Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by ...radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (
,
,
,
,
, and
), regulators of apoptosis (survivin, Bcl-xL, and emmprin), receptor tyrosine kinases (EGFR and erbB2), genes involved in cellular efflux (
and
), in addition to molecular subtypes (Basal, luminal, and p53-like). The current state of the literature on the prediction of response to NAC based on the presence of these biomarkers is discussed in this review.
Abstract
Metastasis is the principal cause of cancer related deaths. Tumor invasion is essential for metastatic spread. However, determinants of invasion are poorly understood. We addressed this ...knowledge gap by leveraging a unique attribute of kidney cancer. Renal tumors invade into large vessels forming tumor thrombi (TT) that migrate extending sometimes into the heart. Over a decade, we prospectively enrolled 83 ethnically-diverse patients undergoing surgical resection for grossly invasive tumors at UT Southwestern Kidney Cancer Program. In this study, we perform comprehensive histological analyses, integrate multi-region genomic studies, generate in vivo models, and execute functional studies to define tumor invasion and metastatic competence. We find that invasion is not always associated with the most aggressive clone. Driven by immediate early genes, invasion appears to be an opportunistic trait attained by subclones with diverse oncogenomic status in geospatial proximity to vasculature. We show that not all invasive tumors metastasize and identify determinants of metastatic competency. TT associated with metastases are characterized by higher grade, mTOR activation and a particular immune contexture. Moreover, TT grade is a better predictor of metastasis than overall tumor grade, which may have implications for clinical practice.
Aim
The aim of this study was to compare the thermal effects of Ho:YAG and Tm-fiber lasers during lithotripsy in an in-vitro model via real-time temperature measurement.
Methods
We compared a Ho:YAG ...laser (
p
av
up to 100 W, Lumenis, Yokneam, Israel) and a superpulse Tm-fiber laser (SP TFL,
p
av
up to 40 W, NTO IRE-Polus, Fryazino, Russia), both equipped with 200 µm bare-ended fibers. The following settings were used: 0.2 J, 40 Hz (nominal
p
av
8 W). Power meter FieldMaxII-TO (Coherent, Santa Clara, CA, USA) was used to verify output laser power (
p
av
). Each laser was fired for 60 s in two setups: (1) thermos-insulated (quasi-adiabatic) cuvette; (2) actively irrigated setup with precise flow control (irrigation rates 0, 10, 35 mL/min).
Results
Power measurements performed before the test revealed a 10% power drop in Ho:YAG (up to 7.2 ± 0.1 W) and 6.25% power drop in SP TFL (up to 7.5 ± 0.1). At the second step of our experiment, irrigation reduced the respective temperatures in the same manner for both lasers (e.g., at 35 mL/s SP TFL − 1.9 °C; for Ho:YAG laser − 2.8 °C at 60 s).
Conclusion
SP TFL and Ho:YAG lasers are not different in terms of volume-averaged temperature increase when the same settings are used in both lasers. Local temperature rises may fluctuate to some degree and differ for the two lasers due to varying jet streaming caused by non-uniform heating of the aqueous medium by laser light.
Surveillance for small renal masses is a growing choice of management amongst physicians and patients. These decisions, however, can be difficult as patient factors and tumor factors may blur the ...line between continued surveillance and intervention. Currently, there are no biomarkers that are readily available to aid in the decision making for patients with known renal cell carcinoma; however, many show promise. We herein review the literature of the adjunct tools that are currently available for decision making in small renal masses, but also new potential biomarkers that can potentially be of use.
Stereotactic ablative radiotherapy (SAbR) is a promising alternative for selected patients with renal cell carcinoma (RCC) with oligometastasis. The objective of this study was to evaluate the ...potential of SAbR for longitudinal control in patients with persistently oligometastatic RCC. We report the impact of SAbR on tumor control rates as well as its tolerability in systemic therapy-naïve patients with oligometastatic disease (without brain metastases) and assess the effect of SAbR on subsequent first line systemic therapy by comparison to historical controls.
We reviewed patients with metastatic RCC treated with front-line SAbR with a curative intent from 2007 to 2017 at UT Southwestern Kidney Cancer Program. We analyzed local control rates (LCR), toxicity, freedom from systemic therapy (FST), type and duration of first-line systemic therapy, and overall survival (OS). Cox regression and Kaplan-Meier analyses were used.
