Clinical effect of the pathological axillary assessment method in breast cancer without clinical nodal metastasis.

BACKGROUND: This study aimed to assess the clinical effect of the pathological axillary assessment method in breast cancer without clinical lymph node metastasis. METHODS: Data of patients with clinically node-negative breast cancer were retrospectively reviewed. The study period was divided into early (January 2000-July 2007) and late (August 2007-December 2014) periods based on the pathological assessment method used (single-sectional and detailed multi-sectional lymph node processing). In the late period, lymph nodes were evaluated at six levels including immunohistochemistry on each 1.5-2 mm interval section. The axillary diagnostic accuracy and role of chemotherapy were assessed. RESULTS: In 1698 patients, 27 isolated tumor cells (ITCs), 39 micrometastases, and 205 macrometastases were noted. The sensitivity for pathological N0 diagnosis was dependent on clinical T stage, Tis (97.8%), T1 (83.0%), T2 (74.2%), T3 (54.5%), and T4 (63.6%). ITCs and micrometastases were detected only in the late period, and 84.7% and 91.6% of cases in the early and late period, respectively, did not have macrometastases. The 5-year disease-free interval (DFI) rates were 95.2% in node-negative cases, 98.4% in ITCs/micrometastases, and 91.4% in macrometastases (P < 0.001). In multivariate analysis, the predictor for DFI was estrogen receptor negativity (P = 0.013). Chemotherapy did not improve DFI in patients with node-positive breast cancer. CONCLUSIONS: The detailed multi-sectional pathological assessment of axillary lymph nodes detected ITCs and micrometastases. Implementation of chemotherapy should not be based on the minimal nodal metastasis and this type of serially nodal sectioned processing had little clinical significance.

Prospective clinical trial of robotic sentinel lymph node assessment with isosulfane blue (ISB) and indocyanine green (ICG) in endometrial cancer and the impact of ultrastaging (NCT01818739).

OBJECTIVES: To assess the performance sentinel lymph node (SLN) biopsy and effect of ultrastaging in clinically early stage endometrial cancer. METHODS: Patients with endometrial cancer prospectively enrolled after informed consent was obtained. The cervix was injected superficially with 1 mL of ISB and 1 mL of ICG (diluted 1:25) at 3 and 9 o'clock each. SLN biopsy was followed by complete pelvic lymphadenectomy (aortic lymphadenectomy at the discretion of the surgeon). Lymph nodes (LNs) were analyzed by standard sectioning with H&E; ultrastaging of SLN was done retrospectively and blinded to treating physicians. RESULTS: 204 patients received dye injections. In 184 (90.2%) patients at least one SLN was identified. Of all patients, 138 (68%) had bilateral mapping. In the patients with successful mapping of a hemipelvis, ICG detected SLNs in 83% and ISB in 64% of cases (p < 0.0001). Median BMI (kg/m2) for patients with successful mapping was 35.7 compared to 40.1 for those who did not map (p = 0.01). Twenty-three (11.3%) patients had positive LNs. Applying the SLN algorithm, positive nodes were detected in 21/23 (91.3%). The negative predictive value (NPV) was 98.9% (95% CI: 96.01% to 99.71%). Eleven patients had positive SLN with isolated tumor cells (ITCs) or micrometastases detected on ultrastaging. Including these patients, 34 (17%) had positive LNs, increasing the NPV to 99% and sensitivity to 94%. There were no recurrences in patients with ITCs only. CONCLUSIONS: SLN assessment in endometrial cancer is feasible and safe with high NPV (99%). ICG was more effective in detecting SLN compared to ISB. Although ultrastaging detected additional positive LNs, treatment based on standard sectioning appears reasonable but further research is needed.

Validation of a Novel Diagnostic Kit Using the Semidry Dot-Blot Method to Detect Metastatic Lymph Nodes in Breast Cancer: Distinguishing Macrometastases From Nonmacrometastases.

BACKGROUND: The semidry dot-blot method is a diagnostic procedure for detecting lymph node (LN) metastases using the presence of cytokeratin (CK) in lavage fluid from sectioned LNs. We evaluated 2 novel kits that use newly developed anti-CK-19 antibodies to diagnose LN metastases in breast cancer. PATIENTS AND METHODS: We examined 159 LNs dissected that we sliced at 2-mm intervals and washed with phosphate-buffered saline. The suspended cells in the lavage were centrifuged and lysed to extract protein. This extracted protein was used with a low-power and a high-power kit to diagnose LN metastasis. Diagnoses on the basis of the kits were compared with pathological diagnoses. RESULTS: Of the 159 LNs, 68 were assessed as positive and 91 as negative in permanent section examination. Sensitivity, specificity, and accuracy of the low-power kit for detecting LN metastases was 83.8%, 100%, and 93.1%, respectively. Those of the high-power kit were 92.6%, 92.3%, and 92.5%, respectively. Combining the low- and high-power kit results, those for distinguishing macrometastases were 94.5%, 95.2%, and 95.0%, respectively. Diagnosis was achieved in approximately 20 minutes, at a cost of less than $30 USD. CONCLUSION: The kits were accurate, fast, and cost-effective in diagnosing LN metastases without the loss of LN tissue.

