Clinicopathological analysis of superior mediastinal lymph node metastases in medullary thyroid carcinoma / 中华肿瘤杂志

Objective: To investigate the clinicopathological characteristics of superior mediastinal lymph node metastases (sMLNM) in medullary thyroid carcinoma (MTC). Methods: This retrospective analysis enrolled the patients who were treated for sMLNM of MTC in our hospital from May 2012 to January 2021. All patients were suspected of sMLNM due to preoperative imaging. According to the pathological results, the patients were divided into two groups named sMLNM group and the negative superior-mediastinal-lymph-node group. We collected and analyzed the clinical features, pathological features, pre- and post-operative calcitonin (Ctn), and carcinoembryonic antigen (CEA) levels of the two groups. Logistic regression analysis was used to analyze risk factors, and receiver operation characteristic (ROC) curves were drawn to determine the optimal cut-off values of preoperative Ctn and preoperative CEA for predicting sMLNM. Results: Among the 94 patients, 69 cases were in the sMLNM group and 25 cases were in the non-SMLNM group. Preoperative Ctn level (P=0.003), preoperative CEA level (P=0.010), distant metastasis (P=0.022), extracapsular lymph node invasion (P=0.013), the number of central lymph node metastases (P=0.002) were related to sMLNM, but the multivariate analysis did not find any independent risk factors. The optimal threshold for predicting sMLNM by pre-operative Ctn is 1500 pg/ml and AUC is 0.759 (95% CI: 0.646, 0.872). The sensitivity, specificity, positive predictive value, and negative predictive value of diagnosis are 61.2%, 77.3%, 89.1%, 39.5%, respectively. In patients who underwent mediastinal lymph node dissection through transsternal approach, the metastatic possibility of different levels from high to low were level 2R (82.3%, 28/34), level 2L (58.8%, 20/34), level 4R (58.8%, 20/34), level 3 (23.5%, 8/34), level 4L (11.8%, 4/34). Postoperative complications occurred in 41 cases (43.6%), and there was no perioperative death in all cases. 14.8% (12/81) of the patients achieved biochemical complete response (Ctn≤12 pg/ml) one month after surgery, 5 of these patients were in sMLNM group. Conclusions: For patients who have highly suspicious sMLNM through imaging, combining with preoperative Ctn diagnosis can improve the accuracy of diagnosis, especially for patients with preoperative Ctn over 1 500 pg/ml. The superior mediastinal lymph node dissection for the primary sternotomy should include at least the superior mediastinal levels 2-4 to avoid residual lesions. The strategy of surgery needs to be cautiously performed. Although the probability of biochemical cure in sMLNM cases is low, nearly 40% of patients can still benefit from the operation at the biochemical level.

Cytopathological characterization of ascites for the diagnosis of serous ovarian carcinoma / 中华肿瘤杂志

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.

Watch and wait, worth It?

Background: The surgery with total mesorectal excision recommended by R. J. Heald in 1982 is the gold standard. Rectal cancer (RC) surgery has a morbidity rate ranging from 6 to 35%, and it can cause functional issues such as sexual, urinary, and bowel dysfunction in the long term. Neoadjuvant chemoradiotherapy (CRT) has been gaining ground in patients with lesions in the middle and lower rectum. The aim of the present study is to present the experience of a reference service in the treatment of RC. Patients and Methods: A retrospective study involving 53 patients diagnosed with RC between January 2017 and December 2019 with follow-up until December 2020. We examined tumor location, disease stage, digital rectal exam findings, carcinoembryonic antigen (CEA), therapeutic modality offered, and follow-up time. Results: A total of 32% of the patients were men and 68% were women, with a mean age of 60 years old. Location: upper rectum in 6 cases, middle rectum in 21 cases, and lower rectum in 26 cases with evolution from 9.8 to 13.5 months. The most frequent complaints were hematochezia and constipation. A total of 36 patients underwent neoadjuvant therapy: 11 complete clinical response (CCR) (30.5%), 20 (55.5%) partial clinical response (PCR), and no response in 5 patients (14%). The follow-up ranged from 12 to 48 months, with a mean of 30.5 months. A total of 25% of the patients had RC that went beyond the mesorectal fascia, and 22.64% had metastases in other parts of the body when they were diagnosed. Conclusion: Neoadjuvant radio and chemotherapy present themselves as an alternative in the treatment of rectal cancer. In 36 patients, 30.5% had a complete clinical response, 55.5% had a partial clinical response, and 14% had no response. It was worth doing the "Watch and Wait" (W&W) to sample. A definitive colostomy was avoided. However, it is necessary to expand the study to a larger follow-up and more patients. Additionally, it is necessary to implement a multicenter study. (AU)

ALDH3B1 expression is correlated with histopathology and long-term prognosis of gastric cancer / 南方医科大学学报

OBJECTIVE@#To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients.@*METHODS@#We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells.@*RESULTS@#The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells.@*CONCLUSION@#As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.

