Percutaneous endoscopic treatment of benign and malignant renal pelvis carcinoma: A single-center experience

Background Percutaneous nephrolithotomy (PCNL) is a safe and ecient treatment for intro-renal diseases, most of which are calculus disease. In this study, we carried out percutaneous endoscopic nephron-sparing ablation for renal carcinoma in carefully selected patients. Our aim was to evaluate whether percutaneous endoscopic nephron-sparing operation was feasible for patients with renal cell carcinoma. Methods A total of 15 patients with renal pelvis carcinoma were treated with laser evaporation under percutaneous endoscopy between January 2015 and September 2019 ( group I ). Another 13 patients who received standard radical nephroureterectomy were recruited as the control group (group II). We recorded demographic data of the patients, the indication for surgery, tumor pathological grade, size and side of tumor, and the intraoperative and postoperative outcome, including the duration of surgery, length of hospital stay, and complication rate, as well as progression-free survival (PFS). blood loss between the groups. However, the operation time and mean hospital stay were signicantly shorter in group I compared with that in group II ( P < 0.05). But the PFS rate was signicantly higher in group II than in group I (P < 0.05). Conclusions This study shows that laser evaporation under percutaneous endoscopy for renal pelvis carcinoma is a safe, effective, and technically feasible procedure for treating benign and malignant renal pelvis carcinoma.


Introduction
Upper urinary tract urothelial cell carcinoma (UUT-UCC) is still a life-threatening disease. Among UUT-UCCs, renal pelvis carcinoma, which evolves from the renal pelvis and renal calyces, comprises 10% of malignant carcinoma in the kidney. The estimated annual incidence of UUT-UCCs in Western countries is 1-2 new cases/100,000 (1) , and the frequency of urothelial tumors of the upper tract is increasing (2,3) .
Most of the pathological types are transitional cell carcinoma (TCC), and squamous cell carcinoma and adenocarcinoma comprise a small portion. Clinically encountered urothelial cell carcinoma (UCC) can evolve from any location covered by transitional cells and it should be treated as a whole instead of that separately. UCC is usually found in patients aged older than 40 years, and UUT-UCC is three times more prevalent in men than in women (4,5) . There is no difference in the morbidity of UUT-UCC between the left and right kidneys. UUT-UCC can involve both sides in approximately 2-4% of patients (6,7) . The morbidity of renal pelvis TCC is not as high as that for bladder TCC, but the high recurrence rate and progressive trend are similar in the two types of TCC. A total of 60% of UUT-UCCs are invasive at diagnosis compared with only 15-25% of bladder tumors. In 17% of cases of UUT-UCC, concurrent bladder cancer is present.
Recurrence of disease in the bladder occurs in 22-47% of patients with UUT-UCC, whereas recurrence in the contralateral upper tract is observed in 2-6% of patients. In upper urinary tract UCC, a large portion is high grade and invasive cases. Furthermore, in high-grade upper urinary tract UCC, 10-40% of muscle invasive UCC and lymph metastasis are ignored (8) .
The prognosis of UTCC is closely related to tumor grading and staging ( 9) . Typical treatment for renal pelvis TCC is radical nephroureterectomy, including removal of the ipsilateral ureter ori ce. Before wide use of laparoscopic surgery, open radical nephroureterectomy was widely applied with either one or two separate incisions. The ureterovesical junction is dissected either from inside of the bladder or outside.
For a long time, TCUCC was considered a life-threatening disease and the 5-year overall survival rate was only 50%.
Nephron-sparing procedures are performed for some selected patients with localized early-stage renal pelvis TCC, for some patients with a solitary or functional solitary kidney with renal pelvis TCC, or for those who are reluctant to receive nephrectomy. These procedures include bench surgery and autotransplantation, exible ureteroscopy, and percutaneous percutaneous endoscopic surgery.
In this prospective study, we used laser evaporation under percutaneous endoscopy in some carefully selected patients and compared them with a control group to study the e cacy and safety of this nephron-sparing procedure.

Ethical approval
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Research Ethics Committee of Beijing Chaoyang Hospital( No. 2015-3-17-102).Written informed consent was obtained from all patients.

Selection of patients
This study gained approved of ethnic compittee of Beijing Chaoyang Hospital. In this prospective study, 28 patients with renal pelvis carcinoma were recruited from June 2016 to September 2019. Recruitment criteria included all of the following: a unifocal tumor, no evidence of an in ltrative lesion on computed tomography of urology, and the patients provided consent for close follow-up after the operation. Among them, 15 patients had percutaneous endoscopic laser ablation and were classi ed as group I (study group). These included eight patients who were unwilling to receive nephrectomy, three with diabetes and elevated blood creatinine levels, one with a congenital solitary kidney, two with a functional solitary kidney with atrophy, and one in whom the pathology result was benign renal pelvis carcinoma. The other 13 patients with renal pelvis TCC who received radical nephroureterectomy were classi ed as group II (control group).

Procedure
In both groups, specimens for a pathological examination were obtained with exible ureteroscopy before the operation.
In group I, 15 patients were treated with endoscopic laser evaporation under percutaneous endoscopic laser ablation. A percutaneous tunnel was established under ultrasound guidance and then dilated to F24 (Figure 1 ,2). The tumor was evaporated with laser under percutaneous nephroscopy(Figure3,4,5). And then regular follow up with exible ureteroscopy ( Figure 6). In group II, 13 patients received laparoscopic radical nephroureterectomy. Among them, two patients were transferred to open surgery because of serious adhesion.
We collected data on demographics of the patients, the indication for surgery, tumor pathological grade, tumor size and side, and intraoperative and postoperative outcome, including the duration of surgery, length of hospital stay, and complication rate, as well as the patient's progression-free survival (PFS).

