Skip to main content


Front. Oncol., 04 October 2021
Sec. Genitourinary Oncology
This article is part of the Research Topic The role of Precision Medicine in the Genitourinary Cancer View all 6 articles

Comparing Oncological Outcomes and Surgical Complications of Hand-Assisted, Laparoscopic and Robotic Nephroureterectomy for Upper Tract Urothelial Carcinoma

Ching-Chia Li,,Ching-Chia Li1,2,3Chao-Hsiang Chang,Chao-Hsiang Chang4,5Chi-Ping Huang,Chi-Ping Huang4,5Jian-Hua Hong,Jian-Hua Hong6,7Chao-Yuan HuangChao-Yuan Huang6I-Hsuan Alan ChenI-Hsuan Alan Chen8Jen-Tai LinJen-Tai Lin8Chi-Wen LoChi-Wen Lo9Chih-Chin Yu,Chih-Chin Yu9,10Jen-Shu Tseng,,Jen-Shu Tseng11,12,13Wun-Rong Lin,Wun-Rong Lin11,12Wei-Che Wu,Wei-Che Wu7,14Shiu-Dong Chung,Shiu-Dong Chung14,15Thomas Y. Hsueh,Thomas Y. Hsueh16,17Allen W. ChiuAllen W. Chiu18Yung-Tai ChenYung-Tai Chen19Shin-Hong ChenShin-Hong Chen19Yuan-Hong JiangYuan-Hong Jiang20Yao-Chou Tsai,Yao-Chou Tsai21,22Bing-Juin Chiang,,Bing-Juin Chiang23,24,25Wei Yu Lin,,Wei Yu Lin26,27,28Yeong-Chin Jou,Yeong-Chin Jou29,30Chia-Chang Wu,,Chia-Chang Wu31,21,32Hsiang-Ying Lee,,,*Hsiang-Ying Lee1,2,33,34*Hsin-Chih Yeh,,,*Hsin-Chih Yeh1,2,3,33*
  • 1Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  • 2Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 4Department of Urology, China Medical University and Hospital, Taichung, Taiwan
  • 5School of Medicine, China Medical University, Taichung, Taiwan
  • 6Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
  • 7Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
  • 8Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  • 9Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei City, Taiwan
  • 10School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan
  • 11Department of Urology, MacKay Memorial Hospital, Taipei, Taiwan
  • 12Department of Urology, Mackay Medical College, New Taipei City, Taiwan
  • 13Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 14Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan
  • 15Graduate Program in Biomedical Informatics, College of Informatics, Yuan-Ze University, Chung-Li, Taiwan
  • 16Division of Urology, Department of Surgery, Taipei City Hospital Renai Branch, Taipei, Taiwan
  • 17Department of Urology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 18College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 19Department of Urology, Taiwan Adventist Hospital, Taipei, Taiwan
  • 20Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
  • 21Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • 22Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan
  • 23College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
  • 24Department of Urology, Cardinal Tien Hospital, New Taipei City, Taiwan
  • 25Department of Life Science, College of Science, National Taiwan Normal University, Taipei, Taiwan
  • 26Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
  • 27Chang Gung University of Science and Technology, Chiayi, Taiwan
  • 28Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  • 29Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
  • 30Department of Health and Nutrition Biotechnology, Asian University, Taichung, Taiwan
  • 31Department of Urology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
  • 32TMU Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei, Taiwan
  • 33Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
  • 34Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Purpose: This study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.

Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.

Results: Among the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p <0.001).

Conclusions: Minimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings.


Upper tract urothelial carcinoma (UTUC) is a relatively rare malignant tumor, accounting for 5–10% of urothelial carcinoma (1). However, it is reported that the incidence of UTUC in Taiwan is as high as 30–40% (2). UTUC shows more aggressive features than bladder cancer, and more than 60% of patients have invasive disease at the time of diagnosis (3). Radical nephroureterectomy (NU) with bladder cuff excision is still recognized as the gold standard treatment for nonmetastatic UTUC (1). After decades of development, minimally invasive surgeries (MIS) including hand-assisted laparoscopic NU (HALNU), laparoscopic NU (LNU) and robotic NU (RNU) have been introduced as an alternative to open NU (ONU) and widely accepted for the treatment of UTUC.

