Purpose
Lockdown during the COVID-19 pandemic compelled urologists to change access to healthcare, especially for oncology patients. Teleconsultation is a safe way to receive medical advice without a ...risk of infection, and was implemented urgently in our academic centres. Our purpose was to evaluate patient and physician satisfaction with teleconsultation set up during the COVID-19 pandemic.
Methods
From March 16th 2020, all face-to-face consultations were cancelled in France, except for emergencies. Teleconsultation was started immediately by five senior urologists in two academic hospitals. All patients received an email survey including the validated Teleconsultation Satisfaction Questionnaire (TSQ) and demographic questions. Data were collected prospectively. Physicians also responded to the TSQ. Patient satisfaction was measured objectively with the validated 14-item TSQ. Each item was scored on a 5-point Likert scale. Factors associated with positive satisfaction with teleconsultation were assessed by multivariable logistic regression.
Results
Overall, 105 patients replied to the survey (91.3%). Median age was 66 years (IQR: 55‒71) and 95 were men (90.5%). Median overall TSQ score was 67 (IQR: 60‒69); teleconsultation was judged to be a good experience by 88 patients (83.8%) and four physicians (80%). Patients who met their surgeon for the first time were more likely to have a good experience (OR = 1.2 95% CI 1.1‒1.5,
p
= 0.03).
Conclusion
Introduced rapidly during the COVID-19 lockdown, urology teleconsultation attained a high level of satisfaction among both patients and physicians. A major change in telemedicine use is foreseen in the post COVID-19 era.
Purpose We analyzed all available studies assessing the management of node only recurrence after primary local treatment of prostate cancer. Materials and Methods We systematically reviewed the ...literature in January 2015 using the PubMed®, Web of Sciences and Embase® databases according to PRISMA guidelines. Studies exclusively reporting visceral or bone metastatic disease were excluded from analysis. Eight radiotherapy and 12 salvage lymph node dissection series were included in our qualitative study. Results All 248 radiotherapy and 480 salvage lymph node dissection studies were single arm case series including a total of 728 patients. Choline positron emission tomography/computerized tomography was the reference imaging technique for nodal recurrence detection. Globally 50% of patients remained disease-free after short-term followup. Nevertheless, approximately two-thirds of patients received adjuvant hormone therapy, leading an overestimation of prostate specific antigen-free survival rates obtained after salvage treatment. Combining radiotherapy with salvage lymph node dissection may improve oncologic control in the treated region without improving the outfield relapse risk or the prostate specific antigen response. Great heterogeneity among series in adjuvant treatments, endpoints, progression definitions and study populations made it difficult to assess the precise impact of salvage treatment on the prostate specific antigen response and compare outcomes between radiotherapy and salvage lymph node dissection series. Toxicity after radiotherapy or salvage lymph node dissection was acceptable without frequent high grade complications. The benefit of early hormone therapy as the only salvage treatment remains unknown. Conclusions Although a high level of evidence is currently missing to draw any strong conclusion, published clinical series show that in select patients salvage treatment directed to nodal recurrence could lead to good oncologic outcomes. Although the optimal timing of androgen deprivation therapy in this setting is still unknown, such an approach could delay time to systemic treatment with an acceptable safety profile. Future prospective trials are awaited to better clarify this potential impact on well-defined endpoints.
It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components ...such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, although this process is usually spatially and temporally self‐limited, it is unregulated in the case of cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. In this review, we outline the role of stroma in normal healing, cancer and post radiotherapy, with a particular focus on the crosstalk between normal or cancer cells and fibroblasts. Understanding these mechanisms is particularly important as several stromal components have been proposed as potential therapeutic targets.
Stromal modification, a key step in the control of wound healing, tumour progression and radiation‐induced fibrosis, is characterized by the differentiation of quiescent fibroblasts into an activated state, which results in crosstalk among fibroblasts and normal or cancer cells. Understanding these activation mechanisms, which involve extracellular matrix metalloproteinase inducer and transforming growth factor beta, is important because several stromal components are potential therapeutic targets.
