Node Micrometastases Research Articles

Sentinel Nodal Micrometastases Detected by the One- Step Nucleic Acid Amplification Whole Node Assay and the Impact on Adjuvant Treatment and Outcomes in Early Breast Cancers: The First Report from Thailand

Background: The advent of sentinel lymph node biopsy (SLNB) and improvements in histopathological and molecular analysis have increased the detection rate of nodal micrometastases. As compare with conventional method, the one-step nucleic acid amplification (OSNA) assay might detect higher cases of SLN micrometastases. Objective: The present study aimed to assess the impact of OSNA assay on micrometastases detection rate and potential benefit in terms of adjuvant treatment and survival outcome in early breast cancer. Materials and Methods: A retrospective review of patients with sentinel node (SLN) micrometastasis detected by the OSNA assay between 2015 and 2019 was carried out. Clinicopathological, adjuvant treatment, and follow-up data were collected. Ten-year survival benefit with adjuvant chemotherapy was calculated using PREDICT online, version 1.2 (https://breast.predict.nhs.uk/). Results: Between November 2015 and December 2019, 78 out of 721 patients (10.8%) were positive for micrometastasis based on OSNA detection. Three-fourth of cases received adjuvant systemic chemotherapy and 57% were given taxane-based regimen. Using the PREDICT online tool, an estimated 10-year survival in patients who received adjuvant systemic chemotherapy and who did not, were 75% and 66%, respectively (p=0.018). A 10-year survival benefit from chemotherapy among patients who received systemic chemotherapy was 8% compared with 4% with no-adjuvant-therapy cohort. Conclusion: The OSNA assay allows for a more precise detection of SLN micrometastasis compared to conventional pathology and could guide therapeutic decision making. In patients with micrometastasis who received adjuvant systemic chemotherapy, the estimated overall 10-year survival was improved. Keywords: Axillary staging, Breast cancer, Micrometastases, OSNA, Sentinel lymph node biopsy

Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort☆

BackgroundPrognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm.Patients and methodsWe retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i−), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status.ResultsAs determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS.ConclusionLN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.

Emerging photoacoustic and thermoacoustic imaging technologies for detecting primary and metastatic cancer and guiding therapy.

In recent years, there has been a progressive trend towards less invasive technologies for detecting metastatic cancer and guiding therapy with the goal of lower morbidity, better outcomes, and superior cosmetic appearance than traditional methods. This mini-review examines three emerging noninvasive hybrid technologies for detecting primary cancer, metastasis and guiding thermal therapy. Real-time thermoacoustic imaging and thermometry potentially provides valuable and critical feedback for guiding focused microwave ablation therapy. Label-free photoacoustic monitoring of cancer cells is a promising clinical diagnostic and theranostic tool for detecting metastatic disease and monitoring the response to therapy. Finally, immunologically targeted gold nanoparticles combined with photoacoustic imaging is able to detect lymph node micrometastasis in mouse models of breast cancer. These emerging techniques have the potential to improve the decision to biopsy, provide more accurate prognosis, and enhance the efficacy of therapy for early and late stage cancers.

First Surgical National Consensus Conference of the Italian Breast Surgeons association (ANISC) on breast cancer management in neoadjuvant setting: Results and summary

RationaleOn October 15th, 2020, the first Surgical National Consensus Conference on neoadjuvant chemotherapy (NACT) was promoted by the Italian Association of Breast Surgeons (ANISC). MethodThe Consensus Conference was entirely held online due to anti-Covid-19 restrictions and after an introductory four lectures held by national and international experts in the field, a total of nine questions were presented and a digital “real-time” voting system was obtained. A consensus was reached if 75% or more of all panelists agreed on a given question. ResultsA total of 202 physicians, from 76 different Italian Breast Centers homogeneously distributed throughout the Italian country, participated to the Conference. Most participants were surgeons (75%). Consensus was reached for seven out of the nine considered topics, including management of margins and lymph nodes at surgery, and there was good correspondence between the 32 “Expert Panelists” and the “Participants” to the Conference. Consensus was not achieved regarding the indications to NACT for high-grade luminal-like breast tumors, and the need to perform an axillary lymph node dissection in case of micrometastases in the sentinel lymph node after NACT. ConclusionsNACT is a topic of major interest among surgeons, and there is need to develop shared guidelines. While a Consensus was obtained for most issues presented at this Conference, controversies still exist regarding indications to NACT in luminal B-like tumors and management of lymph node micrometastases. There is need for clinical studies and analysis of large databases to improve our knowledge on this subject.

