Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease ...so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC).
Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration.
CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P<0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category.
The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.
Summary
Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire ...motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double‐blind, placebo‐controlled trial investigated the effect of 6 months of supplementation with l‐carnitine, acetyl‐l‐carnitine and other micronutrients on sperm quality in 104 subjects with oligo‐ and/or astheno‐ and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow‐up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.
Background
Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective ...was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG.
Methods
We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal
p
< 0.1, have been selected for the development of a multivariable model.
Results
A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09–1.54;
p
= 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence second vs. lower quartile HR 1.42 (1.12–1.79);
p
= 0.003, third vs. lower quartile HR 1.26 (1.01–1.57);
p
= 0.041; upper vs. lower quartile HR 1.36 (1.1–1.68);
p
= 0.005. The limitations of a retrospective study are applicable.
Conclusion
Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.
Erectile dysfunction (ED), the second most common male sexual disorder, has an important impact on man sexuality and quality of life affecting also female partner's sexual life. ED is usually related ...to cardiovascular disease or is an iatrogenic cause of pelvic surgery. Many non-surgical treatments have been developed with results that are controversial, while surgical treatment has reached high levels of satisfaction. The aim is to evaluate outcomes and complications related to prosthesis implant in patients suffering from ED not responding to conventional medical therapy or reporting side effects with such a therapy. One hundred eighty Caucasian male suffering from ED were selected. The patient population were divided into two groups: 84 patients with diabetes and metabolic syndrome (group A) and 96 patients with dysfunction following laparoscopic radical prostatectomy for prostate cancer (group B). All subjects underwent primary inflatable penile prosthesis implant with an infrapubic minimally invasive approach. During 12 months of follow-up, we reported 3 (1.67%) explants for infection, 1 (0.56%) urethral erosion, 1 (0.56%) prosthesis extrusion while no intraoperative complications were reported. Mean International Index of Erectile Function-5 (IIEF-5) was 8.2 ± 4.0 and after the surgery (12 months later) was 20.6 ± 2.7. The improvement after the implant is significant in both groups without a statistically significant difference between the two groups (P-value 0.65). Mean Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score 1 year after the implant is 72.2 ± 20.7, and there was no statistically significant difference between groups A and B (P-value 0.55). Implantation of an inflatable prosthesis, for treatment of ED, is a safe and efficacious approach; and the patient and partner satisfaction is very high. Surgical technique should be minimally invasive and latest technology equipment should be implanted in order to decrease after surgery common complications (infection and mechanical failure).
Inositol is a carbocyclic sugar polyalcohol. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of major physiological and clinical relevance: myo-inositol and ...D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in kidney, brain and liver and are necessary for functions, such as signal transduction, metabolic flux, insulin signaling, regulation of ion-channel permeability, stress response and embryo development. In this narrative review, we summarize the mechanisms by which myo-inositol and D-chiro-inositol can be synthesized and absorbed and their possible role in the etiopathogenesis of neural tube defects.
We performed an online search in the PubMed database using the following keywords: "inositol", "D-chiro-inositol", "myo-inositol", "neural tube defects and inositol".
Inositol requirements are partly met by dietary intake, while the rest is synthesized endogenously. Inositol deficiency may be involved in the pathogenesis of diseases, such as metabolic syndrome, spina bifida (a neural tube defect), polycystic ovary syndrome and diabetes. Supplementation of the two inositol stereoisomers, D-chiro-inositol and myo-inositol is important to prevent these conditions.
Inositol is fundamental for signal transduction in the brain, kidneys, reproductive organs and other tissues in response to neurotransmitters, hormones and growth factors. Various genes are involved in inositol metabolism and associated pathways. Altered inositol concentrations are observed in several diseases. Analysis of the genes involved in inositol metabolism may provide important information for the clinical management of these conditions.
A standardized method for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma is lacking. A tetrafecta criterion based on a consensus panel ...within the Young Association of Urology Urothelial Group was developed. Patients achieving the tetrafecta showed higher 5-yr overall survival rates than their counterparts.
Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU).
To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC).
This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021.
We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the “RNU-fecta.” A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta.
The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta.
Herein, we present a “tetrafecta” composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field.
In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.