It is well known that compared with open surgery, the benefits of MIS on perioperative outcomes include lower estimated blood loss, lower blood transfusion rate, shorter hospital stay, less pain, fewer wound complications, and shorter recovery time (4, 5). The oncological outcomes of MIS for UTUC have been controversial, but most previous studies have shown that the survival rate is not inferior compared with open method, especially for organ-confined UTUC (6, 7). HALNU is a combination of laparoscopy and a hand port, through which the hand is inserted into the space created by carbon dioxide insufflation and the specimen is retrieved. Compared with other MIS, HALNU is considered to have lower surgical difficulty and similar oncological results, so it is commonly used. The use of robotic systems is also increasing because it is less technically demanding than pure laparoscopy. For experienced surgeons, all MIS approaches are feasible to maintain basic oncological principles. The intramural ureter and surgical specimen must be completely removed as a whole to prevent tumor residue and spillage (8).

Due to its advantages in the perioperative period and advances in laparoscopic devices (9), MIS is being increasingly used as the current standard in many medical centers around the world. However, reports on the oncological efficacy of different MIS have mixed results. In addition, many previous studies included only a limited number of cases for analysis, and a sizable cohort often failed to comprehensively adjust for potential confounding factors or assess cancer-specific outcomes and bladder recurrence (1012). The purpose of this study is to analyze a large-scale retrospective cohort derived from multiple institutions in Taiwan to evaluate the oncological outcomes and postoperative complications of UTUC patients treated with minimally invasive NU (miNU).

Materials and Methods

Patient Collection

This study was approved by our institutional review board [KMUHIRB-E(I)-20180214]. We retrospectively reviewed the updated data of 15 participating hospitals under the Taiwan UTUC Collaboration Group, and a total of 3,333 UTUC patients were identified. After excluding patients undergoing nephron-sparing surgery (n = 448), ONU (n = 1,230), or patients lacking any parameters of interest (n = 315), we finally included 1,340 patients who received miNU between July 2001 and February 2021. The transperitoneal or retroperitoneal approach of miNU was based on the surgeon discretion. According to different MIS techniques, patients were divided into HALNU, LNU and RNU groups. HALNU was performed by combining hand manipulation through hand port and laparoscopic technique. LNU and RNU only used laparoscopic and robotic instruments to perform surgeries.

In addition to the type of miNU, we collected various parameters for analysis, including age, gender, chronic kidney disease (CKD) stage, bladder cancer history, preoperative hydronephrosis, tumor location, tumor size, tumor focality, bladder cuff status and important pathological features, such as cytology, tumor grade, pathological T stage, lymph node involvement, histological variant, concomitant carcinoma in situ (CIS), lymphovascular invasion (LVI) and tumor necrosis. The grade of postoperative complications and the length of hospital stay were also recorded for comparison.

Definitions and Endpoints

The specimens obtained from miNU were examined by genitourinary pathologists using the same criteria. The pathological staging was based on the 2010 TNM (tumor, lymph node, metastasis) system, and the tumor grade was defined according to the 2004 World Health Organization/International Society of Urologic Pathology consensus classification. The postoperative complications were graded by Clavien-Dindo classification. The regular follow-up program strictly follows the standard guidelines. The endpoint was to compare the oncological outcomes between HALNU, LNU and RNU, including overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). The cause of death was determined by the attending doctor or death certificate. The probability of high-grade surgical complications, paralytic ileus, and postoperative end-stage renal disease (ESRD) among the groups was also analyzed.

Statistical Analysis

We used one-way ANOVA (analysis of variance) and Pearson’s chi-square test for continuous and categorical variables to compare differences between groups. The Kaplan-Meier estimator was used to estimate the survival function from time-to-event data, and different survival curves were compared using the log-rank test. The Cox proportional hazards model was selected to evaluate the impact of surgical approaches on the prognosis, without or with correction for confounding factors. A binary logistic regression model was used to compare the risks of postoperative complications in the three groups. We used IBM SPSS Statistics software version 26 for analysis. All statistical analyses were two-tailed, and p <0.05 was considered significant. Variables showing statistical significance were included in the adjustment for multivariate analysis.


In Table 1, we compared the clinical and pathological characteristics of patients receiving NU with three different MIS techniques. There were 741, 458 and 141 cases in the HALNU, LNU and RNU groups, respectively. In cytology (p = 0.023), hydronephrosis (p <0.001), tumor location (p <0.001), tumor grade (p = 0.015), pathological N stage (p <0.001), histological variant (p = 0.001), and CIS (p <0.001), there were significant differences between the three groups. Of note, the HALNU group had the lowest rate of lymphadenectomy (17.4%).


Table 1 Clinicopathological data of UTUC patients receiving minimally invasive nephroureterectomy.