Development and validation of nomograms for predicting axillary non-SLN metastases in breast cancer patients with 1\u20132 positive sentinel lymph node macro-metastases: a retrospective analysis of two independent cohorts

BackgroundIt is reported that appropriately 50% of early breast cancer patients with 1–2 positive sentinel lymph node (SLN) micro-metastases could not benefit from axillary lymph node dissection (ALND) or breast-conserving surgery with whole breast irradiation. However, whether patients with 1–2 positive SLN macro-metastases could benefit from ALND remains unknown. The aim of our study was to develop and validate nomograms for assessing axillary non-SLN metastases in patients with 1–2 positive SLN macro-metastases, using their pathological features alone or in combination with STMs.MethodsWe retrospectively reviewed pathological features and STMs of 1150 early breast cancer patients from two independent cohorts. Best subset regression was used for feature selection and signature building. The risk score of axillary non-SLN metastases was calculated for each patient as a linear combination of selected predictors that were weighted by their respective coefficients.ResultsThe pathology-based nomogram possessed a strong discrimination ability for axillary non-SLN metastases, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.727 (95% CI: 0.682–0.771) in the primary cohort and 0.722 (95% CI: 0.653–0.792) in the validation cohort. The addition of CA 15–3 and CEA can significantly improve the performance of pathology-based nomogram in the primary cohort (AUC: 0.773 (0.732–0.815) vs. 0.727 (0.682–0.771), P < 0.001) and validation cohort (AUC: (0.777 (0.713–0.840) vs. 0.722 (0.653–0.792), P < 0.001). Decision curve analysis demonstrated that the nomograms were clinically useful.ConclusionThe nomograms based on pathological features can be used to identify axillary non-SLN metastases in breast cancer patients with 1–2 positive SLN. In addition, the combination of STMs and pathological features can identify patients with patients with axillary non-SLN metastases more accurately than pathological characteristics alone.

Detection and prognostic significance of isolated tumor cells and micrometastases in pelvic lymph nodes of patients with early ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) accounts for approximately 18% of all epithelial ovarian malignancies in Taiwan and portends a poor prognosis. Here, we sought to investigate whether immunohistochemistry with an anti-pan-cytokeratin antibody cocktail (AE1/AE3) can be used as an adjunct to hematoxylin and eosin (H&E) staining for improving the detection of isolated tumor cells (ITCs) and micrometastasis to pelvic lymph nodes (LNs). We also assessed whether these lesions may predict disease recurrence.Pelvic lymphadenectomy specimens were obtained from 197 patients with stage 1 OCCC who had undergone surgery between 2000 and 2018 from Linkou and Kaohsiung Chang Gung Memorial Hospital. Immunohistochemical staining with AE1/AE3 was applied to a total of 1186 slides. Clusters of metastatic tumor cells, detected immunohistochemically, were classified as ITCs (clusters with diameters of ≤0.2 mm) or micrometastases (tumor cell clusters of >0.2 but ≤2.0 mm). We also assessed the diameter of metastases in patients with positive lymph nodes (stage IIIA1, n = 3, 7 positive nodes).Clusters with a positive AE1/AE3 staining were identified in five (2.53%) of the 197 patients (ITCs, n = 3; micrometastasis, n = 2). Four patients had no evidence of disease recurrence but a patient recurred at follow-up. Metastatic foci of patients with stage IIIA1 disease were all >2.0 mm in size.Immunohistochemical staining with AE1/AE3 can identify micrometastasis or ITCs in LNs missed on routine H&E staining. The role of micrometastasis in predicting recurrent OCCC and implementing on treatment strategies requires further investigation.

Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases.

The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed. We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases. The median follow-up was 7.2years, with a confidence interval (CI) of 7.1-7.3years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80-2.85, p = 0.208) for OS and 1.12 (95% CI 0.63-1.97, p = 0.705) for RFS. Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

Clinical Significance of Lymph Node Micrometastasis in pN0 Gastric Cancer Patients.

Purpose To investigate the relationship between lymph node micrometastasis (LNMM) and clinicopathological factors and to evaluate the prognostic effects of LNMM in pN0 gastric cancer (GC) patients. Methods One hundred and seventy-two GC patients who received radical gastrectomy with D2 lymph node dissection were enrolled in the present study. 1371 negative lymph nodes from level 2 station confirmed by pathology were examined. The LNMM was diagnosed by telomeric repeat amplification protocol/enzyme-linked immunosorbent assay (TRAP-ELISA). The relationship between clinicopathological factors and LNMM was investigated by multivariate analysis. Survival analysis was performed to evaluate the effects of LNMM on prognosis. Results LNMM was detected in 423 lymph nodes from 72 patients. The results showed that invasion depth (OR = 3.755, P = 0.004), TNM staging (OR = 3.152, P = 0.002), lymphatic invasion (OR = 2.178, P = 0.009), and tumor differentiation (OR = 1.266, P = 0.013) were independent risk factors associated with LNMM. Survival analysis showed that patients with LNMM had significantly worse 5-year survival compared with those without LNMM (42% vs. 76.4%, P < 0.05). Multivariate analysis demonstrated that LNMM, tumor size, Lauren type, invasion depth, and lymphatic invasion (P < 0.05) were independently factors associated with 5-year survival. Conclusions The findings showed that tumor invasion depth, TNM staging, lymphatic invasion, and tumor differentiation were independent risk factors associated with LNMM occurrence. Moreover, LNMM is a clinically negative prognostic factor in pN0 GC patients.

Intraoperative Detection of Micrometastases in Whole Excised Lymph Nodes Using Fluorescent Paired-Agent Imaging Principles: Identification of a Suitable Staining and Rinsing Protocol.

Correctly identifying nodal status is recognized as a critical prognostic factor in many cancer types and is essential to guide adjuvant treatment. Currently, surgical removal of lymph nodes followed by pathological examination is commonly performed as a standard-of-care to detect node metastases. However, conventional pathology protocols are time-consuming, yet less than 1 % of lymph node volumes are examined, resulting in a 30-60 % rate of missed micrometastases (0.2-2 mm in size). This study presents a method to fluorescently stain excised lymph nodes using paired-agent molecular imaging principles, which entail co-administration of a molecular-targeted imaging agent with a suitable control (untargeted) agent, whereby any nonspecific retention of the targeted agent is accounted for by the signal from the control agent. Specifically, it was demonstrated that by dual-needle continuous infusion of either an antibody-based imaging agent pair (epidermal growth factor receptor (EGFR) targeted agent: IRDye-800CW labeled Cetuximab; control agent: IRDye-700DX-IgG) or an Affibody-based pair (EGFR targeted Affibody® agent: ABY-029; control agent IRDYe-700DX carboxylate) at 0.3 ml/min. The results demonstrated the possibility to achieve >99 % sensitivity and > 95 % specificity for detection of a single micrometastasis (~0.2 mm diameter) in a whole lymph node within 22 min of tissue processing time. The detection capabilities offer substantial improvements over existing intraoperative lymph node biopsy methods (e.g., frozen pathology has a micrometastasis sensitivity <20 %).

Modified Inguinal Lymph Node Dissection in Groin-Negative Patients of Penile Cancer: Our Experience.