Relationship between preoperative inflammatory indexes and prognosis of patients with rectal cancer and establishment of prognostic nomogram prediction model / 中华肿瘤杂志

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.

The expression of cortactin in colorectal cancer and its relationship with clinicopathological and prognostic parameters / 中华肿瘤杂志

Objective: To investigate the expression of cortactin in colorectal cancer and its correlation with clinicopathological parameters and prognosis. Methods: The expressions of cortactin in normal colorectal mucosal tissue and colorectal cancer tissue in paraffin-embedded tissue microarray from 319 patients who were diagnosed as colorectal cancer and treated in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2009 was detected by immunohistochemistry. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox proportional risk regression model was used for multivariate analysis. Results: The positive expression rates of cortactin in colorectal cancer tissue and normal colorectal mucosal tissue were 61.1% (195/319) and 5.6% (18/319, P<0.001), respectively. T-stage, N-stage, American Joint Committee on Cancer (AJCC) stage, degree of tumor differentiation, neural invasion and preoperative carcinoembryonic antigen (CEA) levels were associated with the expression of cortactin (P<0.05). The positive expression of cortactin was associated with poorer disease-free survival (P=0.036) and overall survival (P=0.043), and the effect was more significant in patients with stage Ⅱ to Ⅲ. For patients with stage Ⅱ-Ⅲ colorectal cancer, postoperative adjuvant therapy was associated with disease-free survival (P=0.007) and overall survival (P=0.015). The vascular tumor embolus, pathological type, preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival (P<0.05). The age, AJCC stage, preoperative CEA level and cortactin expression were independent influencing factors for overall survival (P<0.05). Preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival and overall survival (P<0.05). Conclusion: Cortactin is expressed in colorectal cancer and in stage Ⅱ-Ⅲ patients, it is a potential predictor of colorectal cancer prognosis.

Diagnostic value of serum tumor markers CEA, CYFRA21-1, SCCAg, NSE and ProGRP for lung cancers of different pathological types / 南方医科大学学报

OBJECTIVE@#To evaluate the diagnostic value of the serum tumor markers carcinoembryonic antigen (CEA), cytokeratin-19-fragment (CYFRA21-1), squamous cell carcinoma associated antigen (SCCAg), neuron-specificenolase (NSE) and pro-gastrin-releasing peptide (ProGRP) for lung cancers of different pathological types.@*METHODS@#This study was conducted among patients with established diagnoses of lung adenocarcinoma (LADC, n=137), lung squamous cell carcinoma (LSCC, n=82), small cell lung carcinoma (SCLC, n=59), and benign chest disease (BCD, n=102). The serum tumor markers were detected for all the patients for comparison of the positivity rates and their serum levels. ROC curve was used for analysis of the diagnostic efficacy of these tumor markers either alone or in different combinations.@*RESULTS@#In patients with LADC, the positivity rate and serum level of CEA were significantly higher than those in the other groups (P < 0.05); the patients with LSCC had the highest positivity rate and serum level of SCCAg among the 4 groups (P < 0.05). The positivity rates and serum levels of ProGRP and NSE were significantly higher in SCLC group than in the other groups (P < 0.05). CYFRA21-1 showed the highest positivity rate and serum level in LADC group and LSCC group. With the patients with BCD as control, CEA showed a diagnostic sensitivity of 62.8% and a specificity of 93.1% for LADC, and the sensitivity and specificity of SCCAg for diagnosing LSCC were 64.6% and 91.2%, respectively. CYFRA21-1 had the highest diagnostic sensitivity for LADC and LSCC. The diagnostic sensitivity and specificity of ProGRP for SCLC were 83.1% and 98.0%, respectively. When combined, CYFRA21-1 and CEA showed a high sensitivity (78.8%) and specificity (86.3%) for diagnosing LADC with an AUC of 0.891; CYFRA21-1 and SCCAg had a high sensitivity (84.1%) and specificity (87.3%) for diagnosing LSCC with an AUC of 0.912. NSE combined with ProGRP was highly sensitive (88.1%) and specific (98.0%) for diagnosis of SCLC, with an AUC of 0.952. For lung cancers of different pathological types, the combination of all the 5 tumor markers showed no significant differences in the diagnostic power from a combined detection with any two of the markers (P>0.05).@*CONCLUSION@#CEA, CYFRA21-1, SCCAg, NSE and ProGRP are all related to the pathological type of lung cancers and can be used in different combinations as useful diagnostic indicators for lung cancers.

