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To observe the antitumour efficacy of programmed death 1 (PD-1) inhibitors in the real world and explore the relationship between NRS2002 score or other clinical characteristics and immunotherapy efficacy, we retrospectively analyzed 341 tumor patients who received immune checkpoint inhibitor (ICI) treatment at one center. A total of 341 solid tumor patients treated with ICIs from June 2018 to December 2021 were retrospectively included in this study. Patient characteristics, ICI responses, and survival status were documented, and the relationships between clinical factors and survival were analyzed. Among all patients, the median progression-free survival (PFS) was 5.8 months, and the median overall survival (OS) was 12.5 months. The Performance Status (PS), NRS2002 score, The Naples Prognostic Score (NPS), Lymphocyte and C-reactive protein ratio (LCR), line of therapy, and nutritional support were significantly related to PFS or OS according to univariate analysis. The median PFS and OS were significantly better in the group without nutritional risk (NRS2002 0-2) than those with nutritional risk (NRS2002 ≥ 3) (PFS: HR = 1.82, 95% CI 1.30-2.54, p value < .001; OS: HR = 2.49, 95% CI 1.73-3.59, p value < .001). Cox regression analysis revealed that the NRS2002 score was an independent prognostic factor for both PFS and OS. The objective response rate (ORR) in the group at nutritional risk was lower than that in the group without nutritional risk (8.33% and 19.71%, respectively, p value = .037). Patients at nutritional risk according to the NRS2002 score at initial treatment had a poorer prognosis than those without nutritional risk. The NRS2002 could be used as a preliminary index to predict the efficacy of immune checkpoint inhibitor therapy.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Prognóstico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Intervalo Livre de ProgressãoRESUMO
Objectives: To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study. Methods: We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs. ≤3 days) from the intended date. Dose reduction (actual dose/standard dose * 100%) ≤85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m2) regimen for all cycles. Relative dose intensity (RDI) ≤80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan-Meier and Cox proportional hazard models. Results: There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay (p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and <0.001, respectively. Patients with high 5-FU RDI had better PFS than patients with low 5-FU RDI (p < 0.001). While, there was no statistical difference in OS between the two groups. Then we stratified the analysis by age. In <65 years cohort, both PFS and OS were better in patients with high 5-Fu RDI than in those with low 5-Fu RDI (p < 0.001, p = 0.005, respectively). But, in ≥65 years cohort, OS were better in patients with low 5-Fu RDI than in those with high 5-Fu RDI (p = 0.025). Moreover, both dose reduction and RDI of irinotecan had no statistically significant difference in both PFS and OS. Conclusion: In the advanced colorectal cancer patients who received FOLFIRI based treatment as first-line regimen, chemotherapy dose delay and reduction dose of 5-Fu were associated with worse survival, especially among patients younger than 65 years.
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Neoplasias Colorretais , Redução da Medicação , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/tratamento farmacológico , Comitês de Ética em Pesquisa , Fluoruracila/uso terapêuticoRESUMO
Skin and soft tissue diffusion metastasis (also known as occult cancer) is rare in renal cell carcinoma (RCC). Here, we report an extremely rare case of a 67-year-old male patient with occult primary RCC who developed metastases to the gums, skin, and diffuse soft tissue. The primary renal lesion was missed by computed tomography (CT), ultrasound, and 18F-fluorodeoxyglucose positron emission tomography (PET)/CT, and the diagnosis was confirmed by biopsy of gums and subcutaneous nodules. Subsequent enhanced CT revealed a lesion in the left kidney. The patient had progression-free survival of 16 months after treatment with axitinib and pembrolizumab. Pseudoprogression and tumor heterogeneity pose major challenges in the evaluation of immunotherapy. PET/CT is indispensable especially for cases with multiple metastases, widespread distribution of lesions, and major heterogeneity. In this case, the total lesion glycolysis was calculated by PET/CT and was used to evaluate systemic tumor load before and after immunotherapy, which was calculated as the product of the metabolic tumor volume and the mean standardized uptake value of the target lesion, which increased the accuracy of assessing diffuse lesions. Total lesion glycolysis can be used as a new method to quantitatively evaluate the efficacy of immunotherapy.