Cancer of the penis is an important health problem in India, causing significant morbidity. Involvement of locoregional lymph nodes is the most significant prognostic factor for patients with penile cancer. In this study, we reviewed clinical data of all patients who underwent modified inguinal lymph node dissection as a means to diagnose micro-metastasis in inguinal lymph nodes, and analysed the outcomes. We retrospectively reviewed the hospital clinical charts of patients treated for carcinoma of the penis. Inguinal and distant metastases were assessed by physical examination, ultrasound imaging of the inguinal region, computed tomography of the abdomen and pelvis and a chest radiograph. Patients with clinically negative inguinal lymph nodes underwent modified lymph node dissection (mILND) both to diagnose and stage the disease. Complications occurring during a 30-day period after surgery were defined as early and thereafter as late complications. A total of 40 patients with a mean age of 52.27±13.10 (range 25-73) years underwent mILND. Wedge biopsy from the primary lesion had revealed intermediate-risk disease in 22 (55%) patients and high-risk disease in 18 (45%) patients. Histopathological examination of the primary penile lesion revealed a pT1 lesion in 32 patients and a pT2 lesion in the remaining 8 patients. Fourteen (35%) of the 40 patients showed micro-metastases in the inguinal lymph nodes on frozen sections. The mean follow-up in these patients was 56.6±18.09months. There were no instances of local or systemic recurrences seen in 38 (95%) patients within 5years. Superficial lymph node dissection and where facilities are available DSLNB remain the standard of care in the management of patients with clinically groin-negative (cN0) intermediate- and high-risk groups. Modified inguinal lymph node dissection would be a safe and appropriate alternative to this in all centres that do not have access to newer modalities like DSLNB, video-endoscopic (VEIL) or robotic-assisted techniques.

Influence of lymph node micrometastasis on the staging system for gastric cancer*

Abstract Objective The aim of this study was to investigate the effect of lymph node micrometastasis on the prognosis of patients with gastric cancer and the necessity of integrating it into the gastric cancer staging system. Methods In total, 241 patients with gastric cancer were included. Hematoxylin and eosin staining of lymph nodes was performed, and negative lymph nodes were evaluated by immunohistochemistry to detect micrometastases. Differences in survival rates between stages were evaluated. Results (1) A total of 78 patients (32.4%) had lymph node micrometastases. Compared with the group without micrometastases, the overall recurrence rate, lymph infiltration, vascular invasion, and nerve invasion rate in the micrometastasis group were significantly higher (P &lt; 0.05). (2) According to the standard N staging system, the rates of disease-free survival (DFS) for the N0, N1, N2, N3a, and N3b groups were 96.0%, 84.0%, 67.6%, 59.0%, and 21.7%, respectively. There was no significant difference in survival between N2 and N3a. The cumulative survival curves for N2 and N3a intersected. (3) The N stage of 38 patients (15.8%) differed between the traditional system and the new N staging system reflecting micrometastasis. The DFS for N0, N1, N2, N3a, and N3b were 97.0%, 86.3%, 74.2%, 65.4%, and 29.2%, respectively. There was no significant difference in survival between N2 and N3a, but the cumulative survival curves for N2 and N3a did not intersect. (4) Based on a Cox multivariate analysis, various independent risk factors for recurrence were identified (P &lt; 0.05). Conclusion Lymph node micrometastasis is an important risk factor for gastric cancer recurrence. Lymph node micrometastasis should be considered in TNM staging to determine prognosis and optimal treatment strategies.

Recognition of filigree pattern expands the concept of micropapillary subtype in patients with surgically resected lung adenocarcinoma.

