Prognostic Value of Site-Specific Metastases and Therapeutic Roles of Surgery and Chemotherapy for Patients With Metastatic Renal Pelvis Cancer: A SEER Based Study.

BACKGROUND AND AIMS: There is a lack of research on metastatic renal pelvis cell carcinoma in the current literature. In this study, we aimed to detect distant metastatic patterns in renal pelvis cell carcinoma, and illustrated the affection of different metastatic sites, surgery to primary site and chemotherapy on prognosis outcomes in patients with diverse conditions. METHODS: We collected data between 2010 and 2015 from the Surveillance, Epidemiology and End Results database. Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 424 patients were included in the analysis, the median follow-up time was 5 months (interquartile range (IQR): 2-12) and 391 deaths (92.2%) in all patients were recorded. Among them, 192 (45.3%), 153 (36.1%), 137 (32.3%) and 127 (30.0%) patients were diagnosed with lung, bone, liver and brain metastases, respectively, while only 12 (2.8%) patients had brain metastases. The bi-organ, tri-organ and tetra-organ metastatic pattern was found in 135 (31.8%), 32 (7.5%) and 11 (2.6%) patients, respectively. The multivariate Cox analyses showed that distant lymph nodes (DL) metastases was not an independent prognostic factor for both OS and CSS (OS: Hazard ratios (HR) = 1.1, 95% CI = 0.8-1.4, P = 0.622; CSS: HR = 1.0, 95% CI = 0.8-1.3, P = 0.906). Besides, there was no significant difference of survival in patients with T3-T4 stage (OS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.296; CSS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.224), N2-3 stage (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.351; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.259) and multi-organ metastases (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.359; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.179) between surgery to primary site group and no-surgery to primary site group. CONCLUSION: we described the metastatic patterns of mRPCC and the prognosis outcomes of DL metastases, surgery to primary site and chemotherapy. Our findings provide more information for clinical therapeutic intervention and translational study designs.

U-shaped relationship of age at diagnosis and cancer-specific mortality in primary urachal adenocarcinoma: a cohort study.

BACKGROUND: To examine the association between age at diagnosis and cancer-specific mortality (CSM) in primary urachal adenocarcinoma. METHODS: The data was obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results program (SEER). A total of 393 patients were included in the study. Smooth curve fitting and two-piecewise Cox proportional hazards models were used to identify the nonlinearity between the age at initial diagnosis and cancer-specific survival rate. Survival time between different groups was compared using Kaplan-Meier survival curves and the log-rank test. RESULTS: Using smooth curve fitting we found that the relationship between age at diagnosis and cancer-specific survival takes on a U-shaped curve. The inflection point that we identified for the age at initial diagnosis was 60 years. The log-likelihood ratio test (P<0.05) indicated that the two-piecewise Cox regression model was more appropriate for fitting the correlation of age at diagnosis and CSM. The two-piecewise Cox regression model showed that when the age was <60 years, reduced risk of CSM was significantly associated with increased age (HR: 0.95, P=0.0002). Conversely, when age was >60 years, increased risk of CSM was significantly associated with increased age (HR: 1.05, P=0.0499). CONCLUSIONS: In summary, our study suggested that the relationship between age at diagnosis and cancer-specific survival is nonlinear, and takes on a U-shaped curve. Both younger and older age at initial diagnosis age were associated with increased CSM.

Development and validation of a nomogram to predict survival in patients with metastatic testicular germ cell tumors.

