Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Prevalence of reported penicillin allergy and associations with perioperative complications, length of stay, and cost in patients undergoing elective cancer surgery.

Objective: Up to 10% of patients report penicillin allergy (PA), although only 1% are truly affected by Ig-E-mediated allergies. PA has been associated with worse postoperative outcomes, but studies on the impact of reported PA in cancer patients are lacking, and especially in these multimorbid patients, a non-complicated course is of utmost importance. Methods: Retrospective analysis of patients undergoing elective oncological surgery at a tertiary reference center. Data on surgical site infections (SSI), postoperative complications (measured by Clavien-Dindo classification and Comprehensive Complication Index (CCI)), hospitalization duration, and treatment costs were collected. Results: Between 09/2019 and 03/2020, 152 patients were identified. 16/152 patients (11%) reported PA, while 136/152 (89%) did not. There were no differences in age, BMI, Charlson Comorbidity Index, and smoking status between groups (p > 0.4). Perioperative beta-lactam antibiotics were used in 122 (89.7%) and 15 (93.8%) patients without and with reported PA, respectively. SSI and mean numbers of infections occurred non-significantly more often in patients with PA (p = 0.2 and p = 0.47). The median CCI was significantly higher in PA group (26 vs. 51; p = 0.035). The median hospitalization duration and treatment costs were similar between non-PA and PA groups (4 vs 3 days, p = 0.8; 16'818 vs 17'444 CHF, p = 0.4). Conclusions: In patients undergoing cancer surgery, reported PA is common. Failure to question the unproven PA may impair perioperative outcomes. For this reason, patient and provider education on which reactions constitute a true allergy would also assist in allergy de-labeling. In addition, skin testing and oral antibiotic challenges can be performed to identify the safe antibiotics and to de-label appropriate patients.

Risk of Local Recurrence in Men With Penile Intraepithelial Neoplasia in the Surgical Margin After Penile-sparing Surgery.

PURPOSE: Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis. MATERIAL AND METHODS: This was a retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery. A competing risks survival analysis adjusted for grade, lymphovascular invasion, and stage was performed to assess local recurrence-free survival in patients with penile intraepithelial neoplasia-positive margins and completely negative surgical margins. RESULTS: A negative surgical margin was described in 319 men (85%), whereas penile intraepithelial neoplasia in the surgical margin was found in 59 men (15%). Local recurrence was observed in 30/319 men with a negative surgical margin compared to 11/59 men with penile intraepithelial neoplasia in the surgical margin. Adjusted for T stage and grade, patients with penile intraepithelial neoplasia at the surgical margin had a higher risk to develop a local recurrence than those with a negative surgical margin without penile intraepithelial neoplasia (HR 1.51, 95% CI 1.07-2.12, P = .019). CONCLUSIONS: Men with a penile intraepithelial neoplasia-positive surgical margin have an increased risk to experience local recurrence compared to men with a negative surgical margin and should undergo closer surveillance and/or adjuvant treatment.

The Value of Fournier's Gangrene Scoring Systems on Admission to Predict Mortality: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review and meta-analyze the predictive value of the Fournier gangrene severity index (FGSI), the simplified FGSI (SFGSI), and the Uludag FGSI (UFGSI) on mortality in patients affected by Fournier's Gangrene (FG). METHODS: A search was performed in PubMed, Web of Science, Embase, and the Cochrane Library, from January 2000 to May 2023, to identify original cohorts comparing data between surviving and non-surviving FG patients. The statistical analysis consisted of two parts. First, the mean and standard deviation (SD) of the FGSI, SFGSI, and UFGSI at admission were extrapolated from each study, and the pooled mean difference (MD) with 95% confidence interval (95% CI) was obtained using the Der Simonian-Laird random-effect model. Second, to evaluate the accuracy of the FGSI, SFGSI, and UFSGI in predicting mortality, true positive (TP), false positive (FP), true negative (TN), and false negative (FN) values were extracted where possible and reported in 2 × 2 contingency tables. The sensitivity, specificity, and AUC values were pooled, and summary receiver operating characteristic (SROC) curves were constructed. RESULTS: Overall, forty studies comprising 2257 patients were included. The pooled analysis revealed that the FGSI, SFGSI, and UFGSI values at admission were higher in non-survivors than survivors (MD: 5.53 (95% CI: 4.68-6.37); MD: 2.41 (95% CI: 1.06-3.77); and MD: 5.47 (95% CI: 3.68-7.26), respectively). Moreover, the AUC values of the FGSI, SFGSI, and UFGSI were 0.90 (95% CI: 0.87-0.92), 0.84 (95% CI: 0.80-0.87), and 0.94 (95% CI: 0.92-0.96), respectively. CONCLUSIONS: The higher scores of the FGSI, SFGSI, and UFGSI on admission were associated with mortality. Moreover, when comparing accuracy rates, the UFGSI exhibited the highest AUC value.

