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Background: Clinically localized renal cell carcinoma is treated primarily with surgery followed by observation or adjuvant sunitinib in selected high-risk patients. The checkpoint inhibitor immunotherapeutic agents nivolumab and ipilimumab have recently shown a survival benefit in the first-line metastatic setting. To date, there have been no reports on the response of localized renal cancer to modern immunotherapy. We report a remarkable response of an advanced tumor thrombus to combined immunotherapy which facilitated curative-intent resection of the non-responding primary renal tumor. We characterized the tumor microenvironment within the responding and non-responding tumors., Case Presentation: A 54-year-old female was diagnosed with a locally advanced clear cell renal cell carcinoma with a level IV tumor thrombus of the vena cava. She was initially deemed unfit for surgical resection due to poor performance status. She underwent neoadjuvant immunotherapy with nivolumab and ipilimumab with a complete response of the vena cava and renal vein tumor thrombus, but had stable disease within her renal mass. She underwent complete surgical resection with negative margins and remains disease-free longer than 1 year after her diagnosis with no further systemic therapy. Notably, pathologic analysis showed a complete response within the vena cava and renal vein, but substantial viable cancer remained in the kidney. Multichannel immunofluorescence was performed and showed marked infiltration of immune cells including CD8 + T cells and Batf3 + dendritic cells in the thrombus, while the residual renal tumor showed a non-T cell-inflamed phenotype., Conclusions: Preoperative immunotherapy with nivolumab and ipilimumab for locally advanced clear cell renal cancer resulted in a complete response of an extensive vena cava tumor thrombus, which enabled curative-intent resection of a non-responding primary tumor. If validated in larger cohorts, preoperative immunotherapy for locally advanced renal cell carcinoma may ultimately impact surgical planning and long-term prognosis.

Purpose: To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d'Urologie and International Consultation on Urological Diseases., Methods: A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion., Results: The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients., Conclusions: The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.

Background and Purpose: Patients who are undergoing laparoscopic ablative therapy (LAT) are often older with more comorbidities in comparison with patients who are undergoing laparoscopic partial nephrectomy (LPN). A matched control study was performed to compare the surgical and functional outcomes of LPN and LAT., Patients and Methods: A prospectively maintained database of 250 patients who underwent nephron-sparing surgery was explored. Fifty-one LAT patients (21 and 30 laparoscopic radiofrequency and cryoablation, respectively) were matched with 51 LPN patients. A comparison of preoperative, operative, and postoperative outcomes was performed., Results: The groups were similar in age, sex, body mass index, preoperative estimated glomerular filtration rate (eGFR), number of comorbidities and tumor size. Patients who were undergoing LAT had a lower incidence of endophytic tumor and higher incidence of upper pole and midpolar tumors. Hilar vessels clamping was performed in LPN (47/51 patients). Mean estimated blood loss and operative time were higher in those undergoing LPN (P<0.01). There was no significant difference in transfusion rate and hospital stay, however. Mean follow-up was 27 and 18 months in LAT and LPN, respectively (P<0.01). The mean percent decline of eGFR at the last follow-up was 10 (95% confidence interval [CI]: 4-15) and 7.5 (95% CI: 4-11), respectively (P<0.43). In comparison with baseline, eGFR declined significantly (P<0. 01), but there was no difference between the groups., Conclusion: Despite renal ischemia, longer operative time, and higher blood loss associated with LPN, the hospital stay and long-term functional outcomes are similar to those of LAT in a matched control study.

Purpose: Partial nephrectomy has been established as a standard of care for T(1a) renal tumors. Laparoscopic partial nephrectomy (LPN) has been described as more difficult to perform than open partial nephrectomy (OPN). We compare our series of LPN and OPN., Patients and Methods: From October 2002 to January 2006, 76 LPNs were performed for patients with clinical T(1a) tumors. These patients were matched with a cohort of patients who underwent OPN for solitary tumors of 4 cm or smaller in diameter. The cohorts were compared with regard to demographics, perioperative data, and outcomes., Results: The patient populations were demographically similar. Although mean tumor size was smaller in the laparoscopic cohort (2.5 v 2.9 cm, P=0.002), the OPN cohort demonstrated shorter operative (193 v 225 min, P=0.004) and ischemia times (20.5 v 32.8 min). LPN was associated with less blood loss (212 v 385 mL, P<0.001) and shorter hospital stay (2.5 v 5.6 days, P<0.001), however. One positive margin occurred in each of the LPN and OPN cohorts. Intraoperative complications were similar, although LPN was associated with fewer postoperative complications. Of note, two LPN (2.6%) patients had emergent reoperation and complete nephrectomy because of postoperative hemorrhage., Conclusions: Despite increased operative and ischemia times, LPN patients demonstrated quicker recovery and fewer postoperative complications. Two patients in the LPN group, however, had emergent complete nephrectomy because of hemorrhage. We conclude that LPN is still an evolving alternative to OPN in patients with small renal tumors.