Univariate Survival Analysis

Kaplan-Meier analysis showed that OS (p = 0.010) and CSS (p = 0.037) were significantly different between the three miNU groups (Figures 1A, B). The 5-year OS and CSS rates of HALNU were 71% and 80%, respectively, LNU were 74% and 86%, and RNU were 82% and 87%. In univariate analysis, the significant factors for both OS and CSS were age, CKD, history of bladder cancer, hydronephrosis, pathological T and N stages, histologic variant, LVI, tumor necrosis and types of surgery (Table 2, all p <0.05). As for BRFS, there was no statistical difference between the groups (Figure 1C, p = 0.822). Gender, bladder cancer history, tumor location, tumor focality, histologic variant, and CIS were significantly associated with bladder recurrence (Table 2, all p <0.05).


Figure 1 Compare Kaplan-Meier curves between patients receiving different minimally invasive nephroureterectomy by log-rank test. (A) Overall survival, p = 0.010. (B) Cancer-specific survival, p = 0.037. (C) Bladder recurrence-free survival, p = 0.822.


Table 2 Comparative univariate survival analysis of UTUC patients receiving minimally invasive NU.

Multivariate Survival Analysis

As shown in Table 3, CKD was a prognostic factor of OS (p <0.001) rather than CSS, while tumor size (p = 0.009) and focality (p = 0.043) were significant for CSS but not for OS. The independent significant parameters for both OS and CSS were age (p <0.001; p = 0.008), history of bladder cancer (p = 0.001; p <0.001), hydronephrosis (p = 0.005; p = 0.010), pathological T stage (p <0.001; p <0.001), pathological N stage (p = 0.031; p = 0.006), histological variant (p = 0.030; p = 0.004), LVI (p = 0.028; p = 0.017), and type of surgery (p = 0.007; p = 0.047). Specifically, after adjusting for various confounding factors, patients receiving HALNU had the worst OS and CSS. In multivariate analysis, different MIS approaches had no effect on bladder recurrence (p = 0.829). Instead, gender (p <0.001), bladder cancer history (p = 0.002), histologic variant (p = 0.038), and CIS (p = 0.026) were significantly correlated with BRFS.


Table 3 Comparative multivariate survival analysis of UTUC patients receiving minimally invasive NU.

Postoperative Complications

There were significant differences in postoperative complications and hospital stay according to the MIS methods (Table 1). HALNU was significantly associated with higher Clavien-Dindo complications (p = 0.033), more paralytic ileus (p = 0.034), more postoperative ESRD (p = 0.001), and longer hospital stay (p = 0.002). Through logistic regression (Table 4), the HALNU group also had the highest risk of major complications (p = 0.011), ileus (p = 0.012), and ESRD (p <0.001). After correcting the confounders that can affect postoperative renal function, namely CKD and hydronephrosis, the HALNU approach still had a significantly higher chance of ESRD than the LNU or RNU method (p <0.001).


Table 4 Comparative univariate/multivariate logistic regression analysis for postoperative complications.


ONU with bladder cuff excision is the standard of treatment for UTUC. With the development of new surgical techniques, miNU has become a popular method. However, the efficacy and safety of MIS approach for locally advanced UTUC has been a concern. In the latest version of guideline, T3/T4 and/or node-positive tumors are contraindications for LNU (1). The study of Shigeta et al. conducted a subgroup analysis and the results showed that CSS and BRFS rates of the LNU group in T3 patients were lower than those of the ONU group (13). Similarly, Kim et al. demonstrated that in pT3/T4 patients, the 5-year OS and CSS rates in the LNU group were lower than those in the ONU group (14). Therefore, concerns about compromised oncological integrity may prevent surgeons from choosing MIS for these patients. Nevertheless, several studies have reported comparable oncological outcomes for open and MIS approaches (6, 1517), which are believed to depend on following rigorous oncological principles.