The PI3K/AKT pathway is considered to play a major role in bladder carcinogenesis, but its relationships with other molecular alterations observed in bladder cancer remain unknown. We investigated ...PI3K/AKT pathway activation in a series of human bladder urothelial carcinomas (UC) according to PTEN expression, PTEN deletions and FGFR3, PIK3CA, KRAS, HRAS, NRAS and TP53 gene mutations. The series included 6 normal bladder urothelial samples and 129 UC (Ta n = 25, T1 n = 34, T2–T3–T4 n = 70). Expression of phospho‐AKT (pAKT), phospho‐S6‐Ribosomal Protein (pS6) (one downstream effector of PI3K/AKT pathway) and PTEN was evaluated by reverse phase protein Array. Expression of miR‐21, miR‐19a and miR‐222, known to regulate PTEN expression, was also evaluated. pAKT expression levels were higher in tumors than in normal urothelium (p < 0.01), regardless of stage and showed a weak and positive correlation with pS6 (Spearman coefficient RS = 0.26; p = 0.002). No association was observed between pAKT or pS6 expression and the gene mutations studied. PTEN expression was decreased in PTEN‐deleted tumors, and in T1 (p = 0.0089) and T2–T3–T4 (p < 0.001) tumors compared to Ta tumors; it was also negatively correlated with miR‐19a (RS = −0.50; p = 0.0088) and miR‐222 (RS = −0.48; p = 0.0132), but not miR‐21 (RS = −0.27; p = 0.18) expression. pAKT and PTEN expressions were not negatively correlated, and, on the opposite, a positive and moderate correlation was observed in Ta (RS = 0.54; p = 0.0056) and T1 (RS = 0.56; p = 0.0006) tumors. Our study suggests that PI3K/AKT pathway activation occurs in the entire spectrum of bladder UC regardless of stage or known most frequent molecular alterations, and independently of low PTEN expression.
What's new?
Although a suspected player in bladder carcinogenesis, involvement of the PI3K/AKT pathway in human bladder urothelial carcinoma (UC) has been little explored. Here, reverse phase protein array was used to investigate PI3K/AKT pathway activation and expression of PTEN, a PI3K/AKT pathway downregulator, in a series of human UCs characterized by genetic alterations frequently observed in UC. Analysis revealed elevated pAKT expression and PI3K/AKT pathway activation across UCs, despite the different molecular alterations and independent of the loss of PTEN. The findings support the idea that the PI3K/AKT pathway is of therapeutic significance in UC.
Objective
To assess the impact of hospital volume (HV) and surgeon volume (SV) on perioperative outcomes of robot‐assisted partial nephrectomy (RAPN).
Patients and Methods
All consecutive patients ...who underwent a RAPN from 2009 to 2015, at 11 institutions, were included in a retrospective study. To evaluate the impact of HV, we divided RAPN into four quartiles according to the caseload per year: low HV (<20/year), moderate HV (20–44/year), high HV (45–70/year), and very high HV (>70/year). The SV was also divided into four quartiles: low SV (<7/year), moderate SV (7–14/year), high SV (15–30/year), and very high SV (>30/year). The primary endpoint was the Trifecta defined as the following combination: no complications, warm ischaemia time (WIT) <25 min, and negative surgical margins.
Results
In total, 1 222 RAPN were included. The mean (sd) caseload per hospital per year was 44.9 (26.7) RAPNs and the mean (sd) caseload per surgeon per year was 19.2 (14.9) RAPNs. The Trifecta achievement rate increased significantly with SV (69.9% vs 72.8% vs 73% vs 86.1%; P < 0.001) and HV (60.3% vs 72.3% vs 86.2% vs 82.4%; P < 0.001). The positive surgical margins (PSM) rate (P = 0.02), length of hospital stay (LOS; P < 0.001), WIT (P < 0.001), and operative time (P < 0.001), all decreased significantly with increasing SV. The PSM rate (P = 0.02), LOS (P < 0.001), WIT (P < 0.001), operative time (P < 0.001), and major complications rate (P = 0.01), all decreased significantly with increasing HV. In multivariate analysis adjusting for HV and SV (model 3), HV remained the main predictive factor of Trifecta achievement (odds ratio OR 3.70 for very high vs low HV; P < 0.001), whereas SV was not associated with Trifecta achievement (OR 1.58 for very high vs low SV; P = 0.34).
Conclusion
In this multicentre study HV and SV both greatly influenced RAPN perioperative outcomes, but HV appeared to have a greater impact than SV.
This study addresses the sensitivity of different peripheral CD4
T-lymphocyte subsets to irradiation (IR) and identifies potential targets for the prevention or treatment of radiation-induced ...toxicity.