Our study aimed to validate the clinicopathological characteristics and prognosis of lung adenocarcinoma (ADC) with a filigree pattern and to further investigate the relationship between the filigree pattern and the classical micropapillary (MP) pattern. We retrospectively reviewed the clinical and pathologic characteristics of 461 Chinese patients with completely resected ADC (stage I, 310; stage II, 44; stage III, 107). The filigree pattern was more likely to be observed in ADC with a higher stage (p = 0.003) and the classical MP pattern (p < 0.001). Patients with filigree-predominant ADC showed poor survival, similar to those with classical MP-predominant ADC. Multivariate analysis confirmed that the presence of the filigree pattern was an independent prognostic factor for recurrence-free survival (hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.50-2.68; p < 0.001) and overall survival (OS; HR, 1.83; 95% CI, 1.34-2.50; p < 0.001). Patients with both classical MP-positive and filigree-positive ADC had the worst survival compared with those with the filigree pattern or classical MP pattern alone. In stage I, ADC with both the filigree and classical MP patterns had a higher incidence of micrometastasis than ADC with the filigree pattern or classical MP pattern alone. Lymph node micrometastasis indicated poor survival in patients with ADC with the filigree pattern or classical MP pattern. Similar clinicopathologic features between patients with the filigree pattern and the classical MP pattern support the inclusion of the filigree pattern in the MP category. Recognition of the filigree pattern could provide helpful prognostic information, especially for stage I ADC.

Does small volume metastatic lymph node disease affect long-term prognosis in early cervical cancer?

Objective: As sentinel lymph node (SLN) biopsy is evolving to an accepted standard of care, clinicians are being faced with more frequent cases of small-volume nodal metastatic disease. The objective of this study was to describe the management and measure the effect on recurrence rates of nodal micrometastasis and isolated tumor cells (ITC) in patients with early-stage cervical cancer at 2 high-volume centers.

188 Poster - Outcomes of breast cancer patients with nodal micrometastasis treated with sentinel lymph node biopsy versus axillary lymph node dissection

188 Poster - Outcomes of breast cancer patients with nodal micrometastasis treated with sentinel lymph node biopsy versus axillary lymph node dissection

Does the presence of nodal micrometastases or isolated tumor cells increase the risk of recurrent endometrioid adenocarcinoma? A case control study

Objective: The purpose of this case control study was to explore whether the presence of micrometastases (MMs) or isolated tumor cells (ITCs) is associated with an increased the risk for recurrence in women with fully staged, stage I–II endometrioid endometrial cancer.

Invited Commentary: FIGO Staging Classification for Cervical Cancer-Behold the Big Picture.

Invited Commentary: FIGO Staging Classification for Cervical Cancer-Behold the Big Picture.

Detection of Micrometastasis in Bulky Lymph Nodes Cervical Carcinoma Stage IA-IIB Using Cytokeratin AE1/AE3

BackgroundCervical uterine carcinoma is a primary malignant disease of the uterine cervix. The presence or absence of metastasis in lymphnodes does not alter the stage but affects recurrence, survival, and therapy. Immunohistochemistry stains of the AE1/AE3cytokeratin can assist in the diagnosis and determine the small focus of carcinoma metastasis. In this study, we analyzedimmunohistochemistry cytokeratin AE1/AE3 could determine micrometastasis in bulky lymph nodes negative.MethodsThis study used cross-sectional design. The sample consisted of 52 cases of stage IA-IIB cervical carcinoma performed by radicalhysterectomy and lymphadenectomy accompanied by negative bulky lymph nodes at the Department of Anatomical PathologyFaculty of Medicine University of Indonesia/Cipto Mangunkusumo Hospital (FKUI/RSCM) from January 2011 to June 2017. Allcases stained by immunohistochemistry cytokeratin AE1/AE3.ResultsBulky Lymph Nodes Cervical Carcinoma stage IA-IIB, histopathologic diagnose of non keratinized squamous cell carcinoma,moderate differentiation degree, no lymphovascular invasion and deepest invasion &gt;5.0 mm. Immunohistochemistry staining ofAE1/AE3 cytokeratin showed no micrometastasis in all cases.ConclusionThe immunohistochemistry staining of AE1/AE3 cytokeratin used in Bulky Lymph Nodes Cervical Carcinoma stage IA-IIB could notdetected micrometastasis in all cases.