The results of our multi-institution series indicated that both LNU and RNU had better survival rates than HALNU in multivariate analysis, and underlying plausible reasons were hypothesized. The first assumption is that the quality of lymph node dissection (LND), which can be affected by surgical methods and lead to prognostic variations. In patients undergoing radical prostatectomy for prostate cancer, a large difference in pelvic LND between open and MIS approaches (83.1% vs 16.9%) was reported (18). Although the benefits of conventional lymphadenectomy for UTUC were controversial, a meta-analysis concluded that LND may prolong CSS in patients with muscle-invasive disease (19). This concept was supported by previous studies. Abe et al. showed that when performing regional LND, the survival outcome between LNU and ONU was equivalent (20). In the study of Kim et al. (14), the worse OS and CSS in the LNU group may be attributed to the lower LND rate (13.0%) compared with the ONU group (21.0%). In addition, previous studies demonstrated that LND was more likely to be performed with robot assistance, resulting in higher lymph node yield than other MIS (11, 7 and 5 nodes were obtained with RNU, LNU and HALNU, respectively) (7, 10). In our study, a similar trend was found in the proportion of lymphadenectomy with different miNU (RNU: 41.1%, LNU: 32.5%, HALNU: 17.4%; p <0.001), and the RNU group did have the highest LND rate. In a large population cohort of 16,619 UTUCs, 15.4% of cases underwent LND (10). It can be inferred that although the proportion of LND in our HALNU group is not low, meticulous LND in the LNU and RNU groups may translate into better survival outcomes.

The probability of carrying out LND in different MIS may also be related to the surgeon’s experience. When performing minimally invasive radical prostatectomy, Prasad et al. proved that high-volume surgeons were more likely to execute pelvic LND than low-volume surgeons (27.7% vs 5.7%) (18). In this cohort, the enrolled cases spanned 20 years, and therefore multiple surgeons were included. LNU and RNU were generally performed by experienced hands who can accomplish LND proficiently. On the contrary, most surgeons can perform HALNU with ease, but a considerable number of inexperienced surgeons may be responsible for a relatively lower LND rate, leading to a worse prognosis.

For tumor extraction, an endobag will be used to retrieve the specimen during LNU and RNU. However, when performing HALNU, the specimen will not be placed in an isolation bag before it is removed by hand through the hand port. Therefore, HALNU may have a higher risk of inadvertent tumor contamination or spillage into adjacent tissues. An article from Japan indicated that the recurrence-free survival of HALNU was significantly lower than that of LNU (21). In addition, the higher incidence of high-grade complications in the HALNU group may be related to poor survival. Lastly, patients undergoing HALNU had significantly worse renal function during the postoperative follow-up period compared with the LNU or RNU groups. Impaired renal function was associated with an increase in cardiovascular events (22) and hindered the use of cisplatin-based adjuvant chemotherapy, both of which caused a worse prognosis. Based on these assumptions, our results indicated that LNU and RNU can achieve better survival outcomes than HALNU.

Postoperative systemic therapies may affect clinical outcomes. In the HALNU, LNU, and RNU groups, 165 (22.3%), 112 (24.5%), and 34 (24.1%) patients received chemotherapy after surgery, and 7 (0.9%), 3 (0.7%), and 1 (0.7%) patients received postoperative immunotherapy. There was no statistical difference in systemic treatment between the three groups (p = 0.894). We attempted to incorporate this factor for analysis and found that the use of systemic therapy is harmful to survival outcomes, which is obviously unreasonable. We suppose the main reason is that we are unable to determine whether these therapies are used for adjuvant, salvage or palliative purpose. Therefore, we did not include this parameter in the multivariate analysis.

Compared with ONU, miNU has advantages in perioperative results, such as less bleeding and faster recovery. Among different miNU, our results showed that HALNU had the longest hospital stay, which may be related to more pain caused by a large incision and hand manipulation. Patients receiving HALNU also had more postoperative ileus. If more opioid analgesics are given because of wound pain, gastrointestinal motility may decrease (23). Direct hand contact with the intestines can trigger local inflammation, which in turn impairs bowel movements (24). In addition, the major Clavien-Dindo complications were highest in HALNU and lowest in RNU. Three-dimensional vision, greater flexibility, instrument accuracy, and better ergonomics of RNU may translate into lower complications (25, 26). A meta-analysis of NU techniques has demonstrated that RNU has a low incidence of intraoperative complications (7). In short, it is assumed that more delicate surgical procedures can reduce postoperative complications.

In our study, there was no significant difference in preoperative renal function between the three MIS groups, but patients who received HALNU had a higher incidence of postoperative ESRD. In theory, removal of the diseased kidney will activate the compensatory hyperfiltration and hypertrophy of the other kidney, so the decline in renal function is tolerable if the contralateral kidney is healthy. It has been reported that the estimated glomerular filtration rate of American patients after NU has decreased by an average of 24% (27). However, when comparing the renal outcome of patients with renal cell carcinoma and UTUC in Taiwan after radical surgery, the latter had a significantly higher rate of worsening renal function or ESRD (28). The endemic specific risk factors of UTUC in Taiwan, including arsenic contamination in drinking water and herbs containing aristolochic acid, are potential culprits; a dose-dependent association between the two and CKD has been demonstrated (29, 30). After long-term exposure to these nephrotoxic carcinogens, UTUC can precede renal dysfunction, leading to postoperative renal function deterioration. HALNU was common decades ago, but LNU and RNU gradually became popular after the Taiwan government banned aristolochic acid in 2003. Therefore, the poor renal outcome in the HALNU group may be due to the continuous renal damage caused by carcinogenic nephrotoxin.