This study was performed on peripheral blood mononuclear cells or sorted peripheral memory lymphocytes of CCR6
mucosa-homing Th17/CCR6
Th and regulatory T subtypes of healthy volunteers. Cells were irradiated with a 2 Gy with or without pharmacologic inhibitors of different signaling pathways. Senescence of irradiated cells was assessed by resistance to apoptosis and determination of various senescence-associated biomarkers (senescence associated b-galactosidase activity, p16Ink4a-, p21Cdkn1a-, gH2A.X-, H2A.J expression). Cytokine production was measured in supernatants of irradiated cells by Luminex technology.
Not all CD4
memory T lymphocyte subsets were equally radiosensitive. High sensitivity of CCR6
Th17 lymphocytes to IR-induced senescence was shown by expression of the histone variant H2A.J, higher SA-b-Gal activity, and upregulation of p16
and p21
expression. Lower Annexin V staining and cleaved caspase-3, and higher expression of antiapoptotic genes Bcl-2 and Bcl-xL LF, showed that CCR6
Th17 lymphocytes were more resistant to IR-induced apoptosis than CCR6
memory Th and regulatory T lymphocytes. After a 2 Gy IR, both CCR6
Th17 and CCR6
cells acquired a moderate senescence-associated secretory phenotype, but only CCR6
Th17 cells secreted interleukin 8 (IL-8) and vascular endothelial growth factor-A (VEGF-A). Pharmacologic targeting of reactive oxygen species (ROS), mitogen-activated protein kinases (MAPKs), and mammalian target of rapamycin (mTOR) signaling pathways prevented the expression of senescent markers and IL-8 and VEGF-A expression by CCR6
Th17 cells after IR.
This study suggests that IR induces senescence of CCR6+Th17 lymphocytes associated with secretion of IL-8 and VEGF-A that may be detrimental to the irradiated tissue. ROS-MAPKs signaling pathways are candidate targets to prevent this CCR6
Th17-dependent radiation-induced potential toxicity. Finally, the ratio of circulating H2A.J
senescent CCR6
Th17/CD4
T lymphocytes may be a candidate marker of individual intrinsic radiosensitivity.
Objectives
To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety ...of various surgical approaches in this setting, and to develop a machine‐learning‐based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging.
Materials and Methods
Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi‐institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine‐learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease‐free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G‐computation for pT3a tumours.
Results
A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a‐upstaged RCC. The UroCCR‐15 predictive model presented an area under the receiver‐operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio HR 1.08, P = 0.7; OS: HR 1.03, P > 0.9).
Conclusions
Our study shows that machine‐learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.
Although human epidermal growth factor receptor 2 (HER2) may represent a therapeutic target, its evaluation in urothelial carcinoma of the bladder does not rely on a standardized scoring system by ...immunohistochemistry or fluorescent in situ hybridization (FISH), as reflected by various methodology in the literature and clinical trials. Our aim was to improve and standardize HER2 amplification detection in bladder cancer. We assessed immunohistochemical criteria derived from 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for breast cancer and investigated intratumoral heterogeneity in a retrospective multicentric cohort of 188 patients with locally advanced urothelial carcinoma of the bladder. Immunohistochemistry was performed on 178 primary tumors and 126 lymph node metastases, eligible cases (moderate/strong, complete/incomplete membrane staining) were assessed by FISH. HER2 overexpression was more frequent with 2013 ASCO/CAP than 2007 ASCO/CAP guidelines (p < 0.0001). The rate of positive HER2 FISH was similar between primary tumor and lymph node metastases (8%). Among positive FISH cases, 48% were associated with moderate/strong incomplete membrane staining that were not scored eligible for FISH by 2007 ASCO/CAP criteria. Among 3+ immunohistochemistry score cases, 67% were associated with HER2-positive FISH. Concordance between primary tumors and matched lymph node metastases was moderate for immunohistochemistry (κ = 0.54 (CI 95%, 0.41-0.67)) and FISH (κ = 0.50 (CI 95%, 0.20-0.79)). HER2-positive FISH was more frequent in micropapillary carcinomas (12%) and carcinoma with squamous differentiation (11%) than in pure conventional carcinoma (6%). Intratumoral heterogeneity for HER2 immunohistochemistry was observed in 7% primary tumor and 6% lymph node metastases; 24% positive HER2 FISH presented intratumoral heterogeneity. Our study suggests that HER2 evaluation should include an immunohistochemistry screening step with eligibility for FISH including incomplete/complete and moderate/strong membrane staining. Spatial or temporal intratumoral heterogeneity prompts to perform evaluation on both tumor and lymph node, and for each histological variant observed.
PDF