Risk Factors for Relapse in Nonseminomatous Testicular Cancer After Postchemotherapy Retroperitoneal Lymph Node Dissection With Viable Residual Cancer.

PURPOSE: No consensus exists on the management of men with nonseminoma and viable nonteratomatous germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection (pcRPLND) specimen after first-line chemotherapy. We analyzed surveillance versus different adjuvant chemotherapy regimens and the influence of time to pcRPLND on oncologic outcomes. METHODS: Data on 117 men treated with cisplatin-based first-line chemotherapy between 1990 and 2018 were collected from 13 institutions. All patients had viable nonteratomatous germ cell tumor in the pcRPLND specimen. Surgery was performed after a median of 57 days, followed by either surveillance (n = 64) or adjuvant chemotherapy (n = 53). Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: After controlling for International Germ Cell Cancer Cooperative Group risk group and percent of viable malignant cells found at RPLND, no difference was observed between men managed with surveillance or adjuvant chemotherapy regarding PFS (hazard ratio [HR], 0.72 [95% CI, 0.32 to 1.6]; P = .4), CSS (HR, 0.69; 95% CI, 0.20 to 2.39; P = .6), and OS (HR, 0.78 [95% CI, 0.25 to 2.44]; P = .7). No statistically significant differences for PFS, CSS, or OS were observed on the basis of chemotherapy regimen or in men treated with pcRPLND ≤57 versus >57 days after first-line chemotherapy. Residual disease with <10% versus ≥10% viable cancer cells were associated with a longer PFS (HR, 3.22 [95% CI, 1.29 to 8]; P = .012). Relapse in the retroperitoneum was observed in 34 (29%) men. CONCLUSION: Men with a complete resection at pcRPLND and <10% viable cells have favorable outcomes without further treatment. Complete retroperitoneal resection seems more important than early pcRPLND.

"Single Knot-Single Running Suture" Vesicourethral Anastomosis with Posterior Musculofascial Reconstruction during Robot-Assisted Radical Prostatectomy: A Step-by-Step Guide of Surgical Technique.

Background: Our aim is to describe Gallucci's (VV-G) technique for vesicourethral anastomosis and posterior musculofascial reconstruction (PMFR) during robot-assisted radical prostatectomy (RARP) and to assess early urinary continence recovery and perioperative outcomes. VV-G consists of a "single knot-single running suture" vesicourethral anastomosis with PMFR. Methods: Between September 2019 and October 2021, we prospectively compared VV-G vs. conventional Van Velthoven anastomosis (VV-STD) during RARP. We excluded patients with urinary incontinence, pelvic radiotherapy, and urethral and BPH surgery prior to RARP. Social continence (SC) recovery, perioperative complications, and length of hospital stay (LOS) were compared between VV-G vs. VV-STD. SC was defined as 0-1 pad/die. We applied 1:1 propensity score matching (PSM) adjusting for different covariates (age, Charlson Comorbidity Index, BMI, prostate volume, nerve-sparing and lymph node dissection). Results: From 166 patients, 1:1 PSM resulted in two equally sized groups of 40 patients each with no residual differences (all p ≥ 0.2). VV-G yielded higher 3-month SC rates than VV-STD (97.5 vs. 55.0%, p < 0.001). A tiny difference was still recorded at one-year follow-up (97.5 vs. 80.0%, p = 0.029, HR: 2.90, 95% CI: 1.74-4.85, p < 0.001). Conversely, we observed no differences in any perioperative complications (15.0 vs. 22.5%, OR: 0.61, 95% CI 0.19-1.88, p = 0.4) and LOS (3 vs. 4 days, Δ: -0.69 ± 0.61, p = 0.1). Conclusions: VV-G significantly improved early SC recovery without increasing perioperative morbidity. In our opinion, VV-G represents an easy-to-learn and easy-to-teach technique due to its single-suture, single-knot, and symmetrical design.