Postoperative transient elevation of serum cancer antigen 125 in non-small cell lung cancer patients

SUMMARY OBJECTIVE: The aim of this retrospective study was to investigate the correlation of transiently elevated postoperative serum cancer antigen 125 levels and prognosis in patients with non-small cell lung cancer. METHODS: A total of 181 non-small cell lung cancer patients with normal levels of preoperative serum cancer antigen 125 were statistically summarized in this study. RESULTS: Out of the analyzed patients, 22 (12.2%) showed elevation of serum cancer antigen 125 within one month after surgery. Serum cancer antigen 125 level decreased to normal at three months postoperation. Serum cancer antigen 125 was positively correlated with pro-brain natriuretic peptide in non-small cell lung cancer postoperative patients (p=0.00035). Univariate analysis did not find significant difference in disease progression survival between those who experienced cancer antigen 125 elevation in the early postoperation and those who did not (p=0.646). CONCLUSIONS: In conclusion, transient elevation of cancer antigen 125 is associated to pro-brain natriuretic peptide increase after pulmonary surgery in non-small cell lung cancer patients.

Rendimiento del antígeno carcinoembrionario como prueba diagnóstica del cancer colorrectal / Effectiveness of carcinoembryonic antigen to diagnose colorectal cancer / Desempenho do antígeno carcinogênico embrionário como teste diagnóstico do câncer colorretal

Resumen: Introducción: el antígeno carcinoembrionario (CEA) es un marcador tumoral de seguimiento y no una prueba de tamizaje y diagnóstico en cáncer colorrectal (CCR). Sin embargo, en la práctica clínica habitual se continúa solicitando con fines de diagnóstico inicial. Objetivo: evaluar el rendimiento del CEA para el diagnóstico de CCR en el Hospital Maciel y en la Cooperativa Médica de Florida, en el período 2000-2019. Material y método: se trata de un estudio prospectivo de evaluación del CEA como prueba diagnóstica del CCR. Los criterios de inclusión fueron: 1) videocolonoscopía total en los usuarios sin CCR y videocolonoscopía total o parcial para aquellos con CCR y la confirmación histológica de adenocarcinoma; 2) contar con determinación de CEA dentro de los 30 días previos o posteriores a la videocolonoscopía, y 3) para la estadificación, el informe anatomopatológico de la pieza quirúrgica y la confirmación histológica de metástasis a distancia. El número de casos incluidos se determinó por un mínimo de diez casos en cada celda de la tabla de contingencia. Resultados: se analizaron 211 casos. El análisis general determinó una sensibilidad de 33,6%, especificidad 70,4%, valor predictivo positivo (VPP) 69,1%, valor predictivo negativo (VPN) 35%, exactitud 45,9%. Para el estadio II, sensibilidad 18,8%, especificidad 70,4%, VPP 30%, VPN 56,2%, exactitud 49,5%. Estadio III: sensibilidad 31,6%, especificidad 70,4%, VPP 36,4%, VPN 65,8%, exactitud 56,8%. Estadio IV: sensibilidad 65%, especificidad 70,4%, VPP 55,3%, VPN 78,1%, exactitud 68,4%. Conclusiones: el CEA como prueba de confirmación diagnóstica del CCR muestra un bajo rendimiento, siendo aun menor en estadios precoces de la enfermedad.

