A predictive tool to estimate the risk of axillary metastases in breast cancer patients with negative axillary ultrasound.

BACKGROUND: Sentinel node biopsy (SNB) is the "gold standard" in axillary staging in clinically node-negative breast cancer patients. However, axillary treatment is undergoing a paradigm shift and studies are being conducted on whether SNB may be omitted in low-risk patients. The purpose of this study was to evaluate the risk factors for axillary metastases in breast cancer patients with negative preoperative axillary ultrasound. METHODS: A total of 1,395 consecutive patients with invasive breast cancer and SNB formed the original patient series. A univariate analysis was conducted to assess risk factors for axillary metastases. Binary logistic regression analysis was conducted to form a predictive model based on the risk factors. The predictive model was first validated internally in a patient series of 566 further patients and then externally in a patient series of 2,463 patients from four other centers. All statistical tests were two-sided. RESULTS: A total of 426 of the 1,395 (30.5 %) patients in the original patient series had axillary lymph node metastases. Histological size (P < 0.001), multifocality (P < 0.001), lymphovascular invasion (P < 0.001), and palpability of the primary tumor (P < 0.001) were included in the predictive model. Internal validation of the model produced an area under the receiver operating characteristics curve (AUC) of 0.731 and external validation an AUC of 0.79. CONCLUSIONS: We present a predictive model to assess the patient-specific probability of axillary lymph node metastases in patients with clinically node-negative breast cancer. The model performs well in internal and external validation. The model needs to be validated in each center before application to clinical use.

International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

Outcome of patients with ductal carcinoma in situ and sentinel node biopsy.

BACKGROUND: In sentinel node biopsy (SNB), tumor-positive findings, mainly micrometastases and isolated tumor cells (ITC) have been found in up to 8%-16% of patients with pure ductal carcinoma in situ (DCIS) or microinvasive DCIS (DCISM). The prognostic significance of such findings is largely unknown. The aim of this study is to examine the outcome of DCIS and DCISM patients with SNB. METHODS: A total of 280 breast cancer patients with pure or microinvasive DCIS underwent SNB between April 2001 and December 2010 at the Breast Surgery Unit of Helsinki University Central Hospital. Patient, tumor, SNB procedure, and follow-up data were gathered. The median follow-up was 50 months (range 7-123 months). RESULTS: Altogether, 21 patients had tumor-positive sentinel node findings. Of these, 14 were in pure DCIS patients (1 macrometastasis, 1 micrometastasis, 12 ITC) and 7 in DCISM patients (1 macrometastasis, 2 micrometastases, 4 ITC). Also, 16 patients, 10 with pure DCIS and 6 with DCISM, underwent completion axillary lymph node dissection (ALND). Only 1 of them, a patient with DCISM, had additional tumor positive finding in the ALND. During a median follow-up of 50 months (range 7-123 months) there were 5 local recurrences. One patient with pure DCIS and tumor-negative SNB developed overt axillary metastases and later also distant metastases. CONCLUSIONS: DCIS and DCISM patients do have tumor positive findings, but a majority of these are ITC or micrometastases. In light of this study, these findings do not affect the outcome of DCIS or DCISM patients.

A simple nomogram to evaluate the risk of nonsentinel node metastases in breast cancer patients with minimal sentinel node involvement.

BACKGROUND: Tumor-positive sentinel node biopsy (SNB) suggests a risk of nonsentinel node metastases in breast cancer. This risk is lower after micrometastasis or isolated tumor cells (ITC) in the sentinel node (SN), and recent studies suggest that completion axillary lymph node dissection (ALND) might not improve outcome in these patients. We aim to validate existing predictive models and to develop a new model for micrometastatic and ITC patients. METHODS: A series of 484 patients with micrometastases or ITC in SN followed by ALND was used to evaluate factors affecting nonsentinel node involvement. Logistic regression analysis was performed to construct a predictive model, which was validated by a separate series of 51 patients. RESULTS: Only 7.2% of patients had additional metastases on completion ALND. Tumor diameter and multifocality associated with nonsentinel status on multivariate analysis. A predictive model was constructed showing good [area under the curve (AUC) 0.791] discrimination in the validation series. Previously published models performed poorly in our patient population. CONCLUSIONS: Nonsentinel node metastases are rare with micrometastasis or ITC in SN. Most published predictive models for nonsentinel node involvement perform poorly in the present patient population. We developed a new predictive model which seems to perform well in discriminating patients with more than 10% risk of additional metastases. However, the presented nomogram needs to be validated with an independent patient series to evaluate its accuracy, especially for high-risk patients.

The prevalence of non-sentinel node metastases in breast cancer patients with sentinel node micrometastases.

AIMS: The aim of the study was to estimate the prevalence of and risk factors for non-sentinel node (NSN) involvement in breast cancer patients with sentinel node (SN) micrometastases. METHODS: Eighty-four patients with SN micrometastases were included. Both the SN and NSN were examined using serial sectioning and immunohistohemistry. Various indices were evaluated as possible risk factors for NSN involvement. RESULTS: NSN involvement was found in 22/84 patients. The median size of the NSN metastases was 1.25 mm (0.01-12 mm). The NSN metastases were larger than 2 mm in 8 patients and smaller than 0.2 mm in 6 patients. NSN involvement was observed in 14/35 patients with metastatic findings in all removed SN. Three of the 23 patients with 2 or 3 tumour negative SN had NSN metastases. None of the 12 patients with 4 or more uninvolved SN had NSN metastases. NSN involvement could not excluded by other patient, tumour or sentinel node related factors. CONCLUSIONS: Every fourth patient will have residual disease in the axilla, 10% even large metastases, if axillary clearance is omitted in patients with SN micrometastases. The risk of NSN involvement seems negligible in patients with a single SN micrometastasis and four or more healthy SN harvested.

Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer.

Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SN metastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.

Local recurrence of stage 1 and 2 breast cancer after skin-sparing mastectomy and immediate breast reconstruction in a 15-year series.

AIMS: Since the introduction of skin-sparing mastectomy (SSM) in 1991 concerns on local control and recurrence rates have been discussed in the literature. The aim of this study is to examine in particular incidence of local recurrence in a 15-year consecutive series of breast cancer patients having undergone SSM and immediate breast reconstruction (IBR) at a single population-based institution. METHODS: One hundred and forty-six consecutive patients with either stage 1 or 2 breast cancer who underwent SSM followed by IBR from 1992 to 2006 were included in this study. A retrospective review of patient records was conducted. RESULTS: During a mean follow-up time of 51 months, four local recurrences of the native breast skin were accounted for. In addition, three regional lymph node recurrences and four systemic recurrences took place. All of the local and regional recurrences were handled by salvage surgery followed by adjuvant oncological therapies. During a mean follow-up of 35 months after the detection and treatment of the locoregional recurrences none of the patients developed new recurrences. CONCLUSIONS: Our present study concludes that SSM followed by IBR seems oncologically sound procedure for stage 1 and 2 breast cancer patients. In addition, local recurrences and regional lymph node recurrences are not always associated with systemic relapse.

Sentinel node biopsy with intraoperative diagnosis in patients undergoing skin-sparing mastectomy and immediate breast reconstruction.

AIMS: False negative cases in the intraoperative assessment of sentinel node (SN) metastases in breast cancer prompt for a secondary axillary lymph node dissection (ALND). Such ALND is technically demanding and prone to complications in patients with immediate breast reconstruction (IBR) if there is a microvascular anastomosis or the thoracodorsal pedicle of a latissimus dorsi flap in the axilla. This study aims to evaluate the feasibility of the intraoperative diagnosis of sentinel node biopsy (SNB) in breast cancer patients undergoing IBR. METHODS: Sixty-two consecutive breast cancer patients undergoing SNB with the intraoperative diagnosis of SN metastases simultaneously with mastectomy and IBR between 2004 and 2006 were included in this study. Results of the SNB and especially the false negative cases in the intraoperative diagnosis were evaluated. RESULTS: Eleven patients had tumor positive SN. Nine of these cases were detected intraoperatively. The two false negative cases in the intraoperative diagnosis constituted of isolated tumor cells only. CONCLUSIONS: Our present study suggests that SNB with intraoperative diagnosis of SN metastases is feasible in patients undergoing IBR if the risk of nodal metastasis is low and the sensitivity of intraoperative SNB diagnosis is high.

Adenocarcinoma of the renal pelvis in an elderly woman.

Adenocarcinoma of the renal pelvis is so rare that many reviews of renal tumours fail to include any instance of this lesion. We present a 75-year-old female patient with no previous history of urological disease in whom a renal pelvic tumour was diagnosed. Histological examination after radical nephroureterectomy proved the tumour to be a rare adenocarcinoma. The course of the disease, the possible predisposing factors, the treatment of the tumour and the prognosis are discussed.

Imaging of a parapharyngeal hemangiopericytoma. Radioimmunoscintigraphy (SPECT) with indium-111-labeled anti-CEA antibody, and comparison to digital subtraction angiography, computed tomography, and immunohistochemistry.

A 27-year-old male patient with a parapharyngeal hemangiopericytoma was investigated radiologically with orthopantomography, computed tomography, and digital subtraction angiography before the operation. Because a malignancy was suspected, the patient was imaged with gamma camera using radiolabeled monoclonal anticarcinoembryonal antigen antibody including single photon emission computed tomography. The radioantibody accumulated strongly into the neoplasm. Tumor to background ratio was 2.2. Samples of the excised tumor were stained immunohistochemically for desmin, vimentin, muscle actin, cytokeratin, CEA (carcinoembryonic antigen), and factor VIII. They showed that the antibody uptake was of unspecific nature and not due to CEA expression in the tumor.

Bone formation after distraction osteotomy of the radius in sheep.

Gradual distraction by external fixation was performed one week after osteotomy of the radius in 12 sheep. Bone regeneration in the distraction area was studied by light and electron microscopy. One week after starting the distraction the gap was composed of hematopoietic cells and fibroblasts. The collagen production had already started and it continued actively throughout the distraction period. The collagen produced by the fibroblasts in the central interzone of the gap was organized according to the direction of the distraction. The osteoblasts were lined up along the collagen bundles and osteoid formation was most active around the capillaries. Mineralization started two weeks after the beginning of the distraction. After cessation of the distraction, separate groups of cartilaginous cells were found in some specimens among the newly formed bone. Our findings suggest that osteogenesis as a result of gradual distraction occurs through the whole distraction area with preceding formation of organized collagen matrix. The bone structure in the distracted segment represents an organized lamellar structure at an early stage of the osteogenesis.