• Journal of Gastric Cancer
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• v.15 no.1
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• pp.1-9
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• 2015

Recently, lymph node micrometastasis has been evaluated for its prognostic value in gastric cancer. Lymph node micrometastasis cannot be detected via a usual pathologic examination, but it can be detected by using some other techniques including immunohistochemistry and reverse transcription-polymerase chain reaction assay. With the development of such diagnostic techniques, the detection rate of lymph node micrometastasis is constantly increasing. Although the prognostic value of lymph node micrometastasis remains debatable, its clinical impact is apparently remarkable in both early and advanced gastric cancer. At present, studies on the prognostic value of lymph node micrometastasis are evolving to overcome its current limitations and extend the scope of its application.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8387-8390
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• 2016

Background: Treatment of biochemical failure after radical prostatectomy for prostate cancer is largely empirically based. The use of PSA kinetics has been used as a guide to determine local or systemic treatment of biochemical failure. We here compared PSA kinetics with detection of bone marrow micrometastasis as methods to determine local or systemic relapse. Materials and Methods: A transversal study was conducted of men with biochemical failure, defined as a serum PSA >0.2ng/ml after radical prostatectomy. Consecutive patients having undergone radical prostatectomy and with biochemical failure were enrolled and clinical and pathological details were recorded. Bone marrow biopsies were obtained from the iliac crest and touch prints made, micrometastasis (mM) being detected using anti-PSA. The clinical parameters of total serum PSA, PSA velocity, PSA doubling time and time to biochemical failure, age, Gleason score and pathological stage were registered. Results: A total of 147 men, mean age $71.6{\pm}8.2years$, with a median time to biochemical failure of 5.5 years (IQR 1.0-6.3 years) participated in the study. Bone marrow samples were positive for micrometastasis in 98/147 (67%) of patients at the time of biochemical failure. The results of bone marrow micrometastasis detected by immunocytochemistry were not concordant with local relapse as defined by PSA velocity, time to biochemical failure or Gleason score. In men with a PSA doubling time of < six months or a total serum PSA of >2,5ng/ml at the time of biochemical failure the detection of bone marrow micrometastasis was significantly higher. Conclusions: The detection of bone marrow micrometastasis could be useful in defining systemic relapse, this minimally invasive procedure warranting further studies with a larger group of patients.

• Journal of Chest Surgery
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• v.36 no.5
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• pp.348-355
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• 2003

Background: The prognostic significance of lymph node micrometastasis in non-small cell lung cancer remains controversial. We therefore investigated the clinicopathologic factors related to lymph node micrometastsis and evaluated the clinical relevance of micrometastasis with regard to recurrence. Material and Method: Five hundred six lymph nodes were obtained from 41 patients with stage 1 non-small ceil lung cancer who underwent curative resection between 1994 and 1998. Immunohistochemical staining using anti-cytokeratin Ab was used to detect micrometastasis in these lymph nodes. Result: Micrometastatic tumor cells were identified in pN0 lymph nodes in 14 (34.1%) of 41 patients. The presence of lymph node micrometastasis was not related to any clinicopathoiogic factor (p) 0.05). The recurrence rate was higher in patients with micrometastasis (57.1%) than in those without (37.0%), but the difference was not significant (p=0.22). Patients with micrometastasis had a lower 5-year recurrence-free survival rate (48.2%) than those without micrometastasis (64.1%), with a borderline significance (p=0.11), The S-year recurrence-free survival rate (25.0%) in the patients with 2 or more micrometastatic lymph nodes was significantly lower than that in the patients with no or single micrometastasis (p=0.02). In multivariate analysis, multiple lymph node micromestasis us was a significant independent predictor of recurrence (p=0.028, Risk ratio=3.568). Conclusion: Immunehistochemical anti-cytokeratin staining was a rapid, sensitive, and easy way of detecting lymph node micrometastasis. The presence of lymph node micrometastasis was not significantly associated with the recurrence, but had a tendency toward a poor prognosis in stage 1 non-small cell lung cancer. Especially, the presence of multiple micrometastatic lymph nodes was a significant and independent predictor of recurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2657-2662
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• 2013

