Dose-response of localized renal cell carcinoma after stereotactic body radiation therapy: A meta-analysis.

BACKGROUND: Stereotactic ablative radiation therapy (SBRT) is an emerging treatment option for primary renal cell carcinoma (RCC), particularly in patients who are unsuitable for surgery. The aim of this review is to assess the effect of increasing the biologically equivalent dose (BED) via various radiation fractionation regimens on clinical outcomes. METHODS: A literature search was conducted in PubMed (Medline), EMBASE, and the Cochrane Library for studies published up to October 2023. Studies reporting on patients with localized RCC receiving SBRT were included to determine its effectiveness on local control, progression-free survival, and overall survival. A random effects model was used to meta-regress clinical outcomes relative to the BED for each study and heterogeneity was assessed by I2. RESULTS: A total of 724 patients with RCC from 22 studies were included, with a mean age of 72.7 years (range: 44.0-81.0). Local control was excellent with an estimate of 99 % (95 %CI: 97-100 %, I2 = 19 %), 98 % (95 %CI: 96-99 %, I2 = 8 %), and 94 % (95 %CI: 90-97 %, I2 = 11 %) at one year, two years, and five years respectively. No definitive association between increasing BED and local control, progression-free survival and overall survival was observed. No publication bias was observed. CONCLUSIONS: A significant dose response relationship between oncological outcomes and was not identified, and excellent local control outcomes were observed at the full range of doses. Until new evidence points otherwise, we support current recommendations against routine dose escalation beyond 25-26 Gy in one fraction or 42-48 Gy in three fractions, and to consider de-escalation or compromising target coverage if required to achieve safe organ at risk doses.

The impact of multidisciplinary cancer conferences on overall survival: a meta-analysis.

BACKGROUND: Multidisciplinary cancer conferences consist of regular meetings between diverse specialists working together to share clinical decision making in cancer care. The aim of this study was to systematically review and meta-analyze the effect of multidisciplinary cancer conference intervention on the overall survival of patients with cancer. METHODS: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials for studies published up to July 2023. Studies reporting on the impact of multidisciplinary cancer conferences on patient overall survival were included. A standard random-effects model with the inverse variance-weighted approach was used to estimate the pooled hazard ratio of mortality (multidisciplinary cancer conference vs non-multidisciplinary cancer conference) across studies, and the heterogeneity was assessed by I2. Publication bias was examined using funnel plots and the Egger test. RESULTS: A total of 134 287 patients with cancer from 59 studies were included in our analysis, with 48 467 managed by multidisciplinary cancer conferences and 85 820 in the control arm. Across all cancer types, patients managed by multidisciplinary cancer conferences had an increased overall survival compared with control patients (hazard ratio = 0.67, 95% confidence interval = 0.62 to 0.71, I2 = 84%). Median survival time was 30.2 months in the multidisciplinary cancer conference group and 19.0 months in the control group. In subgroup analysis, a positive effect of the multidisciplinary cancer conference intervention on overall survival was found in breast, colorectal, esophageal, hematologic, hepatocellular, lung, pancreatic, and head and neck cancer. CONCLUSIONS: Overall, our meta-analysis found a significant positive effect of multidisciplinary cancer conferences compared with controls. Further studies are needed to establish nuanced guidelines when optimizing multidisciplinary cancer conference integration for treating diverse patient populations.

Outcomes of Digit Replantation in Children: A Systematic Review.

Background: Children have been suggested to benefit from digit replantation due to a greater neurogenerative capacity. We aimed to conduct a systematic review on digit replantation in children to provide a comprehensive overview of survival rates and functional outcomes. Methods: A systematic literature search was conducted on Ovid MEDLINE, Embase, and the Cochrane Controlled Register of Trials for studies published between 1980 and 2023. We included peer-reviewed studies reporting on digit survival rates in pediatric patients under the age of 18 years who underwent single or multiple digit replantations distal to the metacarpophalangeal joint. Preoperative, intraoperative, and postoperative outcomes were extracted, and pooled estimates were derived using univariable analysis. Results: Twenty-two studies reporting on 761 patients and 814 digit replantations were included in our study. Most replantations occurred in the index (n = 74), Tamai zone I (n = 168), and from clean-cut injuries (n = 190). The mean survival rate was 76% (n = 618/814), with a mean range of motion at the distal interphalangeal joint ranging from 64 degrees to 90 degrees and two-point discrimination ranging from 3.8 mm to 6.4 mm. Compared with clean-cut injuries, digit replantations from avulsion [odds ratio (OR), 0.81; 95% confidence interval (CI), 0.74-0.89] or crush (OR, 0.71; 95% CI, 0.59-0.82) injuries were associated with a lower odds of survival. Digit replantations performed with two venous (OR, 1.43, 95% CI; 1.28-1.59) or arterial anastomoses (OR, 1.65; 95% CI, 1.48-1.81) were associated with a higher odds of survival. Conclusions: Our systematic review suggests that digit replantation may be a viable option in children. Further research is required to explore functionality after digit replantation in diverse pediatric populations.

