Downstaging and Pathological Complete Response of Locally Recurrent Sarcomatoid Renal Cell Carcinoma under Pembrolizumab and Lenvatinib: A Case Report and Review of Literature.

The advent of immune checkpoint inhibition opened new perspectives for patients with recurrent or metastasized renal cell carcinoma. In case of recurrent disease, surgical resection remains the most promising therapeutic option. Surgical resection is associated with improved overall survival and demonstrated curative potential given complete resection of metastases can be performed. This report presents the case of a patient with local recurrence of dedifferentiated sarcomatoid renal cell carcinoma approximately 1 year after initial open lumbar nephrectomy. After initial evaluation, surgical removal was deemed infeasible and an induction therapy with pembrolizumab and lenvatinib was initiated. After 3 months, corresponding to 5 cycles of pembrolizumab, the tumor showed a partial response on imaging control and was successfully resected en bloc. Histopathological examination of the specimen revealed no evidence of viable neoplastic cells. This is the first report describing a complete pathological response of a locally recurrent dedifferentiated sarcomatoid renal cell carcinoma after treatment with pembrolizumab and lenvatinib. Overall, the combination therapy was well tolerated with a maximum Common Terminology Criteria for Adverse Events Level of Two. These findings underline the potential of multimodal therapeutic strategies for recurrent renal cell carcinoma, such as induction therapies to downstage initially nonresectable masses, and highlight the need for prospective studies to allow for evidence-based treatment plans.

Different ureteral access sheaths sizes for retrograde intrarenal surgery.

PURPOSE: There is a trend toward miniaturization in endourological stone therapy. Good visibility, intrarenal pressures and temperature control should be ensured by ureteral sheaths. In the context of the present study, 10/12 Charr. sheaths and 12/14 Charr. sheaths for flexible ureterorenoscopy were investigated regarding stone-free rate, complication rate and efficacy for laser lithotripsy. METHODS: From January 2020 to January 2022, 100 patients each with kidney stone up to 1.5 cm in diameter were included in the study. Use of a 12/14 Charr. vs. 10/12 Charr. ureteral sheath for flexible ureterorenoscopy was compared. Perioperative data, stone size, volume and density, laser energy, laser duration, stone-free rates and complications based on Clavien-Dindo classification were retrospectively analyzed. RESULTS: For both groups of ureteral access sheaths, there were no differences in median surgery duration (10/12 Charr: 29 min (7-105 min) vs. 12/14 Charr: 34 min (9-95 min); p = 0.33), overall complication rate (p = 0.61) and hospitalization (p = 0.155). There were no differences in stone-free rates (97.9% vs. 92.7%, p = 0.37). Laser lithotripsy duration usingholmium laser was 1.9 min (0.1-10.8 min) vs. 3.8 min (0.2-20.7 min) (p < 0.01) and applied laser energy was 3.1 J (0.15 J-10.29 J) vs. 6.8 J (1.07 J-26.77 J) (p < 0.01) for 12/14 Charr. sheaths and 10/12 Charr. sheaths, respectively. CONCLUSION: In terms of stone-free rates, there are no differences between the 10/12 and 12/14 Charr. ureteral access sheaths. The laser duration and energy was increased with 10/12 Charr. sheaths without showing increased risk for clinical complications like trauma or inflammation.

Personalized Prediction of Patient Radiation Exposure for Therapy of Urolithiasis: An Application and Comparison of Six Machine Learning Algorithms.

The prediction of radiation exposure is an important tool for the choice of therapy modality and becomes, as a component of patient-informed consent, increasingly important for both surgeon and patient. The final goal is the implementation of a trained and tested machine learning model in a real-time computer system allowing the surgeon and patient to better assess patient's personal radiation risk. In summary, 995 patients with ureterorenoscopy over a period from May 2016 to December 2019 were included. According to the suggestions based on actual literature evidence, dose area product (DAP) was categorized into 'low doses' ≤ 2.8 Gy·cm2 and 'high doses' > 2.8 Gy·cm2 for ureterorenoscopy (URS). To forecast the level of radiation exposure during treatment, six different machine learning models were trained, and 10-fold crossvalidated and their model performances evaluated in training and independent test samples. The negative predictive value for low DAP during ureterorenoscopy was 94% (95% CI: 92-96%). Factors influencing the radiation exposure were: age (p = 0.0002), gender (p = 0.011), weight (p < 0.0001), stone size (p < 0.000001), surgeon experience (p = 0.039), number of stones (p = 0.0007), stone density (p = 0.023), use of flexible endoscope (p < 0.0001) and preoperative stone position (p < 0.00001). The machine learning algorithm identified a subgroup of patients of 81% of the total sample, for which highly accurate predictions (94%) were possible allowing the surgeon to assess patient's personal radiation risk. Patients without prediction (19%), the medical expert can make decisions as usual. Next step will be the implementation of the trained model in real-time computer systems for clinical decision processes in daily practice.

