• Journal of Gastric Cancer
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• 제15권1호
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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.

• Journal of Chest Surgery
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• 제36권5호
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• pp.348-355
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• 2003

배경: 폐암에서 임파절 전이는 가장 중요한 예후 인자로 알려져 있다. 그러나 임파절에 전이 병소가 없는 제1기 비소세포 폐암의 경우에도 근치적 절제술 후 약 30∼40%의 환자가 종양의 재발이나 원격 전이로 사망하게 된다. 이것은 진단 혹은 수술 당시 이미 국소 임파절이나 다른 장기에 미세전이가 일어났을 가능성을 시사한다. 이에 저자들은 근치적 절제술을 시행한 제1기 비소세포 폐암 환자의 임파절을 면역조직화학 염색하여 임파절 미세전이를 조사하고, 미세전이 여부와 임상양상과의 연관성을 알아보았다. 대상 및 방법: 종격동 및 폐문부 임파절 절제술과 함께 근치적 절제술이 시행된 원발성 폐암 환자 중, 술 후 제1기 비소세포 폐암 환자로 확진된 41명으로부터 절제된 506개의 임파절을 anti-cytokeratin 항체를 이용한 면역조직화학염색법을 이용하여 미세전이 여부를 조사하였다. 결과: 대상환자 총 41명 중 14명(34.1%)에서 임파절 미세전이가 발견되었으며, 미세전이 여부는 여러 임상 병리학적 요소들과 유의한 관련성을 보이지 않았다. 평균 50개월의 추적 기간에 미세전이 양성군의 재발률은 57.1%로 음성군(37.0%)에 비해 높았으나 통계적 유의성은 없었다(p=0.22). 또한 미세전이 양성군의 5년 무병생존율은 48.2%로 64.1%인 음성군에 비해 낮은 경향을 보였지만 한계적 유의성만을 확인할 수 있었다(p=0.11). 그러나 2개 이상의 임파절에서 미세전이가 발견된 환자들의 5년 무병생존율은 25.0%로서 다른 환자들에 비해 통계적으로 유의하게 낮았다(p=0.02). 다변량 분석 결과, 제1기 비소세포 폐암 환자에 있어서 다발성 임파절 미세전이는 독립적인 재발의 예측인자임을 확인할 수 있었다(p=0.028). 결론: 항cytokeratin 항체를 이용한 면역조직화학염색을 통하여 신속하고 용이하게 임파절 미세전이를 발견할 수 있었다. 제1기 비소세포 폐암 환자에서 임파절 미세전이가 예후에 나쁜 영향을 미침을 통계적으로 유의하게 입증하지는 못하였지만 그 경향은 밝혀 낼 수 있었고, 특히 다발성 임파절 미제전이가 재발에 영향을 주는 독립적인 예후인자임을 밝혀낼 수 있었다.

• Journal of Gastric Cancer
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• 제2권1호
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제31권2호
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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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• 제14권4호
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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.

• Tuberculosis and Respiratory Diseases
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• 제57권4호
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• pp.345-350
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• 2004

연구 배경 : 병리적 병기 I기의 비소세포 폐암 환자를 대상으로 림프절 미세 전이의 빈도와 임상적 의의를 알아보고자 연구를 하였다. 방 법 : 수술적 절제를 시행한 29예의 환자에서 총 806개의 파라핀 포매 상태로 보관된 종격동 림프절을 이용하였다. 미세 전이를 확인하기 위하여 림프절 파라핀 불럭으로 2개의 절편을 만들었고 첫 번째 절편은 H & E 염색을, 두 번째 절편은 cytokeratin AE1/AE3 항체를 이용하여 암세포의 미세 전이를 확인하고자 면역 조직화학 염색을 하였다. 결 과 : 대상 환자의 병리적 병기 IA는 10예 이었고 IB는 19예이었다. 면역 조직화학 염색을 시행한 파라핀 블록 수는 총 246개이었고 림프절 수는 총 806개이었다. H & E 염색으로 총 806개의 림프절을 관찰하였으나 암세포의 미세 전이는 관찰되지 않았다. Cytokeratin AE1/AE3 항체를 이용한 면역 조직화학 염색에서 총 806개의 림프절 중 3개(0.37%)에서 관찰되었다. 대상 환자의 평균 관찰 기간은 34.2개월이었고 관찰 기간 중 9예에서 사망이 관찰되었다. 사망 원인은 폐암 진행: 4예, 수술 후 합병증: 3예, 동반 질환: 2예 이었다. 질병의 진행으로 사망한 환자 모두에서 림프절 미세 전이 소견이 관찰되지 않았으며, 림프절 미세 전이가 관찰된 3예의 환자 모두 생존 중이다. 결 론 : 림프절 미세 전이를 발견을 위한 면역 조직화학 염색은 시행한 806개의 림프절중 0.37%에서만 미세전이가 관찰되어 임상적 상용에 어려움이 있을 것으로 생각된다.