An investigation of the sex-specific genetic architecture of fitness in Drosophila melanogaster.

In dioecious populations, the sexes employ divergent reproductive strategies to maximize fitness and, as a result, genetic variants can affect fitness differently in males and females. Moreover, recent studies have highlighted an important role of the mating environment in shaping the strength and direction of sex-specific selection. Here, we measure adult fitness for each sex of 357 lines from the Drosophila Synthetic Population Resource in two different mating environments. We analyze the data using three different approaches to gain insight into the sex-specific genetic architecture for fitness: classical quantitative genetics, genomic associations, and a mutational burden approach. The quantitative genetics analysis finds that on average segregating genetic variation in this population has concordant fitness effects both across the sexes and across mating environments. We do not find specific genomic regions with strong associations with either sexually antagonistic (SA) or sexually concordant (SC) fitness effects, yet there is modest evidence of an excess of genomic regions with weak associations, with both SA and SC fitness effects. Our examination of mutational burden indicates stronger selection against indels and loss-of-function variants in females than in males.

A systematic evaluation of youtube as an information source for male infertility.

This study evaluates YouTube videos (YTVs) focused on male infertility to assess information quality and identify high-quality content that can reliably facilitate care. Top 50 YTVs based on relevance were identified using the keyword "male infertility." A checklist, adapted from American Urological Association guidelines addressing male infertility, was developed to assess YTV content. Two investigators extracted YTV features (including duration, likes, views, upload date), classified creators and ranked YTVs based on checklist scores. YTVs were then assigned grades A-D based on checklist scores. Kruskal-Wallis test and ANOVA were employed to draw associations between grades, content creator, and YTV features. Higher grades were associated with shorter video duration (p = 0.0305). Most YTVs (23/42) were created by healthcare-related organizations. Of the 42 YTVs included in the final analysis, 31% (13/42) explicitly defined infertility as an inability to conceive after 12 months of unprotected intercourse. Ninety percent (38/42) discussed male infertility evaluation methods, while 71% (30/42) discussed various interventions. Various content creators have adopted YouTube to discuss male infertility, and healthcare practitioners should be aware of YouTube's potential influence on patient understanding of male infertility. Knowledge gaps identified in YTVs can help improve patient counseling and enable practitioners to direct patients to reliable content.

Inflammatory myofibroblastic tumour of genitourinary system.

Two cases of inflammatory myofibroblastic tumour (IMT) involving the genitourinary system are presented. One patient with mass of urinary bladder came in with lower abdominal pain whereas the second patient complained of right flank pain and investigations showed a mass involving the right kidney. At present, no specific guidelines exist for the management of inflammatory myofibroblastic tumours. In this case report, we will discuss the work-up and the management stratégies adopted for each case.

The Impact of Microsurgical Repair of Subclinical and Clinical Varicoceles on Total Motile Sperm Count: Is There a Difference?

