Browsing by Author "Maniar, Viraj"

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    OTL-38-Guided Fluorescent Imaging in Renal Cell Cancer Robotic Partial Nephrectomy
    (Mary Ann Liebert, Inc., 2017-02-06) Bahler, Clinton D.; Maniar, Viraj; Marley, Kristen N.; Kheyfets, Steven V.; Shum, Cheuk Fan; Sundaram, Chandru P.; Urology, School of Medicine
    Introduction and Objective: The folate receptor (FR) protein is upregulated in numerous epithelial malignancies while having limited expression on normal tissues. This overexpression of FR in renal-cell carcinoma (RCC) can be exploited by attaching nearly any therapeutic or imaging agent for delivery to cancer cells. In one of its first applications, platinum-resistant ovarian cancer, folate was used to deliver pegylated liposomal doxorubicin (a folate-linked vinca alkaloid) and improved progression-free survival versus standard treatment. RCCs are thought to be the second highest FR-expressing cancer. OTL-38 is a folate analogue conjugated with a fluorescent dye that emits light in the near infrared spectrum. This longer wavelength allows for deeper penetration of the fluorescent light through tissues with the potential to better image tumors beneath adipose tissue or deeper into organ parenchyma. We are currently conducting a pilot, phase 2, nonrandomized study in patients with RCC, scheduled to undergo primary, partial, or radical nephrectomy. The aim is to explore the use of OTL-38 and fluorescence imaging to observe RCC at the margins of resection in partial nephrectomy and in lymph node(s) or other metastases for radical nephrectomy. Methods: Currently two patients have participated in the trial to date with an accrual target of 20 patients. The first was a 67-year-old male with an incidental 2.2 cm right-sided renal mass, and the second was a 70-year-old male with an enlarging 2 cm renal mass. Per protocol, both patients were administered OTL-38 in the preoperative area 1 hour before the procedure. Subsequently, both procedures were performed with robotic assistance as per normal routine with the use of Firefly fluorescence to aid in observation of OTL-38 uptake. Results: Intraoperative guidance through OTL-38 demonstrated minimal to no uptake of the OTL-38 as seen by Firefly fluorescence (green color). Surprisingly, the normal renal parenchyma showed strong uptake of OTL-38 as seen by Firefly fluorescence. Both pathology reports revealed conventional clear cell RCC. Immunohistochemistry slides of the tumor revealed only mild staining for folate. In contrast, immunohistochemistry slides of the normal renal parenchyma in the surgical margin revealed a strongly positive stain for folate. Conclusions: In conclusion, our first two patients' renal tumors did not stain strongly for folate; however, the normal renal parenchyma did, which served as an intraoperative guide to confirm a negative margin. Further study of patients will reveal whether folate receptors are, in fact, predominant or not in renal cell cancer.
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    Standardized Reporting of Microscopic Renal Tumor Margins: Introduction of the Renal Tumor Capsule Invasion Scoring System
    (Elsevier, 2017-01) Snarskis, Connor; Calaway, Adam C.; Wang, Lu; Gondim, Dibson; Hughes, Ian; Idrees, Mohammad; Kleithermes, Stephanie; Maniar, Viraj; Picken, Maria M.; Boris, Ronald S.; Gupta, Gopal N.; Department of Urology, School of Medicine
    Purpose Renal tumor enucleation allows for maximal parenchymal preservation. Identifying pseudocapsule integrity is critically important in nephron sparing surgery by enucleation. Tumor invasion into and through the capsule may have clinical implications, although it is not routinely commented on in standard pathological reporting. We describe a system to standardize the varying degrees of pseudocapsule invasion and identify predictors of invasion. Materials and Methods We performed a multicenter retrospective review between 2002 and 2014 at Indiana University Hospital and Loyola University Medical Center. A total of 327 tumors were evaluated following removal via radical nephrectomy, standard margin partial nephrectomy or enucleation partial nephrectomy. Pathologists scored tumors using our i-Cap (invasion of pseudocapsule) scoring system. Multivariate analysis was done to determine predictors of higher score tumors. Results Tumor characteristics were similar among surgical resection groups. Enucleated tumors tended to have thinner pseudocapsule rims but not higher i-Cap scores. Rates of complete capsular invasion, scored as i-Cap 3, were similar among the surgical techniques, comprising 22% of the overall cohort. Papillary histology along with increasing tumor grade was predictive of an i-Cap 3 score. Conclusions A capsule invasion scoring system is useful to classify renal cell carcinoma pseudocapsule integrity. i-Cap scores appear to be independent of surgical technique. Complete capsular invasion is most common in papillary and high grade tumors. Further work is warranted regarding the relevance of capsular invasion depth as it relates to the oncologic outcome for local recurrence and disease specific survival.
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    Variability in stone composition and metabolic correlation between kidneys in patients with bilateral nephrolithiasis
    (Elsevier, 2019-12-20) Rivera, Marcelino E.; Nottingham, Charles U.; Borofsky, Michael S.; Kissel, Suzanne M.; Maniar, Viraj; Dauw, Casey A.; York, Nadya E.; Krambeck, Amy E.; Lingeman, James E.; Urology, School of Medicine
    Introduction: To evaluate the clinical significance of discordant stone analyses in patients undergoing bilateral ureteroscopy. Methods: A retrospective chart review was performed for all patients undergoing stone extraction with bilateral ureteroscopy at our institution in an aim to identify patients who had bilateral stone analysis and 24-hour urine chemistry data available. Stones were then classified based upon the dominant present (>50%). Twenty-four hour urinalysis results were reviewed and statistical analysis performed comparing discordant and concordant patient populations, assessing significant differences that would potentially influence clinical management. Results: We identified 79 patients (158 renal units) who had bilateral stones removed at the time of ureteroscopy. The majority of stones were classified as calcium oxalate (CaOx) (60.1%) followed by calcium phosphate (CaP) (27.8%), brushite (5.1%), uric acid (UA) (4.4%) and cystine (2.5%). Discrepancies in stone classifications were present 24% of the time. Evaluation of 24-hour urinalysis results demonstrated that patients with CaOx:CaP stone discordance compared to CaOx:CaOx concordant stone formers were more likely to have an elevated pH (p=0.02) and lower uric acid supersaturation (p=0.01). Conclusions: Discrepancies in stone mineral content are common in patients with bilateral stone disease. A single stone analysis from one side in the setting of bilateral stone disease is insufficient for management of patients with bilateral renal stones, and may lead to mismanagement when this misrepresented information is utilized in addition to 24-hour urinalysis results. At least one stone analysis should be performed from both sides during a bilateral stone extraction procedure.