Is intraoperative touch imprint cytology indicated in the surgical treatment of early breast cancers?

INTRODUCTION: Intraoperative touch imprint cytology (TIC) of the sentinel lymph node(s) (SLN(s)) in the treatment of breast cancer has significantly reduced the number of axillary block dissections (ABD) required during second surgeries. Based on recent studies, ABD was not considered necessary if the presence of tumor cells/micrometastasis was confirmed in the SLN(s) or in the case of macrometastases in a patient group meeting the inclusion criteria for the ACOSOG Z0011 study. Our aim was to determine the sensitivity and usefulness of TIC with regard to these results. METHODS: TICs of the SLN(s) were examined in 1168 patients operated on for breast cancer. The method was also analyzed retrospectively based on the guidelines for the Z0011 study. During TIC, new samples were cut every 250 µm; impression smears were evaluated after being stained with hematoxylin eosin. RESULTS: TIC confirmed metastasis in 202 cases (202/1168, 17.29%). Metastasis was confirmed in SLN(s) in 149 additional cases during a final histological examination. The sensitivity of TIC was found to be 57.18%, and its specificity was 99.63%. An analysis was then performed except for cases that met the inclusion criteria for the Z0011 study and with metastasis smaller than 2 mm (micrometastasis/isolated tumor cells) considered to be positive during intraoperative cytology. The sensitivity of the method decreased to 34.23%, while its specificity was still high at 99.76%. CONCLUSIONS: Based on the new guidelines for ABD, imprint cytology cannot be considered a beneficial and cost-effective intervention in the surgical treatment of early breast cancer.

Optical innovations in surgery.

BACKGROUND: In the past decade, there has been a major drive towards clinical translation of optical and, in particular, fluorescence imaging in surgery. In surgical oncology, radical surgery is characterized by the absence of positive resection margins, a critical factor in improving prognosis. Fluorescence imaging provides the surgeon with reliable and real-time intraoperative feedback to identify surgical targets, including positive tumour margins. It also may enable decisions on the possibility of intraoperative adjuvant treatment, such as brachytherapy, chemotherapy or emerging targeted photodynamic therapy (photoimmunotherapy). METHODS: This article reviews the use of optical imaging for intraoperative guidance and decision-making. RESULTS: Image-guided cancer surgery has the potential to be a powerful tool in guiding future surgical care. Photoimmunotherapy is a theranostic concept (simultaneous diagnosis and treatment) on the verge of clinical translation, and is highlighted as an effective combination of image-guided surgery and intraoperative treatment of residual disease. Multispectral optoacoustic tomography, a technique complementary to optical image-guided surgery, is currently being tested in humans and is anticipated to have great potential for perioperative and postoperative application in surgery. CONCLUSION: Significant advances have been achieved in real-time optical imaging strategies for intraoperative tumour detection and margin assessment. Optical imaging holds promise in achieving the highest percentage of negative surgical margins and in early detection of micrometastastic disease over the next decade.

[Analysis of intraoperative molecular assessment of sentinel lymph nodes in breast carcinoma].

OBJECTIVE: To evaluate the reliability and application of GeneSearch(TM) breast lymph node assay (Genesearch), a real-time fluorescence quatitative PCR method, in intraoperative assay of metastasis in sentinel lymph nodes (SLNs) from breast cancer patients. METHODS: Totally 140 SLNs from 80 patients with breast carcinoma were prospectively studied from May 2010 to August 2010. The 80 patients included 78 women and 2 men who ranged in age from 29 to 85 years, and the median age is 49 years. The expression of CK19 and mammaglobulin in all 140 SLNs were detected by Genesearch, and the results were compared with that of histological evaluation of both frozen and paraffin-embedded sections. RESULTS: Among SLNs, by histological analyses, there were 121 without metastasis, 17 with macrometastasis, 2 with micrometastasis, and none of isolated tumor cell. By Genesearch, there were 119 without metastasis and 21 with metastasis. Genesearch showed sensitivity of 89.4%, positive predictive value of 81.0%, negative predictive value of 98.3% and specificity of 96.7% by comparing to histological analyses. The concordance between Genesearch and histological analysis was 95.7%. The sensitivity of Genesearch was 15/17 for macrometastasis and 2/2 for micrometastasis. CONCLUSIONS: Genesearch detection presents high sensitivity and specificity in evaluating metastasis of sentinel lymph nodes in breast cancer, but strict performance technically is necessary to avoid false positive and false negative results. Inability of further subtyping for the positive cases might be the key limitations for wide application of this method.