Factores perioperatorios, inmunidad y recurrencia del cáncer / Perioperative factors, immunity and cancer recurrence

Introducción: Los criterios de calidad en la cirugía oncológica radical se basan en la extirpación completa del tumor, con márgenes libres, sin enfermedad macroscópica residual, con una linfadenectomía adecuada y mínima manipulación tumoral posible. A pesar de conseguir estos objetivos, puede quedar enfermedad residual no visible o micrometástasis, con potencial de crecimiento y diseminación dependiendo de la capacidad tumoral y de las defensas del huésped. Objetivos: Evaluar la influencia de los factores perioperatorios sobre la inmunidad del paciente oncológico intervenido quirúrgicamente y el efecto potencial de los fármacos anestésicos en la recurrencia, así como otros factores perioperatorios que pueden afectar la diseminación tumoral a largo plazo. Métodos: Se realizó una búsqueda bibliográfica electrónica de los artículos de los últimos 10 años que cumplieran con el objetivo trazado. Desarrollo: Durante el periodo perioperatorio la activación de la respuesta al estrés quirúrgico desencadena una serie de reacciones neuroendocrinas, humorales e inmunitarias complejas. La cirugía, con indudable potencial curativo, se relaciona con un estado de inmunosupresión por activación del eje HPA (hipotálamo- hipofisario- adrenal) y la inflamación. Por otro lado, la anestesia produce cambios biomoleculares que afectan la inmunidad celular y el número de NK (natural killer), que puede influir en la recurrencia del cáncer a largo plazo. Conclusiones: Disminuir el estrés quirúrgico y el psicológico, controlar el dolor quirúrgico, mantener normotermia, y una juiciosa transfusión sanguínea, además una técnica anestésica con disminución del consumo de opiáceos, puede resultar favorecedora para proteger la respuesta inmune antimetastásica del organismo y puede tener un efecto benéfico en la enfermedad oncológica(AU)

Introduction: The quality criteria in radical oncological surgery are based on complete tumor removal, with free margins, without residual macroscopic disease, with adequate lymphadenectomy and minimal possible tumor manipulation. Despite achieving these objectives, non-visible residual disease or micrometastasis may remain, likely to grow and spread depending on tumor capacity and the host's defenses. Objectives: To evaluate the influence of perioperative factors on the immunity of cancer patients operated on and the potential effect of anesthetic drugs on recurrence, as well as other perioperative factors that may affect long-term tumor spread. Methods: An electronic bibliographic search was carried out of the articles published in the last ten years and that fulfilled the established objective. Development: During the perioperative period, activation of the response to surgical stress triggers a series of complex neuroendocrine, humoral and immune reactions. Surgery, with unquestionable curative potential, is related to a state of immunosuppression due to activation of the hypothalamic-pituitary-adrenal axis and inflammation. On the other hand, anesthesia produces biomolecular changes that affect cellular immunity and the number of natural killers, which can influence cancer recurrence in the long term. Conclusions: To reduce surgical and psychological stress, to control surgical pain, to maintain normothermia, and a judicious blood transfusion, in addition to an anesthetic technique with reduced opiates usage, can be beneficial to protect the body's antimetastatic immune response and can have a beneficial effect on oncological disease(AU)

Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases / Journal of the Korean Cancer Association, 대한암학회지

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.

A Nomogram for Predicting the Oncotype DX Recurrence Score in Women with T1-3N0-1miM0 Hormone Receptor‒Positive, Human Epidermal Growth Factor 2 (HER2)‒Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

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.

Is the frozen section examination for sentinel lymph node necessary in early breast cancer patients?

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.

