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False-negative rates in sentinel-node in breast cancer
choice of population samples in our study. The choice of respondents for an opinion survey is not straightforward. It is obvious that the opinion of those who ignore the subject being studied is meaningless. However, when dealing with new medical methods, the opinion of people with experience in the field or those with publications on the subject, is not necessarily better than that of other respondents because they may not be objective and unbiased. In our survey, we interviewed surgeons whose principal activity is breast-cancer and gynaecological-cancer surgery. All were affiliated with hospitals attached to the seven existing Belgian universities. With the exception of two surgeons, they had all begun to do SLNB in their patients. At least four of the surgeons are involved in the teaching of SLNB to other surgeons. Keshtgar and Ell are undoubtedly well aware that, in oncology and nuclear medicine, and in SLNB, Belgian physicians are quite active. Keshtgar and Ell considered our choice of female physicians and paramedics as potential patients inappropriate. We agree that these women are not representative of patients with breast cancer, but this is because they are much better informed. They made their choices knowing the advantages and the inconveniences of the proposed alternatives. These women did not discover SLNB for the first time through a short and unexpected explanation by their physicians. It is easier to convince patients who are in an emotionally difficult situation to accept an experimental technique than physicians and paramedics acting as potential patients. The notion of SLNB is attractive and potentially useful. An open-minded approach would help to define the exact place of the technique in the management of patients with breast cancer, and allow patients to enjoy the benefits. *S Rozenberg, F Liebens, H Ham Department of Gynaecology and Nuclear Medicine, CHU St Pierre, Free University of Brussels, 1000 Brussels, Belgium
Sir—As more experience is being gained with the use of SLNB in breastcancer patients, this procedure will eventually replace ALND for nodal staging. However, SLNB is not perfect, and some false-negative results are to be expected. S Rozenberg and colleagues1 reported on an interview-based study among Belgian breast surgeons and female hospital staff that was done to assess the acceptable false-negative rate
774
for SLNB. They concluded that the role of SLNB for management of breast cancer is in question because even small false-negative rates are a strong argument against the application of the technique. Such contention is based on the premise that ALND is a perfect gold standard with which to compare other methods of nodal staging. At our centre, preliminary results with SLNB were good 2 and the falsenegative rate was low. As recommended,3 our protocol included microstaging techniques for the sentinel node, such as serial sectioning and immunostains that cannot be applied to full axillary clearance samples. An update of our data, including the first 100 accrued T1-T2 patient, showed a sensitivity of 95% and a false-negative rate of 5% for a total nodal involvement prevalence of 38%. Implementation of SLNB at our institution has led to the up-stage of one patient with a metastatic intramammary lymph node and normal ALND undergoing breastpreserving surgery, and five with a solitary sentinel-node micrometastasis (<0·2 mm) that would have otherwise escaped pathological detection. 4 Micrometastases have a well-known influence on prognosis.5 Therefore, ALND may carry some risk of false negativity for nodal disease. With the upstaging effect of SLNB in our series, the false-negativity rate for ALND was 16%, and sensitivity dropped to 84%. SLNB is minimally invasive and has no sequelae, but can also potentially improve nodal assessment with fewer false-negative results. For patients to decide the preferred method of nodal staging we should inform them about the chance of false-negative results associated with each technique. *M Fraile, M Rull, A Alastrué, E Castellà, A Barnadas Hospital Universitari Germans Trias I Pujol, 08916 Barcelona, Spain 1
Rozenberg S, Liebens F, Ham H. The sentinel node in breast cancer: acceptable false-negative rate. Lancet 1999; 353: 1937–38. 2 Fraile M, Rull M, Julián FJ, Castellà E, Barnadas A, Alastrué A. Biopsia selectiva del ganglio centinela en pacientes con cáncer de mama: primeros resultados. Med Clin (Barc) 1999; 113: 52–53. 3 Turner RR, Olilla DW, Stern S, Giuliano AE. Optimal histopathological examination of the sentinel node for breast carcinoma staging. Am J Surg Pathol 1999; 23: 263–67. 4 Schreiber RH, Pendas S, Ku NN, et al. Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node. Ann Surg Oncol 1999; 6: 95–101. 5 International (Ludwig) breast cancer study group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 1990; 335: 1565–68.
Diagnosis of relative adrenal insufficiency in critically ill patients Sir—Although critically ill patients generally show raised plasma cortisol concentrations, some patients have an inadequate production of cortisol in relation to the seriousness of their disease—so-called relative adrenal insufficiency. These intensive care patients may benefit from supplementation with stress doses of hydrocortisone. 1,2 Diagnosis of this syndrome is therefore of great importance. However, the best available clue to diagnosis is fast clinical and haemodynamic improvement after substitution with 100–200 mg hydrocortisone per day.3 Serum cortisol concentrations, stimulation tests with adrenocorticotropic hormone analogues (synacthen), or serum electrolyte disturbances are not very useful in this group of patients. In search of more refined aids to diagnosis, Albertus Beishuizen and colleagues (May 15, p 1675) 4 describe 40 patients with relative eosinophilia (>3% of total leucocyte count) out of 570 critically ill patients. Low-dose (1 g) synacthen stimulation test was abnormal in ten patients with relative eosinophilia. Treatment with steroids resulted in haemodynamic improvement in seven patients. The investigators state that relative eosinophilia should be thought of as a warning sign of insufficient adrenocortical function. However, eosinophilia was used as inclusion criterion to enter the study; so we do not know which proportion of the remaining 530 patients, who did not show eosinophilia, might have had relative adrenal insufficiency (insufficient for the temporary increased needs). Furthermore, eosinophilia was not significantly different between the groups. Separation into groups on the basis of an abnormal synacthen test seems uncertain, because reference values are determined under standard circumstances and therefore cannot be applied to the whole population on the intensive care unit. The low basal cortisol concentrations in the group with so-called adequate response after 1 g synacthen could suggest secondary adrenal insufficiency. However, would they also benefit from glucocorticoid administration? We are in need of tools to diagnose relative adrenal insufficiency syndrome, because this condition has therapeutic consequences in severely ill patients.
