Investigation of confocal microscopy for differentiation of renal cell carcinoma versus benign tissue. Can an optical biopsy be performed?

OBJECTIVE: Novel optical imaging modalities are under development with the goal of obtaining an "optical biopsy" to efficiently provide pathologic details. One such modality is confocal microscopy which allows in situ visualization of cells within a layer of tissue and imaging of cellular-level structures. The goal of this study is to validate the ability of confocal microscopy to quickly and accurately differentiate between normal renal tissue and cancer. METHODS: Specimens were obtained from patients who underwent robotic partial nephrectomy for renal mass. Samples of suspected normal and tumor tissue were extracted from the excised portion of the kidney and stained with acridine orange. The stained samples were imaged on a Nikon E600 C1 Confocal Microscope. The samples were then submitted for hematoxylin and eosin processing and read by an expert pathologist to provide a gold-standard diagnosis that can later be compared to the confocal images. RESULTS: This study included 11 patients, 17 tissue samples, and 118 confocal images. Of the 17 tissue samples, 10 had a gold-standard diagnosis of cancer and seven were benign. Of 118 confocal images, 66 had a gold-standard diagnosis of cancer and 52 were benign. Six confocal images were used as a training set to train eight observers. The observers were asked to rate the test images on a six point scale and the results were analyzed using a web based receiver operating characteristic curve calculator. The average accuracy, sensitivity, specificity, and area under the empirical receiver operating characteristic curve for this study were 91%, 98%, 81%, and 0.94 respectively. CONCLUSION: This preliminary study suggest that confocal microscopy can be used to distinguish cancer from normal tissue with high sensitivity and specificity. The observers in this study were trained quickly and on only six images. We expect even higher performance as observers become more familiar with the confocal images.

Total Autologous Fascia Lata Anterior and Apical Pelvic Organ Prolapse Repair: A New Technique and Initial Experience.

OBJECTIVE: To address renewed interest in nonmesh transvaginal Pelvic Organ Prolapse (POP) repair since the FDA reclassification of transvaginal mesh, our goal was to develop a transvaginal sacrospinous fixation for anterior and apical POP using only autologous fascia lata. We report our experience in 33 patients. METHODS: Autologous Anterior and Apical Pelvic Organ Prolapse (AAA-POP) repair utilizes a 4 × 14 cm piece of fascia lata harvested through a 3-4-inch upper thigh incision. The graft is reconfigured to provide apical fixation to the sacrospinous ligaments and distal fixation to the obturator fascia. Patients were followed by history, SEAPI scores, POP-Q scores, and Visual Analogue Pain Score. Treatment success was defined as absence of symptomatic anterior or apical POP. RESULTS: Thirty-three patients (mean age 63, mean follow-up 12 months) underwent AAA-POP. Treatment was successful in 31 patients (94%), and 2 failures were due to uterine prolapse. Mean harvest site Visual Analog Pain score was 0.27. Five and 7 patients developed nonbothersome thigh bulges and wound paresthesias, respectively. All 4 harvest-site seromas resolved, with 2 requiring simple aspiration. Eleven patients developed urinary retention, 10 (91%) of them after concurrent pubovaginal sling. All resolved after sling loosening (6 patients) or sling lysis (4 patients). CONCLUSION: AAA-POP is an efficacious treatment for patients desiring nonmesh POP repair. Postoperative harvest site issues are minor and typically resolve with expectant management. Patients should be counseled about the potential risk of failure with a uterine-sparing approach and the risk of urinary retention with concurrent pubovaginal sling.

Whole-transcriptome sequencing identified gene expression signatures associated with aggressive clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of kidney cancer, yet molecular biomarkers have not been used for the prognosis of ccRCC to aide clinical decision making. This study aimed to identify genes associated with ccRCC aggressiveness and overall survival (OS). Samples of ccRCC tumor tissue were obtained from 33 patients who underwent nephrectomy. Gene expression was determined using whole-transcriptome sequencing. The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) RNA-seq data was used to test association with OS. 290 genes were differentially expressed between tumors with high and low stage, size, grade, and necrosis (SSIGN) score (≥7 vs. ≤3) with P ADJ<0.05. Four genes, G6PD, APLP1, GCNT3, and PLPP2, were also over-expressed in advanced stage (III and IV) and high grade (3 and 4) ccRCC and tumor with necrosis (P ADJ<0.05). Investigation stratifying by stage found that APLP1 and PLPP2 overexpression were significantly associated with poorer OS in the early stage (Quartile 1 vs. Quartile 4, HR = 3.87, 95% CI:1.25-11.97, P = 0.02 and HR = 4.77, 95% CI:1.37-16.57, P = 0.04 respectively). These genes are potential biomarkers of ccRCC aggressiveness and prognosis that direct clinical and surgical management.

The Timed Up and Go Test as a Measure of Frailty in Urologic Practice.

OBJECTIVE: To evaluate the prevalence of frailty, a known predictor of poor outcomes, among patients presenting to an academic nononcologic urology practice and to examine whether frailty differs among patients who did and did not undergo urologic surgery. METHODS: The Timed Up and Go Test (TUGT), a parsimonious measure of frailty, was administered to patients ages ≥65. The TUGT, demographic data, urologic diagnoses, and procedural history were abstracted from the medical record into a prospective database. TUGT times were categorized as nonfrail (≤10 seconds), prefrail (11-14 seconds), and frail (≥15 seconds). These times were evaluated across age and urologic diagnoses and compared between patients who did and did not undergo urologic surgery using chi-square and t tests. RESULTS: The TUGT was recorded for 78.9% of patient visits from December 2015 to May 2016. For 1089 patients, average age was 73.3 ± 6.3 years; average TUGT time was 11.6 ± 6.0 seconds; 30.0% were categorized as prefrail and 15.2% as frail. TUGT times increased with age, with 56.9% of patients age 86 and over categorized as frail. Times varied across diagnoses (highest average TUGT was 14.3 ± 11.9 seconds for patients with urinary tract infections); however, no difference existed between patients who did and did not undergo surgery (P = .94). CONCLUSION: Among our population, prefrailty and frailty were common, TUGT times increased with age and varied by urologic diagnosis, but did not differ between patients who did and did not undergo urologic surgery, presenting an opportunity to consider frailty in preoperative surgical decision making.

The Case of an Obstructed Stone at the Distal Urethra.

This report highlights a presentation of urinary calculus impacted at the urethral meatus and bedside extraction after evaluation with point-of-care ultrasound (POCUS). Visualization of a stone at the urethral meatus prompted a point-of-care ultrasound of the penile shaft and glans. The ultrasound ruled out anatomic variations such as urethral diverticula and as a result bedside removal was expedited. The stone was successfully removed with traction and intraurethral lidocaine gel without urethral lesions or injury to the meatus. Bedside ultrasound is readily available in the emergency department and can be used to characterize urethral foreign bodies, evaluate urethral anatomy, and assess the likelihood of bedside removal.