BACKGROUND: To develop a nomogram to predict cancer-specific survival (CSS) in patients with metastatic testicular germ cell tumors (mTGCTs). METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression models were used to identify factors associated with CSS. Survival times between different groups were compared using Kaplan-Meier survival curves and the log-rank test. A nomogram visualization model was established using the R language to predict survival rates. Harrell's concordance index (C-index), the area under the receiver operating characteristic curve (AUC) and calibration plots were used to assess the performance of the model. RESULTS: We analyzed the data of 949 patients. The median follow-up time was 32 months (range 0 to 83 months), and 224 (23.60%) patients died before the last follow-up, of whom 193 (20.33%) died of mTGCTs. The site of distant metastases was an independent prognostic factor for CSS. Compared to patients without involvement of the corresponding organ, patients with bone, brain, liver, and lung involvement had worse CSS. We also found that age, histological type, surgery, radiation therapy, chemotherapy, metastatic site and insurance status affected the CSS of patients with mTGCTs. We used these prognostic factors to construct our nomogram. Harrell's C-index for CSS was 0.739. The AUC and calibration plots indicated good performance of the nomogram. CONCLUSIONS: A nomogram for predicting CSS in patients with mTGCTs has been developed, which can help patients and clinicians accurately predict mortality risk and recommend personalized treatment modalities.

Development and validation of a nomogram for predicting survival in patients with non-metastatic primary adenocarcinoma of the bladder.

BACKGROUND: To develop a nomogram for predicting cancer-specific survival (CSS) of patients with non-metastatic primary adenocarcinoma of the bladder (NMACB). METHODS: We used a retrospective cohort study design. Patient data were obtained from the SEER database, univariate and multivariate Cox regression analyses were performed to identify factors associated with CSS. A nomogram visualization model was established using R language software to predict survival rate. Harrell's concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC) in addition to calibration plots were used to assess the performance of the model. RESULTS: A total of 1,635 patients were included in the study. A multivariate Cox regression model indicated that age, histological type, grade, stage, and surgery were independent covariates associated with CSS. Using these prognostic factors, a nomogram was constructed. Harrell's C indices for CSS were 0.729 in the training cohort and 0.716 in the validation cohort. AUC values were 0.769, 0.735 and 0.724 for 1, 3, and 5-year in the training cohort, and 0.738, 0.727 and 0.713 for 1, 3 and 5-year in the validation cohort, respectively. The AUC values and calibration plots indicated that the nomogram provided good predictive performance. CONCLUSIONS: A nomogram for predicting CSS in patients with NMACB was developed to assist clinicians in the accurate prediction of mortality risk to allow them to recommend a personalized treatment modality.

[Low-dose PDE5 inhibitors for erectile dysfunction with subclinical metabolic syndrome].