Intraoperative imprint cytology versus histological diagnosis for the detection of sentinel lymph nodes in breast cancer treated with neoadjuvant chemotherapy

OBJECTIVES: To compare imprint cytology and paraffin section histology for sentinel lymph node detection in women with breast cancer treated with neoadjuvant chemotherapy. METHOD: A cross-sectional study and report of the sentinel lymph node statuses of 64 patients with breast cancer who underwent intraoperative imprint cytology and neoadjuvant chemotherapy in a referral cancer institute in Rio de Janeiro, Brazil, between 2014 and 2016. RESULTS: The mean age was 51 years. The most common histological type was invasive ductal carcinoma (93.75%), and the most common differentiation grade was 2 (62.5%). Overall, 153 lymph nodes were identified, with a mean of 2.39/case. Thirty-four lymph nodes tested positive for malignancy by imprint cytology, and 55 tested positive by histology. Of the 55 positive lymph nodes, 41 (74.5%) involved macrometastases, and 14 (25.5%) involved micrometastases. There were 21 false negatives with imprint cytology, namely, 7 for macrometastases and 14 for micrometastases, resulting in a rate of 17.6%. The sensitivity of imprint cytology was 61.8%, with a specificity and positive predictive value of 100%, a negative predictive value of 82.4% and an accuracy of 86.3%. The method presented null sensitivity for the identification of micrometastases. CONCLUSIONS: The false-negative rate with imprint cytology was associated with the number of sentinel lymph nodes obtained. The rate found for complete response to neoadjuvant chemotherapy was comparable to the rates reported in the literature. The accuracy of imprint cytology was good, and its specificity was excellent for sentinel lymph node detection; however, the method was unable to detect lymph node micrometastases.

Research Progress of Lymph Node Micrometastasis in Non-small Cell Lung Cancer / 中国肺癌杂志

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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Detection of occult lymph node tumor cells in node-negative gastric cancer patients / Identificação de células tumorais ocultas em linfonodos de pacientes com câncer gástrico classificados como pn0

ABSTRACT Background: The presence of lymph nodes metastasis is one of the most important prognostic indicators in gastric cancer. The micrometastases have been studied as prognostic factor in gastric cancer, which are related to decrease overall survival and increased risk of recurrence. However, their identification is limited by conventional methodology, since they can be overlooked after routine staining. Aim: To investigate the presence of occult tumor cells using cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically lymph node negative (pN0) by H&E. Methods: Forty patients (T1-T4N0) submitted to a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The results for metastases, micrometastases and isolated tumor cells were also associated to clinicopathological characteristics and their impact on stage grouping. Tumor deposits within lymph nodes were defined according to the tumor-node-metastases guidelines (7th TNM). Results: A total of 1439 lymph nodes were obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in 24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006) and perineural invasions (p=0.04), as well as peritumoral lymphocytic response (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally negative lymph nodes by H&E. The histologic stage of two patients was upstaged from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three among 12 CK-positive patients (25%) had disease recurrence (p=0.65). Conclusion: The CK-immunostaining is an effective method for detecting occult tumor cells in lymph nodes and may be recommended to precisely determine tumor stage. It may be useful as supplement to H&E routine to provide better pathological staging.

RESUMO Racional: A presença de metástase em linfonodos é um dos indicadores prognósticos mais importantes no câncer gástrico. As micrometástases têm sido estudadas como fator prognóstico no câncer gástrico, sendo relacionadas à diminuição da sobrevida global e aumento do risco de recidiva da doença. Entretanto, sua identificação é limitada pela metodologia convencional, uma vez que podem não ser identificadas pela rotina histopatológica por meio da coloração de H&E. Objetivo: Investigar a presença de células tumorais ocultas através de imunoistoquimica utilizando as citoqueratinas (CK) AE1/AE3 em pacientes com câncer gástrico com linfonodos histologicamente classificados como negativos por H&E. Métodos: Quarenta pacientes (T1-T4N0) submetidos à gastrectomia potencialmente curativa com linfadenectomia D2 foram avaliados. A presença de metástases, micrometástases e células tumorais isoladas foram correlacionadas com características clínicopatológicas e impacto no estadiamento. Os depósitos tumorais nos linfonodos foram classificados de acordo com o sistema TNM (7º TNM). Resultados: Um total de 1439 linfonodos foi obtido (~36 por paciente). Células tumorais foram detectadas por imunoistoquimica em 24 linfonodos de 12 pacientes (30%). As células neoplásicas estavam presentes na forma isolada ou em cluster. Invasão tumoral (p=0,002), venosa (p=0,016), linfática (p=0,006) e perineural (p=0,04), assim como resposta linfocítica peritumoral (p=0,012) foram correlacionadas com linfonodos CK-positivos que originalmente eram negativos à H&E. Dois pacientes tiveram o estadiamento alterado, migrando do estádio IB para IIA. Quatro dos 28 CK-negativos (14,3%) e três dos 12 CK-positivos (25%) tiveram recorrência da doença (p=0,65). Conclusão: A imunoistoquimica é meio eficaz para a detecção de células tumorais ocultas em linfonodos, podendo ser recomendada para melhor determinar o estágio do tumor. Ela pode ser útil como técnica complementar à rotina de H&E, de modo a fornecer melhor estadiamento patológico.