Background: Intraoperative sentinel lymph node biopsy has now become the standard of care for patients with clinically node negative breast cancer for diagnosis and also in order to determine the need for immediate axillary clearance. Several large scale studies confirmed the diagnostic reliability of this method. However, micrometastases are frequently missed on frozen sections. Recent studies showed that both disease free interval and overall survival are significantly affected by the presence of micrometastatic disease. The aim of this study was to determine the sensitivity and specificity of intraoperative frozen section analysis of sentinel lymph nodes (SLNs) for the detection of breast cancer micrometastasis and to evaluate the status of non-sentinel lymph nodes (non-SLNs) in those patients subjected to further axillary sampling. Materials and Methods: We performed a retrospective study on 154 patients who underwent SLN biopsy from January 2008 till October 2011. The SLNs were sectioned at 2 mm intervals and submitted entirely for frozen sections. Three levels of each section submitted are examined and the results were compared with further levels on paraffin sections. Results: Overall 40% of patients (62/154) were found to be SLN positive on final (paraffin section) histology, out of which 44 demonstrated macrometastases (>2mm) and 18 micrometastases (<2mm). The overall sensitivity and specificity of frozen section analysis of SLN for the detection of macrometastasis was found to be 100% while those for micrometastasis were 33.3% and 100%, respectively. Moreover 20% of patients who had micrometastases in SLN had positive non-SLNs on final histology. Conclusions: Frozen section analysis of SLNs lacks sufficient accuracy to rule out micrometastasis by current protocols. Therefore these need to be revised in order to pick up micrometastasis which appears to have clinical significance. We suggest that this can be achieved by examining more step sections of blocks.

• Journal of Gastric Cancer
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• v.2 no.1
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• pp.5-11
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• 2002

Purpose: The purpose of this study is to identify immunohistochemical evidence of lymph-node micrometastasis in histologic node-negative gastric cancer patients and to evaluate the prognostic significance of lymph-node micrometastasis.Materials and Methods: A retrospective study of 50 gastric cancer patients who underwent curative resections from October 1990 to November 1994 was performed. Two consecutive sections were prepared: one for ordinary hematoxylin and eosin staining, and the other for immunohistochemical staining with Pan cytokeratin antibody (Novocastra, UK). In the univariate analysis, the survival rate was calculated using the Life Table Method, and the multivariate analysis was determined using a Cox Proportional HazardsModel. The statistical analyses of the relationships between the clinicopathologic factors and micrometastases were performed by using a Chi-square test. Results: Of 2522 harvested lymph nodes, 81 ($4.1\%$) nodes and 19 ($38\%$) of 50 patients were identified as having lymphnode micrometastases by using immunohistochemical staining for cytokeratin. The incidence of lymph-node micrometastases was significantly higher in diffuse type carcinomas ($54\%$, P=0.024) and in patients with serosal invasion ($52.2\%$, P=0.05). For patients with lymph-node micrometastases (n=19), the 5-year survival rate was significantly decreased ($73.7\%$, P=0.015). The Lauren's classirication (P=0.021) and the depth of invasion (P=0.035) were shown by multivariate analysis to have a significant relationship with the presence of micrometastases. Multivariate analysis revealed that lymph-node micrometastasis was independently correlated with survival in histologic node-negative gastic cancer patients. Conclusion: The presence of cytokeratin detected lymphnode micrometastases correlates with the worse prognosis for patients with histologic node-negative gastric cancer.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.345-350
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• 2004

Background : To evaluate the frequency and clinical significance of lymph node micrometastasis in patients of non-small-cell lung cancer pathologically staged to be T1-2,N0. Method : From consecutive 29 patients of non-small-cell lung cancer who received curative operation and routine systemic nodal dissection, we immunohistochemically examined 806 lymph nodes from mediastinal, hilar and peribronchial lesion. All slides were stained with hematoxylin and eosin staining for one section and with cytokeratin AE1/AE3 antibody for another consecutive section of same lymph node to find out micrometastasis. Results : In 806 lymph nodes examined, no tumor cell was seen on hematoxylin and eosin staining and micrometastic foci were shown to be on 0.37%(3) of 806 lymph nodes, in which were upper paratracheal, interlobar and peribronchial lymph node. These three positive stains constitute 10.3%(3) of the 29 patients with non-small-cell lung cancer. Nine patients died from disease progression(4), postoperative complication(3) and concomitant diseases(2). The four patients with disease progression did not show evidence of micrometastasis on their lymph node examination. Conclusion : The frequency of lymph node micrometastasis was in 0.37% of 806 lymph nodes examined. The study results might suggested that routine analysis of micrometastasis on the lymph node didn't give any clinical implication on patients with non-small-cell lung cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.2
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• pp.105-115
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• 2005

