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BACKGROUND: Prostate-specific antigen (PSA) remains the most useful marker for screening, risk categorization, and follow-up in patients with prostate cancer. In the obese population, several studies have revealed that obesity may not only inversely interfere with the concentration of PSA, but also increase the risk of prostate cancer. Thus, we considered using the body mass weighted PSA levels, presented as serum PSA concentration multiplied by body weight or body mass index (BMI), instead of traditional PSA concentration, as potential markers to predict locally advanced prostate cancer after prostatectomy. METHODS: We retrospectively collected and analyzed data acquired from a single institute at which robot-assisted laparoscopic radical prostatectomy was performed. A total of 174 patients underwent radical prostatectomy, and the collected data included age, PSA level, body weight, BMI, and pathology results. RESULTS: A total of 174 patients were diagnosed with adenocarcinoma of the prostate by needle biopsy, and most (N = 165) were considered to have localized disease on preoperative multiparameter magnetic resonance imaging. After prostatectomy, 73% (N = 127) of the patients remained in the localized disease group (group A) and 27% (N = 47) of the patients were reclassified to the locally advanced prostate cancer (group B). The value of PSA was higher in group B (16.9 vs 11.2 ng/dL; p = 0.062), but there was no statistically significant difference between the two groups. After using the numerical values of PSA × body weight and PSA × BMI, a statistically significant difference emerged between the two groups ( p = 0.0198 in PSA × BW; p = 0.0110 in PSA × BMI). CONCLUSION: The body mass-weighted PSA levels, instead of the traditional PSA concentration, may be better markers for predicting non-organ-confined disease after surgery. It may also be useful in screening and risk categorization.
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Índice de Masa Corporal , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Antígeno Prostático Específico/sangre , Persona de Mediana Edad , Estudios Retrospectivos , AncianoRESUMEN
This study aimed to explore the existence of circulating tumor cells (CTCs) in patients with muscle-invasive bladder cancer (MIBC) and their predictive potential for response to neoadjuvant chemotherapy (NAC). From 33 blood samples of MIBC patients, CTCs were isolated by cell surface markers and enriched by the IsoFlux™ device, followed by morphological and immunofluorescent identification. CTCs were detected at baseline in all samples. Immunofluorescence confirmed the tumor origin. MIBC patients were stratified by NAC response into the disease control (DC) and progressive disease (PD) groups. In the DC group, the number of CTCs decreased significantly after four courses of NAC (p < 0.0001). CTC counts in 7.5 mL after four NAC cycles were highly correlated with postoperative pathological T stage (p < 0.0001). Our study demonstrated that CTCs might represent a valuable predictive marker for NAC response in MIBC. CTC detection in MIBC patients could allow early arrangement of radical cystectomy for NAC non-responders to prevent disease progression while receiving the NAC courses.
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BACKGROUND: Combination therapy with the administration of GW5074 and sorafenib significantly induced necrotic death in various cancer cells in vivo, as well as prolonging the survival of an animal disease model due to significant suppression of the primary and metastatic lesions. We sought to determine the safety, tolerability, pharmacokinetics, and anti-tumor activity of this co-administration therapy in patients with refractory advanced solid cancers. METHODS: Twelve patients were enrolled. Eligible subjects received different dosages of GW5074 in one of the three dose cohorts (Cohort 1: 750 mg daily, Cohort 2: 1500 mg daily, Cohort 3: 750 mg twice daily) plus 200 mg of sorafenib daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) at phase 1. Furthermore, the expression level of phosphorylated DAPKS308 in primary tumor, metastatic tumor, and circulating tumor cells (CTC) were evaluated to investigate the relationship between biomarker and the efficacy profile. RESULTS: Among the 12 enrolled patients in this phase 1 trial, most adverse effects (AE) were grade 1, with two being grade 3. The most frequent AE of all grades were weight loss and hypertension, occurring in 16.7% of participants. Eight patients (66.7%) had the disease controlled by receiving co-administration therapy of GW5074 and sorafenib. GW5074 was found to have poor absorption, as increasing the dosage did not result in a significant increase in the bioavailability of GW5074 in subjects. Furthermore, the expression level of phosphorylated DAPKS308 in tumor and CTCs were correlated with the disease control rate (DCR) and duration of response (DOR). CONCLUSIONS: Co-administration therapy of GW5074 and sorafenib demonstrated a favorable safety profile and showed anti-tumor activity in a variety of tumor types. However, the solubility of GW5074 is not satisfactory. A future phase 2a trial will be carried out using the new salted form that has been proven to be more effective.