THE LANCET • Vol 354 • August 28, 1999
Sir—As more experience is being gained with the use of SLNB in breastcancer patients, this procedure will eventually replace ALND for nodal staging. However, SLNB is not perfect, and some false-negative results are to be expected. S Rozenberg and colleagues1 reported on an interview-based study among Belgian breast surgeons and female hospital staff that was done to assess the acceptable false-negative rate
774
for SLNB. They concluded that the role of SLNB for management of breast cancer is in question because even small false-negative rates are a strong argument against the application of the technique. Such contention is based on the premise that ALND is a perfect gold standard with which to compare other methods of nodal staging. At our centre, preliminary results with SLNB were good 2 and the falsenegative rate was low. As recommended,3 our protocol included microstaging techniques for the sentinel node, such as serial sectioning and immunostains that cannot be applied to full axillary clearance samples. An update of our data, including the first 100 accrued T1-T2 patient, showed a sensitivity of 95% and a false-negative rate of 5% for a total nodal involvement prevalence of 38%. Implementation of SLNB at our institution has led to the up-stage of one patient with a metastatic intramammary lymph node and normal ALND undergoing breastpreserving surgery, and five with a solitary sentinel-node micrometastasis (<0·2 mm) that would have otherwise escaped pathological detection. 4 Micrometastases have a well-known influence on prognosis.5 Therefore, ALND may carry some risk of false negativity for nodal disease. With the upstaging effect of SLNB in our series, the false-negativity rate for ALND was 16%, and sensitivity dropped to 84%. SLNB is minimally invasive and has no sequelae, but can also potentially improve nodal assessment with fewer false-negative results. For patients to decide the preferred method of nodal staging we should inform them about the chance of false-negative results associated with each technique. *M Fraile, M Rull, A Alastrué, E Castellà, A Barnadas Hospital Universitari Germans Trias I Pujol, 08916 Barcelona, Spain 1
Rozenberg S, Liebens F, Ham H. The sentinel node in breast cancer: acceptable false-negative rate. Lancet 1999; 353: 1937–38. 2 Fraile M, Rull M, Julián FJ, Castellà E, Barnadas A, Alastrué A. Biopsia selectiva del ganglio centinela en pacientes con cáncer de mama: primeros resultados. Med Clin (Barc) 1999; 113: 52–53. 3 Turner RR, Olilla DW, Stern S, Giuliano AE. Optimal histopathological examination of the sentinel node for breast carcinoma staging. Am J Surg Pathol 1999; 23: 263–67. 4 Schreiber RH, Pendas S, Ku NN, et al. Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node. Ann Surg Oncol 1999; 6: 95–101. 5 International (Ludwig) breast cancer study group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 1990; 335: 1565–68.
Diagnosis of relative adrenal insufficiency in critically ill patients Sir—Although critically ill patients generally show raised plasma cortisol concentrations, some patients have an inadequate production of cortisol in relation to the seriousness of their disease—so-called relative adrenal insufficiency. These intensive care patients may benefit from supplementation with stress doses of hydrocortisone. 1,2 Diagnosis of this syndrome is therefore of great importance. However, the best available clue to diagnosis is fast clinical and haemodynamic improvement after substitution with 100–200 mg hydrocortisone per day.3 Serum cortisol concentrations, stimulation tests with adrenocorticotropic hormone analogues (synacthen), or serum electrolyte disturbances are not very useful in this group of patients. In search of more refined aids to diagnosis, Albertus Beishuizen and colleagues (May 15, p 1675) 4 describe 40 patients with relative eosinophilia (>3% of total leucocyte count) out of 570 critically ill patients. Low-dose (1 g) synacthen stimulation test was abnormal in ten patients with relative eosinophilia. Treatment with steroids resulted in haemodynamic improvement in seven patients. The investigators state that relative eosinophilia should be thought of as a warning sign of insufficient adrenocortical function. However, eosinophilia was used as inclusion criterion to enter the study; so we do not know which proportion of the remaining 530 patients, who did not show eosinophilia, might have had relative adrenal insufficiency (insufficient for the temporary increased needs). Furthermore, eosinophilia was not significantly different between the groups. Separation into groups on the basis of an abnormal synacthen test seems uncertain, because reference values are determined under standard circumstances and therefore cannot be applied to the whole population on the intensive care unit. The low basal cortisol concentrations in the group with so-called adequate response after 1 g synacthen could suggest secondary adrenal insufficiency. However, would they also benefit from glucocorticoid administration? We are in need of tools to diagnose relative adrenal insufficiency syndrome, because this condition has therapeutic consequences in severely ill patients.
THE LANCET • Vol 354 • August 28, 1999