Anterior Sphincter-sparing Suturing of the Vesicourethral Anastomosis During Robotic-assisted Laparoscopic Radical Prostatectomy.

Background: Continence is an important functional outcome after robotic-assisted laparoscopic radical prostatectomy (RARP), and modifications of the surgical technique may improve outcomes. Objective: To illustrate a novel RARP technique and to describe the observed continence outcomes. Design setting and participants: A retrospective study of men treated with RARP between 2017 and 2021 was conducted. Surgical procedure: During RARP, periprostatic structures are preserved, the intraprostatic urethra is partially spared, and the anterior anastomosis stitches involve the plexus structures but not the anterior urethra. Measurements: A descriptive analysis of the pathological, functional, and short-term oncological outcomes was performed. Results and limitations: Of 640 men, 448 (70%) with at least 1 yr of follow-up and a median age of 66 yr were included. The median operative time was 270 min and the prostatic volume 52 ml. The transurethral catheter was removed after a median of 3 d, and leakage of urine in the first 24 h after catheter removal was observed in 66/448 patients (15%). Positive surgical margins were reported in 104/448 (23%). Prostate-specific antigen persistence after prostatectomy was observed in 26/448 (6%). During a median follow-up of 2 yr (interquartile range 1-3 yr), the biochemical recurrence after prostatectomy was observed in 19/448 patients (4%). One year after prostatectomy, 406/448 patients (91%) were continent and required no pad at all, while 42/448 (9%) required at least one pad per day. Conclusions: Not stitching the anterior urethra is a novel technical modification and may improve continence outcomes. Patient summary: We describe a novel way to stitch the bladder neck to the urethra after removal of the prostate using a surgical robotic system. Our technique appeared safe, with promising urinary continence results.

Risk of residual cancer after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumour and International Germ Cell Cancer Cooperative Group intermediate/poor prognosis: A multi-institutional retrospective cohort study.

INTRODUCTION: Current guidelines recommend surveillance in metastatic non-seminomatous germ cell tumour patients treated with first-line-chemotherapy and a complete clinical response (normalisation of serum tumour markers and residual masses <1 cm). However, this recommendation is based on a series including patients with good prognosis according to International Germ Cell Cancer Cooperative Group prognostic group (IGCCCG-PG). The aim of this study was to analyse the proportion of residual teratoma and survival among patients with intermediate/poor IGCCCG-PG and a complete clinical response after first-line-chemotherapy. MATERIAL & METHODS: This is a retrospective study of men with intermediate/poor IGCCCG-PG, who had a complete clinical response after first-line chemotherapy. Patients were either followed by surveillance or treated with post-chemotherapy retroperitoneal lymph node dissection (pcRPLND). RESULTS: Between 2009 and 2018, 143 men with intermediate (n = 83) or poor (n = 60) IGCCCG-PG were treated at 11 international centres. Among 33 patients treated with pcRPLND, the specimen showed teratoma and viable cancer in 16 (48%) and 4 (12%). During a median a 7-year follow-up, 20/110 (18%) patients managed with surveillance relapsed, of whom seven (6%) had a retroperitoneal-only relapse versus 2/33 patients managed with pcRPLND relapsed. No difference was observed regarding overall survival (OS) among men treated with pcRPLND or surveillance (5-year OS, 93% and 89%, p-value = 0.35). The median time-to-recurrence among men on surveillance was 1.3 years (range: 0.3-9.1), and the most common sites of relapses included retroperitoneum (11%), chest (5%), and bones (4%). CONCLUSIONS: While most men with intermediate/poor IGCCCG-PG harbour teratoma/cancer in the retroperitoneum despite a complete response to first-line-chemotherapy, only 6% managed with surveillance relapsed in the retroperitoneum. There was no significant difference in OS between the two groups.

Association Between Antibiotic Prophylaxis Before Cystectomy or Stent Removal and Infection Complications: A Systematic Review.