Summary: Introduction: carcinoembryonic antigen (CEA) is a tumor marker used for follow up rather than a screening and diagnostic test for colorectal cancer (CCR). However, it continues to be requested in the regular clinical practice for initial diagnosis. Objective: to evaluate the effectiveness of CEA to diagnose colorectal cancer at Maciel Hospital and Cooperativa Medica de Florida Hospital from 2000 to 2019. Method: prospective study to evaluate CEA as a diagnostic test for colorectal cancer. The following inclusion criteria were used: 1) total videocolonoscopy in all users without CLC and total or partial videocolonoscopy for those with CRC and histologic confirmation of adenocarcinoma; 2) CEA determination within 30 days before or after videocolonoscopy and 3) for the purpose of staging, pathology report of the surgical piece and histological confirmation of distant metastases. The number of cases included was defined by a 10-case minimum in each cell of the contingency table. Results: 211 cases were analysed. The general analysis revealed 33.6% sensitivity, 70.4% specificity, VPP 69.1%, VPN 35%, accuracy 45.9%. In the case of staging II, sensitivity was 18.8%, specificity 70.4%, VPP 30%, VPN 56.2%, accuracy 49.5%. In the case of staging III, sensitivity 31.6%, specificity 70.4%, VPP 36.4%, VPN 65.8%, accuracy 56.8%. In the case of staging IV, sensitivity 65%, specificity 70.4%, VPP 55.3%, VPN 78.1%, accuracy 68.4%. Conclusions: CEA evidences low effectiveness to diagnose colorectal cancer, and it is still less effective in early stages of the disease.

Resumo: Introdução: o antígeno carcinogênico embrionário (CEA) é um marcador tumoral de acompanhamento e não um teste de rastreamento e diagnóstico em câncer colorretal (CRC). No entanto, na prática clínica de rotina, continua a ser solicitado nos diagnósticos iniciais. Objetivo: avaliar o desempenho do CEA no diagnóstico de câncer colorretal nos Hospitais Maciel de Montevidéu e da Cooperativa Médica de Florida, no período 2000-2019. Material e método: este é um estudo prospectivo avaliando o CEA como teste diagnóstico para câncer colorretal. Os critérios de inclusão foram: 1) videocolonoscopia total em usuários sem CCR e videocolonoscopia total ou parcial naqueles com CCR e confirmação histológica de adenocarcinoma; 2) determinação do CEA 30 dias antes ou após a videocolonoscopia e 3) estadiamento, laudo anatomopatológico da peça cirúrgica e confirmação histológica de metástases à distância. O número de casos incluídos foi determinado por um mínimo de 10 casos em cada célula da tabela de contingência. Resultados: foram analisados 211 casos. A análise geral determinou uma sensibilidade de 33,6%, especificidade 70,4%, VPP 69,1%, VPN 35%, precisão 45,9%. Para o estágio II, sensibilidade 18,8%, especificidade 70,4%, PPV 30%, NPV 56,2%, precisão 49,5%. Estágio III, sensibilidade 31,6%, especificidade 70,4%, PPV 36,4%, NPV 65,8%, precisão 56,8%. Estágio IV, sensibilidade 65%, especificidade 70,4%, PPV 55,3%, NPV 78,1%, precisão 68,4%. Conclusões: o CEA como teste de confirmação diagnóstica do câncer colorretal apresenta baixo desempenho, sendo ainda menor nos estágios iniciais da doença.

Preoperative differentiation of benign and malignant non-epithelial ovarian tumors: clinical features and tumor markers / Diferenciação pré-operatória de tumores ovarianos não epiteliais benignos e malignos: características clínicas e marcadores tumorais

Abstract Objective To evaluate the role of clinical features and preoperativemeasurement of cancer antigen 125 (CA125), human epididymis protein(HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cordstromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, amongmalignant, fourwere immatureteratomas. Themost common tumors in the sex cordstromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign andmalignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant caseswere diagnosed at initial stages with good prognosis. Themeasurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

Resumo Objetivo Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. Métodos Cento e dezenovemulheres consecutivas comtumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. Resultados Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estromamalignos foram tratadas comcirurgia preservadora de fertilidade. Cinco (71,4%)mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. Conclusão Os tumores de ovário não epiteliais foram benignos namaioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico préoperatório desses tumores.