Statistical analysis
Analysis was carried out using SPSS software version 20 for Windows (IBM Corp., Armonk, NY, USA).
Comparative t-test analysis was used between the two groups. A P value <0.05 was considered statistically signi cant.

Results
Among the patients with renal pelvis carcinoma, there were 21 men and seven women, with mean age of 56 years (range from 33-78). All patients received exible ureteroscopy at 7-22 days before tumor ablation or nephrectomy. The tumor size ranged from 1.0-4.5 cm. With regard to pathology, 27 patients had epithelial cell carcinoma, 14 had grade I, 13 had grade II, and one in group I had benign hemangiopericytoma.
There were no signi cant differences in age, sex, tumor size, and pathological grading between the two groups. Postoperation, the follow-up time was 1-56 months, with a mean follow-up of 32 months.
In group I, the mean operation time was 118 min (65-236 min), the mean blood loss was 110 ml (55-220 ml), and the mean hospital stay was 9 days (7-12 days). During follow-up, two patients died and two had recurrence; among them, one had systematic bone metastasis. The PFS rate was 66.7% (10/15).
In group II, the mean operation time was 265 min (185-436 min), the mean blood loss was 133 ml (85-240 ml), and the mean hospital stay was 13 days (9-16 days). During the follow-up, two patients died and there was no local or systematic metastasis. The PFS rate was 84.6% (11/13).
There was no signi cant difference in blood loss between the two groups. However, the operation time and mean hospital stay were signi cantly shorter in group I than in group II (both P<0.05). The PFS rate was signi cantly higher in group II than in group I (P<0.05). (See table 1 and 2) Discussion UUT-UCC is a frequently encountered disease that urologists have experienced for a long time. Like UCC of others evolved from other location, the etiology of UUT-UCC is still unclear. Among possible factors involved in UUT-UCC, the most clearly related factor is smoking (10) . Other involved factors include those associated with the workplace, such as dye manufacturing, rubber chemistry, pharmaceutical producing, painting, and leather manufacturing [11] . Additionally, chronic infection, including human papillomavirus and schistosome infection, can be responsible for UUT-UCC. Another possible factor related to UUT-UCC is inheritance. Absence or loss of heterozygosity of tumor suppressor genes, such as P53, Rb, and p21, can lead to susceptibility.
Standard treatment of UUT-UCC is radical nephroureterectomy. In past decades, organ-sparing surgery or precise surgery in other surgical elds has rapidly developed and dramatically changed the surgeon's concept. However, because of the high malignancy of UUT-UCC, it is still regarded as a lethal disease. Therefore, kidney-sparing surgery is not commonly considered for this disease.
In our clinical practice, we rst carried out this nephron-sparing procedure in patients with a special condition, such as those with a congenital solitary kidney or functional solitary kidney, or those unwilling to receive radical nephrectomy. Local re-occurrence or the metastasis rate is still high during the postoperation follow-up in these patients. In recent years, based on evidence-based medicine, many guidelines have recommended strict criteria for kidney-sparing surgery in patients with UUT-UCC. These include a unifocal tumor, tumor <1 cm, low-grade tumor, no evidence of an in ltrative lesion on CTU, and understanding of strict follow-up after surgery. A laser should usually be used for endoscopic treatment and exible ureteroscopy is preferred to rigid ureteroscopy, regardless of whether the tumor is in the renal pelvis, or distal-, mid-, or proximal ureter.
In previous reports, most of these procedures were nished by laser via exible ureteroscopy. This retrograde pathway is often affected by the condition of the ureter and a large portion of patients require placement of the ureteral sheath rst before a second-stage treatment. When using a exible ureteroscope, several factors, such as a narrow and con ned space, make tumor ablation di cult and slow, and increase the chance of infection. Additionally, tumors are sometimes not accessible, especially for tumors at the inferior calices. With wide application of percutaneous endoscopic surgery, it is no longer only suitable for kidney stone treatment. The percutaneous approach has advantages, including a wide lumen space, su cient liquid out ow, and accessibility to target calices. Percutaneous endoscopy surgery can provide a better view, and more importantly, it can lower renal pelvic pressure by free liquid out ow and signi cantly reduce occurrence of postoperation sepsis compared with exible ureteroscopy. Furthermore, bladder chemotherapy can also be applied via a renal stula tube after this procedure. After removal of the stula, bladder instillation therapy can be performed when ureter double-J stent was still kept.
In previous research, no report using percutaneous endoscopy laser ablation patients with UCC was reported.In our study, we compared patients with renal pelvis carcinoma who were treated with laser evaporation under percutaneous endoscopy and those who had standard radical nephroureterectomy. This is the rst prospective study to compare these treatments in Chinese patients with UUT-UCC. Our preliminary study showed that laser evaporation under percutaneous endoscopy for renal pelvis carcinoma was a safe, effective, and technically feasible procedure for treating benign and malignant renal pelvis carcinoma. However, our ndings require further con rmation with a larger number of samples.

Consent for publication
All data and images in the article have been consent to publish from related patients.
Availability of data and material: All data and operation video can be searched from data base in Dept. of Urology , Beijing Chaoyang Hospital Funding none

Con icts of interest
There are no nancial con icts of interests to disclose.  Figure 1 Page 11/12 Photograph showing puncture and dilation to establish PCNL access.

Figure 2
Ultrasound-guided PCNL to establish access.

Figure 3
Endoscopic view of renal carcinoma in PCNL.

Figure 4
Biopsy of a tumor via PCNL.

Figure 6
Follow-up 3 months after laser evaporation under PCNL.

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download. reviseoncologyletter nal.doc onco3673.pdf