PURPOSE: Sentinel lymph node (SLN) biopsy (SLNB) is widely performed for axillary staging in patients with breast cancer. Based on the results of frozen section examination (FSE), surgeons can decide to continue further axillary dissections. This study aimed to verify the accuracy of FSE for SLNs. METHODS: We reviewed the records of 4,219 patients who underwent SLNB for primary invasive breast cancer between 2007 and 2016 at the Severance Hospital. We evaluated factors associated with the false-negative results of FSE for SLNs using the Generalized Estimating Equations model. RESULTS: A total of 1,397 SLNs from 908 patients were confirmed to be metastatic. Seventy-one patients (1.7%) had confirmed pathologic N2 or N3 stage. Among metastatic SLNs, micrometastasis was found in 234 (16.8%). The overall accuracy of SLNB was 98.5%. The sensitivity and false-negative rate of FSE were 86.4% and 13.6%, respectively. Several clinicopathological factors, including the size of SLN metastases, suspicious preoperative axillary lymph nodes, and luminal B subtype, were associated with a higher rate of false-negative results. CONCLUSION: Most patients were not indicated for axillary lymph node dissection. Some patients may show transition in their permanent pathology due to the size of the metastatic node. However, the false-negative results of FSE for SLNs based on the size of the metastatic node did not change our practice. Therefore, intraoperative FSE for SLN should not be routinely performed for all breast cancer patients.
Biopsy ; Breast Neoplasms ; Breast ; False Negative Reactions ; Frozen Sections ; Humans ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Pathology ; Phenobarbital ; Sentinel Lymph Node Biopsy ; Surgeons

PURPOSE: This preliminary study was conducted to evaluate the association between Oncotype DX (ODX) recurrence score and traditional prognostic factors. We also developed a nomogram to predict subgroups with low ODX recurrence scores (less than 25) and to avoid additional chemotherapy treatments for those patients. MATERIALS AND METHODS: Clinicopathological and immunohistochemical variables were retrospectively retrieved and analyzed from a series of 485 T1-3N0-1miM0 hormone receptor-positive, human epidermal growth factor 2‒negative breast cancer patients with available ODX test results at Asan Medical Center from 2010 to 2016. One hundred twenty-seven patients (26%) had positive axillary lymph node micrometastases, and 408 (84%) had ODX recurrence scores of ≤25. Logistic regression was performed to build a nomogram for predicting a low-risk subgroup of the ODX assay. RESULTS: Multivariate analysis revealed that estrogen receptor (ER) score, progesterone receptor (PR) score, histologic grade, lymphovascular invasion (LVI), and Ki-67 had a statistically significant association with the low-risk subgroup. With these variables, we developed a nomogram to predict the low-risk subgroup with ODX recurrence scores of ≤25. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval [CI], 0.85 to 0.96). When applied to the validation group the nomogram was accurate with an area under the curve = 0.88 (95% CI, 0.83 to 0.95). CONCLUSION: The low ODX recurrence score subgroup can be predicted by a nomogram incorporating five traditional prognostic factors: ER, PR, histologic grade, LVI, and Ki-67. Our nomogram, which predicts a low-risk ODX recurrence score, will be a useful tool to help select patients who may or may not need additional ODX testing.
Breast Neoplasms ; Breast ; Chungcheongnam-do ; Drug Therapy ; Epidermal Growth Factor ; Estrogens ; Female ; Humans ; Humans ; Logistic Models ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Micrometastasis ; Nomograms ; Prognosis ; Receptors, Progesterone ; Recurrence ; Retrospective Studies ; ROC Curve

PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). MATERIALS AND METHODS: Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed. RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs. CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.
Breast Neoplasms ; Breast ; Carcinoma, Ductal ; Chemotherapy, Adjuvant ; Cohort Studies ; Drug Therapy ; Epidermal Growth Factor ; Estrogens ; Humans ; Multivariate Analysis ; Neoplasm Micrometastasis ; Prognosis ; Recurrence

The incidence and mortality of lung cancer rank top in China. One important factor is the occurrence of metastasis. With the development of science technology, the effect of surgical treatment on lung cancer is improved. Moreover, the use of targeted therapy has achieved a new height for the treatment of lung cancer. However, the recurrence rate remains high even the tumor was completely resected at early stage. The occurrence of lymph node micrometastasis is considered as one of the plausible explanations. The difficulty indetecting micrometastasis has been greatly reduced. Although studies dig deeper into the lymph node micrometastasis, there are still some controversies including the selection of surgical procedures, the pathological staging and prognosis about patients with lymph node micrometastasis. This review manages to generalize the latest research progress of lymph node micrometastasis.
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Biomarkers, Tumor ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Neoplasm Micrometastasis ; Risk Factors