OBJECTIVE: To investigate the effects of low-dose PDE5 inhibitors on metabolic parameters and erectile function in ED patients with subclinical metabolic syndrome (SCMS). METHODS: Totally, 132 ED patients, aged 21－61 (mean 34.5) years, were treated in the Andrology Clinic of the First Hospital of Wenzhou Medical University from April 2017 to May 2018. According to the diagnostic criteria, we divided the patients into groups A (simple ED, n = 40), B (ED with SCMS, n = 34) and C (ED with MS, n = 58) to receive 3 months of oral administration of tadalafil at 5 mg qd at bedtime, and followed them up for 3 months after drug withdrawal. During the treatment, we advised the patients to keep a healthy diet, change bad habits, participate in regular physical exercise, and maintain psychological balance. Before and right after medication and at 3 months after drug withdrawal, we recorded the changes in the IIEF-5 scores, abdominal circumference, blood pressure and levels of fasting blood sugar (FBS), triglyceride (TG) and high-density lipoprotein (HDL) of the patients. RESULTS: The IIEF-5 scores showed statistically significant differences at different time points between groups A and C (P < 0.01), remarkably higher right after treatment than before treatment and at 3 months after drug withdrawal in group B (19.71 ± 2.40 vs 10.21 ± 3.92 and 16.29 ± 2.41, P < 0.01). At 3 months after drug withdrawal, the abdominal circumference was significantly smaller in group A than in B and C (ï¼»78.10 ± 6.00ï¼½ vs ï¼»84.15 ± 8.17ï¼½ and ï¼»91.53 ± 11.49ï¼½ cm, P < 0.01) and the HDL level lower in group C than in A and B (ï¼»0.96 ± 0.15ï¼½ vs ï¼»1.27 ± 0.14ï¼½ and ï¼»1.16 ± 0.2ï¼½] mmol/L, P < 0.01). Systolic blood pressure exhibited statistically significant differences between any two time points in group C (P < 0.05 or P < 0.01) but not in group A (P > 0.05) or B (P > 0.05). Diastolic blood pressure was markedly lower in group B right after medication and at 3 months after drug withdrawal than before treatment (ï¼»75.62 ± 10.70ï¼½ and ï¼»74.65 ± 9.90ï¼½ vs ï¼»78.00 ± 11.42ï¼½ mmHg, P < 0.05), and so was it in group C (ï¼»82.19 ± 10.36ï¼½ and ï¼»82.40 ± 10.09ï¼½ vs ï¼»86.71 ± 12.32ï¼½ mmHg, P < 0.05), but manifested no significant difference between any two time points in group A (P > 0.05). There were statistically significant differences in the FBS level among different time points in groups A and C (P < 0.05) but not in B between post-treatment and 3 months after drug withdrawal (ï¼»5.34 ± 0.60ï¼½ vs ï¼»5.36 ± 0.40ï¼½ mmol/L, P > 0.05), and so were there in the TG level among different time points in groups A and C (P < 0.05) but not in B between pre- and post-treatment (ï¼»1.80 ± 0.98ï¼½ vs ï¼»1.64 ± 1.19ï¼½ mmol/L, P > 0.05). CONCLUSIONS: Periodic administration of low-dose sustained-release PDE5 inhibitors with health education and lifestyle guidance may reverse ED with SCMS and improve most of the related metabolic parameters.

[Diagnosis and treatment of male urethritis in urology and andrology: A status survey].

OBJECTIVE: To investigate the status quo of the diagnosis and treatment of male urethritis (MU) in urology and andrology. METHODS: According to The Guidelines for Clinical Diagnosis and Treatment of Sexually Transmitted Diseases (2017), we designed 27 questions on the prevalence, diagnosis, treatment, and prognosis of MU. Using these questions, we conducted a questionnaire investigation among urological, andrological and other relevant clinicians with different professional titles, followed by an analysis of the compliance of the doctors to the Guidelines. RESULTS: Totally, 116 valid questionnaires were collected from 86 urological, 28 andrological and 2 other relevant doctors, including 22 professors, 36 associate professors, 40 attending doctors and 16 resident doctors. MU was found mostly in those aged 20－40 years and more than half of the patients had a history of unclean sex, gonococcal urethritis significantly less prevalent than non-gonococcal, with Ureaplasma urealyticum as the most common pathogen of non-gonococcal urethritis. As for the compliance to the Guidelines in the diagnosis of MU, 22.73% of the professors, 16.67% of the associate professors, 15.00% of the attending doctors and 12.50% of the resident doctors examined the eyes, mouth and perianus (P > 0.05), 40.91% of the professors, 58.33% of the associate professors, 40.00% of the attending doctors and 37.50% of the resident doctors conducted HIV and syphilis screening (P > 0.05), and 86.36% of the professors, 77.78% of the associate professors, 70.00% of the attending doctors and 75.00% of the resident doctors performed genital mycoplasma screening (P > 0.05). Concerning the treatment of MU, 50.00% of the professors, 47.22% of the associate professors, 22.50% of the attending doctors and 43.75% of the resident doctors used anti-Chlamydia trachomatis drugs for gonococcal urethritis (P > 0.05), 0.00% of the professors, 11.11% of the associate professors, 5.00% of the attending doctors and 31.25% of the resident doctors prescribed 1g single-dose oral azithromycin for non-gonococcal urethritis (P < 0.05), 13.64% of the professors, 33.33% of the associate professors, 17.50% of the attending doctors and 6.25% of the resident doctors medicated persistent or recurrent non-gonococcal urethritis for >4 weeks (P > 0.05), 63.64% of the professors, 83.33% of the associate professors, 57.50% of the attending doctors and 62.50% of the resident doctors treated asymptomatic trachomatis and mycoplasma infections according to the proposed medication in the Guidelines (P > 0.05). As regards the results of treatment, the cure rate of gonococcal urethritis was 100.00% by professors, 97.22% by associate professors, 95.00% by attending doctors and 81.25% by resident doctors (P > 0.05), and that of non-gonococcal urethritis was 86.36% by professors, 61.11% by associate professors, 62.50% by attending doctors and 37.50% by resident doctors (P < 0.05). CONCLUSIONS: Urological and andrological clinicians do not strictly follow the Guidelines in the diagnosis and treatment of male urethritis. There are significant differences in the dosing of azithromycin and results of treatment of non-gonococcal urethritis among doctors with different professional titles, but not in the other aspects.