• Journal of Gastric Cancer
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• 제16권1호
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• pp.14-20
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• 2016

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.

• Archives of Plastic Surgery
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• 제42권4호
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• pp.478-483
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• 2015

Due to the fact that it reliably results in positive outcomes, lymph node flap transfer is becoming an increasingly popular surgical procedure for the prevention and treatment of lymphedema. This technique has been shown to stimulate lymphoangiogenesis and restore lymphatic function, as well as decreasing infection rates, minimizing pain, and preventing the recurrence of lymphedema. In this article, we investigate possible additional benefits of lymph node flap transfer, primarily the possibility that sentinel lymph nodes may be used to detect micrometastasis or in-transit metastasis and may function as an additional lymphatic station after the excision of advanced skin cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.55-60
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• 2014

Background: Whether sentinel lymph node biopsy (SLNB) should be performed in patients with pure ductal carcinoma in situ (DCIS) of the breast has been a question of debate over the last decade. The aim of this study was to identify factors associated with microinvasive disease and determine the criteria for performing SLNB in patients with DCIS. Materials and Methods: 125 patients with DCIS who underwent surgery between January 2000 and December 2008 were reviewed to identify factors associated with DCIS and DCIS with microinvasion (DCISM). Results: 88 patients (70.4%) had pure DCIS and 37 (29.6%) had DCISM. Among 33 DCIS patients who underwent SLNB, one patient (3.3%) was found to have isolated tumor cells in her biopsy, whereas 1 of 14 (37.8%) patients with DCISM had micrometastasis (7.1%). Similarly, of 16 patients (18.2%) with pure DCIS and axillary lymph node dissection (ALND) without SLNB, none had lymph node metastasis. Furthermore, of 20 patients with DCISM and ALND, only one (5%) had metastasis. In multivariate analysis, the presence of comedo necrosis [relative risk (RR)=4.1, 95% confidence interval (CI)=1.6-10.6, P=0.004], and hormone receptor (ER or PR) negativity (RR=4.0, 95%CI=1.5-11, P=0.007), were found to be significantly associated with microinvasion. Conclusions: Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with comedo necrosis or hormone receptor negativity are more likely to have a microinvasive component in definitive pathology following surgery, and should be considered for SLNB procedure along with patients who will undergo mastectomy due to DCIS.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.317-321
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• 2016

Detection of micrometastasis in sentinel lymph nodes (SLNs) is a very useful tool for appropriate assessment of the clinical stage of disease in breast cancer patients. Early identification of clinically relevant disease could lead to early treatment or staging approaches for breast cancer patient. Micrometastases in SLNs of women with invasive breast cancer are of great significance in this context. In this study we examined SLN biopsies considered to have small numbers of cancerous cells by real time RT-PCR. All of the samples underwent immunohistochemical staining for cytokeratin for confirmation of the presence or absence of micrometastases. BUB1b expression assay of selected patients with and without metastasis showed overexpression in the former, but not in normal breast and lymph node tissue. Our results may be taken into account in the discussion about the merits of routine use of molecular assessment in pathogenetic studies of SLNs.