Impact of Stone Localization before Emergency Ureteral Stenting on Further Stone Treatment.

INTRODUCTION: Ureter stones leading to severe pain and urosepsis are usually treated by emergency primary ureteral stenting. However, this intervention can significantly change the location of the stone, potentially also changing the preferred method and/or technical aspects of definitive treatment. We analyzed stone location changes and consequences after emergency ureteral stent insertion prior to secondary ureterorenoscopy. METHODS: We performed a retrospective analysis of stone locations in 649 patients with a mean age of 52 ± 16 years who were treated with ureterorenoscopy for symptomatic stones from May 2016 to December 2019. All patients with single unilateral ureterolithiasis undergoing definitive stone treatment by secondary ureterorenoscopy were included. In 469 patients, ureteral stone localization before emergency ureteral stenting and at subsequent ureterorenoscopy was evaluated. Additionally, the use of flexible ureterorenoscopy for complete stone removal was also recorded. RESULTS: Inadvertent repositioning of ureteral stones with a mean diameter of 6.9 (±3.1) mm after ureteral stenting was observed in 45.6%. 119 (25.4%) ureteral stones were displaced back into the kidney. Proximal stones showed a particularly high incidence of repositioning into the renal pelvis (42%, p < 0.05). The majority of cases required the use of flexible ureterorenoscopy showed a primary proximal ureteral localization (60 of 85 patients, 70.5%). DISCUSSION/CONCLUSION: Emergency ureteral stenting for ureterolithiasis may change the location of a stone, potentially affecting therapy planning, particularly in the case of proximal stones. Imaging control prior to definitive stone treatment is thus especially advisable for proximal ureteral stones.

Neural Networks Modeling for Prediction of Required Resources for Personalized Endourologic Treatment of Urolithiasis.

When scheduling surgeries for urolithiasis, the lack of information about the complexity of procedures and required instruments can lead to mismanagement, cancellations of elective surgeries and financial risk for the hospital. The aim of this study was to develop, train, and test prediction models for ureterorenoscopy. Routinely acquired Computer Tomography (CT) imaging data and patient data were used as data sources. Machine learning models were trained and tested to predict the need for laser lithotripsy and to forecast the expected duration of ureterorenoscopy on the bases of 474 patients over a period from May 2016 to December 2019. Negative predictive value for use of laser lithotripsy was 92%, and positive predictive value 91% before application of the reject option, increasing to 97% and 94% after application of the reject option. Similar results were found for duration of surgery at ≤30 min. This combined prediction is possible for 54% of patients. Factors influencing prediction of laser application and duration ≤30 min are age, sex, height, weight, Body Mass Index (BMI), stone size, stone volume, stone density, and presence of a ureteral stent. Neuronal networks for prediction help to identify patients with an operative time ≤30 min who did not require laser lithotripsy. Thus, surgical planning and resource allocation can be optimised to increase efficiency in the Operating Room (OR).

Donor-dependent variances of human adipose-derived stem cells in respect to the in-vitro endothelial cell differentiation capability.

Human adipose-derived stem cells (ASC) have been shown to differentiate into mature adipocytes and to play an important role in creating the vasculature, necessary for white adipose tissue to function. To study the stimulatory capacity of ASC on endothelial progenitor cells we used a commercially available co-culture system (V2a - assay). ASC, isolated from lipoaspirates of 18 healthy patients, were co-cultured for 13 d on endothelial progenitor cells. Using anti CD31 immunostaining, cells that had undergone endothelial differentiation were quantified after the defined co-cultivation period. Endothelial cell differentiation was observed and demonstrated by an increase in area covered by CD31+ cells compared with less to no endothelial cell differentiation in negative and media-only controls. Enzyme-linked immunosorbent assay (ELISA) for vascular endothelial growth factor (VEGF) in supernatant medium collected during the co-cultivation period revealed elevated VEGF levels in the co-culture samples as compared with ASC cultures alone, whereas no increase in adiponectin was detected by ELISA. These findings help to provide further insights in the complex interplay of adipose derived cells and endothelial cells and to better understand the diversity of ASCs in respect of their stimulatory capacity to promote angiogenesis in vitro.