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OBJECTIVE: There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response. METHODS: Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed. RESULTS: Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome. CONCLUSION: We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.
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Carcinoma de Células Renales , Neoplasias Renales , Células Neoplásicas Circulantes , Apoptosis , Antígeno B7-H1 , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , LigandosRESUMEN
BACKGROUND: This study aimed to investigate the presence of circulating tumor cells (CTCs) in patients with penile squamous cell carcinoma (PSCC). METHODS: CTCs were isolated from 14 patients with PSCC, 6 patients with balanoposthitis, and 6 healthy individuals. CTCs were enriched based on cell surface markers and filtered through the IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. RESULTS: CTCs were found in all PSCC blood samples but not in balanoposthitis samples and samples from healthy individuals. Immunofluorescence studies confirmed the tumor origin. When the patients with PSCC were stratified according to metastatic inguinal lymph node status, a statistically significant difference was observed in the number of detected CTCs. CONCLUSION: Our study showed that CTCs in PSCC may represent a valuable marker for differentiating PSCC from other tumors. Based on the correlation with some clinical parameters, CTC analysis is possibly relevant for noninvasive monitoring of disease progression and prognosis. The results also suggested a potential role of CTCs in preventing overtreatment, such as inguinal lymph node dissection.
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Biomarcadores de Tumor , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Células Neoplásicas Circulantes , Neoplasias del Pene/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/cirugía , Humanos , MasculinoRESUMEN
To compare perioperative circulating tumor cells (CTC) in primary upper tract urothelial carcinoma (UTUC) patients who underwent hand-assisted retroperitoneoscopic nephroureterectomy (HANU) or robotic-assisted nephroureterectomy (RANU). A total of 29 patients received RANU (n = 10) or HANU (n = 19). Peripheral blood samples were collected before, 24 h after surgery (POh24) and on postoperative day 28 (POD28). The demographic and pathologic data are similar in both groups. RANU had a longer operative time (p = 0.031), less bleeding volume (p = 0.004), and comparable pain sore (p = 0.169). The mean CTC numbers before surgery (2.4 vs. 2.3, p = 0.482), POh24 (2.4 vs. 1.9, p = 0.668) and POD28 (0.5 vs. 0.6, p = 0.280) were not significant different among groups. The amount of CTCs in both groups decreased and reached similar level on POD28. No significant difference of overall and intravesical recurrence rate between the two approaches. In comparison to RANU, more surgical manipulation does not affect tumor cell translocation into the bloodstream in UTUC patients who received HANU. However, a longer follow-up would be needed for the final comparison of tumor recurrence.
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Células Neoplásicas Circulantes/patología , Nefroureterectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Urológicas/patología , Neoplasias Urológicas/cirugía , Anciano , Biomarcadores de Tumor , Manejo de la Enfermedad , Femenino , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Nefroureterectomía/efectos adversos , Pronóstico , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del TratamientoRESUMEN
Clinical bladder tumor histological analysis shows that high expression of S1PR1 is associated with poor patient prognosis. However, there are no studies that describe the underlying mechanism. To investigate the relative distribution and actual function of S1PR1 in bladder tumors, we analyzed multiple clinical databases in combination with tumor purity and immune cell infiltration simulations, as well as databases of well-defined histological phenotypes of bladder cancer, and single-cell sequencing of adjacent normal tissues and bladder tumors, and further compared them with bladder cancer cell lines. The results showed that S1PR1 expression was generally higher in normal tissues than in bladder cancer tissues, and its distribution was mainly in endothelial cells or immune cells. The association between high S1PR1 expression and poor prognosis may be due to tumor invasion of adjacent normal tissues, where highly expressed S1PR1 may affect prognostic interpretation. The effect of S1PR1 itself on cancer cells was associated with cell adhesion, and in bladder cancer cells, S1PR1 expression was negatively correlated with cell motility. Moreover, the use of FTY-720 will cause an increased metastatic ability of bladder cancer cells. In conclusion, we suggest that the use of S1PR1-specific inhibition as a synergistic treatment requires more observation and consideration.