Purpose: The lymph node status assessed by conventional histological examination is the most important prognostic factor in patients undergoing surgery for oral squamous cell carcinoma. The presence of lymph node metastasis has a strong adverse impact on patient survival even after extended radical resection. Despite these findings, tumour recurrence is not rare after surgery, even when histological examination shows no lymph node metastasis. Recently, molecular-genetically and immunohistochemically demonstrated micrometastasis to the lymph nodes has been shown to have a significant adverse influence on survival in patients with squamous cell carcinoma and histologically negative nodes. The present study sought to determine the incidence and clarify the clinical significance of molecular-genetically and immunohistochemically demonstrated nodal micrometastases and to correlate these data with the stage of oral cancer. Methods: Lymph nodes systematically removed from 71 patients who underwent curative resection between 1998 and 2003 with head and neck squamous cell carcinoma were examined molecular-genetically to detect cytokeratin 5 mRNA with RT-PCR and immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes. Results: micrometastases were detected in 43(60%) of 71 patients by RT-PCR and 26(36%) of 71 patients by immunohistochemistry. By RT-PCR analysis, patients exhibiting a positive band for CK 5 mRNA had a significantly worse prognosis than those were RT-PCR negative. By immunohistochemistry, the presence of micrometastasis did not predict patient outcome. Conclusion: Micrometastases detected by RT-PCR may be of clinical value in identifying patients who may be at high risk for recurrence and who are therefore likely to benefit from systemic adjuvant therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5057-5061
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• 2016

The present study was conducted to assess error rates with diagnosis using intra-operative frozen sections, and to indicate ways to increase overall performance. Over a period of two years, 227 cases were biopsied intra-operatively. Errors were observed in 14 cases. Four of these were sampling errors, one by a pathologist and three by surgeons. In seven cases incorrect interpretations were made. Epithelial dysplasia was observed on definitive histology in two cases which was not reported intra-operatively. One case was of ectopic thyroid. In cases of oral cancer where sentinel lymph nodes were sampled, immunohistochemistry for cytokeratin was performed to facilitate identification of micrometastasis. Only single case displayed tumor deposits which was not evident morphologically. Resection margins were reported in seventy eight cases. Some 18% (14/50) benefited from revision of margins; overall sensitivity of intra-operative frozen sections for marginal status was 71.4%, with a specificity of 90.3%. Overall sensitivity was 75% and specificity was 97.5%. Careful observation, pathologist experience and knowledge of limitations help in improving the overall diagnostic outcome.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.797-806
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• 1999

Background: About 20% of small cell lung cancer(SCLC) patients have bone marrow(EM) metastasis at the time of diagnosis and the remaining patients are also considered with micrometastasis. In an attempt to detect EM micrometastasis, we used cytokeratin(CK)-20 as a molecular marker, which is specific for epithelial cells. Method: A sensitive RT-PCR assay was used to compare CK-20 expression both in SCLC cell line H209 and normal leukocyte and to evaluate EM aspirates of 28 SCLC patients. Result: H209 cell line showed CK-20 expression but normal leukocyte did not, suggesting CK-20 expression is lung tissue-specific. Of 28 patients(11 limited disease, 17 extensive disease), only 2(1/11, 1/17) samples tested revealed positive signal for CK-20. Two patients with CK-20 expression had EM metastasis or multiple bone involvement during follow-up. Conclusion: Although circulating tumor cells were detected in EM of small portion of patients with bone metastasis, CK-20 doesn't seem to be a reliable marker for the detection of micrometastasis in SCLC. This study emphasizes that identification of more specific marker for micrometastsis is mandatory prior to clinical application.

• Journal of Gastric Cancer
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• v.3 no.3
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• pp.128-133
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• 2003

Purpose: The benefits of the 'no-touch' isolation techniquethat is usually performed to prevent the circulation of tumor cells are not evident. The aim of this study was to determine whether the no-touch isolation technique for treating gastrointestinal cancers could prevent the circulation of tumor cells detected by reverse transcriptase polymerase chain reaction (RT-PCR). Matrials and Methods: By using RT-PCR to amplify mRNAs for two specific epithelial markers, carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20), we examined 34 gastric cancer patients who had been histologically diagnosed and 22 patients had undergone serosal and peritoneal brushing. Results: In 10 ($29.4\%$) of the 34 gastric cancer patients, we detected CK20 mRNA before manipulation, and in 17 ($51.5\%$) of those patients, after we detected it. The density of the CK20 mRNA band was increased in 11 cases ($33.3\%$) and the density was decreased in 2 cases ($6.1\%$). In 16 ($48.5\%$) of the 34 gastric cancer patients, we detected CEA mRNA before manipulation, and in 17 ($51.5\%$) patients after we detected it. The density of the CEA mRNA band was increased in 8 cases ($24.2\%$) and decreased in 3 cases ($9.1\%$). Conclusion: These result suggest that the ' no-touch isolation technique ' might be useful when operating on advanced gastric cancer patients and that serosal or Douglas pouch brushing can be used to determine the status of micrometastasis.