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Carcinoma de Células Renais , Neoplasias Renais , Neoplasias de Tecidos Moles , Masculino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/terapia , Compostos Radiofarmacêuticos , Fluordesoxiglucose F18 , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/terapia , Imunoterapia , Estudos Retrospectivos , Carga Tumoral , PrognósticoRESUMO
BACKGROUND: Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood. METHODS: The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments. RESULTS: AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells. CONCLUSIONS: In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Oxaliplatina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação para Baixo , RNA Longo não Codificante/genética , MicroRNAs/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismoRESUMO
Chemotherapy-related thrombocytopenia (CIT) is a significant adverse event during chemotherapy, which can lead to reduced relative dose intensity, increased risk of serious bleeding and additional medical expenditure. Herein, we aimed to develop and validate a predictive nomogram model for prediction of CIT in patients with solid tumor. From Jun 1, 2018 to Sep 9, 2021, a total of 1541 patients who received 5750 cycles of chemotherapy were retrospectively enrolled. Cox regression analysis was performed to identify predictive factors to establish the nomogram model for CIT. The incidence of chemotherapy-induced thrombocytopenia was 21.03% for patient-based and 10.26% for cycles of chemotherapy. The top five solid tumors with CIT are cervix, gastric, bladder, biliary systemic, and ovarian. The incidence of chemotherapy dose delays in any cycle because of CIT was 5.39%. Multivariate analysis showed that tumor site, treatment line, AST, oxaliplatin, and capecitabine were significantly associated with CIT. Moreover, we established a nomogram model for CIT probability prediction, and the model was well calibrated (Hosme-Lemeshow P = 0.230) and the area under the receiver operating characteristic curve was 0.844 (Sensitivity was 0.625, Specificity was 0.901). We developed a predictive model for chemotherapy-induced thrombocytopenia based on readily available and easily assessable clinical characteristics. The predictive model based on clinical and laboratory indices represents a promising tool in the prediction of CIT, which might complement the clinical management of thrombocytopenia.
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Anemia , Antineoplásicos , Neoplasias , Trombocitopenia , Feminino , Humanos , Estudos Retrospectivos , Antineoplásicos/efeitos adversos , Neoplasias/complicações , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Trombocitopenia/tratamento farmacológico , Anemia/complicaçõesRESUMO
OBJECTIVE: The aim of the current study was to explore the association between age and outcomes in breast cancer. METHODS: Patients during 2010-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and breast cancer-specific death (BCSD) were taken as endpoints. The restrict cubic spline graph (RCS) was used to explore the relationship between age and outcomes in patients, and the cumulative incidence of BCSD and non-BCSD was calculated using the Gray method. Age-specific gene expression profiles were studied using RNA sequence data from the Cancer Genome Atlas (TCGA) database to explore whether there were young age-related gene or gene sets. RESULTS: A total of 142,755 patients with breast cancer were included. The hazard ratio (HR) of OS for Patients with stage I-III breast cancer was roughly stable before 53 years old and increased significantly after that, and the HR of BCSD for these patients showed a U-shaped distribution when plotted against age, with patients younger than 50 years and patients older than 70 years experiencing the worst survival. Further stratified analysis according to molecular subtype revealed that the U-shaped distribution of the HR of BCSD with was only found in the Hormone receptor-positive/HER2-negative (HoR+/HER2-) subgroup. The cumulative incidence plots showed that young age was associated with worse BCSD in the breast cancer patients with stage I-III and HoR+/HER2- subgroup. In stage IV breast cancer, there was a linearity of the relationship between poor OS and increasing age. We failed to find any differentially expressed age-specific genes between 20-40 years and 41-60 years groups in 258 patients with stage I-III and HoR+/HER2- subtype. CONCLUSION: Young age could predict worse BCSD of patient with stage I-III and HoR+/HER2- breast cancer. The escalating therapy was recommended to young age breast cancer with stage I-III and HoR+/HER2- subtype.
