. RESULTS: The SN detection rate for T2 > 3 cm was 94 % in the scintigraphy and 96 % with the probe, with no statistically significant differences between T < 3 cm (97 % and 98 %). In T2 > 3 cm, the final staging was 45 % pN0, 8 % pN1mi, 34 % pN1a, 11 % pN2a and 2 % pN3a. We found statistically significant differences (p < 0.05) when compared with palpable T < 3 cm and non-palpable cancer (62 % pN0 and 74 % pN0, respectively). In the follow-up of T2 > 3 cm (median 42.88 months) we did not find any axillary relapse which could be considered a false negative of the technique. CONCLUSION: The detection of sentinel lymph nodes is feasible and safe in tumours larger than 3cm with clinically negative axilla. Axillary lymph node dissection can be avoided in 45 % of these patients and therefore, we consider that they should be included as a general indication in breast cancer SN detection.

Staging the axilla with selective sentinel node biopsy in patients with previous excision of non-palpable and palpable breast cancer.

PURPOSE: To present our experience in the therapeutic approach of the sentinel node biopsy (SNB) in patients with previous excision of the breast cancer, divided in non-palpable and palpable lesions, in comparison with time treatment and stagement of breast cancer. METHODS: In the period 2001-2006, 138 patients with prior diagnostic excisional biopsy (96 non-palpable and 42 palpable breast cancer) and 328 without previous surgery (32 non-palpable; 296 palpable cancer) were treated. The combined technique ((99m)Tc-colloidal rhenium and isosulfan blue dye) was the approach for sentinel lymph node (SLN) detection. Axillary lymph node dissection (ALND) was completed only when the SLN was positive for metastasis or not located. RESULTS: Detection rate, if there was prior surgery, was 95% for non-palpable and 98% for palpable cancer, and 99% for one-time treatment group. Metastasis rate in the SLN was 15% in non-palpable cancer (14/91), significantly smaller than in palpable breast cancer (39% if prior surgery and 37% in one-time surgery). According to tumoral size, ALND metastasis rate was similar for T1 and T2 tumors (43-44%). In the follow-up of the groups with prior diagnostic biopsy or surgery of the breast cancer we have not found any false negative in the axilla. CONCLUSION: The detection of the SLN is also feasible in patients with previous surgery of breast cancer. Because SLN metastasis rates are significantly smaller in non-palpable lesions, the effort in screening programs for early detection of breast cancer and also in improving histopathological confirmation of malignancy with ultrasound or stereotactic guided core biopsies must continue.

Value of NT-proBNP determinations in the follow-up of heart transplantation.

BACKGROUND: The N-terminal pro-brain natriuretic peptide (NT-proBNP) has been useful in the diagnosis and follow-up of heart failure. Whether it can be useful in the detection of acute rejection (AR) after heart transplantation (HT) has not been addressed. Our aim was to assess the prognostic value of NT-proBNP determinations after HT. METHODS: We analyzed 137 endomyocardial biopsies (EMB) performed in 51 patients as assessment of AR and correlated them with NT-proBNP determinations. The value of NT-proBNP in the early follow-up of the novo HT was also assessed. RESULTS: AR grade > or =3A was diagnosed in 10 of the 137 performed biopsies. There were no significant differences in NT-proBNP values between patients with or without AR (1047 +/- 629 versus 1886 +/- 3026 pg/mL, P = NS). There were 24 de novo HT, in these patients increased NT-proBNP levels showed an inverse significant correlation with time since HT (r = -0.40, P = .0001). During follow-up, 15 of the novo HT had a descending NT-proBNP curve over time, and in the remaining 9 (37%) a late increase of NT-proBNP values were observed. Those 9 patients had the following complications: AR > or =3A in 5 cases, 1 death, 2 required a permanent pacemaker, and in the last patient a significant EMB could not be obtained. CONCLUSIONS: NT-proBNP values follow a descending curve early after HT. During the first months, a late increase of NT-proBNP value was associated with HT complications, with AR being the most frequent. Isolated increased NT-proBNP levels were not useful for the detection of AR. More studies are needed to establish the prognostic value of NT-proBNP after HT.

Acute quadriplegic myopathy with loss of thick (myosin) filaments following heart transplantation.