Significance of micrometastases in the calculation of the lymph node ratio for papillary thyroid cancer

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.

Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma

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.

Micrometastasis in Gastric Cancer / 대한소화기학회지

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.

The Detection of Messenger RNA for Carcinoembryonic Antigen and Cytokeratin 20 in Peritoneal Washing Fluid in Patients with Advanced Gastric Cancer / 대한소화기학회지

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.

Diagnosis of micrometastasis in muscle invasive bladder cancer through immunohistochemistry analysis: is there indication for routine evaluation?

Background: Muscle invasive bladder cancer (BC) has a mortality rate of 50% in 5 years, despite the aggressive treatments currently used. The diagnosis of latent tumor cells in histologically normal lymph nodes (LN) may have prognostic value and may explain the tumoral recurrence in BC. Methods: Here we evaluated the use of the AE1AE3 cytokeratin marker through immunohistochemical examination of LNs to diagnose micrometastasis in patients with BC undergoing radical cystectomy (RC) and lymph node dissection. Sixty-one patients with pN0 diseases who were submitted to RC were studied. Conventional histological evaluation indicated that these patients did not have lymph node metastasis. Histological sections were reviewed and analyzed by immunohistochemistry (IHC) using the AE1AE3 antibody in single sections. Results: The total number of removed LNs was 832, averaging 13.64 LNs per patient. The IHC evaluation revealed that LN from 2/61 (3.27%) patients had micrometastasis. At the time of the last follow-up, 41% of all patients were in complete disease remission and 41.1% had died from BC. Conclusions: Our study shows that histological analysis using hematoxylin eosin (HE) method by experienced pathologists is sufficient for the diagnosis of LN metastasis and, therefore, there is no indication for routine IHC evaluation in patients at histopathological pN0 stage. (AU)

Lymph node micrometastasis in stage I and II rectal cancer

PURPOSE: The aim of this study was to determine the rate of lymph node (LN) micrometastasis in patients with stage I and II rectal cancer.METHODS: One hundred eighty patients with either stage I or II rectal carcinoma who underwent curative resection between 1995 and 2010 were included. Forty-eight patients received neoadjuvant chemoradiotherapy. Two sections from each LN were stained with hematoxylin and eosin (H&E) and with CK20 by immunohistochemistry (IHC), respectively.RESULTS: A total of 2,257 LNs with a median of 12.5 LNs per patient were examined. For IHC staining, CK20-positive neoplastic cells were found in 4 of the 2,257 LNs (0.2%) from 3 of the 180 patients (1.7%), and all corresponding H&E re-stained sections confirmed that these neoplastic cells were present. Three of four neoplastic cells were micrometastasis, and one was macrometastasis. All occult neoplastic cells were found in 3 of the 85 patients (3.5%) with stage II disease.CONCLUSION: We observed a 3.5% rate of occult neoplastic cells in stage II rectal cancer. Interestingly, the results of IHC staining corresponded with those of H&E re-stained sections, suggesting that the examination of H&E stained section by a competent pathologist may replace IHC staining.

Application of sentinel lymph node tracer techniques in prostate caner / 中华男科学杂志

The sentinel lymph node (SLN) is the first node receiving lymphatic drainage of a tumor and best reflects tumor metastasis. Whether there is a micrometastasis in SLN determines the choice of pelvic lymph node dissection for prostate cancer and is closely related to later treatment and prognosis. Therefore, precise localization of SLN is essential. This review discusses the application of SLN tracer techniques, such as preoperative imaging and intraoperative lymphoscintigraphy and localization of SLN, in prostate cancer.