Although this study provides important insights for comparing MIS techniques of NU, it does have some limitations. First, it is carried out in retrospective design. Second, RNU is a relatively new approach and is being increasingly implemented, so there are fewer patients in this group and the follow-up period is shorter. Third, despite the large case number, this study involves multiple institutions, spanning 2 decades, and inevitably has a heterogeneous background. Differences in the experience of multiple surgeons may also be a source of bias. Lastly, we do not know the exposure dose of endemic risk factors, so we cannot assess the indolent damage to the kidneys of these carcinogenic nephrotoxins. Nevertheless, this is by far the largest cohort formed by miNU. All previous studies larger than ours came from database analysis and usually lacked key clinical, pathological and oncological information for each patient. As the first and largest cohort to compare the outcomes between HALNU, LNU and RNU, this study was strengthened by comprehensively correcting the effects of confounding covariates.

There is evidence that miNU is safe and feasible to treat UTUC. We demonstrated that compared with LNU and RNU, HALNU has a worse survival rate and more postoperative complications. The quality of LND, surgeon experience, the use of endobag, direct contact with hands and intestines, and exposure to nephrotoxic carcinogens are all possible factors that can explain our findings. It is essential to adhere to the oncological principle with skilled techniques during the operation, and subtle and careful surgery can achieve better outcomes.

Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics Statement

The studies involving human participants were reviewed and approved by Kaohsiung Medical University Hospital [KMUHIRB-E(I)-20180214]. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

Author Contributions

Y-CT, TH, and H-CY conceived the project. All authors collected the data. H-CY analyzed the results. H-YL and C-CL drafted the manuscript. H-CY edited the manuscript. All authors contributed to the article and approved the submitted version.


This study was supported by Kaohsiung Municipal Ta-Tung Hospital (kmtth-109-R04) and supported partially by the Ministry of Science and Technology (MOST 109-2314-B-037-095), Kaohsiung Medical University (KMU-KI109002), Kaohsiung Medical University Hospital (KMUH-DK(C)110006), Kaohsiung Medical University Regenerative Medicine and Cell Therapy Research Center (KMU-TC109A02), and Kaohsiung Medical University Center for Liquid Biopsy and Cohort Research (KMU-TC109B05).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We thank Dr. Yu-Tsai Li for statistical assistance and all members of the Taiwan Upper Tract Urothelial Carcinoma Collaboration Group. All members of the Taiwan Upper Tract Urothelial Carcinoma Collaboration group: Allen W. Chiu, Bing-Juin Chiang, Chao-Hsiang Chang, Chao-Yuan Huang, Cheng-Huang Shen, Cheng-Kuang Yang, Cheng-Ling Lee, Chen-Hsun Ho, Che-Wei Chang, Chia-Chang Wu, Chieh-Chun Liao, Chien-Hui Ou, Chih-Chen Hsu, Chih-Chin Yu, Chih-Hung Lin, Chih-Ming Lu, Chih-Yin Yeh, Ching-Chia Li, Chi-Ping Huang, Chi-Rei Yang, Chi-Wen Lo, Chuan-Shu Chen, Chung-Hsin Chen, Chung-You Tsai, Chung-Yu Lin, Chun-Hou Liao, Chun-Kai Hsu, Fang-Yu Ku, Hann-Chorng Kuo, Han-Yu Weng, Hao-Han Chang, Hong-Chiang Chang, Hsiao-Jen Chung, Hsin-Chih Yeh, Hsu-Che Huang, Ian-Seng Cheong, I-Hsuan Alan Chen, Jen-Kai Fang, Jen-Shu Tseng, Jen-Tai Lin, Jian-Hua Hong, Jih-Sheng Chen, Jungle Chi-Hsiang Wu, Kai-Jie Yu, Keng-Kok Tan, Kuan-Hsun Huang, Kun-Lin Hsieh, Lian-Ching Yu, Lun-Hsiang Yuan, Hao-Lun Luo, Marcelo Chen, Min-Hsin Yang, Pai-Yu Cheng, Po-Hung Lin, Richard Chen-Yu Wu, See-Tong Pang, Shin-Hong Chen, Shin-Mei Wong, Shiu-Dong Chung, Shi-Wei Huang, Shuo-Meng Wang, Shu-Yu Wu, Steven Kuan-Hua Huang, Ta-Yao Tai, Thomas Y. Hsueh, Ting-En Tai, Victor Chia-Hsiang Lin, Wei-Chieh Chen, Wei-Ming Li, Wei-Yu Lin, Wen-Hsin Tseng, Wen-Jeng Wu, Wun-Rong Lin, Yao-Chou Tsai, Yen-Chuan Ou, Yeong-Chin Jou, Yeong-Shiau Pu, Yi-Chia Lin, Yi-Hsuan Wu, Yi-Huei Chang, Yi-sheng Lin, Yi-Sheng Tai, Yu-Khun Lee, Yuan-Hong Jiang, Yu-Che Hsieh, Yu-Chi Chen, Yu-Ching Wen, Yung-Tai Chen, Zhe-Rui Yang.


