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Castration-resistant prostate cancer (CRPC) is an important research focus in the field of prostate cancer. The adjustment of its diagnosis criteria also directly impacts the clinical diagnosis and treatment practice, as well as the design and implementation of the relevant clinical trials. The Prostate Cancer Clinical Trials Working Group (PCWG) has published several consensuses to provide further reference in clinical practice and trials design. In PCWG3, the recommended PSA cut-off value to confirmed CRPC diagnosis was further lowered from 2 ng / ml to 1 ng/ml. The update of PCWG3 may have a profound impact on the clinical diagnosis, treatment and trials design of prostate cancer in the future.
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OBJECTIVES@#To investigate the effects of injury time, postmortem interval (PMI) and postmortem storage temperature on mRNA expression of glycoprotein non-metastatic melanoma protein B (Gpnmb), and to establish a linear regression model between Gpnmb mRNA expression and injury time, to provide aimed at providing potential indexes for injury time estimation.@*METHODS@#Test group SD rats were anesthetized and subjected to blunt contusion and randomly divided into 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h groups after injury, with 18 rats in each group. After cervical dislocation, 6 rats in each group were collected and stored at 0 ℃, 16 ℃ and 26 ℃, respectively. The muscle tissue samples of quadriceps femoris injury were collected at 0 h, 12 h and 24 h postmortem at the same temperature. The grouping method and treatment method of the rats in the validation group were the same as above. The expression of Gpnmb mRNA in rat skeletal muscle was detected by RT-qPCR. The Pearson correlation coefficient was used to evaluate the correlation between Gpnmb mRNA expression and injury time, PMI, and postmortem storage temperature. SPSS 25.0 software was used to construct a linear regression model, and the validation group data was used for the back-substitution test.@*RESULTS@#The expression of Gpnmb mRNA continued to increase with the prolongation of injury time, and the expression level was highly correlated with injury time (P<0.05), but had little correlation with PMI and postmortem storage temperature (P>0.05). The linear regression equation between injury time (y) and Gpnmb mRNA relative expression (x) was y=0.611 x+4.489. The back-substitution test proved that the prediction of the model was accurate.@*CONCLUSIONS@#The expression of Gpnmb mRNA is almost not affected by the PMI and postmortem storage temperature, but is mainly related to the time of injury. Therefore, a linear regression model can be established to infer the time of injury.
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Animals , Rats , Glycoproteins , Linear Models , Melanoma , Membrane Glycoproteins/genetics , Postmortem Changes , Rats, Sprague-Dawley , RNA, Messenger/metabolism , Time FactorsABSTRACT
Objective: To investigate the effects of radical radiotherapy combined with different chemotherapy regimens (fluorouracil-based versus docetaxel plus cisplatin) on the incidence of radiation intestinal injury and the prognosis in patients with non-metastatic anal squamous cell carcinoma. Methods: A retrospective cohort study was conducted to recruit non-metastatic anal squamous cell carcinoma patients who underwent chemoradiotherapy in the Sixth Affiliated Hospital of Sun Yat-sen University and Nanfang Hospital from July 2013 to January 2021. Inclusion criteria: (1) newly diagnosed anal and perianal squamous cell carcinoma; (2) completed radical radiotherapy combined with concurrent chemotherapy; (3) tumor could be evaluated before radiotherapy. Exclusion criteria: (1) no imaging evaluation before treatment, or the tumor stage could not be determined; (2) patients undergoing local or radical resection before radiotherapy; (3) distant metastasis occurred before or during treatment; (4) recurrent anal squamous cell carcinoma. A total of 55 patients (48 from the Sixth Affiliated Hospital of Sun Yat-sen University and 7 from Nanfang Hospital) were given fluorouracil (the 5-FU group, n=34) or docetaxel combined with the cisplatin (the TP group, n=21). The evaluation of radiation intestinal injury, hematological toxicity and 3-year disease-free survival (DFS) rate were compared between the two groups. The effects of chemotherapy regimen and other clinicopathological factors on the incidence and severity of acute and chronic radiation intestinal injury were analyzed. The assessment of radiation intestinal injury was based on the American Cancer Radiotherapy Cooperation Group (RTOG) criteria. Results: During radiotherapy and within 3 months after radiotherapy, a total of 45 patients developed acute radiation intestinal injury, including 18 cases of grade 1 (32.7%), 22 cases of grade 2 (40.0%) and 5 cases of grade 3 (9.1%). No patient developed chronic radiation intestinal injury. Among the 34 patients in the 5-FU group, 21 had grade 2-3 radiation intestinal injury (21/34, 61.8%), which was significantly higher than that in the TP group (6/21, 28.6%) (χ(2)=5.723, P=0.017). Multivariate analysis showed that 5-FU chemotherapy regimen was an independent risk factor for radiation intestinal injury (HR=4.038, 95% CI: 1.250-13.045, P=0.020). With a median follow-up period of 26 (5-94) months, the 3-year DFS rate of patients in TP group and 5-FU group was 66.8% and 77.9%, respectively, whose difference was not significant (P=0.478). Univariate analysis showed that the DFS rate was associated with sex, age, tumor location, T stage, N stage, and induction chemotherapy (all P<0.05), while the DFS rate was not associated with chemotherapy regimen or radiation intestinal injury (both P>0.05). Multivariate analysis revealed that age ≥ 50 years old was an independent risk factor affecting the prognosis of patients (HR=8.301, 95% CI: 1.130-60.996, P=0.038). Conclusions: For patients with non-metastatic anal squamous cell carcinoma, radical radiotherapy combined with TP chemotherapy regimen can significantly reduce the incidence of radiation intestinal injury as compared to 5-FU regimen. However, due to the short follow-up time, the effect of different chemotherapy regimens on the prognosis is not yet clear.
