Purpose
To validate a German translation of the convalescence and recovery evaluation (CARE) as an electronic patient-reported outcome measure (ePROM) and use it to assess recovery after major ...urological surgery.
Methods
The CARE questionnaire was provided to patients scheduled for major urological surgery preoperatively, at discharge and 6 weeks postoperatively, using an ePROM system. Cronbach’s alpha, inter-scale correlations and confirmatory factor analysis (CFA) were used to validate the translation. Mixed linear regression models were used to identify factors influencing CARE results, and a multivariable logistic regression analysis was done to determine the predictive value of CARE results on quality of life (QoL).
Results
A total of 283 patients undergoing prostatectomy (
n
= 146, 51%), partial/radical nephrectomy (
n
= 70, 25%) or cystectomy (
n
= 67, 24%) responded to the survey. Internal consistency was high (
α
= 0.649–0.920) and the CFA showed a factor loading > 0.5 in 17/27 items. Significant main effects were found for the time of survey and type of surgery, while a time by type interaction was only found for the gastrointestinal subscale (
χ
(
4
)
2
= 30.37,
p
<
0.0001
) and the total CARE score (TCS) (
χ
(
4
)
2
= 13.47,
p
=
0.009
) for cystectomy patients, meaning a greater score decrease at discharge and lower level of recovery at follow-up. Complications demonstrated a significant negative effect on the TCS (
χ
(
2
)
2
= 8.61,
p
=
0.014
). A high TCS at discharge was an independent predictor of a high QLQ-C30 QoL score at follow-up (OR = 5.26, 95%-CI 1.42–19.37,
p
=
0.013
).
Conclusion
This German translation of the CARE can serve as a valid ePROM to measure recovery and predict QoL after major urological surgery.
Study Type – Therapy (case series)
Level of Evidence 4
What’s known on the subject? and What does the study add?
To date radiation therapy has had no oncological implication in renal cell carcinoma. ...Its use was limited to palliation in painful bone lesions. Radiation therapy was considered ineffective as renal cell cancer is resistant to the commonly used doses of radiotherapy. Side effects in combination with systemic therapy were not known, but heavy skin toxicities were expected. Only a few cases of combined radiation with systemic therapy were published.
This is the only series where consecutive patients have been treated simultaneously with sunitnib and hypo‐fractionated high‐dose radiotherapy. Side effects were similar to those expected with systemic therapy or radiation therapy alone. Oncological results are extremely encouraging.
OBJECTIVE
• To analyse the safety and efficacy of simultaneous standard anti‐angiogenic therapy and stereotactic radiosurgery (SRS) in patients with spinal and cerebral metastases from renal cell carcinoma.
PATIENTS AND METHODS
• In all, 106 patients with spinal (n= 55) or cerebral (n= 51) metastatic lesions and an Eastern Cooperative Oncology Group status of 0 or 1 were treated with sorafenib or sunitinib and simultaneous SRS.
• The primary endpoint was local control.
• Secondary endpoints were toxicity and overall survival.
RESULTS
• Median follow up was 14.7 months (range 1–42 months). Forty‐five patients were treated with sunitinb and 61 patients with sorafenib. Two patients had asymptomatic tumour haemorrhage after SRS.
• No skin toxicity, neurotoxicity or myelopathy occurred after SRS, and SRS did not alter the adverse effects of anti‐angiogenic therapy.
• Local tumour control 15 months after SRS was 98% (95% confidence interval 89–99%). The median pain score before SRS was 5 (range 1–8) and was lowered to 0 (range 0–2, P < 0.01) after SRS. There were no treatment‐related deaths or late complications after SRS.
• Overall survival was 17.4 months in patients with spinal lesions and 11.1 month in patients with cerebral lesions (P= 0.038).
CONCLUSIONS
• Simultaneous systemic anti‐angiogenic therapy and SRS for selected patients with renal cell carcinoma who have spinal and cerebral metastases is safe and effective.
• Single‐fraction delivery allows for efficacious integration of focal radiation treatment into oncological treatment concepts without additional toxicity.
• Further studies are needed to determine the limits of SRS for renal cell carcinoma metastases outside the brain and spine.