Flow Cytometry for Detection and Quantification of Micrometastases in Sentinel Lymph Nodes from Patients with Primary Melanoma

BackgroundDetection of micrometastases in the regional lymph nodes is one of the most important prognostic factors for melanoma patients. Our aim was to evaluate the suitability of flow cytometry for rapid quantification of disseminated melanoma cells in sentinel lymph nodes (SLN). Methods132 SLNs from 104 patients diagnosed with melanoma were analyzed by flow cytometry, utilizing the extracellular marker melanoma-associated chondroitin sulfate proteoglycan, in addition to quantitative immunocytology and conventional histopathology, including immunohistochemistry. For quantification, the number of melanoma-positive cells per million lymph node cells (disseminated cancer cell density, DCCD) detected by flow cytometry was compared to the DCCD obtained by immunocytology. ResultsCompared to histopathology and immunocytology, flow cytometry exhibited a sensitivity of 50% and a specificity of 85%. DCCDs of immunocytology and flow cytometry of the 37 immunocytologically positive SLNs showed a positive correlation (Spearman's ρ = 0.7, P < 0.0001). In 10 SLNs from 9 patients with high tumor load, the flow cytometric DCCD was 8-fold higher on average than the immunocytologic DCCD. ConclusionsAlthough flow cytometry is not yet suitable for early detection of metastatic melanoma, it promises to become a valuable tool for rapidly quantifying tumor load in high-risk patients.

The advantage of one-step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients.

Generally, the postoperative examination of lymph nodes (LNs) is based on a microscopic examination of one hematoxylin and eosin (HE)‐stained slide; however, an examination of only one part of the LN might lead to incorrect staging of the tumor due to tissue allocation bias. Although multilevel sectioning and the use of immunohistochemistry (IHC) have improved the detection of micrometastases in LNs, this approach is laborious, time‐consuming, and costly. A novel molecular technique for the detection of LN metastases of tumors, called one‐step nucleic acid amplification (OSNA), is a rapid and semi‐quantitative examination quantifying the number of cytokeratin 19 (CK‐19) mRNA copies derived from a tumor. OSNA is already in clinical use for the diagnosis of LN metastasis in breast cancer patients; however, the use of OSNA is under investigation with promising results for colorectal cancer (CRC). The present review assessed recent studies on OSNA vs a histopathological examination and its implications for CRC staging and treatment. A total of 16 studies of OSNA in CRC yielded by a PubMed search were reviewed. Among them, seven studies evaluating the diagnostic performance revealed that OSNA had a high specificity (96.8%), high concordance rate (96.0%), and negative predictive value (98.6%) in a pooled assessment. In addition, four studies examining the utility of OSNA in sentinel LNs (SLNs) and two studies focusing on upstaging in pathologically node‐negative CRC patients were also reviewed. Multicenter prospective studies with a large cohort of CRC patients are warranted to reveal the benefits of OSNA in the future.

Diagnostic criteria of sentinel lymph node micrometastasis or macrometastasis based on tissue rinse liquid-based cytology in gynecological cancer.

This study aimed to establish intraoperative diagnostic criteria of sentinel lymph node (SLN) micro-/macrometastasis on the basis of tissue rinse liquid-based cytology (TRLBC) in gynecological cancer. We enrolled 214 patients with gynecological cancer who underwent rapid diagnosis of SLN metastasis on the basis of TRLBC from a total of 490 SLNs. For slides that were classified as positive for atypical cells on cytological inspection, we counted the number of clusters (an atypical cell mass consisted of three or more cells) and the number of single cells (an atypical cell other than clusters). Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of predicting SLN micro-/macrometastasis. On cytological inspection, 36 slides were classified as positive for atypical cells, while 21 slides (4.3%) were true positive, 15 (3.1%) were false positive, and 454 (92.6%) were true negative. There were no false negative results in this study. The area under the ROC curve for the number of cluster was superior to that for the number of single cells for distinguishing micro-/macrometastasis from negative/isolated tumor cells (0.86 vs. 0.67, P = 0.032). The optimum cut-off value of the number of clusters was 5 for distinguishing these two categories. TRLBC is a highly sensitive alternative for detecting SLN metastasis as a rapid intraoperative diagnosis. Counting the number of atypical cell clusters might be useful for distinguishing micro-/macrometastasis from isolated tumor cells.