Comparison of serum NEDD-9, CA 15-3, and CEA levels and PET metabolic parameters in breast cancer patients with 18 F-FDG PET / CT

SUMMARY OBJECTIVE Analyze the over expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) deregulated associated with a poor prognosis in various carcinomas. Our objective was to investigate the relationship between the levels of NEDD-9, CA 15-3, and CEA and PET (SUVmax, MTV40, TLG40) with the clinical parameters of patients with breast cancer (BC). METHODS One hundred and eleven patients (82 BC patients who underwent 18F-FDG PET/CT and 29 healthy controls) were evaluated. SUVmax, MTV, and TLG of the primary tumor were compared with the molecular and histopathological subtypes. 18F-FDG, MTV, and TLG were evaluated based on the clinical data, i.e., nodal involvement, distant metastasis, ER and PR status, Ki-67, serum levels of NEDD-9, CA15-3, and CEA. We compared the NEDD-9 in the BC and healthy control groups. RESULTS The mean ± SD of SUVmax in the 82 patients was 13.0 ± 8.6. A statistically significant relationship (p = 0.022) was found between the molecular subtypes and 18F-FDG uptake. The relationship between 18F-FDG uptake and TLG measured in patients <50 years, ER-PR negativity, and HER2 positivity were statistically significant (p=0.015, 0.007, 0.046, and 0.001, respectively). MTV40, TLG40, and CA 15-3 in metastatic patients were statistically significant (p=0.004, 0.005, and 0.003, respectively). NEDD-9 in the BC group was significantly higher than in the healthy group (p=0.017). There was a positive correlation between SUVmax and Ki67 and CA 15-3; MTV40 and CEA; CA 15-3, CEA, SUVmax, and MTV40; a negative correlation was found between CEA, TLG40, and age. CONCLUSION The use of SUVmax, MTV40, and TLG40 parameters with NEDD-9 and tumor markers has been shown to provide a high diagnostic, predictive, and prognostic value for the management of BC. This is considered to be the basis of interventions focused on the treatment objectives related to NEDD-9.

RESUMO OBJETIVO Analisar a associação da superrexpressão das células NEDD-9 ao prognóstico negativo em vários tipos de carcinoma. Nosso objetivo foi investigar a relação entre os níveis de NEDD-9, CA 15-3 e CEA e PET (SUVmax, MTV40, TLG) e os parâmetros clínicos em pacientes com câncer de mama (CM). MÉTODOS Cento e onze pacientes (82 pacientes de CM submetidos a 18F-FDG PET/TC e 29 controles saudáveis) foram avaliados. SUVmax, MTV, e TLG do tumor primário foram comparados nos subtipos molecular e histopatológico. A captação de 18F-FDG, MTV, e TLG foi avaliada com base em dados clínicos (envolvimento nodal, metástase distante, status de ER e PR, Ki-67, níveis séricos de NEDD-9, CA15-3 e CEA). Foi comparada a NEDD-9 do grupo de CM e o controle saudável. RESULTADOS A média ± DP de SUVmax de 82 pacientes foi de 13,0 ± 8,6. Uma relação estatisticamente significativa (p=0,022) foi encontrada entre subtipos moleculares e captação de 18F-FDG. A relação entre captação de 18F-FDG e TLG medida em pacientes com idade <50 anos, ER-PR negativo e HER2 positivo foi estatisticamente significativa (p=0,015; 0,007; 0,046; e 0,001, respectivamente). MTV40, TLG40 e CA 15-3 em pacientes metastáticos foram estatisticamente significantes (p=0,004, 0,005 e 0,003, respectivamente). NEDD-9 no grupo BC foi significativamente maior do que no grupo saudável (p=0,017). Uma correlação positiva foi encontrada entre SUVmax e Ki67 e CA 15-3; MTV40 e CEA; CA 15-3, CEA, SUVmax e MTV40; uma correlação negativa foi encontrada entre CEA, TLG40 e idade. CONCLUSÃO O uso dos parâmetros SUVmax, MTV40 e TLG40 com NEDD-9 e marcadores tumorais demonstrou um alto valor diagnóstico, preditivo e prognóstico para o manejo do CM. Isso é considerado a base para intervenções focadas nos objetivos de tratamento relacionados às NEDD9.