PURPOSE: Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma (HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR). MATERIALS AND METHODS: First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosed resectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determine their influence on survival. RESULTS: Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031–25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031–25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027–0.497; p=0.004). CONCLUSION: AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.
Carcinoma, Hepatocellular* ; Classification* ; Humans ; Liver Neoplasms* ; Liver* ; Neoplasm Micrometastasis* ; Prothrombin ; Recurrence ; Risk Factors ; Vitamin K

Although the incidence and mortality rate of gastric cancer have been steadily declining, gastric cancer is still the fourth most common cancer in the world and more than 50% of cases occur in Eastern Asia. In Korea, gastric cancer is the second most common cancer and third cause of cancer related death. The standard surgical procedure for resectable advanced gastric cancer is D2 lymphadenectomy with radical gastrectomy. Even though R0 resection was completed, recurrence is relatively common, and contributes to the limited survival of the patients in gastric cancer. As a clinically relevant factor for detection of the recurrence, the presence of isolating tumor cells has been introduced and it is so called as ‘micrometastasis’. Numerous immunohistochemistry and molecular studies have shown that micrometastasis can be demonstrated not only in lymph nodes but also in such body compartments as the bone marrow, peritoneal cavity and blood. Herein, we review the current knowledge and evidence of the prognostic significance of micrometastasis in peritoneal, lymph node, bone marrow. Also, we discuss the current state of research on the circulating tumor cell in peripheral blood.
Bone Marrow ; Far East ; Gastrectomy ; Humans ; Immunohistochemistry ; Incidence ; Korea ; Lymph Node Excision ; Lymph Nodes ; Mortality ; Neoplasm Micrometastasis* ; Neoplastic Cells, Circulating ; Peritoneal Cavity ; Prognosis ; Recurrence ; Stomach Neoplasms*

BACKGROUND/AIMS: Peritoneal micrometastasis is known to play an important role in the recurrence of gastric cancer. However, its effects remain equivocal. Herein, we examine the messenger RNA (mRNA) as tumor markers, carcinoembryonic antigen (CEA), and cytokeratin 20 (CK20), in peritoneal washing fluid. Moreover, we evaluate whether these results could predict the recurrence of gastric cancer following curative resection. METHODS: We prospectively enrolled 132 patients with gastric cancers, who had received an operation, between January 2010 and January 2013. The peritoneal lavage fluid was collected at the operation field and semi-quantitative PCR was performed using the primers for CEA and CK20. We excluded patients with stage IA (n=28) early gastric cancer, positive cytologic examination of peritoneal washings (n=7), and those who were lost during follow up (n=18). RESULTS: A total of 79 patients with gastric cancers were enrolled, and the mean follow-up period was 39.95±19.25 months (range, 5-72 months). According to the multivariate analysis, T4 stage at the initial diagnosis was significantly associated with recurrence. All cases of recurrence were CEA positive and 6 cases were CK20 positive. The positive and negative predictive values of CEA were 32.0% and 100%, respectively, whereas those of CK20 were 37.5% and 71.4%, respectively. Disease free survival of CK20-negative cases was 36.17±20.28 months and that of CK20-positive cases was 32.06±22.95 months (p=0.39). CONCLUSIONS: It is unlikely that the real time polymerase chain reaction results of mRNA for CEA and CK20 in peritoneal washing fluid can predict recurrence. However, negative results can convince surgeons to perform curative R0 resection.
Biomarkers, Tumor ; Carcinoembryonic Antigen* ; Diagnosis ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Keratin-20* ; Keratins* ; Multivariate Analysis ; Neoplasm Micrometastasis ; Peritoneal Lavage ; Polymerase Chain Reaction ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Recurrence ; RNA, Messenger* ; Stomach Neoplasms* ; Surgeons