Objectives: The intraoperative complexity of laparoscopic partial nephrectomy (LPN) for upper pole renal tumors is recognized. We report on the technical feasibility and operative outcomes of LPN for upper pole tumors (UPLPN) and lower pole tumors (LPLPN), and open partial nephrectomy (UPOPN) for upper pole tumors., Methods: We retrospectively reviewed our database of LPNs performed by a single surgeon from October 2002 to February 2006. All solitary, upper and lower pole tumors in patients with a normal contralateral kidney were included. The perioperative outcomes were assessed. UPOPNs performed in the same institution by a separate surgeon were analyzed and compared separately with the UPLPN group., Results: Three groups, UPLPN (20 patients), LPLPN (33 patients), and UPOPN (24 patients), were analyzed. The UPLPN and LPLPN groups had similar perioperative outcomes. The intraoperative and postoperative major complications were also comparable between the UPLPN and LPLPN groups (17% versus 12%, P = 0.68 and 22% versus 6%, P = 0.07, respectively). The mean pathologic tumor size was larger (3.2 versus 2.3 cm, P = 0.05) and the mean operative time significantly shorter (187 versus 244 minutes, P = 0.02) in the UPOPN group than in the UPLPN group. The UPOPN group had a trend toward fewer intraoperative complications compared with the UPLPN group (4% versus 17%, P = 0.17). The final pathologic surgical margins were negative in all three groups., Conclusions: LPN for upper pole renal tumors is technically feasible and may have comparable outcomes to LPN for lower pole tumors. However, performing open nephron-sparing surgery is still the standard of care because it may offer fewer complications and reduce the risk of ischemic damage to the kidney.

Metachronous presentation of metastatic renal cell carcinoma (RCC) to the ureter is extremely rare. We report a solitary metachronous metastatic RCC in the contralateral ureter 14 months after right radical nephrectomy for Fuhrman grade 2 pT3a clear cell disease after the patient re-presented with gross hematuria. The proximal left ureteral lesion was excised followed by ileal-ureteral interposition. Pathologic examination confirmed metastatic RCC. To date, only 51 cases of metastatic RCC to the ureter have been reported, with only 6 occurring metachronously in the contralateral ureter. Also, we report the presence of focal extramedullary hematopoiesis occurring within this metastatic lesion.

Objectives: To present our technique, modifications, and experience of laparoscopic partial nephrectomy (LPN). Nephron-sparing surgery is an increasingly accepted treatment for selected T1a kidney tumors. Because of the more complex surgical technique involved, LPN is evolving more slowly than laparoscopic radical nephrectomy., Methods: The data of 41 consecutive patients with T1a tumors who had undergone LPN from October 2002 to March 2004 were retrospectively reviewed. Four main considerations in our surgical technique were consistently used: (a) LPN was performed in the transperitoneal approach, (b) a suture traction system was placed on the kidney when tumor visualization was challenging, (c) sutures and bolsters were preloaded on the abdominal wall, and (d) hemostasis and closure of the renal defect was performed using Lapra-Ty clips, eliminating knot-tying., Results: The mean patient age was 63.1 years. The mean warm ischemia time was 29.7 minutes, and the mean surgical time was 226.5 minutes. In 26 of 41 patients, the collecting system was entered and repaired. The median estimated blood loss was 150 mL, with a mean tumor size of 2.2 cm. Three cases were converted to open surgery. Five complications (13.2%) occurred. The median hospital stay was 2 days. Of the 41 specimens, 11 were benign. All surgical margins were negative. The mean follow-up was 7.5 months., Conclusions: Although technically challenging, LPN is emerging as an alternative to open partial nephrectomy. With several easily applied technical considerations, we have simplified LPN, making the procedure more efficient. We believe that the technical considerations we describe can increase the feasibility and ease of LPN for Stage T1a exophytic renal tumors.

Introduction: To describe a novel partial nephrectomy technique that uses small intestine submucosa (SIS) to ensure a watertight closure of the collecting system and minimize parenchymal bleeding. The indications for nephron-sparing surgery have increased in recent years. The most prevalent complications after partial nephrectomy include urinary leakage/fistula and parenchymal bleeding. Porcine SIS has been used in animal models to reconstruct portions of the urinary tract successfully., Technical Considerations: Twenty-two consecutive patients underwent 24 partial nephrectomies that required entry into the collecting system for presumed renal cell carcinoma. After temporary occlusion of the renal vessels and renal hypothermia, the tumor and a margin of normal parenchyma were excised. The cut surface was cauterized with an argon beam coagulator, and visible vessels were suture ligated. The collecting system was reapproximated with interrupted, absorbable sutures. A multilayer piece of hydrated SIS was sutured in place over the exposed collecting system and parenchymal defect with several figure-of-eight chromic sutures. With a mean follow-up of 18.4 months, none of the 22 patients experienced postoperative urinary leaks/fistulas or postoperative hemorrhage requiring transfusion. The serum creatinine returned to within 0.2 mg/dL of baseline in all patients after surgery., Conclusions: We describe a novel technique of partial nephrectomy using SIS, which, we believe, aids in closure of the collecting system and decreases parenchymal bleeding.