CONTEXT: Patients undergoing radical cystectomy frequently suffer from infectious complications, including urinary tract infections (UTIs) and surgical site infections (SSIs) leading to emergency department visits, hospital readmission, and added cost. OBJECTIVE: To summarize the literature regarding perioperative antibiotic prophylaxis, ureteric stent usage, and prevalence of infectious complications after cystectomy. EVIDENCE ACQUISITION: A systematic review of PubMed/Medline, EMBASE, Cochrane Library, and reference lists was conducted. EVIDENCE SYNTHESIS: We identified 20 reports including a total of 55 306 patients. The median rates of any infection, UTIs, SSIs, and bacteremia were 40%, 20%, 11%, and 6%, respectively. Perioperative antibiotic prophylaxis differed substantially between reports. Perioperative antibiotics were used only during surgery in one study but were continued over several days after surgery in all other studies. Empirical use of antibiotics for 1-3 d after surgery was described in 12 studies, 3-10 d in two studies, and >10 d in four studies. Time to stent removal ranged from 4 to 25 d after cystectomy. Prophylactic antibiotics were used before stent removal in nine of 20 studies; two of these studies used targeted antibiotics based on urine cultures from the ureteric stents, and the other seven studies used a single shot or 2 d of empirical antibiotics. Studies with any prophylactic antibiotic before stent removal found a lower median percentage of positive blood cultures after stent removal than studies without prophylactic antibiotics before stent removal (2% vs 9%). CONCLUSIONS: We confirmed a high proportion of infectious complications after cystectomy, and a heterogeneous pattern of choice and duration of antibiotics during and after surgery or stent removal. These findings highlight a need for further studies and support quality prospective trials. PATIENT SUMMARY: In this review, we observed wide variability in the use of antibiotics before or after surgical removal of the bladder.

Treatment Outcomes for Men with Clinical Stage II Nonseminomatous Germ Cell Tumours Treated with Primary Retroperitoneal Lymph Node Dissection: A Systematic Review.

CONTEXT: Guidelines recommend primary retroperitoneal lymph node dissection (RPLND) as a treatment option for tumour marker-negative stage II nonseminomatous germ cell tumour (NSGCT). OBJECTIVE: To review the literature on oncological outcomes for men with stage II NSGCT treated with RPLND. EVIDENCE ACQUISITION: A systematic review of studies describing clinicopathological outcomes following primary RPLND in stage II NSGCT was conducted in the MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. Baseline data, perioperative and postoperative parameters, and oncological outcomes were collected. EVIDENCE SYNTHESIS: In total, 12 of 4387 studies were included, from which we collected data for 835 men. Among men with clinical stage II NSGCT, pathological stage II was confirmed in 615 of 790 patients (78%). Most studies administered adjuvant chemotherapy in cases with large lymph nodes, multiple affected lymph nodes, or persistently elevated tumour markers. Recurrence was observed in 12-40% of patients without adjuvant chemotherapy and 0-4% of patients who received adjuvant chemotherapy. CONCLUSIONS: The literature describing RPLND in clinical stage II NSGCT is heterogeneous and no meta-analysis was possible, but RPLND can provide accurate staging and may be curative in selected patients. PATIENT SUMMARY: We reviewed the literature to summarise results after surgical removal of enlarged lymph nodes in the back of the abdomen in men with testis cancer. This procedure provides accurate information on how far the cancer has spread and may provide a cure in selected patients.

Diagnostic Performance of Contrast-Enhanced Ultrasound in the Evaluation of Small Renal Masses: A Systematic Review and Meta-Analysis.

Ultrasound (US) is a highly sensitive imaging tool in the detection of renal masses. However, the detection rate of small renal masses (SRMs) (<4 cm) is still limited. In this scenario, contrast-enhanced ultrasound (CEUS) is a relatively novel, but increasingly utilized, diagnostic modality which aims to increase the overall diagnostic ability in the identification of SRMs. In consequence, we performed a systematic review (SR) and pooled meta-analysis to investigate the diagnostic performance of CEUS in the evaluation of SRMs confirmed by pathology. A SR up to April 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The diagnostic performance of CEUS was evaluated basing on malignant vs. benign SMRs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) from eligible studies were pooled, and summary receiver operating characteristic (SROC) curves were constructed for each endpoint. Overall, five qualified studies were deemed suitable for this meta-analysis. Finally, diagnostic performance of CEUS showed an accuracy of 0.93 in detecting malignant masses (sensitivity of 0.94, PPV of 0.95, specificity of 0.78, and NPV of 0.73). Taken together, CEUS may represent a promising minimally invasive diagnostic tool for characterization of SMRs, since it allows clinicians to identify malignant lesions.