[Protective effect of tadalafil against ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the protective effect of phosphodiesterase type 5 inhibitors (tadalafil) on the testis following testicular ischemia-reperfusion injury in rats. METHODS: Eighty-four healthy adult male SD rats were randomly and equally divided into groups A (sham operation), B (testicular torsion + low-dose tadalafil), C (testicular torsion + high-dose tadalafil), and D (testicular torsion + placebo). Models were established in the latter three groups by 7200 torsion of the right testis for 2 hours. The animals in groups A and B were treated by gavage with tadalafil at the dose of 0. 5 mg per kg per day, those in group C at 2 mg per kg per day, and those in group D with saline at the same dose. After 3, 7, and 14 days of treatment, the torsioned testes were harvested for evaluation of the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis tissue. The pathological changes in the testis were observed under the light microscope. RESULTS: At 3, 7, and 14 days, the SOD activity was (254.46 +/- 7.43), (278.49 +/- 8.33), and (317.99 +/- 3.31) nU/mg prot in group B, and (277.12 +/- 8.80), (309.40 +/- 2.14), and (320.39 +/- 4.72) nU/mg prot in group C, all obviously higher than in D ([223.21 +/- 4.65], [231.45 +/- 4.16] and [248.28 +/- 5.74] nU/mg prot), while the MDA content was lower in the former two groups than in the latter. At 3 and 7 days, the SOD activity was significantly higher and the MDA level significantly lower in group C than in B (both P < 0.01) , while at 14 days, neither showed any remarkable differences between the two groups (P > 0.05). No obvious histopathological change was observed in the testis tissue of group A. At 3 and 7 days, pathological examination of the testis tissue revealed significant differences in the number of seminiferous epithelial layers, testicular histological score, and seminiferous tubule diameter in group B (P < 0.01), but the three indexes at 14 days in group B and at 7 days in group C exhibited no remarkable differences from those at 14 days in group A. CONCLUSION: Tadalafil can alleviate testicular ischemia-reperfusion injury following testis torsion/detorsion in a time- and dose-dependent manner.

[Expression and clinical significance of glycoprotein non-metastatic melanoma protein B in human renal cell carcinoma].

OBJECTIVE: To investigate the role of glycoprotein non-metastatic melanoma protein B (GPNMB) in renal cell carcinoma (RCC). METHODS: The method of immunohistochemistry (IHC) and Western blot were utilized to examine the expression of GPNMB in RCC and the normal adjacent tissues matched. RESULTS: The expression of GPNMB was lower in RCC than in the matched normal adjacent tissues (P=0.022). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of RCC and the detection of GPNMB may be useful for the early diagnosis of tumor and its development.

[CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity and regulates StAR expression in a transgenic mouse model].