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Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Feminino , Neoplasias da Mama/metabolismo , Estadiamento de Neoplasias , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Programa de SEER , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Hormônios , PrognósticoRESUMO
BACKGROUND: The standard surgical procedure for ≤ 2 cm non-small cell lung cancer (NSCLC), including the number of lymph nodes sampled (nLN) and surgical modality, remains controversial. This study was designed to determine the optimal cohort in which sublobectomy could be an alternative to lobectomy. MATERIALS (OR PATIENTS) AND METHODS: Patients from 1998 to 2017 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff value of nLN was identified using a restrictive cubic spline graph (RCS). Kaplan-Meier analysis was used to determine cancer-specific survival (CSS). The COX proportional hazard regression model was used to identify the influence of clinical and demographic variables on survival, and propensity score matching (PSM) was used to balance differences in baseline characteristics. Finally, we used an external cohort from a single-center medical institution to verify the conclusions drawn from the SEER database. RESULTS: A total of 6150 patients were included. The sublobectomy subgroup included segmentectomy (308, 5.0%) and wedge resection (1611, 26.2%). The cutoff value for nLN was 7. In the nLN ≥7 subgroup of the PSM cohort, the CSS of segmentectomy and wedge resection was close to that of the lobectomy subgroup (P = .12), whereas in the nLN <7 subgroup, the CSS of the lobectomy subgroup was significantly higher than that of the sublobectomy with P < .001). Surgical methods, nLN, age, sex, and differentiated grade were independent predictors of CSS. External cohort validation: A total of 1106 patients from the Affiliated Jinhua Hospital of Zhejiang University School of Medicine between 2013 and 2020 were included. The grouping criteria were consistent with the SEER database. In the nLN≥7 subgroup, sublobectomy had a survival outcome similar to that of lobectomy (P = .81). CONCLUSION: Sublobectomy and nLN < 7 were strongly associated with poorer CSS for early-stage NSCLC. On the premise of nLN ≥ 7, sublobectomy could provide similar survival outcomes to lobectomy for these patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Pneumonectomia/métodos , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/patologia , Linfonodos/cirurgia , Linfonodos/patologiaRESUMO
OBJECTIVE: To evaluate the effect of resection of primary lesion and chemotherapy on survival of patients with metastatic colorectal neuroendocrine carcinoma (CRNEC). METHODS: Clinical data of 393 patients with metastatic CRNECs between January 2010 and December 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, including 171 patients who received resection of primary lesion and 221 patients who did not undergo surgery. With the propensity score matching method 172 non-operated patients were selected as controls. Kaplan-Meier method and Log-rank test were used to evaluate the survival differences, while the prognostic factors were analyzed by Cox proportional-hazards model. Metastatic CRNEC patients from January 2001 to December 2021 in Affiliated Jinhua Hospital, Zhejiang University School of Medicine were selected for validation. RESULTS: Compared with non-operated patients, patients who received resection had longer cause-specific survival ( P<0.05). Patients with resected positive lymph nodes>8 had a poorer prognosis compared to those with resected positive lymph nodes≤8 ( P<0.05). Multivariate analysis showed that gender, location of primary lesion and treatments were independent risk factors for cause-specific survival in patients with metastatic CRNEC (all P<0.05). For metastatic CRNEC patients with resection of primary lesion, rectal neuroendocrine carcinoma, positive resected lymph nodes≤8 and resection of primary lesion combined with chemotherapy were associated with better cause-specific survival (all P<0.05). CONCLUSIONS: Patients with metastatic CRNEC may benefit from resection of primary lesion, and resection of primary lesion combined with chemotherapy might be the better strategy for metastatic CRNECs. The number of positive lymph nodes resected is correlated with the prognosis of patients.
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Carcinoma Neuroendócrino , Neoplasias Colorretais , Humanos , Estadiamento de Neoplasias , Prognóstico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/cirurgia , Modelos de Riscos ProporcionaisRESUMO
Objective: Chemotherapy-induced thrombocytopenia (CIT) can lead to chemotherapy dose delay or reduction, and even serious bleeding. This study aimed to develop a CIT-predicting model based on the laboratory indices of cancer patients undergoing chemotherapy. Material and Methods: From Jun 1, 2017 to Dec 30, 2021, a total of 2043 patients who had received 7676 cycles of chemotherapy were retrospectively enrolled. A logistic regression analysis was performed to identify predictive factors, on the basis of which a nomogram model for predicting CIT was established. A bootstrapping technique was applied for internal validation. A generalized additive mixed model (GAMM) was constructed to analyze the trends in the changes of aspartate aminotransferase (AST), ratio of AST to alanine transaminase (ALT) (AST/ALT ratio), and platelet (PLT) count in patients with solid tumors. P values ≤0.05 were considered statistically significant. Results: The patient-based incidence of CIT was 20.51% and the cycle-based incidence was 10.01%. The multivariate analysis showed that AST level, AST/ALT ratio, and total bilirubin (Tbil), white blood cell (WBC), platelet (PLT), hemoglobin (Hb) levels were significantly associated with the risk of CIT. The GAMM analysis showed that PLT level was inversely associated with AST/ALT ratio and AST level, more significantly with AST/ALT ratio. And both exhibited statistically predictive abilities for CIT. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.793, a sensitivity of 0.543 and a specificity of 0.930. Conclusion: The AST/ALT ratio was inversely associated with the CIT risk in cancer patients. The GAMM model based on laboratory indices presented a high accuracy in predicting the risk of CIT, and a potential to be translated into clinical management.