Acute quadriplegic myopathy with loss of thick (myosin) filaments (AQM-LTF) is an acute toxic myopathy observed in critically ill patients and is characterized by proximal or diffuse weakness of extremities and difficulty in weaning from mechanical ventilation. In recent years, this myopathy has been described in transplanted patients, although only 5 cases have been reported following heart transplantation. We present 3 new cases and review the previous literature. We conclude that the clinical picture and outcome of AQM-LTF in heart-transplanted patients do not differ from those observed in other critically ill patients (transplanted and non-transplanted). Therefore, because AQM-LTF is often clinically suspected muscle biopsy should be quickly performed to confirm the diagnosis so that physical therapy may begin as soon as possible.

Prognostic value of serum cytokines in patients with congestive heart failure.

BACKGROUND: Increased levels of circulating cytokines have been previously reported in patients with congestive heart failure; however, whether they have prognostic implications is still unknown. The aim of this study was to assess the prognostic implications of elevated serum cytokines in patients with heart failure and to identify the predictors of cytokine activation. METHODS AND RESULTS: We assessed neurohormonal determinations, circulating cytokines, ejection fraction (EF) and end-diastolic and end-systolic left ventricular lengths in 87 patients (aged 57 +/- 9 years) with left ventricular dysfunction (EF 24% +/- 6%). In 48 patients, we also assessed cytokine receptors. During follow-up (mean, 14 +/- 9 months), 8 patients died and 12 had new heart failure episodes that required hospital admission, 5 of whom underwent heart transplantation. The univariate predictors of these events were serum interleukin-6 (IL-6) (p = 0.00001), New York Heart Association (NYHA) functional class (p = 0.0004), tumor necrosis factor-soluble receptor I (p = 0. 001), atrial natriuretic peptide (p = 0.002), tumor necrosis factor-soluble receptor II (p = 0.004), angiotensin II (p = 0.006), serum interleukin-1 beta (p = 0.01), and plasma renin activity (p = 0.02). Increased serum interleukin-6 (>10 pg/ml) was a significant predictor of death or new heart failure episodes according to the Kaplan-Meier survival method by log-rank test (p = 0.004). By Cox regression analysis, serum IL-6 (p = 0.0005) and the NYHA functional class (p = 0.005) were identified as independent predictors of prognosis. CONCLUSIONS: In patients with congestive heart failure, increased serum IL-6 was identified as a powerful independent predictor of the combined end point: death, new heart failure episodes, and need for heart transplantation.

Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure.

AIMS: The aim of the study was to assess the incidence and clinical implications of increased plasma angiotensin II despite chronic ACE inhibitor therapy in patients with heart failure. METHODS AND RESULTS: The studied population consisted of 70 patients (mean age 59+/-9 years). Plasma renin activity and plasma concentration of aldosterone, norepinephrine, atrial natriuretic peptide, angiotensin II, tumour necrosis factor, interleukin-6 and interleukin-1B were assessed at 6 months of ACE inhibitor therapy. Mean left ventricular ejection fraction was 24+/-5% and the end-systolic and end-diastolic diameters were 59+/-9 and 71+/-8 mm, respectively. Despite chronic enalapril or captopril therapy, 35 patients (50%) had increased plasma angiotensin II (median 33 pg. ml(-1), range 17-84), while it was in the normal range in the remaining 35 patients (median 10 pg. ml(-1), range 5-15). Plasma renin activity (P=0.005), interleukin-6 (P=0.004), New York Heart Association functional class III-IV (P=0. 006), furosemide dose (P=0.01), lack of beta-blocker therapy (P=0. 04) and norepinephrine (P=0.04) were univariately associated with increased angiotensin II. Multivariate regression analysis identified the plasma renin activity (0.0004), norepinephrine (0.02) and interleukin-6 (0.03) as independent predictors of plasma angiotensin II. During follow-up (35+/-29 months), nine (12.8%) patients died and 13 had new heart failure episodes. Increased plasma angiotensin II, despite ACE inhibitor therapy, was a significant predictor of death or heart failure according to the Kaplan-Meier survival method by log rank test (P=0.002). CONCLUSION: Fifty per cent of patients with heart failure, ha increased plasma angiotension II despite chronic ACE inhibitor therapy. These patients had higher neurohormonal activation and poor prognosis.

Serum interleukin-6 in congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Increased serum interleukin-6 (IL-6) was associated with a higher incidence of New York Heart Association functional classes III to IV and worse left ventricular function during follow-up. Patients with elevated serum IL-6 had poor prognosis. These results reinforce the concept that increased serum IL-6 may also play an important role in disease progression.