OBJECTIVE: To observe the effects of CMTM2 on cyclophosphamide (CP)-induced reproductive toxicity and the expression of steroidogenic acute regulatory (StAR) protein in the transgenic mouse model. METHODS: Twenty CMTM2 transgenic mice were equally divided into a CMTM2 + CP and a CMTM2 + NS group, the former intraperitoneally injected with CP at 50 mg per kg per d, while the latter with the equivalent dose of normal saline, both for 7 days. Another 20 wild C57BL/6J mice were randomly assigned to a WT + CP and a WT + NS group, treated the same way above. After 30 days, all the mice were sacrificed and their epididymides and testes removed for measurement of the serum testosterone level by radioimmunoassay, determination of sperm concentration and motility by light microscopy and detection of the expression of StAR by Western blot. RESULTS: The levels of serum testosterone, sperm concentration and sperm motility were significantly decreased in the CMTM2 + CP group as compared with the CMTM2 + NS group ([42.98 +/- 3.25] nmol/L vs [46.74 +/- 3.38] nmol/L, [16.89 +/- 1.17 ] x 10(6)/ml vs [24.68 +/- 0.95 ] x 10(6)/ml, [72.75 +/- 1.25]% vs [85.14 +/- 1.12]%, P < 0.05), but remarkably less than in the WT + CP group ([37.97 +/- 4.17] nmol/L, [12.75 +/- 1.02] x 10(6)/ml, [50.52 +/- 1.37] %) (P < 0.05). However, the expression of StAR was significantly higher in the CMTM2 + CP than in the WT + CP group (1.16 +/- 0.07 vs 0.69 +/- 0.08, P < 0.05). CONCLUSION: CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity via regulating the expression of StAR, and hence plays a protective role in the reproductive system.

[Free fatty acids induce proliferation of human renal carcinoma 786-O cell line via integrin-linked kinase].

OBJECTIVE: To investigate the effects of free fatty acids on cell proliferation and integrin-linked kinase (ILK) expression in human renal carcinoma 786-O cell line. METHODS: The 786-O cells were exposed to normal medium and different concentrations of oleic acid (OA) carried by de-fatty bovine serum albumin (d-BSA). The MTT assay and the flow cytometry assay were performed respectively for cell proliferation and apoptosis after the treatment with OA for 48 h. The expressions of ILK, Akt and p-Akt were detected by Western blot. RESULTS: The MTT assay showed that the cell viabilities of 0.05 mmol/L, 0.1 mmol/L and 0.2 mmol/L OA groups were increased gradually, as compared with the blank control (absorbance: 0.657 ± 0.056, 0.682 ± 0.028, 0.718 ± 0.042 vs. 0.495 ± 0.034; all P<0.001). The effects of OA on cells apoptosis were not significant (apoptotic rates: 2.42% ± 0.25% vs. 2.33% ± 0.87% vs. 2.25%± 0.51%, P=0.082). After being treated with OA, the expressions of ILK and p-Akt were increased in 786-O cells. CONCLUSION: The results suggested that free fatty acids could promote the development of renal cell carcinoma via up-regulating ILK/Akt pathway, which may reveal the relations between metabolic disturbance and renal carcinoma to a certain extent.

[Establishment of a CMTM2 transgenic mouse model and the alteration of its serum testosterone level].

OBJECTIVE: To establish a transgenic mouse model systemically expressing the CMTM2 gene and study the effect of the CMTM2 expression on the reproductive system of mice in vivo. METHODS: Transgenic mice were generated by microinjection of pRevTRE-CMTM2 and the genotype was detected by PCR. The expression of CMTM2 was determined by RT-PCR, Western blot and immunohistochemistry, and the serum testosterone level was measured by radioimmunoassay. RESULTS: The CMTM2 gene was highly expressed in the testis of the transgenic mouse models and in their offspring as well. The level of serum testosterone was significantly increased in the transgenic models as compared with the wild-type mice ([46.04 +/- 3.72] vs [42.43 +/- 3.80] nmol/L, P < 0.05). CONCLUSION: The transgenic mouse model was established successfully, which could highly express the CMTM2 gene. It is indicated that CMTM2 may influence steroidogenesis and testosterone secretion in transgenic mice.