OBJECTIVE: To determine if subclinical varicocele repair produces similar results to palpable varicocele repair. METHODS: Retrospective review was performed on 190 infertile men who underwent a microsurgical varicocele repair by two surgeons from 2009 to 2017. Improvement in total motile sperm count (TMC) that enables men limited to in vitro fertilization (IVF) or intrauterine insemination (IUI) to undergo IUI or natural conception (upgrade) is clinically meaningful. Using TMC, men were grouped into three pre- and postoperative categories: IVF, (TMC < 5 million), IUI (TMC 5-9 million), or natural pregnancy (TMC > 9 million). Changes in category after varicocele repair were assessed. We compared the proportion of men in each category with clinical varicoceles to those with subclinical varicoceles. RESULTS: Men with clinical and subclinical varicoceles had improvements in TMC after surgery (change in TMC of 9.3 ± 19.5, 7.7 ± 22.6 million, P < 0.001 for both, respectively). There was no difference in TMC improvement between men with clinical and subclinical varicoceles (P = 0.66). Of men initially limited to IVF, 11% improved to IUI, and 38% to natural pregnancy. Of patients starting in IUI category, 22% transitioned to natural pregnancy category. No difference exists in the proportion of men who "upgraded" between palpable or subclinical varicoceles. CONCLUSION: Men with subclinical varicoceles have similar, clinically meaningful improvement in TMC after varicocele repair compared with men with palpable varicoceles.

Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis.

BACKGROUND: The Glutathione S-transferases (GSTs) genes deletion polymorphisms have been associated with the progression of several cancers. The association studies between the 2 GSTs (GSTM1 and GSTT1) null polymorphisms with the susceptibility to renal cell carcinoma (RCC) have been inconclusive. Therefore, with the inclusion of our own data, we performed a comprehensive meta-analysis to assess the association between these 2 polymorphisms and the risk of RCC. METHODS: A systematic literature search was carried out for studies published in the PubMed, EMBASE, Cochrane library, and Google Scholar from 1997 to December 2014. Results were stated as pooled odds ratios (ORs) for nonparametric data after heterogeneity analysis with 95% CI using fixed effect or random effect model. RESULTS: We systematically selected 13 relevant studies after thorough searches from the databases. Data showed no association between the GSTM1 and the GSTT1 null genotypes and the risk of RCC (OR = 1.01; CI: 0.92-1.11; P = 0.89 for GSTM1 and OR = 1.14; CI: 0.91-1.42; P = 0.25 for GSTT1). No association was found when the data were stratified according to the geographical/ethnic basis, source of control, and the risk factor evaluation. Subgroup analysis of occupational exposure to pesticides showed an inverse association of the active genotypes of both GSTM1 and GSTT1 polymorphisms with the exposed group of RCC (P<0.00001 and P<0.00001, respectively). The combined null genotype of the GSTM1/GSTT1 significantly increased the susceptibility to RCC by 1.4-fold (P = 0.001). This association remained significant for the Asian populations in subgroup analysis (OR = 1.8; CI: 1.30-2.49; P = 0.0004). CONCLUSION: In conclusion, this meta-analysis suggests that the 2 GSTs deletion polymorphisms independently have no association with the risk of RCC. However, combination of both deletions increases the risk of developing the RCC.

Unique molecular alteration patterns in von Hippel-Lindau (VHL) gene in a cohort of sporadic renal cell carcinoma patients from Pakistan.

BACKGROUND: Renal cell carcinoma (RCC) is the most frequent form of kidney cancer in adults. Somatic mutations that inactivate the von Hippel-Lindau (VHL) gene are the most common cause of RCC. The frequencies of molecular changes in the VHL gene in RCCs vary among different populations. So far, a single chromosomal-based study has been reported from a South Asian population. This report presents, for the first time, the somatic changes and promoter hypermethylation in VHL in a cohort of 300 RCC patients from Pakistan. METHODS: To identify mutations in the VHL gene, direct DNA sequencing was carried out. Epigenetic silencing was investigated by using methylation-specific polymerase chain reaction. RESULTS: Our data showed molecular alterations in the VHL gene in 163 (54%) renal cell carcinoma patients. Somatic mutations were found in 87 (29%) patients and 35 novel mutations were identified. VHL promoter hyper-methylation analysis showed epigenetic changes in 106 (35%) out of 300 patients. Patients who had no evidence of molecular alterations in the VHL gene were significantly younger than patients who carried some molecular change. Molecular alterations in the VHL gene were not restricted to clear-cell RCCs (ccRCCs). CONCLUSIONS: This is the first report that identifies molecular aberrations in the VHL gene from a South Asian population. The frequency of somatic mutation is lower and that of promoter hypermethylation is higher when compared with data from other parts of the world. The data has important implications in the population-specific application of tailored preventive and therapeutic regimens in non-familial RCCs.