1. Rouprêt M, Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update. Eur Urol (2021) 79:62–79. doi: 10.1016/j.eururo.2020.05.042

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Lee HY, Yeh HC, Wu WJ, He JS, Huang CN, Ke HL, et al. The Diagnostic Ureteroscopy Before Radical Nephroureterectomy in Upper Urinary Tract Urothelial Carcinoma Is Not Associated With Higher Intravesical Recurrence. World J Surg Oncol (2018) 16:135. doi: 10.1186/s12957-018-1411-9

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E, et al. Outcomes of Radical Nephroureterectomy: A Series From the Upper Tract Urothelial Carcinoma Collaboration. Cancer (2009) 115:1224–33. doi: 10.1002/cncr.24135

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Ni S, Tao W, Chen Q, Liu L, Jiang H, Hu H, et al. Laparoscopic Versus Open Nephroureterectomy for the Treatment of Upper Urinary Tract Urothelial Carcinoma: A Systematic Review and Cumulative Analysis of Comparative Studies. Eur Urol (2012) 61(6):1142–53. doi: 10.1016/j.eururo.2012.02.019

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Walton TJ, Novara G, Matsumoto K, Kassouf W, Fritsche H-M, Artibani W, et al. Oncological Outcomes After Laparoscopic and Open Radical Nephroureterectomy: Results From an International Cohort. BJU Int (2011) 108:406–12. doi: 10.1111/j.1464-410X.2010.09826.x

PubMed Abstract | CrossRef Full Text | Google Scholar

6. Lee H, Kim HJ, Lee SE, Hong SK, Byun SS. Comparison of Oncological and Perioperative Outcomes of Open, Laparoscopic, and Robotic Nephroureterectomy Approaches in Patients With Non-Metastatic Upper-Tract Urothelial Carcinoma. PLoS One (2019) 14:e0210401. doi: 10.1371/journal.pone.0210401

PubMed Abstract | CrossRef Full Text | Google Scholar

7. Veccia A, Antonelli A, Francavilla S, Simeone C, Guruli G, Zargar H, et al. Robotic Versus Other Nephroureterectomy Techniques: A Systematic Review and Meta-Analysis of Over 87,000 Cases. World J Urol (2020) 38:845–52. doi: 10.1007/s00345-019-03020-1

PubMed Abstract | CrossRef Full Text | Google Scholar

8. Braun AE, Srivastava A, Maffucci F, Kutikov A. Controversies in Management of the Bladder Cuff at Nephroureterectomy. Transl Androl Urol (2020) 9(4):1868–80. doi: 10.21037/tau.2020.01.17

PubMed Abstract | CrossRef Full Text | Google Scholar

9. Rassweiler JJ, Teber D. Advances in Laparoscopic Surgery in Urology. Nat Rev Urol (2016) 13:387–99. doi: 10.1038/nrurol.2016.70

PubMed Abstract | CrossRef Full Text | Google Scholar

10. Pearce SM, Pariser JJ, Patel SG, Steinberg GD, Shalhav AL, Smith ND. The Effect of Surgical Approach on Performance of Lymphadenectomy and Perioperative Morbidity for Radical Nephroureterectomy. Urol Oncol Semin Orig Investig (2016) 34:121.e15–21. doi: 10.1016/j.urolonc.2015.09.008