[Inhibitory effect of CMTM5 on xenografted human prostatic cancer in nude mice].

OBJECTIVE: To investigate the inhibitory effect of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5) on xenografted human prostatic cancer in nude mice and its action mechanism. METHODS: We established a model of xenografted prostatic cancer by inoculating PC-3 cells subcutaneously into nude mice, and 3 weeks later injected CMTM5 adenovirus locally into the tumor followed by daily observation of the tumor volume and body weight of the experimental animals. All the rats were killed 2 weeks after CMTM5 injection and the tumor tissue harvested for detection of the inhibitory effect of CMTM5 on the expressions of VEGF and NF-kappaB proteins by immunohistochemistry. RESULTS: The tumor volume was significantly smaller and body weight of the CMTM5-treated mice were (573.39 +/- 175.24) mm3 and (0.55 +/- 0.11) g, respectively, significantly decreased as compared with those of the controls ([1482.50 +/- 327.86] mm3 and [1.31 +/- 0.29] g) (P = 0.03 and P = 0.027). Immunohistochemistry showed that the expressions of VEGF and NF-kappaB were obviously down-regulated in the CMTM5 group in comparison with the control group. CONCLUSION: CMTM5 suppresses the growth of prostate cancer by down-regulating the expressions of VEGF and NF-kappaB.

[Research advances in CKLF-like MARVEL transmembrane domain containing member 5].

CKLF-like MARVEL transmembrane domain containing member(CMTM)is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM5 belongs to this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily(TM4SF). CMTM5 is broadly expressed in normal adult and fetal human tissues, but is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM5 may inhibit the proliferation, migration, and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear, CMTM5 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM5 may be a new target in the gene therapies for tumors, while further studies on CMTM5 and its anti-tumor mechanisms are warranted.

[Expression of glycoprotein non-metastatic melanoma protein B in prostate cancer and its significance].

OBJECTIVE: To investigate the expression of glycoprotein non-metastatic melanoma protein B (GPNMB) in prostate cancer and its clinical significance. METHODS: The expression of GPNMB was analysed in 63 prostate cancer and 3 heterosexual hyperplasia prostate tissue and 8 benign prostatic hyperplasia samples by immunohistochemical staining, with integral optical density(IOD) value representing expression level of positive cells. RESULTS: The expression of GPNMB was lower in benign prostatic hyperplasia (BPH, IOD=70 017.49) than in Atypical hyperplasia (IOD=101 547.33, P=0.000 1) . The expression of GPNMB in tumor (IOD= 162 027.54) was higher than in non-tumor group (IOD=79 290.97), which included BPH and atypical hyperplasia (P=0.000 1). But GPNMB expression level was not positively elevated with degree of malignancy of prostate cancer. However, the expression of GPNMB in low pathological grading(IOD=177 944.30) was higher than that in high pathological grading(IOD=150 885.81, P=0.013). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of prostate cancer and its detection may be useful for the early diagnosis of prostate cancer.

[CMTM5 inhibits the tumor cell behavior of prostate cancer by downregulation of HER2].

OBJECTIVE: To discover whether there is any other pathway than EGFR which has interaction with HER2 that makes a different down stream on cancer manners and whether CMTM5 plays a role in HER2 related tumor performance. METHODS: HER2 and CMTM5 were detected on prostate cancer tissue chip using IHC. The protein levels of HER2, Cyclin D1 and CMTM5 were compared had with or without CMTM5 plasmid transfection on PC3 cell line to insure their relationship. RESULTS: The author demonstrated that the HER2 had been up regulated in prostate cancer epithelium while CMTM5 down regulated. Overexpression of CMTM5 in PC3 could lower the HER2 and Cyclin D1 protein level. CONCLUSION: The results suggest that in prostate cancer HER2 has a different partner in the signaling transduction other than EGFR as in a traditional pathway. CMTM5 may have a chance to be chosen as the next potential treatment bio-target of prostate cancer.