Abstract The development of neuromuscular junctions exhibits profound remodeling that brings from an immature state characterized by multiple motoneuronal inputs per muscle fiber, to a mature ...mononeuronal innervation. This striking elimination process occurs both perinatally and during adult reinnervation, and is also widely present in the developing CNS. The accelerating influence of the amount of impulse activity on this process, has been shown by various studies, but a more subtle role of the time correlation of action potential firing in the competing inputs, has also been suggested. Here we explore the latter influence using a rat adult model of neuromuscular junction formation, that is reinnervation following a motor nerve crush. This shares all important features with perinatal development, especially the strict juxtaposition of the competing inputs. In fact the regenerating axons converge on a single cluster of postsynaptic receptors, that is the original endplate of each muscle fiber. This focus on the spatial aspect of competition between nerve endings was missing in our previous experiments employing a similar paradigm. We impose a chronic synchronous firing to the competing terminals, by in vivo electrical stimulation of their axons distal to a sciatic nerve conduction block. Control preparations, with similar post-crush reinnervation, are left with their natural impulse activity unperturbed. We find that the experimental muscles display a prolonged duration of polyneuronal innervation with respect to controls, indicating that hebbian mechanisms participate in the synapse elimination process. Another aspect dealt with in our study is the genuine nature of the polyneuronal innervation occurring during adult muscle reinnervation, because it is supported by both confocal microscopy and by appropriate electrophysiological tests that exclude electrical coupling of myofibers by gap junctions.
Background
The management of stage T1 poorly differentiated G3 bladder cancer invading the lamina propria continues to be debated. These tumours are associated with a high risk of recurrence and ...progression; concomitant carcinoma in situ and/or multifocality are negative prognostic factors. Choosing between a preserving approach such as trans-urethral resection of the bladder (TURB) followed by maintenance bacillus Calmette-Guerin (BCG) and an invasive approach like cystectomy is critical.
Patients and methods
Overall, 80 patients underwent TURB and RE-TURB followed by intra-vesical induction treatment with BCG plus maintenance (Group A) while 72 patients underwent immediate radical cystectomy with extended lymphadenectomy (Group B). Patients were divided into 3 subgroups: uni-focal tumours, multi-focal tumours and carcinoma in situ associated lesions. In Group A, time to first recurrence and time to progression were analysed. A comparison was made between Group A and Group B regarding progression-free survival, cancer-specific survival and overall survival with a median follow-up time of 8.3 years.
Results
As far as concerns Group A patients, 42 recurrences (52.5%) were reported in a median time of 10.4 months (range 3–26) and 25 progressions (31.2%) in a median time of 25 months (range 3–68). As far as concerns time to first recurrence and time to progression, both the Kaplan–Meier survival curves obtained are significant and
P
values are, respectively, 0.0263 and 0.0011. Comparing Groups A and B patients, 25 progressions (31.2%) in a median time of 25 months (range 3–68) and 18 progressions (25%) in a median time of 25.9 months (range 4–72), respectively, were recorded. Regarding overall survival, at 10 years, 24 deaths (42.5%) occurred in a median time of 55.4 months (range 12–94) in Group A and 42 deaths (58.3%) in a median time of 54.9 months (10–100) in Group B. Cancer-specific survival was evaluated in Group A with a total of 18 deaths (22.5%) in a median time of 47.5 months (range 16–78), and in Group B with a total of 16 deaths (22.2%) in a median time of 45.7 months (range 16–88). The progression-free survival Kaplan–Meier curve is not significant, the
P
value being 0.3801; the overall survival curve is significant with a
P
value of 0.0487 while the cancer-specific survival curve is not significant with a
P
value of 0.9762.
Discussion
In Group A, considering “time to first recurrence”, the difference is greater between unifocal lesions and multifocal or Cis-associated lesions. Conversely, for “time to progression”, there is a greater difference between unifocal and multifocal tumours and Cis-associated tumours. Looking at “progression-free survival” in Group A and Group B patients, there is no statistically significant difference, like in cancer-specific survival. A statistically significant difference was observed in overall survival being in favour of conservative treatment thus reflecting that conservative treatment is not burdened by all the surgical and post-operative complications of cystectomy.
Conclusions
Although NMIBC invading the lamina propria, stage G3, with or without Cis-associated lesions are burdened both by a high volume of recurrences and progressions, cystectomy could be considered an aggressive approach. New biological markers are now needed which are able to predict the behaviour of the cancer and to guide the decision-making process between conservative or aggressive treatment.
Science with the Cherenkov Telescope Array The Cta Consortium, The Cta Consortium
The Astrophysical journal. Supplement series,
01/2019, Letnik:
240, Številka:
2
eBook, Journal Article, Book
Recenzirano
Odprti dostop
This book summarizes the science to be carried out by the upcoming Cherenkov Telescope Array, a major ground-based gamma-ray observatory that will be constructed over the next six to eight years. The ...major scientific themes, as well as core program of key science projects, have been developed by the CTA Consortium, a collaboration of scientists from many institutions worldwide. CTA will be the major facility in high-energy and very high-energy photon astronomy over the next decade and beyond. CTA will have capabilities well beyond past and present observatories. Thus, CTA's science program is expected to be rich and broad and will complement other major multiwavelength and multimessenger facilities. This book is intended to be the primary resource for the science case for CTA and it thus will be of great interest to the broader physics and astronomy communities. The electronic version (e-book) is available in open access.
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