CrossRef Full Text | Google Scholar

11. Tinay I, Gelpi-Hammerschmidt F, Leow JJ, Allard CB, Rodriguez D, Wang Y, et al. Trends in Utilisation, Perioperative Outcomes, and Costs of Nephroureterectomies in the Management of Upper Tract Urothelial Carcinoma: A 10-Year Population-Based Analysis. BJU Int (2016) 117:954–60. doi: 10.1111/bju.13375

PubMed Abstract | CrossRef Full Text | Google Scholar

12. Lenis AT, Donin NM, Faiena I, Salmasi A, Johnson DC, Drakaki A, et al. Role of Surgical Approach on Lymph Node Dissection Yield and Survival in Patients With Upper Tract Urothelial Carcinoma. Urol Oncol (2018) 36:9.e1–9. doi: 10.1016/j.urolonc.2017.09.001

CrossRef Full Text | Google Scholar

13. Shigeta K, Kikuchi E, Abe T, Hagiwara M, Ogihara K, Anno T, et al. Long-Term Oncologic Outcomes of Laparoscopic Versus Open Radical Nephroureterectomy for Patients With T3N0M0 Upper Tract Urothelial Carcinoma: A Multicenter Cohort Study With Adjustment by Propensity Score Matching. Ann Surg Oncol (2019) 26:3774–81. doi: 10.1245/s10434-019-07623-1

PubMed Abstract | CrossRef Full Text | Google Scholar

14. Kim HS, Ku JH, Jeong CW, Kwak C, Kim HH. Laparoscopic Radical Nephroureterectomy Is Associated With Worse Survival Outcomes Than Open Radical Nephroureterectomy in Patients With Locally Advanced Upper Tract Urothelial Carcinoma. World J Urol (2016) 34:859–69. doi: 10.1007/s00345-015-1712-3

PubMed Abstract | CrossRef Full Text | Google Scholar

15. Rai BP, Shelley M, Coles B, Biyani CS, El-Mokadem I, Nabi G. Surgical Management for Upper Urinary Tract Transitional Cell Carcinoma. Cochrane Database Syst Rev (2011) (4):CD007349. doi: 10.1002/14651858.CD007349.pub2

PubMed Abstract | CrossRef Full Text | Google Scholar

16. Kitamura H, Maeda T, Tanaka T, Fukuta F, Kobayashi K, Nishiyama N, et al. Comparison of Laparoscopic, Hand-Assisted, and Open Surgical Nephroureterectomy. JSLS (2014) 18:288–93. doi: 10.4293/108680813X13794522666842

PubMed Abstract | CrossRef Full Text | Google Scholar

17. Miyazaki J, Nishiyama H, Fujimoto H, Ohyama C, Koie T, Hinotsu S, et al. Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association. J Endourol (2016) 30:520–5. doi: 10.1089/end.2015.0757

PubMed Abstract | CrossRef Full Text | Google Scholar

18. Prasad SM, Keating NL, Wang Q, Pashos CL, Lipsitz S, Richie JP, et al. Variations in Surgeon Volume and Use of Pelvic Lymph Node Dissection With Open and Minimally Invasive Radical Prostatectomy. Urology (2008) 72:647–52. doi: 10.1016/j.urology.2008.03.067

PubMed Abstract | CrossRef Full Text | Google Scholar

19. Yang D, Chen Q, Song X, Wang J, Che X, Zhu Z, et al. Effect of Lymph Node Dissection on the Outcomes of Upper Tract Urothelial Carcinomas: A Meta-Analysis. Expert Rev Anticancer Ther (2014) 14:667–75. doi: 10.1586/14737140.2014.895670

PubMed Abstract | CrossRef Full Text | Google Scholar

20. Abe T, Kondo T, Harabayashi T, Takada N, Matsumoto R, Osawa T, et al. Comparative Study of Lymph Node Dissection, and Oncological Outcomes of Laparoscopic and Open Radical Nephroureterectomy for Patients With Urothelial Carcinoma of the Upper Urinary Tract Undergoing Regional Lymph Node Dissection. Jpn J Clin Oncol (2018) 48:1001–11. doi: 10.1093/jjco/hyy128

PubMed Abstract | CrossRef Full Text | Google Scholar

21. Kamihira O, Hattori R, Yamaguchi A, Kawa G, Ogawa O, Habuchi T, et al. Laparoscopic Radical Nephroureterectomy: A Multicenter Analysis in Japan. Eur Urol (2009) 55:1397–407. doi: 10.1016/j.eururo.2009.03.003

PubMed Abstract | CrossRef Full Text | Google Scholar

22. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. N Engl J Med (2004) 351:1296–305. doi: 10.1056/NEJMoa041031