Oncological Follow-up Strategies for Testicular Germ Cell Tumours: A Narrative Review.

Context: The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition: A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis: Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions: Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary: In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients.

Lymphovascular and perineural invasion are risk factors for inguinal lymph node metastases in men with T1G2 penile cancer.

PURPOSE: To analyse the risk of inguinal lymph node (ILN) metastases in T1G2 penile cancer stratified by lymphovascular invasion (LVI), perineural invasion (PNI) and tumour size. METHODS: Retrospective study of men with localised T1G2 penile cancer with non-palpable lymph nodes and no local recurrence during follow-up at six European institutional high-volume centres was performed. ILN involvement was defined as cancer detected during ultrasound-guided fine-needle aspiration cytology, core needle biopsy, dynamic sentinel lymph node biopsy, ILN dissection or inguinal recurrence during follow-up. Uni- and multivariable logistic regression analyses were performed. RESULTS: In the cohort of 554 men with T1G2 penile cancer, from 6 European institutions, ILN metastases were observed in 46/554 men (8%, 95% confidence interval (CI) 6-11%). Men with both, LVI- and PNI- primary cancers had the lowest risk of ILN involvement (6%) whereas men with LVI + or PNI + showed ILN metastases in 22% and 30%. In multivariable regression, men with LVI + or PNI + had higher odds for ILN metastases compared to men with LVI- and PNI- (OR 3.9, 95% CI 1.6-9.0, p value < 0.01) Tumour size was not associated with ILN risk (OR 1.01 95% CI 0.99-1.04, p = 0.17). CONCLUSION: Approximately, one out of ten men with T1G2 overall and one out of four men with either LVI + or PNI + still have ILN metastases despite being clinically node negative. Therefore, invasive ILN staging should strongly be recommended in T1G2 with LVI + or PNI + but importantly, must be discussed in patients with T1G2 with LVI- or PNI-.

PhaseX: an X-ray phase-contrast imaging simulation code for matter under extreme conditions.

We present PhaseX, a simulation code for X-ray phase-contrast imaging (XPCI), specially dedicated to the study of matter under extreme conditions (of pressure and density). Indeed, XPCI can greatly benefit the diagnosis of such states of matter. This is due to the noticeable contrast enhancement obtained thanks to the exploitation of both attenuation and phase-shift of the electromagnetic waves crossing the sample to be diagnosed. PhaseX generates synthetic images with and without phase contrast. Thanks to its modular design PhaseX can adapt to any imaging set-up and accept as inputs objects generated by hydrodynamic or particle-in-cell codes. We illustrate Phase-X capabilities by showing a few examples concerning laser-driven implosions and laser-driven shock waves.

The data-driven future of high-energy-density physics.

High-energy-density physics is the field of physics concerned with studying matter at extremely high temperatures and densities. Such conditions produce highly nonlinear plasmas, in which several phenomena that can normally be treated independently of one another become strongly coupled. The study of these plasmas is important for our understanding of astrophysics, nuclear fusion and fundamental physics-however, the nonlinearities and strong couplings present in these extreme physical systems makes them very difficult to understand theoretically or to optimize experimentally. Here we argue that machine learning models and data-driven methods are in the process of reshaping our exploration of these extreme systems that have hitherto proved far too nonlinear for human researchers. From a fundamental perspective, our understanding can be improved by the way in which machine learning models can rapidly discover complex interactions in large datasets. From a practical point of view, the newest generation of extreme physics facilities can perform experiments multiple times a second (as opposed to approximately daily), thus moving away from human-based control towards automatic control based on real-time interpretation of diagnostic data and updates of the physics model. To make the most of these emerging opportunities, we suggest proposals for the community in terms of research design, training, best practice and support for synthetic diagnostics and data analysis.

Use of multilayer targets for achieving off-Hugoniot states.

We present an approach for the realization of extreme off-Hugoniot states of matter in laser-driven shock experiments. The method is based on the application of impedance-mismatch effect in sandwich targets. In order to verify this model we have realized numerical simulations using the two-dimensional hydrocode multi in three-layer targets (gold-aluminum-gold) with laser intensities ∼ 10(14) W/cm(2) and obtained pressures ∼ 10 Mbar. Results show the possibility of obtaining high pressures with relatively small temperatures for a low-impedance material sandwiched between layers with high density material.