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Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.
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Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti-tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2-overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2-overexpressing bladder cancer.
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Curcumina , Neoplasias de la Vejiga Urinaria , Apoptosis , Línea Celular Tumoral , Curcumina/farmacología , Diarilheptanoides , Humanos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/genética , Receptor ErbB-2 , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. The RNAseq analysis and cytokines assay demonstrated that TNF-α stimulated ADSCs proliferation and pro-inflammatory genes that correlated to leukocytes differentiation were upregulated. We found that upregulation of TLR2 or PTGS2 toward to IRF7 gene-associated with immunomodulatory and antitumor pathway under TNF-α treatment. In TNF-α-treated ADSCs cultured with the bladder cancer (BC) cell medium, the results showed that apoptosis ratio and OCT-4 and TLR2 genes which maintained the self-renewal ability of stem cells were decreased. Furthermore, the cell survival regulation genes including TRAF1, NF-kB, and IRF7 were upregulated in TNF-α-treated ADSCs. Additionally, these genes have not been upregulated in BC cell medium. A parallel study showed that tumor progressing genes were downregulated in TNF-α-treated ADSCs. Hence, the study suggests that TNF-α enhances the immunomodulatory potential of ADSCs during tumorigenesis and provides insight into highly efficacious MSC-based therapeutic options for BC.
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Inflamación/patología , Células Madre Mesenquimatosas/patología , Microambiente Tumoral , Factor de Necrosis Tumoral alfa/farmacología , Neoplasias de la Vejiga Urinaria/patología , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Carcinogénesis/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Madre Embrionarias Humanas/efectos de los fármacos , Células Madre Embrionarias Humanas/metabolismo , Humanos , Inmunomodulación/efectos de los fármacos , Terapia de Inmunosupresión , Factor 7 Regulador del Interferón/genética , Factor 7 Regulador del Interferón/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunologíaRESUMEN
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose solution was performed. After 1 week, we conducted a urodynamic test, bladder staining, and ECM-related gene expression analysis to examine the treatment's efficacy. We found that dextrose treatment could recover the instability of the bladder, reduce frequent urination, and improve the glycosaminoglycan layer regeneration and the bladder wall thickness along with a significant intense expression of CD44 receptors. Furthermore, we enrolled 29 IC/BPS patients with previous hyaluronic acid/Botox treatment for more than 6 months with remained unchanged condition. In this study, they received intravesical injections of 10% dextrose solution followed by assessments for up to 12 weeks. Patient characteristics and a 3-day voiding diary before treatment were recorded. Patient responses were examined using IC/BPS-related questionnaires. Moreover, expressions of growth factors and cytokines were analyzed. The results demonstrated that dextrose prolotherapy in patients with IC/BPS reduced the frequency of treatment over time, with the mean number of treatments being 3.03 ± 1.52, and significantly reduced the incidence of nocturia and questionnaire scores associated with symptoms. Dextrose prolotherapy significantly enhanced EGF level and, in contrast, reduced the level of HGF, PIGF-1, and VEGF-D after several weeks following treatment. The cytokine analysis showed that the expressions of IL-12p70 and IL-10 were significantly up-regulated after dextrose prolotherapy in IC/BPS patients. The levels of most growth factors and cytokines in IC/BPS patients had no significant difference and showed a similar tendency as time progressed when compared to healthy controls. Overall, the alteration of growth factors and cytokines exhibited safe treatment and potential stimulation of tissue remodeling. In summary, our study demonstrated that dextrose prolotherapy is a promising treatment strategy for IC/BPS disease management.
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OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a disease of unmet medical need. While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects. Switchable CAR-T cells whereby activity of the CAR-T cell is controlled by dosage of a tumour antigen-specific recombinant Fab-based 'switch' to afford a fully tunable response may overcome this translational barrier. DESIGN: In this present study, we have used conventional and switchable CAR-T cells to target the antigen HER2, which is upregulated on tumour cells, but also present at low levels on normal human tissue. We used patient-derived xenograft models derived from patients with stage IV PDAC that mimic the most aggressive features of PDAC, including severe liver and lung metastases. RESULTS: Switchable CAR-T cells followed by administration of the switch directed against human epidermal growth factor receptor 2 (HER2)-induced complete remission in difficult-to-treat, patient-derived advanced pancreatic tumour models. Switchable HER2 CAR-T cells were as effective as conventional HER2 CAR-T cells in vivo testing a range of different CAR-T cell doses. CONCLUSION: These results suggest that a switchable CAR-T system is efficacious against aggressive and disseminated tumours derived from patients with advanced PDAC while affording the potential safety of a control switch.