Performances of CYFRA 21-1, Carcinoembryonic Antigen and Their Combination for Lung Cancer Diagnosis

Increased Progastrin-Releasing Peptide Expression is Associated with Progression in Gastric Cancer Patients

Biomarcadores mamarios en procesos metastásicos en mujeres ecuatorianas / Breast biomarkers in metastatic processes in Ecuadorian women

Resumen Introducción: Los biomarcadores tumorales CA 15-3 y CEA son predictores de metástasis en el cáncer de mama; no obstante, existe división de criterios de las ventajas de determinarlos de forma individual o conjunta. Objetivo: Evaluar la asociación de los biomarcadores tumorales CA 15-3 y CEA, por separado y en conjunto, en relación a la enfermedad metastásica en mujeres ecuatorianas con cáncer de mama. Métodos: Se realizó un estudio de prevalencia, en base a la información obtenida de las historias clínicas de 90 mujeres con cáncer de mama. Se identificaron los marcadores (CA 15-3, CEA y el conjunto de los dos (CA 15-3 ­ CEA) y se buscó la asociación con presencia o no de metástasis mediante prueba exacta de Fisher e índice Kappa de Cohen. Además, se determinó la sensibilidad, especificidad y valores predictivos positivos y negativos de cada marcador tumoral y en conjunto. Resultados: La prevalencia de carcinoma ductal invasivo en etapas localmente avanzadas de IIB a IIIC fue 77.8%. El sistema óseo y pulmonar fueron lugares frecuentes de invasión. De manera individual y conjunta existe una relación estadísticamente significativa (P <0.05) entre el valor de los biomarcadores y la presencia de procesos metastásicos, siendo CA15-3 y CA15-3-CEA los de mayor concordancia. CA15-3 presentó sensibilidad (S) 55% y especificidad (E) 91%. CEA tuvo (S) 30%; (E) 96%. En conjunto presentaron (S) 40%; (E) 100%. Conclusiones: La presencia de metástasis y mayor carga tumoral se correlacionan con la positividad de los biomarcadores tumorales CA 15-3-CEA, lo cual refuerza la utilidad clínica de evaluar los dos biomarcadores en conjunto.

Background: CA 15-3 and CEA tumor markers are metastasis predictors in breast cancer; however, criteria of the advantages in determining them in an individual or joint way are still not consensual. Objective: To evaluate the association of CA 15-3 and CEA tumor markers, in individual or joint way, in Ecuadorian patients diagnosed with metastatic breast cancer. Methods: A prevalence study was carried out, based on the information obtained from the medical records of 90 women with breast cancer. The markers CA 15-3, CEA were identified individually and together (CA 15-3 - CEA) and the association between the presence or absence of metastasis was established by using Fisher's exact test and Cohen's Kappa index. In addition, the sensitivity, specificity, positive and negative predictive values of each tumor marker as individual element and as a whole were determined Results: The prevalence of invasive ductal carcinoma in locally advanced stages from IIB to IIIC was 77.8%. The bone and lung system were frequent sites of cancer spread. There was a statistically significant relation (p<0.05) between the individual or whole biomarkers values and the presence of metastatic processes, being CA 15-3 and CA 15-3-CEA the ones with the highest concordance. CA 15-3 presented 55% sensitivity and 91% specificity. CEA presented 30% sensitivity and 96% specificity. As a whole, those have 40% sensitivity and 100% specificity. Conclusions: A higher tumor burden and metastatic development correlate with CA15-3-CEA biomarker positivity as a set, reinforcing the clinical benefit of evaluating both biomarkers simultaneously

Visceral obesity is not correlated with lymph node metastases nor Colorectal cancer survival / Obesidade visceral não está correlacionada a metastases nos linfonodos ou cancer coloretal

ABSTRACT Introduction: The presence of lymph node metastasis in colorectal cancer is determinant for prognosis and for treatment planning. The relationship between visceral fat and the prognosis is not fully documented in the literature, so this study intended to evaluate whether there is a relationship between the presence of visceral obesity and the presence of lymph node metastases and the prognosis of patients with colorectal cancer. Materials and methods: A sample of 68 patients who underwent surgery for colorectal cancer at Hospital de Braga between 1/1/2007 and 31/12/2007 was constructed, and their clinical and pathological data were recorded. Visceral fat, subcutaneous, and total fat areas were measured on preoperative computed tomography. Visceral obesity was defined as a ratio of visceral fat to total fat area >0.29. The ratio of metastatic lymph node (; number of metastatic lymph node/number of lymph node examined) was calculated. Results: There was a significant association between visceral obesity and male sex (p = 0.032). Patient survival at 5 and 10 years of follow-up was higher in patients with subcutaneous obesity in both periods, but not significant. There was a significant association between the ratio of metastatic lymph node and survival at 5 and 10 years (p = 0.03 and p = 0.002, respectively), with higher survival when ratio of metastatic lymph node = 0% and worse for ≥ 18%. Conclusion: In this study, no significant association was observed between visceral obesity and the number of metastatic lymph node, nor with survival at 5 and 10 years.