Subject(s)
Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Chemoradiotherapy , Cisplatin/therapeutic use , Fluorouracil/therapeutic use , Neoplasm Recurrence, Local , Retrospective StudiesABSTRACT
Objective:The clinical heterogeneity of non-metastatic castration-resistant prostate cancer is high, and precise and individualized treatment is required for different patients to achieve maximum benefits. Three cases of non-metastatic castration-resistant prostate cancer were reported in this paper. One case received apalutamide + leproprillin treatment, one received radical prostatectomy, and one received radiotherapy + abiraterone treatment. After a period of follow-up, the three patients all benefited to varying degrees.
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Prostate cancer is one of the most common cancers threatening the health of males. The incidence of prostate cancer in China is on the rise. Non-metastatic castration-resistant stage is a special disease stage during the progression of prostate cancer, early identification of nmCRPC and prompt intervention can help delay disease progression and prolong patient survival. In recent years, many studies demonstrated the efficacy of novel androgen receptor inhibitors such as apalutamide, in prolonging metastasis-free survival and time to symptomatic progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This article reviews the recent progress of novel androgen receptor inhibitors for nmCRPC.
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Prostate cancer is cancer of the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, some grow relatively quickly. The cancer cells may spread from the prostate to other area of the body, particularly the bones and lymph nodes. Factors that increase the risk of prostate cancer include older age, a family history of the disease, and race. About 99% of cases occur in males over the age of 50. Clinical features include hematuria, dysuria (painful urination),nocturia(urination at night). Lower blood levels of vitami D may increase the risk of developing prostate cancer. Infection with the sexually transmitted diseases, chlamydia, gonorrhea, syphilis and prostatitis seem to increase risk of prostate cancer. Diagnosis can be confirmed by digital rectal examination (DRE) with prostate-specific antigen (PSA) blood test, cystoscopy, transrectal ultrasonography and biopsy (The removal of small pieces of the prostate for microscopic examination). Medicines like 5-alpha-reductase inhibitors (finasteride and dutasteride) reduce the overall risk of prostate cancer. Apalutamide, sold under the brand name Erleada, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC). It is taken by mouth. Apalutamide was first described in 2007 and was approved for the treatment of prostate cancer in February 2018. Apalutamide is used in conjunction with castration, either via bilateral orchiectomy or gonadotropin-releasing hormone analogue (GnRH analogue) therapy, as a method of androgen deprivation therapy in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC).