Recent advances in mass spectrometry (MS)‐based technologies are now set to transform translational cancer proteomics from an idea to a practice. Here, we present a robust proteomic workflow for the ...analysis of clinically relevant human cancer tissues that allows quantitation of thousands of tumor proteins in several hours of measuring time and a total turnaround of a few days. We applied it to a chemorefractory metastatic case of the extremely rare urachal carcinoma. Quantitative comparison of lung metastases and surrounding tissue revealed several significantly upregulated proteins, among them lysine‐specific histone demethylase 1 (LSD1/KDM1A). LSD1 is an epigenetic regulator and the target of active development efforts in oncology. Thus, clinical cancer proteomics can rapidly and efficiently identify actionable therapeutic options. While currently described for a single case study, we envision that it can be applied broadly to other patients in a similar condition.
In this study, we present a rapid and robust clinical mass spectrometry(MS)‐based proteomic workflow for the analysis of solid tumors. We demonstrate that this novel platform can be implemented in a clinical setting to efficiently identify actionable therapeutic options in a chemorefractory cancer patient.
Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. ...Two cohorts of patients with PCa who underwent radical prostatectomy (
= 40,
= 56) and benign prostate hyperplasia (BPH) controls (
= 8,
= 11) were profiled for
expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC;
= 131,
= 29 controls) and The Cancer Genome Atlas (TCGA;
= 497,
= 53 controls)) served for validation. SMPDL3B's impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of
was seen in PCa compared to BPH (
< 0.001 each). A lower expression of
was associated with a shorter overall survival (OS) (
= 0.005) in long term follow-up. A
overexpression in PCa tissue was confirmed in the validation cohorts (
< 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival (
= 0.011) and progression-free interval (
< 0.001) were shorter. Knockdown of
impaired PC3 cell migration but not proliferation (
= 0.0081). In summary,
is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.
Objectives
To compare the operative and functional result of partial and radical nephrectomy in renal cell carcinomas of stages pT2–3a.
Methods
Consecutive patients with renal cell carcinoma of ...stages pT2–3a, cN0 and cM0, who underwent partial or radical nephrectomy between January 2005 and October 2019 at a tertiary care center were included. Data were collected retrospectively. End‐points included severe postoperative complications (Clavien–Dindo classification ≥3), acute and chronic renal function impairment, and overall survival. Uni‐ and multivariable outcome analyses were based on logistic regression.
Results
A total of 158 patients were included (110 radical nephrectomy and 48 partial nephrectomy). Over time, partial nephrectomy was increasingly used. A RENAL score ≥10 was the only independent predictor influencing the surgical approach (radical nephrectomy vs partial nephrectomy, odds ratio 8.62, 95% confidence interval 3.32–22.37, P < 0.001). No significant differences in complications for radical nephrectomy versus partial nephrectomy were found (12.7% vs 8.3%, P = 0.424). Renal function was better preserved in the partial nephrectomy group (the latest chronic kidney disease stage ≥3: radical nephrectomy 73% vs partial nephrectomy 41%, P = 0.005). The surgical approach was a significant factor for chronic kidney disease (odds ratio 51.07, 95% confidence interval 3.57–730.59, P = 0.004). Overall survival did not significantly differ between radical nephrectomy and partial nephrectomy (mean overall survival 85.86 months, 95% confidence interval 3.83–78.36 vs 81.28 months, 95% confidence interval 4.59–72.29, P = 0.702).
Conclusions
In selected patients, partial nephrectomy can be used in large or locally advanced renal cell carcinoma. Compared with radical nephrectomy, it allows better preservation of renal function without harboring an increased risk of severe postoperative complications.
Purpose
To analyze and share our experience with ultra-mini-PCNL using the urological Dyna-CT in small infants.
Methods
A retrospective analysis was performed on all infants younger than 3 years of ...age who underwent ultra-mini-PCNL at our institution since 2016. Operating time, fluoroscopy time, dose area product (DAP), stone-free status, intra- and postoperative complications and the duration of hospital stay were analyzed.
Results
A total of nine interventions conducted on eight children were evaluated. The mean age of infants was 22.8 ± 11.9 months. The mean operation time and the mean fluoroscopy time were 119.2 ± 51.8 min, and 190.4 ± 93.8 s, respectively. The mean DAP was 11.4 ± 6.9 μGym
2
and the stone clearance at 3 months was 87.5%. No major postoperative complications were assessed, and no transfusion was given. The mean hospital stay was 4 (IQR 3–6) days.
Conclusion
Ultra-mini-PCNL utilizing the urological Dyna-CT can safely and effectively be performed in small infants with kidney stones. In this setting, the urological Dyna-CT allows for a very low radiation exposure.
Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a ...potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy state. Given exosomes may precondition target tissue, the present work aims to investigate if leukemia-derived exosomes contribute to a permissive phenotype of the blood-cerebrospinal fluid barrier (BCSFB). Leukemia-derived exosomes were isolated by ultracentrifugation from the cell lines SD-1, Nalm-6, and P12-Ichikawa (P12). Adhesion and uptake to CP epithelial cells and the significance on subsequent ALL transmigration across the barrier was studied in a human BCSFB in vitro model based on the HiBCPP cell line. The various cell lines markedly differed regarding exosome uptake to HiBCPP and biological significance. SD-1-derived exosomes associated to target cells unspecifically without detectable cellular effects. Whereas Nalm-6 and P12-derived exosomes incorporated by dynamin-dependent endocytosis, uptake in the latter could be diminished by integrin blocking. In addition, only P12-derived exosomes led to facilitated transmigration of the parental leukemia cells. In conclusion, we provide evidence that, to a varying extent, leukemia-derived exosomes may facilitate CNS invasion of ALL across the BCSFB without destruction of the barrier integrity.
Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly ...overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo- and radiotherapy in vitro. Therefore, we investigated the effects of HO-1 and its metabolites biliverdin, carbon monoxide and iron on PaCa cells. PaCa cell lines with divergent HO-1 expression patterns were used in a murine orthotopic cancer model. HO-1 expression and activity was regulated by zinc (inhibition) and cobalt (induction) protoporphyrin. Furthermore, the influence of cellular HO-1 levels and its metabolites on effects of standard chemotherapy with gemcitabine was tested in vivo and in vitro.
High HO-1 expression in PaCa cell lines was associated with increased chemoresistance in vitro. Chemoresistance to gemcitabine was increased during HO-1 induction in PaCa cells expressing low levels of HO-1. The inhibition of HO-1 activity in pancreatic tumors with high HO-1 boosted chemotherapeutic effects in vivo significantly. Furthermore, biliverdin and iron promoted PaCa resistance to chemotherapy. Consequently, specific iron chelation by desferrioxamine revealed profound anticancerous effects.
In summary, the inhibition of HO-1 and the chelation of iron in PaCa cells were associated with increased sensitivity and susceptibility of pancreatic tumors to chemotherapy in vivo. The metabolites biliverdin and iron seem to be involved in HO-1-mediated resistance to anticancer treatment. Therefore, HO-1 inhibition or direct interference with its metabolites may evolve new PaCa treatment strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Urothelial bladder cancer ranks among the 10 most frequently diagnosed cancers worldwide. In our previous study, the transmembrane protein neuropilin-2 (NRP2) emerged as a predictive marker in ...patients with bladder cancer. NRP2 consists of several splice variants; the most abundant of these, NRP2a and NRP2b, are reported to have different biological functions in lung cancer progression. For other cancer types, there are no published data on the role of these transcript variants in cancer progression and the clinical outcome. Here, we correlate
and its two most abundant transcript variants,
and
, with the clinical outcome using available genomic data with subsequent validation in our own cohort of patients with muscle-invasive bladder cancer. In addition to
,
and the NRP ligands
and
were studied. Only
emerged as an independent prognostic marker for shorter cancer-specific survival in muscle-invasive bladder cancer in our cohort of 102 patients who underwent radical cystectomy between 2008 and 2014 with a median follow-up time of 82 months. Additionally, we demonstrate that high messenger expression of
,
,
and
associates with a more aggressive disease (i.e., a high T stage, positive lymph node status and reduced survival).
IntroductionRandomised controlled trials comparing robotic-assisted partial nephrectomy (RAPN) and open PN (OPN) are lacking. Therefore, we aim to report the study protocol and a trial update for a ...randomised controlled feasibility trial comparing RAPN versus OPN for renal neoplasms.Methods and analysisThe ROBOtic assisted versus conventional Open Partial nephrectomy II trial is designed as a single-centre, randomised, open-label, feasibility trial. Participation will be offered to patients with renal neoplasms and deemed feasible for both, OPN and RAPN. We aim to enrol 50 patients within 15 months using a 1:1 allocation ratio. The primary endpoint of the trial is feasibility of recruitment and will be successful if one third of eligible patients agree to participate. Secondary endpoints include perioperative results, health-related quality of life, inflammatory response as well as surgical ergonomics of the operating team. If the primary outcome, feasibility of recruitment, is successful, the secondary results of the trial will be used for planning a confirmative phase III trial.Ethics and disseminationEthical approval was obtained from the local institutional review board (Ethik-Kommission II at Heidelberg University: 2020-542N). Results will be made publicly available in peer-reviewed scientific journals and presented at appropriate congresses and social media.Trial registration numberNCT04534998.
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