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Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Inmunoterapia Adoptiva/métodos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Animales , Antígenos de Neoplasias/genética , Biopsia con Aguja , Carcinoma Ductal Pancreático/inmunología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Inmunoterapia/métodos , Invasividad Neoplásica/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Pancreáticas/inmunología , Receptor ErbB-2/genética , Estadísticas no Paramétricas , Resultado del Tratamiento , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial-mesenchymal transition of cancer cells. In 25 stage I-IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.
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Antígenos de Protozoos/metabolismo , Molécula de Adhesión Celular Epitelial/metabolismo , Células Neoplásicas Circulantes/metabolismo , Adaptación Fisiológica , Línea Celular Tumoral , Separación Celular , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal , Humanos , Leucocitos Mononucleares/metabolismo , Magnetismo , Masculino , Mesodermo/metabolismo , Microesferas , Estadificación de Neoplasias , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Unión Proteica , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Recombinantes/metabolismoRESUMEN
It has been demonstrated that even localized tumors without clinically apparent metastasis give rise to circulating tumor cells (CTCs). A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients' outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, 'liquid biopsy', which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis-initiating capabilities based on their stemness properties and invasiveness and thus are critical for the patients' clinical outcome. As compared to non-tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and characterizing these circulating cancer stem cells, but also highlights current technological limitations.
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Whether sexual function is affected by circumcision is a subject of considerable debate among advocate and opponent opinions. We analyzed the sexual function of young men, and the differences between those who were uncircumcised and circumcised, in Taiwan. A total of 506 patients who received circumcision between January 2009 and March 2011 at the urology department in our center were enrolled. Before circumcision, the patients' sexual performances were evaluated using the International Index of Erectile Function-5 (IIEF-5), and the Brief Male Sexual Function Inventory (BMSFI) questionnaires. They were evaluated using the questionnaires again, after a postoperative interval of 90 days. Furthermore, intravaginal ejaculation latency times (IELT) of the patients were also measured. The IELT and scores in five main domains of the BMSFI, and IIEF, before and after circumcision, were analyzed. A total of 442 patients were available for follow up. The mean age was 25.14 ± 4.46 years (range = 19-35 years). The differences in the BMSFI scores were statistically significant (p < 0.001), especially in increasing sex drive after circumcision (p < 0.001). The IIEF-5 score showed no statistically difference before and after circumcision (p = 0.141). However, after the circumcision, the participants had more erection confidence (p < 0.001), more difficulty in maintaining erections in completing intercourse (p = 0.01), and showed lower IELT scores (p = 0.06). The sexual performance, especially with regards to sex drive and mental erection confidence, seemed to have improved among the patients after circumcision. Our findings may help urologists to better counsel young men receiving circumcisions.