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Objective To systematically evaluate the expression of microvascular invasion (MVI) in predicting the clinical prognosis of patients with non-metastatic renal cell cancer (nmRCC) after surgical operation.Methods The relevant search strategy,including and excluding criteria for the relevant literature were developed by two independent researchers.Pubmed,EMBASE,China National Knowledge Infrastructure (CNKI),and Wanfang databases were searched from the inception to May 2018 for the study of tumor prognosis in the patients of nmRCC with MVI following surgical resection.The search language was English and Chinese.The methodological quality of the included studies was assessed by the NOS.Stata 12.0 software and Review Manager 5.3 were used to perform a clinical meta-analysis of relevant literature data.Results A total of 25 related clinical studies were included,published from 2004 to 2018.There were 6 741 patients with nmRCC,of which 1 768 cases of MVI,with a proportion rate of 26.2％.The results showed that the patients with MVI in pathological sections had a lower cancer-specific survival rate (CSS) [HR =1.51,95％ CI(1.41-1.62),P ＜0.001],recurrence-free survival rate(RFS) [HR =1.47,95％ CI (1.26-1.71),P＜0.001] and overall survival rate(OS) [HR=1.37,95％C1(1.19-1.57),P＜ 0.001].Egger's publication bias analysis showed no significant publication bias in terms of CSS (t =1.43,P=0.176),RFS (t =1.21,P=0.253) and OS(t =0.37,P=0.725).Conclusions MVI had a significant poor outcome in patients with surgical resection of nmRCC.It can be used as an independent risk factor to evaluate the postoperative prognosis of those patients.
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@#The use of high- or low-dose radio-iodine therapy (RAIT) for initial thyroid remnant ablation in post-thyroidectomised patients diagnosed with differentiated thyroid cancer (DTC) with no distant metastases has long been a subject of much debate. Meta-analyses and systematic reviews have been previously made using both randomised control trials (RCTs) and observational studies without due regard to differences in study design. Hence, amore focused meta-analysis of available RCTs alone was conducted to determine the presence of a compelling difference between the initial remnant ablation success rates of high- and low-dose RAIT in post-thyroidectomised DTC patient without distant demtastases. An extensive search of PubMed and Cochrane Central register of RCTs (up to August 2013) was performed by two reviewers, which was completed by hand search of referencesfrom releveangt articles and review papers published from 1996 to 2012. The two reviewers independtly selected eligible studies, with disagreement resolved by consensus. The inclusion criteria were as follows: (a) randomised controlled trials, (b) post-thyroidectomised adult subjects diagnosed with well differentiated thyroid cancer and no evidence of distant metastases, and (c) subject randomisation into 30-50 mCi or 100 mCi 131I treatment groups. Studies were exluded if (a) the full text of the study is not available, (b) the study is in another language other than English, and (c) if the data on relative risk was not available or could not be derived from the study. Of eight published RCTs on radio-iodine therapy as of August 2013, only 5 were eligible for this meta-analysis; namely those by JOhansen et al. (1991), Bal et al. (1996), Zaman et al. (2006), Maenpaa et al. (2008) and Caglar et al. (2012). The same two reviewers independenty extracted data from the full text of the selected five studies. Two-by-two tables comparing frequencies of successful and failed remnant ablation using low-dose (30-60 mCi) and high-dise (100 mCi) RAIT were derived from the published results of the included studies, and the weighted and pooled relative risks for successful remnant ablation were computed via the Mantel-Haenszel method using a fixed effects model (cx = 5%). Subgroup analyses were performed based on different definitions of a successful remnant ablation. The pooled relative risk (-0.03) was statistically insignificant (p=0.54) and had poor precision (95% confidence interval of {-0.12,0.06}) even when adjustments to the varied definitions of a successful ablation were performed. Thus, using available RCTs that compare high- and low-dose RAIT for remnant ablation of DTC, there is an apparent trend favoring higher success rates using high-dose RAIT. However, the lack of well designed RCTs precludes recommending high-dose initial RAI ablation, and encourages the present practice of individualized.
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Meta-Analysis , Thyroid Neoplasms , Iodine RadioisotopesABSTRACT
Objective To observe the levels of von willebrand factor (vWF) ,antithrombin (AT) ,D‐dimer (DD) and tissue fac‐tor procoagulant activity (TF‐PCA) on patients with malignant gastrointestinal tumor and then make comparisons .Methods Use machine to detect the vWF、AT、DD and TF‐PCA levels of 50 patients with metastatic gastrointestinal malignant tumor (group C) and another 59 patients with non‐metastatic gastrointestinal malignant tumor (group B) ,and then compare them with those 60 cases of normal physical examination people (group A) .Results Compared with group A ,the levels of vWF、DD and TF‐PCA showed obvious increases (P0 .05) .Conclusion Patients with malignant gastrointestinal tumor have imbalance in coagulation and fibrinolysis system ,and this imbalance is much more obvious in metastatic tumor than non‐metastatic tumor .The prethrombotic state indexes of patients are only correlated to gas‐trointestinal malignant tumor ,but not to the parts where the tumor is in .Therefore ,the detection of vWF、AT、DD and TF‐PCA lev‐els can provide reference for the condition monitoring and prognosis of gastrointestinal malignant tumor .