Re-discussion of lymph node metastasis from gastric cancer on prognostic evaluation / 中华胃肠外科杂志

Lymph node metastasis from gastric cancer is one of the most important events in the progress of disease, which may reflect the disease situation and contribute to evaluate accurately prognosis. Although the detailed mechanism of lymph node metastasis from gastric cancer has not been clearly elucidated, nodal metastasis comprise of a series of events involving the alterations of tumor biological characteristics, including changes of cancer cell proliferation, invasion, chemotaxis, and pathway of lymphatic drainage. As we know, assessment of lymph node metastatic status is significantly associated with both therapeutic strategy and prognostic prediction, It is controversial to adopt the optimal category of lymph node metastasis in clinical practice. Category based on the number of lymph node metastasis (e.g. N stage of UICC TNM classification) is considered as a prominent variable to apply for gastric cancer worldwide, nevertheless, category based on extent of lymph node metastasis (e.g. N stage of JGCA classification) is capable of contributing to the appropriate surgical procedure for patients. It has not reached a consensus for the assessment impacts of several special variables on prognostic evaluation in gastric cancer, including nodal micrometastasis, isolated tumor cells (ITCs) in lymph nodes, and skipping metastasis of lymph nodes, which needs further investigations to determining the application values in gastric cancer.

Exploratory study on influence of biopsy to biological behavior of Tca8113 transplanted tumor / 华西口腔医学杂志

<p><b>OBJECTIVE</b>We 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.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSIONS</b>Biopsy can affect the biological behavior of tongue tumor and can promote growth of primary focus and metastasis.</p>

Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer / 부인종양

OBJECTIVE: The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer. METHODS: In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases. RESULTS: Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080). CONCLUSIONS: It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.

Sentinel Lymph Node Navigation Surgery for Early Gastric Cancer: Is It a Safe Procedure in Countries with Non-Endemic Gastric Cancer Levels? A Preliminary Experience

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.

Sentinel Lymph Node in Breast Cancer: Review Article from a Pathologist's Point of View

Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials.

Study on the correlation between BRAF(V600E) mutation and lymphatic metastases in papillary thyroid cancer staged preoperativelv as N0 / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the prevalence of BRAF(V600E) mutations in small (≤ 2 cm) papillary thyroid carcinoma (PTC), explore the correlation with occult central nodal metastasis (CNM) of clinically-nodal negative (cN0) neck for small (≤ 2 cm) papillary thyroid carcinoma (PTC).@*METHOD@#Primary tumor tissue (paraffin-embedded) from 72 patients with small (≤ 2 cm) cN0 PTC who underwent prophylactic central neck dissection (pCND) was tested for BRAF mutation. by nested PCR, the factors of lymph node metastasis such as clinicopathologic including tumor size, multifocality, extrathyroidal invasion, and BRAF mutations were analyzed. Prediction scores were generated using logistic regression models and BRAF was evaluated to see if it was a risk factor for CNM.@*RESULT@#The prevalence of BRAF was 47.22% (34/72) while the rate of CNM was 36.11% (26/72). Univariate analysis showed that the risk factors of lymph node metastasis for cN0 PTC were significantly correlated with tumor size (P = 0.016), bilateral tumor (P = 0.010), multifocality (P = 0.026), extrathyroidal invasion (P = 0.024), and BRAF mutations (P = 0.041). Univariate analysis showed that tumor size (OR = 2.674, 95% CI = 1.702-3.997), multifocality (OR = 1.371, 95% CI = 1.065-2.087), extrathyroidal invasion (OR = 0.540, 95% CI = 0.396-0.794) and BRAF (OR = 1.647, 95% CI = 1.101-2.463) were risk predictors of CNM.@*CONCLUSION@#The incidence of central neck micrometastatic disease is 36.11% in patients with PTC deemed N0 preoperatively by clinical examination and ultrasound of the neck lymph nodes and intraoperatively by inspection of the central compartment. The factors of high risk of CNM included tumor size, multifocality, extrathyroidal invasion, BRAF mutations. When a patient has the risk factors of lymph node metastasis should be electived prophylactic CCND.