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BACKGROUND: The single progesterone receptor (PR)-positive phenotype (estrogen receptor (ER)-/PR + , sPR positive) is an infrequent and independent biological entity. However, the prognosis of patients with sPR-positive and her-2-negative phenotype is still controversial, and it is not always easy to decide treatment strategies for them. METHODS: Patients during 2010-2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS). The propensity score matching (PSM) method was used to balance differences of characteristics in groups. The Life-Table method was used to calculate 5-year CSS rates and the annual hazard rate of death (HRD). RESULTS: A total of 97,527 patients were included, and only 745 (0.76%) patients were sPR-positive phenotype. The majority of sPR-positive breast cancer were basal-like subtype. Survival analysis showed that the sPR-positive breast cancer had similar prognosis comparing to double hormonal receptor-negative (ER-/PR-, dHoR-negative) breast cancer, and had the highest HRD during the initial 1-2 years of follow-up, then maintained the HRD of almost zero during the late years of follow-up. CONCLUSIONS: The patients with sPR-positive and her-2-negative breast cancer, similar to dHoR-negative breast cancer, had a worse survival, and could benefit from chemotherapy significantly. However, the escalating endocrine therapy was not recommended for sPR-positive patients. The patients with sPR positive should be excluded from future clinical trials concerning endocrine therapy.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Prognóstico , Receptor ErbB-2/genética , Receptores de Estrogênio , Receptores de Progesterona , Análise de SobrevidaRESUMO
BACKGROUND: More than half of early breast cancer recurrences occur after 5 years from the initial diagnosis. An individualized estimate of the risk of late-period breast cancer-specific death (LP-BCSD) after 5 years of endocrine therapy (ET) can improve decision-making for extended endocrine therapy (EET). MATERIALS AND METHODS: A total of 147,059 eligible patients with breast cancer who survived 5+ years after diagnosis between 1990 and 2007 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses based on the competing risk regression model were used to evaluate predictive factors for high risk of LP-BCSD or late-period non-breast cancer-specific death (LP-non-BCSD). Significant factors were used to build a nomogram to individualize estimates of LP-BCSD or LP-non-BCSD. RESULTS: The 5- and 10-year LP-BCSD rates were 5.7% and 10.1%, respectively, and the 5- and 10-year LP-non-BCSD rates were 6.7% and 15.5%, respectively. Young age, black race, single marital status, poor differentiation, large tumor size, lymph node metastasis, and estrogen receptor-positive/progesterone receptor-negative (ER+/PR-) status were independent predictive factors for high risk of LP-BCSD. Age was the most important factor for predicting high risk of LP-non-BCSD. The nomograms, which were based on significant factors identified by the competing risk regression model. A risk score system based on the competing risk nomogram was established to describe the relative risk of LP-BCSD and LP-non-BCSD. CONCLUSION: This study explored the novel endpoint of LP-BCSD for further clinical trials. The risk score system might be highly useful for patient counseling, especially in discussing EET options with elderly or comorbid patients.
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Neoplasias da Mama , Nomogramas , Idoso , Mama/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Programa de SEERRESUMO
BACKGROUND: We conducted this study to evaluate whether patients with T1a/b, node-negative (N-), human epidermal growth factor receptor 2-positive (HER2+) breast cancers benefited from adjuvant therapy, and explored better treatment strategies for these patients. PATIENTS AND METHODS: Patients with T1a/b, N-, HER2+ breast cancers during 2000 through 2004 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Gray test was used to evaluate breast cancer-specific death (BCSD) and non-BCSD. To identify patients more suitable for chemotherapy, subgroup analyses were conducted according to tumor size and estrogen receptor (ER) status, and plots of hazard rate of death (HRD) were drawn to present the changes of BCSD. RESULTS: A total of 2940 patients with T1a/b, N-, HER2+ breast cancers were included; more patients in the T1b group received chemotherapy compared with the T1a group (65.18% vs. 29.30%; P < .001). Patients receiving chemotherapy did not benefit from it (5-year incidences of BCSD: 1.00% in the non-chemotherapy group vs. 1.18% in the chemotherapy group; P = .853). Compared with those in the T1a group, patients in the T1b group had similar prognosis (P = .532), whereas ER status was significantly associated with survival (P = .048). HRD had a peak in years 2 to 5, which was more obvious in the ER- group. CONCLUSION: Chemotherapy, which is mainly decided by tumor size, fails to render survival benefits for patients with T1a/b, N-, HER2+ breast cancers. ER status, rather than tumor size, is important for clinicians to make adjuvant treatment decisions. The peak of BCSD occurs 2 to 5 years after diagnosis, and an at least 5-year follow-up is recommended for these patients.