Purpose: To prospectively evaluate in a multicenter randomized trial the antitumor activity of CD8(+) tumor-infiltrating lymphocytes (TILs) in combination with low-dose recombinant interleukin-2 (rIL-2), compared with rIL-2 alone, after radical nephrectomy in metastatic renal cell carcinoma patients., Patients and Methods: Between December 1994 and March 1997, 178 patients with resectable primary tumors were enrolled at 29 centers in the United States and Europe. Patients underwent total nephrectomy, recovered, and were randomized to receive either CD8(+) TILs (5 x 10(7) to 3 x 10(10) cells intravenously, day 1) plus rIL-2 (one to four cycles: 5 x 10(6) IU/m(2) by continuous infusion daily for 4 days per week for 4 weeks) (TIL/rIL-2 group) or placebo cell infusion plus rIL-2 (identical regimen) (rIL-2 control group). Primary tumor specimens were cultured at a central cell-processing center in serum-free medium containing rIL-2 to generate TILs., Results: Of 178 enrolled patients, 160 were randomized (TIL/rIL-2 group, n = 81; rIL-2 control group, n = 79). Twenty randomized patients received no treatment after nephrectomy because of surgical complications (four patients), operative mortality (two patients), or ineligibility for rIL-2 therapy (14 patients). Among 72 patients eligible for TIL/rIL-2 therapy, 33 (41%) received no TIL therapy because of an insufficient number of viable cells. Intent-to-treat analysis demonstrated objective response rates of 9.9% v 11.4% and 1-year survival rates of 55% v 47% in the TIL/rIL-2 and rIL-2 control groups, respectively. The study was terminated early for lack of efficacy as determined by the Data Safety Monitoring Board., Conclusion: Treatment with CD8(+) TILs did not improve response rate or survival in patients treated with low-dose rIL-2 after nephrectomy.

Endoscopic treatment of patients with upper urinary tract transitional cell carcinoma is recommended in those with tumor in a solitary kidney, bilateral disease, renal dysfunction, and significant intercurrent illness that precludes a major abdominal surgical procedure. Endoscopic management also may be appropriate in selected patients with small, low-grade lesions in the presence of a normal contralateral kidney. Almost all ureteral tumors and some renal collecting system lesions can be managed using rigid and/or flexible ureteroscopy, which is associated with less bleeding and more rapid recovery than a percutaneous approach. However, larger renal malignancies can be managed effectively using percutaneous resection. Six patients with upper tract transitional cell carcinoma underwent endoscopic resection. The antegrade and retrograde surgical techniques are described. With follow-up up to 23 months, local recurrence in two patients was managed successfully by repeat endoscopic resection. No patient has experienced disease progression or developed metastases.

Objectives: To re-examine clear cell cystic lesions of the kidney and to assess their potential clinicopathologic significance, as the long-forgotten diagnosis of benign adenomatous multicystic kidney tumor (Perlmann's tumor) has not been cited in the literature in more than 35 years., Methods: We identified 12 patients between 1959 and 1996 who underwent a radical nephrectomy at our institution and were diagnosed with either adenomatous multicystic clear cell kidney tumor (n = 4) or with renal cell carcinoma (RCC) associated with features of adenomatous clear cell multicystic kidney tumors (n = 8). All diagnoses were reviewed histologically by a single pathologist., Results: Nine of 1 2 patients had Stage T2NOMO disease, and 3 patients had Stage T1 NOMO disease. There were 8 men and 4 women. The average age at the time of surgery was 60.5 years (range 25 to 74). Six patients are still alive with a mean follow-up of 4.7 years (range 1.5 to 16.3) and have no evidence of recurrent disease. Of the 6 patients who died, mean survival time was 8.8 years (range 0 to 15.7). One patient died in the perioperative period, and the other 5 patients died of other causes, unrelated to their kidney tumor., Conclusions: Adenomatous clear cell multicystic kidney disease may represent a histologically distinct benign neoplasm, and its presence in association with RCC may confer a more favorable prognosis. Its distinction from usual solid hemorrhagic or focally necrotic RCC is important.

A radical nephrectomy typically includes early ligation of the renal vessels, excision of the kidney and perinephric tissue, a regional lymphatenectomy, and an adrenalectomy. More controversial may be excision of supradiaphragmatic caval neoplastic extension and adjacent organ resection. Although survival is low in these unfavorable groups of patients, some patients may benefit from the extensive local resection of tumor, including adrenalectomy, lymphatenectomy, caval resection, and resection of adjacent organs.