Joseph Brito

Targeted Imaging of Urothelium Carcinoma in Human Bladders by an ICG pHLIP Peptide Ex vivo

Significance Bladder cancer is the fifth most common cancer. Timely diagnosis and appropriate early management protocols are of paramount significance for improving patient outcomes. This study shows efficient pH-dependent near-infrared imaging of bladder malignant tumors without targeting of normal tissue. Our results demonstrate that the indocyanine green pH low insertion peptide (pHLIP) construct is suitable for use as a predictive clinical marker, specifically staining human bladder tumors after intravesical administration ex vivo. The targeting allows delivery of various imaging probes, which may offer early diagnosis and improve the outcomes of endoscopic and radical surgical resection of urothelial carcinomas. In addition, delivery of therapeutic molecules to cancer cells by pHLIP might open an opportunity for novel targeted treatment of bladder cancers. Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

The role of lymph node dissection in the contemporary management of renal cell carcinoma: A critical appraisal of the evidence

The role of lymph node dissection (LND) in the management of renal cell carcinoma has been controversial. Older studies provided initial support to a potential survival benefit in resection of lymph node metastases, and several predictive models were developed to identify patients with lymph node involvement. However, the only randomized trial on the subject did not report a survival benefit to LND in the nonmetastatic setting. Several studies have recently reexplored the therapeutic benefit of LND. In both nonmetastatic and metastatic settings, LND does not appear to be associated with a survival benefit. Moreover, it does not appear that LND confers a survival advantage to patients at increased risk of lymph node metastases, such as those with preoperative radiographic lymphadenopathy or across increasing probability of lymph node disease. Among patients with clinically isolated lymph node metastases, the majority develop disease progression following surgical resection, suggesting a high prevalence of occult systemic disease. Lymph node metastases appear to have prognostic value in both nonmetastatic and metastatic settings. LND may, therefore, have an increasingly important staging role in the management of renal cell carcinoma.

Endourologic and Open Ureterolithotomy and Common Sheath Reimplant for Large Bladder and Distal Ureteral Calculi.

Abstract A twenty-eight-year-old female with a history of suprapubic pain and recurrent urinary tract infections presents for urology referral with a kidney, ureter, and bladder radiograph showing a 4.4 cm bladder calculus and 6.5 cm distal left ureteral stone. She underwent effective cystolitholapaxy of the bladder stone. Endourologic attempt (left ureteroscopy) was unsuccessful because of ureteral stone burden. Findings at ureteroscopy revealed a duplicated system on the left with the lower pole moiety joining just proximal to the ureteral orifice. The stone was found to be in the upper pole moiety ureter. An open ureterolithotomy was performed with intraoperative ureteroscopic laser lithotripsy and common sheath ureteral reimplant. Furthermore, a previously placed stent was found to be encrusted at the time of the ureterolithotomy. Effective ureteroscopy and lasering were performed through the ureterotomy up to the renal pelvis of the upper pole ureter.