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Mama/patologia , Quimioterapia Adjuvante/estatística & dados numéricos , Mastectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante/estatística & dados numéricos , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Programa de SEER/estatística & dados numéricos , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder arising from mutations of the MEN1 tumor suppressor gene on chromosome 11q13; MEN1 is characterized by the development of neuroendocrine tumors, including those of the parathyroid, gastrointestinal endocrine tissue and anterior pituitary. Additionally, thymic neuroendocrine tumors in MEN1 are also rarely reported. CASE PRESENTATION: This case report observed a family that presented with MEN1 p.L105Vfs mutation, and two of the family members had been diagnosed with thymic neuroendocrine tumor combined with MEN1. To the best of our knowledge, this is the first time such a mutation in the MEN1 gene has been reported. The proband presented with thymic neuroendocrine tumor, parathyroid adenoma and rectum adenocarcinoma. The son of the proband presented with thymic neuroendocrine tumor, gastrinoma, hypophysoma and parathyroid adenoma. Genetic testing revealed the frameshift mutation p.L105Vfs, leading to the identification of one carrier in the pedigree (the patient's younger sister). The proband then underwent parathyroidectomy at the age of 26 years (in 1980) for a parathyroid adenoma. Subsequently, the patient underwent thymectomy, radiotherapy and chemotherapy. The patient is now 64 years old, still alive and still undergoing Lanreotide therapy. CONCLUSION: Thymic neuroendocrine MEN1 is rare, but it accounts for almost 20% of MEN1-associated mortality. Consequently, we should focus on regular clinical screening of the thymus in MEN1 patients.
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Neoplasia Endócrina Múltipla Tipo 1/genética , Tumores Neuroendócrinos/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias do Timo/genética , Mutação da Fase de Leitura , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
OBJECTIVE: This study was performed to identify a reasonable cutoff age for defining older patients with colorectal cancer (CRC) and to examine whether old age was related with increased colorectal cancer-specific death (CSD) and poor colorectal cancer-specific survival (CSS). METHODS: A total of 76,858 eligible patients from the surveillance, epidemiology, and end results (SEER) database were included in this study. The Cox proportional hazard regression model and the Chow test were used to determine a suitable cutoff age for defining the older group. Furthermore, a propensity score matching analysis was performed to adjust for heterogeneity between groups. A competing risk regression model was used to explore the impact of age on CSD and non-colorectal cancer-specific death (non-CSD). Kaplan-Meier survival curves were plotted to compare CSS between groups. Also, a Cox regression model was used to validate the results. External validation was performed on data from 1998 to 2003 retrieved from the SEER database. RESULTS: Based on a cutoff age of 70 years, the examined cohort of patients was classified into a younger group (n = 51,915, <70 years of old) and an older group (n = 24,943, ≥70 years of old). Compared with younger patients, older patients were more likely to have fewer lymph nodes sampled and were less likely to receive chemotherapy and radiotherapy. When adjusted for other covariates, age-dependent differences of 5-year CSD and 5-year non-CSD were significant in the younger and older groups (15.84% and 22.42%, P < 0.001; 5.21% and 14.21%, P < 0.001). Also an age of ≥70 years remained associated with worse CSS comparing with younger group (subdistribution hazard ratio, 1.51 95% confidence interval (CI) [1.45-1.57], P < 0.001). The Cox regression model as a sensitivity analysis had a similar result. External validation also supported an age of 70 years as a suitable cutoff, and this older group was associated with having reduced CSS and increased CSD. CONCLUSIONS: A total of 70 is a suitable cutoff age to define those considered as having elderly CRC. Elderly CRC was associated with not only increased non-CSD but also with increased CSD. Further research is needed to provide evidence of whether cases of elderly CRC should receive stronger treatment if possible.
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Corn starch graft copolymers were prepared from acrylamide/dimethyl diallyl ammonium chloride binary monomers (AM/DMDAAC) by a simultaneous radiation grafting method, and were characterized by FTIR and (1)H NMR techniques, weight measurement and titration method. The copolymers with high grafting ratio and high grafting efficiency of binary monomers were achieved at absorbed doses of 2 kGy and 3 kGy using a 6:9.8:4.2 (w/w/w) ratio of starch/AM/DMDAAC, but their cationic degrees were low. Grafting ratio, grafting efficiency and cationic degree of the copolymers increased with increasing AM content in comonomer mixtures and then decreased at 3kGy using a 6:14 ratio of starch:total comonomers, but their cationic degrees generally decreased with increasing AM content. The grafting ratio, the grafting efficiency and the cationic degree of the copolymers increased, but the grafting efficiency of DMDAAC decreased with varying starch/(AM+DMDAAC) ratio from 6:3 to 6:18 at 3 kGy by using a fixed 7:3 ratio of AM:DMDAAC.