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Objective To observe the expression of glycoprotein non-metastatic melanoma protein B (Gpnmb) in the kidney and urine after ischemic-reperfusion injury (IRI),and explore the relationship between Gpnmb and macrophage phenotypes in the IRI kidney.Methods Male C57BL/6J mice were randomly divided into control group (n =4),sham group (n =4) and IRI group (n =12).Both renal pedieles of mice in IRI group were identified and occluded with microvascular clamps for 30 min.Renal pathological injury was observed by PAS staining.The expression of Gpnmb was examined by real-time PCR and immunofluoresence staining.The location of Gpnmb was observed by flow cytometry and double immunofluoresence staining with F4/80.The mRNA expressions of Gpnmb,CD40,CRR7,CD163 and MMR were examined by real-time PCR.The expression of Gpnmb in the urine was examined by Western blotting and ELISA.Results PAS-stained IRI kidney section showed desquamative epithelia,necrosis debris and a large number of inflammatory cell infiltration.Real-time PCR results showed that there was little expression of Gpnmb in the kidney of control group and sham group.However,the Gpnmb mRNA level in IRI kidneys was highly up-regulated at day 1 and day 2 (both P ＜ 0.01) and followed by a decrease that was similar to the control level at day 3.Double immunofluoresence staining of kidney sections from IRI mice revealed that Gpnmb was predominantly detected in F4/80 positive macrophages.The mRNA expression of Gpnmb was not correlated with M1 macrophage phenotypes CD40 and CCR7,but positively correlated with M2 macrophages phenotypes CD163 and MMR.Western blotting and ELISA result showed that there was significant increase of Gpnmb expression in the urine from IRI mice compared to those of the control group and the sham group (P ＜ 0.01).Conclusions Gpnmb expression is up-regulated in IRI kidney and is associated to M2 macrophages.It may play a role in the process of acute kidney injury.Gpnmb expression is also increased in urine after IR injury and it may be a new biomarker to diagnose AKI.
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Objective: To analyse the Chilean trends in mortality from brain malignancies between 1985 and 1999. Methods: We calculated mortality rates from malignant brain tumors using data obtained from death certificates available at the National Statistics Office. The following International Classification of Diseases categories were selected: 191.0 to 191.9 (ICD-9), and C71.0 to C71.9 (ICD-10). The rates were adjusted using direct standardization. Prais-Winsten methodology was used for time correlation analysis. Results: Sex-specific rates varied from 0.9 to 1.75 per 100.000 in men and from 0.7 to 1.22 in women. The trend was toward a statistically significant increase in mortality from malignant brain tumors in both groups. The analysis by age group showed no statistically significant variation in those below 35 years old, and a statistically significant increase in those between 35 and 39 years old, and in those above 45 years old. Conclusions: The trend in mortality from malignant brain tumors, in Chile, shows a statistically significant increase in those between 35 and 39 years old, and in those above 45 years old.
Existe controversia en el aumento de la incidencia en las tasas de tumores primarios malignos de cerebro. Este incremento podría explicarse por el crecimiento exponencial en el número de Tomografías computarizadas. Objetivo: Evaluar la tendencia de la mortalidad por tumores cerebrales primarios malignos en Chile (TCM). Metodología: Estudio de tasas de mortalidad de datos obtenidos en índices demográficos (años 1985 a 1999). Se utilizó la población de Chile de los años estudiados y se ajustó a la población estimada de 1999. Se usó las categorías 191,0 a 191,9 y C 71-0 a C 71-9 de la Clasificación Internacional, correspondiendo al grupo de tumores malignos del SNC. Se estudiaron tasas específicas por edad y sexo. Se calculó la tendencia utilizando las tasas ajustada por edad y sexo. Se utilizó una prueba de regresión lineal (Prais-Winsten) para mediciones correlacionales en el tiempo (Stata 7). Resultados: Se obtuvo 2.304 TCM. Las tasas específicas por sexo varían entre 0,90 a 1,75 x 100.000 en hombres y de 0,7 a 1,22 en mujeres. La tendencia global de la mortalidad por tumores tiende al ascenso en ambos grupos y es significativamente más alta en hombres (0,47 95 % IC 0,18 a 0,42 p = < 0,005) El estudio por grupos etarios no muestra un aumento significativo en menores de 14 años, ni entre 15 y 34 años. En los grupos de 45 años y más es estadísticamente significativa. Conclusión: La tendencia a la mortalidad por TCM aparece en ascenso en los grupos etarios 35 a 39 años y 45 años y más.