We identified 47 patients with oligometastatic RCC treated with SAbR to 88 metastases; 11 patients had more than 1 SAbR course. The local control rate was 91.5% at 2 years with no reported grade ≥3 toxicity. With a median follow-up of 30 months (interquartile range, 13.7-40.9), median FST from first SAbR was 15.2 months (95% confidence interval CI, 8.8-40.1). The most common systemic therapies initiated after SAbR were pazopanib (60.7%) and sunitinib (14.3%). The duration of first line systemic therapy appeared unaffected by SAbR. Improved FST was observed in patients with metachronous disease (hazard ratio, 2.67; P = .02), solitary metastasis (HR, 2.26; P = .05), and non-bone metastasis (HR, 2.21; P = .04). One-year and 2-year OS after SAbR were 93.1% (95% CI, 80.1-97.7) and 84.8% (95% CI, 69.1-92.9), respectively. Median OS was not reached.
SAbR is an effective and safe treatment for selected patients with oligometastatic RCC, can provide longitudinal disease control without systemic therapy for over a year, and does not appear to adversely affect the effectiveness of first-line systemic therapy once initiated. Prospective validation of these findings is being sought through a phase 2 trial.
•Using the NCDB, patients undergoing CN with modern IO for mRCC exhibited better OS than those treated with IO alone.•CN after prior IO is safe with pathologically favorable tumor ...characteristics.•Defining the role for CN in the modern IO era warrants prospective validation.
Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC.
From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes.
Of 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN.
Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.
Multiple types of T cells have been described and assigned pathophysiologic functions in the kidneys. However, the existence and functions of TCR+CD4+CD8+ (double positive; DP) T cells are ...understudied in normal and diseased murine and human kidneys. We studied kidney DPT cells in mice at baseline and after ischemia reperfusion (IR) and cisplatin injury. Additionally, effects of viral infection and gut microbiota were studied. Human kidneys from patients with renal cell carcinoma were evaluated. Our results demonstrate that DPT cells expressing CD4 and CD8 co-receptors constitute a minor T cell population in mouse kidneys. DPT cells had significant Ki67 and PD1 expression, effector/central memory phenotype, proinflammatory cytokine (IFNγ, TNFα and IL-17) and metabolic marker (GLUT1, HKII, CPT1a and pS6) expression at baseline. IR, cisplatin and viral infection elevated DPT cell proportions, and induced distinct functional and metabolic changes. scRNA-seq analysis showed increased expression of Klf2 and Ccr7 and enrichment of TNFα and oxidative phosphorylation related genes in DPT cells. DPT cells constituted a minor population in both normal and cancer portion of human kidneys. In conclusion, DPT cells constitute a small population of mouse and human kidney T cells with distinct inflammatory and metabolic profile at baseline and following kidney injury.
Given the rarity of testicular germ cell tumors (TGCTs) and the complex aspects of management, we evaluate the effect of hospital TGCT case volume on overall survival outcomes and practice patterns.
...The National Cancer Database was queried for patients diagnosed with seminoma or nonseminomatous germ cell tumor (NSGCT). Hospitals were classified by case volume as high (99th percentile, ≥26.1 cases annually), high-intermediate (95–99th percentile, 14.6–26.0 cases annually), intermediate (75–95th percentile, 6.1–14.5 cases annually), low-intermediate (25–75th percentile, 1.8–6.0 cases annually), and low (25th percentile,<1.8 cases annually). The median (interquartile range) number of TGCT cases per institution per year was 3.4 (1.8–6.1).
A total of 33,417 patients with TGCT diagnosed from 1,239 institutions met inclusion criteria. Despite worse disease characteristics of patients treated at higher volume institutions, hospital volume was positively associated with survival outcomes in more advanced cases of TGCT. In the overall cohort, compared to the high-volume hospitals, patients treated at high-intermediate, intermediate, low-intermediate, and low volume hospitals the hazard ratio for overall mortality was 1.28, 1.45, 1.48, and 1.83, respectively (P<0.05). The association between survival and hospital volume was not apparent for seminoma or stage I NSGCT. Patients treated at higher volume hospitals were more likely to undergo surveillance for stage I seminoma, primary retroperitoneal lymph node dissection (RPLND) for stage I NSGCT, and postchemotherapy RPLND for stage II/III NSGCT.
Our analysis of a nationwide cancer registry demonstrated that increased hospital TGCT case volume was associated with significant differences in management strategies and improved survival outcomes, in particular for more advanced disease.
•Testicular cancer is rare; most hospital only see a handful of cases annually.•Higher hospital case volume associated with improved survival for advanced NSGCT.•Hospital case volume did not influence localized testicular cancer survival.•Hospital case volume influences treatment patterns.
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