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Circuncisión Masculina , Conducta Sexual , Adulto , Eyaculación , Humanos , Masculino , Cuidados Posoperatorios , Cuidados Preoperatorios , Encuestas y Cuestionarios , Taiwán , Adulto JovenRESUMEN
BACKGROUND: Findings related to the influence of the -160C â A promoter polymorphism and haplotypes of the E-cadherin (CDH1) gene have not been consistent in previous studies regarding the risk for sporadic gastric cancer. Investigators in most previous studies detected those genotypes using restriction fragment length polymorphism analysis. Therefore, we conducted a case-control study to investigate the association of the CDH1 - 160C â A promoter polymorphism and haplotypes for cancer risk related to sporadic diffuse and intestinal gastric cancer by direct sequencing analysis. METHODS: We included 107 diffuse gastric cancer cases, 60 intestinal gastric cancer cases and 134 controls. The genotypic polymorphisms in the -160 promoter region, exons and intron-exon boundaries of CDH1 were detected by direct sequencing analysis. Genotype frequencies were compared. The CDH1 - 160C â A promoter polymorphism and four polymorphisms (48 + 6 T â C, 2076C â T, 2253C â T and 1937-13 T â C) were included in the haplotype analyses, which were estimated using the expectation-maximization algorithm. RESULTS: Compared to controls, the frequency of the -160A allele was significantly higher in diffuse gastric cancer cases (P = 0.005), but it was not significantly different in intestinal gastric cancer cases (P = 0.119). Two sets of three-marker haplotypes (-160C â A, 48 + 6 T â C, 2076C â T and -160C â A, 1937-13 T â C, 2253C â T) were associated with the risk of diffuse gastric cancer (P = 0.011 and P = 0.042, respectively). CONCLUSION: Based on direct sequencing analysis, our findings suggest that the CDH1 - 160C â A promoter polymorphism and haplotypes play significant roles in cancer risk for sporadic diffuse gastric cancer, but not for intestinal gastric cancer, in a Taiwanese population.
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Biomarcadores de Tumor/genética , Cadherinas/genética , Haplotipos/genética , Neoplasias Intestinales/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD , Cadherinas/metabolismo , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Técnicas para Inmunoenzimas , Neoplasias Intestinales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas/genética , Análisis de Secuencia de ADN , Neoplasias Gástricas/patología , Adulto JovenRESUMEN
AIM: To investigate the comorbid disease could be the predictors for the elective colectomy in colonic diverticulitis. METHODS: A retrospective chart review of 246 patients with colonic diverticulitis admitted between 2000 and 2008 was conducted, and 19 patients received emergent operation were identified and analyzed. Data were collected with regard to age, sex, albumin level on admission, left or right inflammation site, the history of recurrent diverticulitis, preoperative comorbidity, smoking habits, medication, treatment policy, morbidity, and mortality. Preoperative comorbid diseases included cardiovascular disease, diabetes, pulmonary disease, peptic ulcer disease, gouty arthritis, and uremia. Medications in use included non-steroidal anti-inflammatory drugs, acetylsalicylic acid (Aspirin), and corticosteroids. Univariate and multivariate logistic regression analyses were performed to identify the relevant risk factors correlating to colectomy. RESULTS: The mean age of the 246 patients was 69.5 years (range, 24-94 years). Most diverticulitis could be managed with conservative treatment (n = 227, 92.3%), and urgent colectomy was performed in 19 patients (7.7%). There were three deaths in the surgical group and four deaths in the nonsurgical group. The overall mortality rate in the study was 1.7% among patients with conservative treatment and 15.7% among patients undergoing urgent colectomy. Multiple logistic regression analysis indicated that comorbidities were risk factors for urgent colectomy for diverticulitis. CONCLUSION: To avoid high mortality and morbidity related to urgent colectomy, we suggest that patients with colonic diverticulitis and comorbid diseases may require elective colectomy.
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Colectomía , Diverticulitis del Colon/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Colectomía/efectos adversos , Colectomía/mortalidad , Comorbilidad , Diverticulitis del Colon/diagnóstico , Diverticulitis del Colon/mortalidad , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Selección de Paciente , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
This is a case study of a 61-year-old male who presented with difficult defecation for 1 month. A circumferential submucosal rectal tumor was noted on a digital rectal examination and colonoscopy. Laboratory examination revealed high serum levels of carcinoembryonic antigen (CEA; 43.75 ng/mL) and carbohydrate antigen 19-9 (CA19-9; 11,790 U/mL). In addition, tumor biopsies revealed a poorly differentiated adenocarcinoma of the rectum with intact mucosa. The patient had history of advanced stage-T2 urothelial cell carcinoma of bladder, which had been downstaged to T0 by neoadjuvant chemotherapy followed by radical cystectomy 1 year prior. After investigating the initial bladder tumor specimens, a small portion of the tumor with high CEA expression comparable to the submucosal rectal tumor was found. The size of the tumor was reduced and the levels of the tumor markers decreased after administering FOLFIRI chemotherapy targeted at the adenocarcinoma. Although neoadjuvant chemotherapy may have a selective pressure to eliminate most urothelial cell carcinoma, physicians should be aware that it can lead to rectal metastasis via CEA-producing components.