RESUMO Introdução: A presença de metastização ganglionar no câncer colorretal é determinante como fator de prognóstico e para planear o tratamento. A relação entre a presença de gordura visceral e o prognóstico não está totalmente documentada na literatura. Assim, pretende-se avaliar a existência de relação entre obesidade visceral e a presença de metástases ganglionares e o prognóstico de doentes com câncer colorretal. Materiais e métodos: Construiu-se uma amostra de 68 doentes operados por câncer colorretal no Hospital de Braga, entre 1/1/2007 e 31/12/2007, e registaram-se os seus dados clínico-patológicos e de seguimento. As áreas de gordura visceral, gordura subcutânea e gordura total foram medidas na tomografia computorizada pré-operatória. Obesidade visceral foi definida como um razão da gordura visceral relativamente à área total de gordura >0,29. Calculou-se a razão de linfonodos metastizados. Resultados: Verificou-se uma associação significativa entre obesidade visceral e sexo masculino (p = 0,032). A sobrevida dos pacientes, aos 5 e 10 anos de seguimento, foi superior naqueles com obesidade subcutânea em ambos períodos, contudo não significativa. Verificou-se uma associação significativa entre a sobrevivência em função da razão de linfonodos metastizados, aos 5 e 10 anos (p = 0,03 e p = 0,002; respectivamente), com maior sobrevivência quando a razão de linfonodos metastizados = 0% e pior quando ≥ 18%. Conclusão: Neste estudo não se observou uma associação significativa entre a obesidade visceral e o número de linfonodos metastizados nem com a sobrevida aos 5 e 10 anos.

Indication for and Effect of Adjuvant Chemotherapy for Stage IIa (T3N0M0) Colon Cancer

PURPOSE: The efficacy of adjuvant chemotherapy (AC) in stage IIa colon cancer is controversial. This study aimed to investigate the factors influencing survival in patients with stage IIa colon cancer, the role of AC, and the indications for AC utilization by surgical oncologists. METHODS: Between January 2004 and December 2010, 736 patients with stage IIa colon cancer underwent curative resection in 1 of 6 participating hospitals. Factors related to survival were identified and analyzed according to whether AC was administered or not. After high- and low-risk groups were identified, their respective results were analyzed. RESULTS: The 5-year overall survival (OS) of stage IIa colon cancer was 90.3%. With the exception of poorly differentiated histology, indications for AC did not include typical high-risk factors. The indications for AC were significantly younger patients, higher body mass index (BMI), lower American Society of Anesthesiologists (ASA) physical status classification, and higher histologic grade. BMI, preoperative carcinoembryonic antigen, and harvested lymph node (LN) count were significant factors for disease-free survival, while BMI and ASA physical status classification were significant factors for OS in the chemotherapy group. In the high-risk group, AC was associated with increased OS in univariate analysis. BMI and harvested LN count were statistically significant in multivariate analysis. CONCLUSION: Surgical oncologists consider the patient's condition and postoperative course rather than high-risk factors to determine use of AC. Regardless of AC use, both the extent of surgery and the patient's subsequent status affected the survival rate in the high-risk group. None of the factors identified influenced survival rate in the low-risk group.

Oncologic Outcomes in Patients Who Undergo Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision for Locally Advanced Rectal Cancer: A 14-Year Experience in a Single Institution