PubMed Abstract | CrossRef Full Text | Google Scholar

23. de Boer HD, Detriche O, Forget P. Opioid-Related Side Effects: Postoperative Ileus, Urinary Retention, Nausea and Vomiting, and Shivering. A Review of the Literature. Best Pract Res Clin Anaesthesiol (2017) 3:499–504. doi: 10.1016/j.bpa.2017.07.002

CrossRef Full Text | Google Scholar

24. Bauer AJ, Boeckxstaens GE. Mechanisms of Postoperative Ileus. Neurogastroenterol Motil (2004) 16(Suppl 2):54–60. doi: 10.1111/j.1743-3150.2004.00558.x

PubMed Abstract | CrossRef Full Text | Google Scholar

25. De Groote R, Decaestecker K, Larcher A, Buelens S, De Bleser E, D'Hondt F, et al. Robot-Assisted Nephroureterectomy for Upper Tract Urothelial Carcinoma: Results From Three High-Volume Robotic Surgery Institutions. J Robot Surg (2020) 14:211–9. doi: 10.1007/s11701-019-00965-8

PubMed Abstract | CrossRef Full Text | Google Scholar

26. Autorino R, Zargar H, Kaouk JH. Robotic-Assisted Laparoscopic Surgery: Recent Advances in Urology. Fertil Steril (2014) 102:939–49. doi: 10.1016/j.fertnstert.2014.05.033

PubMed Abstract | CrossRef Full Text | Google Scholar

27. Lane BR, Smith AK, Larson BT, Gong MC, Campbell SC, Raghavan D, et al. Chronic Kidney Disease After Nephroureterectomy for Upper Tract Urothelial Carcinoma and Implications for the Administration of Perioperative Chemotherapy. Cancer (2010) 116:2967–73. doi: 10.1002/cncr.25043

PubMed Abstract | CrossRef Full Text | Google Scholar

28. Lee KH, Chen YT, Chung HJ, Liu JS, Hsu CC, Tarng DC. Kidney Disease Progression in Patients of Upper Tract Urothelial Carcinoma Following Unilateral Radical Nephroureterectomy. Ren Fail (2016) 38:77–83. doi: 10.3109/0886022X.2015.1103638

PubMed Abstract | CrossRef Full Text | Google Scholar

29. Lai MN, Lai JN, Chen PC, Hsieh SC, Hu FC, Wang JD. Risks of Kidney Failure Associated With Consumption of Herbal Products Containing Mu Tong or Fangchi: A Population-Based Case-Control Study. Am J Kidney Dis (2010) 55:507–18. doi: 10.1053/j.ajkd.2009.10.055

PubMed Abstract | CrossRef Full Text | Google Scholar

30. Hsu LI, Hsieh FI, Wang YH, Lai TS, Wu MM, Chen CJ, et al. Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study. Am J Kidney Dis (2017) 70:787–97. doi: 10.1053/j.ajkd.2017.06.012

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: laparoscopic, robotic, nephroureterectomy, upper tract urothelial carcinoma, hand-assisted

Citation: Li C-C, Chang C-H, Huang C-P, Hong J-H, Huang C-Y, Chen I-HA, Lin J-T, Lo C-W, Yu C-C, Tseng J-S, Lin W-R, Wu W-C, Chung S-D, Hsueh TY, Chiu AW, Chen Y-T, Chen S-H, Jiang Y-H, Tsai Y-C, Chiang B-J, Lin WY, Jou Y-C, Wu C-C, Lee H-Y and Yeh H-C (2021) Comparing Oncological Outcomes and Surgical Complications of Hand-Assisted, Laparoscopic and Robotic Nephroureterectomy for Upper Tract Urothelial Carcinoma. Front. Oncol. 11:731460. doi: 10.3389/fonc.2021.731460

Received: 27 June 2021; Accepted: 06 September 2021;
Published: 04 October 2021.

Edited by:

Lu Yang, Sichuan University, China

Reviewed by:

En Meng, National Defense Medical Center, Taiwan
Jeremy Teoh, The Chinese University of Hong Kong, China

Copyright © 2021 Li, Chang, Huang, Hong, Huang, Chen, Lin, Lo, Yu, Tseng, Lin, Wu, Chung, Hsueh, Chiu, Chen, Chen, Jiang, Tsai, Chiang, Lin, Jou, Wu, Lee and Yeh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Hsiang-Ying Lee,; Hsin-Chih Yeh,

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.