PURPOSE: The lymph node ratio (LNR) is an important prognostic factor in papillary thyroid carcinoma (PTC), but micrometastases in cervical lymph nodes (LNs) are not of great clinical importance. In this study, we analyzed the accuracy of prediction of the prognosis depending on whether micrometastases were included in the number of metastatic LNs when calculating LNR. METHODS: The study included 353 PTC patients who underwent total thyroidectomy with neck LN dissection, and calculated LNR by 2 methods according to whether micrometastases were included in the number of metastatic LNs: Method 1 did not and method 2 did include. To compare the predictive values of LNR by the 2 methods, correlation coefficients and receiver operating characteristic (ROC) curves were analyzed. RESULTS: Positive correlations were found between LNR and preablation stimulated thyroglobulin (sTg) levels in both methods, but the correlation between method 1 LNR and preablation sTg level was significantly stronger than that for method 2 (Fisher z = 1.7, P = 0.045). The areas under these 2 independent ROC curves were analyzed; the prognostic efficacy of method 1 LNR was more accurate than that of method 2 LNR, and the difference was statistically significant (P = 0.0001). CONCLUSION: Regional recurrence of PTC can be predicted more accurately by not including micrometastases in the number of metastatic LNs when calculating LNR.
Humans ; Lymph Nodes* ; Methods ; Neck ; Neoplasm Micrometastasis* ; Prognosis ; Recurrence ; ROC Curve ; Thyroglobulin ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

OBJECTIVEWe established an animal model of nude mice with Tca8113 tumor and cut some tissue for biopsy. We also determined the biological behavior and mechanisms of the tumor.

METHODSThe mice were divided into two groups randomly. Mice in both groups were injected with Tca8113 cells into their tongues. The survival condition, growth of primary focus, and metastasis were observed. Hematoxylin and eosin staining and immunohistochemistry were performed on nuclear factor κB (NF-κB), matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 (SDF-1), and Ki67 to determine their distributions within the tumor. Cytokeratin staining was also performed to detect micrometastasis in the submandibular lymph nodes.

RESULTSThe emerging rate of tumor was 97.92%. The weight and survival time of the experimental group were lower than that of the control group, whereas the metastasis ratio was higher. The expression of NF-κB, MMP-9, SDF-1, and MMP-9 in tumors was higher in the experimental group than that in the control group. The expression of NF-κB, MMP-9, VEGF, and SDF-1 was relevant. The microvessel density of the experimental group was higher than that in the control group.

CONCLUSIONSBiopsy can affect the biological behavior of tongue tumor and can promote growth of primary focus and metastasis.

Animals ; Biopsy ; Cell Line, Tumor ; Chemokine CXCL12 ; Disease Models, Animal ; Immunohistochemistry ; Lymph Nodes ; Mice ; Mice, Nude ; NF-kappa B ; Neoplasm Micrometastasis ; Neoplasms ; Vascular Endothelial Growth Factor A

PURPOSE: Early diagnosis of gastric cancer is still the exception in Western countries. In the East, as in Japan and Korea, this disease is an endemic disorder. More conservative surgical procedures are frequently performed in early gastric cancer cases in these countries where sentinel lymph node navigation surgery is becoming a safe option for some patients. This study aims to evaluate preliminary outcomes of patients with early gastric cancer who underwent sentinel node navigation surgeries in Brazil, a country with non-endemic gastric cancer levels. MATERIALS AND METHODS: From September 2008 to March 2014, 14 out of 205 gastric cancer patients underwent sentinel lymph node navigation surgeries, which were performed using intraoperative, endoscopic, and peritumoral injection of patent blue dye. RESULTS: Antrectomies with Billroth I gastroduodenostomies were performed in seven patients with distal tumors. The other seven patients underwent wedge resections. Sentinel basin resections were performed in four patients, and lymphadenectomies were extended to stations 7, 8, and 9 in the other 10. Two patients received false-negative results from sentinel node biopsies, and one of those patients had micrometastasis. There was one postoperative death from liver failure in a cirrhotic patient. Another cirrhotic patient died after two years without recurrence of gastric cancer, also from liver failure. All other patients were followed-up for 13 to 79 months with no evidence of recurrence. CONCLUSIONS: Sentinel lymph node navigation surgery appears to be a safe procedure in a country with non-endemic levels of gastric cancer.
Biopsy ; Brazil ; Early Diagnosis ; Gastrectomy ; Gastroenterostomy ; Humans ; Japan ; Korea ; Liver Failure ; Lymph Node Excision ; Lymph Nodes* ; Neoplasm Micrometastasis ; Recurrence ; Sentinel Lymph Node Biopsy ; Stomach Neoplasms*