PURPOSE: This study evaluated the oncologic outcomes of locally advanced rectal cancer patients who underwent preoperative neoadjuvant chemoradiotherapy (CRT) followed by surgery and determined the prognostic significance of pathologic complete response (pCR). METHODS: Between January 2002 and December 2015, 580 patients with rectal cancer who underwent surgery after neoadjuvant CRT were identified. Survival according to tumor response to CRT and pathologic stage was analyzed using the Kaplan-Meier method, and the Cox proportional hazard model was used to identify factors associated with survival outcomes. RESULTS: A total of 111 patients (23.7%) achieved pCR while the other 469 patients showed residual disease. Patients with pCR had a lower pretreatment carcinoembryonic antigen level and earlier cT classification than those with residual disease. With a median follow-up of 78 months, disease-free survival (DFS) and overall survival (OS) were significantly better in the pCR group than in the residual disease group. The 5-year DFS and 5-year OS for patients with ypStage 0, I, II, or III were 92.5%, 85.1%, 72.2%, 54.3% (P < 0.001) and 94.5%, 91.0%, 83.1%, 69.3%, respectively (P < 0.001). Pathologic AJCC stage after CRT was the most statistically significant independent predictor of OS (HR, 6.97 [95% confidence interval, 3.16–15.39] for stage III vs. stage 0) and DFS (HR, 7.30 [95% confidence interval, 3.63–14.67] for stage III vs. stage 0). CONCLUSION: Rectal cancer patients who achieved pCR showed improved survival compared to those with residual disease after preoperative CRT. Moreover, pCR was an independent indicator of OS and DFS, and pathologic AJCC stage was correlated with survival after preoperative CRT.

Early Systemic Failure After Preoperative Chemoradiotherapy for the Treatment of Patients With Rectal Cancer

PURPOSE: Distant metastasis can occur early after neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer. This study was conducted to evaluate the clinical characteristics of patients who developed early systemic failure. METHODS: The patients who underwent neoadjuvant CRT for a rectal adenocarcinoma between June 2007 and July 2015 were included in this study. Patients who developed distant metastasis within 6 months after CRT were identified. We compared short- and long-term clinicopathologic outcomes of patients in the early failure (EF) group with those of patients in the control group. RESULTS: Of 107 patients who underwent neoadjuvant CRT for rectal cancer, 7 developed early systemic failure. The lung was the most common metastatic site. In the EF group, preoperative carcinoembryonic antigen was higher (5 mg/mL vs. 2 mg/mL, P = 0.010), and capecitabine as a sensitizer of CRT was used more frequently (28.6% vs. 3%, P = 0.002). Of the 7 patients in the EF group, only 4 underwent a primary tumor resection (57.1%), in contrast to the 100% resection rate in the control group (P < 0.001). In terms of pathologic outcomes, ypN and TNM stages were more advanced in the EF group (P < 0.001 and P = 0.047, respectively), and numbers of positive and retrieved lymph nodes were much higher (P < 0.001 and P = 0.027, respectively). CONCLUSION: Although early distant metastasis after CRT for rectal cancer is very rare, patients who developed early metastasis showed a poor nodal response with a low primary tumor resection rate and poor oncologic outcomes.

False-positive Elevations in Carcinoembryonic Antigen Levels at a Health Screening Center

BACKGROUND: Although routine screening of carcinoembryonic antigen (CEA) is not recommended for the early diagnosis of colorectal cancers, CEA levels are frequently measured in practice and during opportunistic health screening programs. We evaluated the frequency of false-positive results according to CEA level at a health screening center. METHODS: The medical records of 25,786 participants who underwent a general health check-up and CEA testing at the Seoul National University Hospital Healthcare System Gangnam Center from March 2015 to February 2016 were reviewed. CEA levels were measured using the Architect i2000sr (Abbott Laboratories, USA). The cut-off level for elevated CEA was 5.0 ng/mL. RESULTS: Among 25,786 participants who underwent CEA screening, 597 (2.3%) had CEA levels >5.0 ng/mL. Among 597 participants with elevated CEA levels, 12 (2.0%) had actual malignancies with CEA levels of 8.3–155.3 ng/mL. Diabetes, smoking, chronic obstructive pulmonary disease, and colonic polyps were considered as causes of false elevation. The false-positive rates of CEA according to level were as follows: 5.1–10.0 ng/mL, 99.5%; 10.1–15.0 ng/mL, 87.2%; 15.1–20.0 ng/mL, 100.0%; >20.0 ng/mL, 33.3%. A subsequent decrease in the CEA level after a 1-month follow-up was observed in 47.6% of all cases with elevated CEA levels. CONCLUSIONS: False elevation in CEA levels in the range of 5.0–20.0 ng/mL is common in patients who underwent testing at a health screening center. False-positive results above 20.0 ng/mL are less common. These data could provide a guide for the interpretation of elevated CEA level at a health screening center.

Exosomal miR-181b-5p Downregulation in Ascites Serves as a Potential Diagnostic Biomarker for Gastric Cancer-associated Malignant Ascites

PURPOSE: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. MATERIALS AND METHODS: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. RESULTS: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). CONCLUSIONS: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.