Risk Factors for Severe 30-d Complications After Minimally Invasive Radical Cystectomy With Ileal Conduit


 Background: To investigate the risk factors for severe complications within 30 days in patients receiving minimally invasive radical cystectomy with ileal conduit(MIRCIC).Methods: 270 consecutive patients who underwent MIRCIC between January 1, 2013 and August 1, 2020 were included. All complications were graded according to the Clavien-Dindo classification(CDC). The comprehensive complication index(CCI) for all complications in each patient was calculated. CDC ≥ Ⅲ or CCI > 33.7 were considered to be severe complications. Univariate and multivariate analysis were conducted by SPSS26.Results: A total of 691 complications were collected from 236 patients and the corresponding overall complications rate was 87.41% (236/270). Patients with CDC ≥ Ⅲ accounted for 23.70% and the incidence of CCI > 33.7 was 22.96%. For the highest CDC grade ≥ Ⅲ, in univariate analysis, the following seven variants were enrolled in a multivariate analysis: BMI (P=0.010), baseline albumin(P=0.065), pT (P=0.082), pN (P=0.026), pTNM (P=0.016), intraoperative blood transfusion (P=0.031), estimated blood loss (P=0.001). In multivariate analysis, BMI ≥ 30kg/m2 (P=0.012) and estimated blood loss ≥ 400ml (P=0.005) were the independent risk factors of CDC ≥ Ⅲ. Hydronephrosis (P=0.050), BMI (P=0.006), pT (P=0.004), pN (P=0.019), pTNM (P=0.000), operative time (P=0.030), estimated blood loss (P=0.001) were the relevant factors in CCI > 33.7. However, BMI ≥ 30kg/m2 (P=0.004) and estimated blood loss (P=0.002) were the independent risk factors of CCI > 33.7.Conclusion: BMI ≥ 30kg/m2 and estimated blood loss ≥ 400ml were found to be independent predictors of 30-d severe complications (CDC ≥ Ⅲ or CCI > 33.7) in patients who underwent MIRCIC.


Surgery
We performed a ve-port technique for both LRC and RARC(one port for the assistant): a 12-mm trocar was placed at 2cm above the navel edge for the camera, the two operating trocar were placed at the navel level with four transverse nger away from the camera port. The forth trocar was placed above the left iliac crest. The last trocar was located on the inner side of the right iliac crest to facilitate the sticking of the ostomy bag. Patient was placed in a steep Trendelenburg (30°) position after establishing the pneumoperitoneum. Severed the ureters close to the bladder; transected seminal vesicles and vasdeferens; detached the dorsal side of the bladder and prostate under the Denonvilliers fascia; clipped the superior vesical arteries; separated and severed lateral ligament of bladder; transected and severed the dorsal venous complex; divided prostatic apex and urethra. The excision for women covers the uterus, fallopian tubes, ovaries, bladder, front vaginal wall and urethra. All patients underwent extracorporeal ileal conduit and standard pelvic lymph node dissection [10] .

Statistical analysis
Categorical variables were presented as the frequency (ratio). Univariate analysis was performed by using chi-square test or sher exact method, and factors with p < 0.1 were admitted into multivariate analysis, which was performed by binary logistic regression model. IBM SPSS26 statistics software was used for statistical analysis and p < 0.05 suggested a statistical difference in the study.   Table 2).

Discussion
MIRC has become a mainstream surgical option for bladder cancer patients with curative intent in most medical centers, because its effectiveness and safeness have been well demonstrated, namely less pain, smaller trauma and quicker recovery [2][3][4][5][6][7][8][9] . The history of LRC can be traced back to 1992 [18] , despite the advantages mentioned above, it has a higher demand on surgeons both in anatomical knowledge and endoscopic skills. The rst robotic surgery system was approved into clinical use in 1994 [19] , and surgical robot provides us with exible mechanical arms and 3-Demesion vision. There was no signi cant difference in effectiveness and safety between RARC and LRC based on the current pooled evidence: the surgery duration, positive surgical margin rate, postoperative recovery and complications were comparable for both approaches [20] . Urinary diversion is a critical step after bladder removal and the choice should take into account the patient's wishes, age, underlying diseases, tumor stage and life expectancy. Ileal conduit is one of the most classic and widely used urinary diversion procedures following bladder resection [10,12] .
The incidence of overall 30-d complications was 87.41% (236/270) in our center, but CDC grade and complications accounted for 87% (606/691). Similarly, a single-center retrospective study captured 2485 complications in 506 patients with a 99.4% (503/506) 30-d complications rate, whereas 84% of them were CDC grade or [13] . However, the 30-d complications rates of MIRC in ve articles included in a meta-analysis were 41.2% (14/34), 66.7% (26/39), 15% (3/20), 43% (52/121) and 45.5% (5/11), respectively [20] . There was still a distinct discrepancy in reporting of complications after radical cystectomy [21] , because those minor complications were neglected by researchers who held such views that single low-lever complication doesn't necessarily impair the postoperative course of patients. Vetterlein et al pointed out that the occurrence of massive minor complications doesn't mean treatment failure, and detailed documentation of postoperative adverse events that potentially damage recovery and quality of life of patients is essential for patient consultation, clinical trial design and treatment e ciency assessment [13] . Besides, severe complication, which can cause serious physical, psychological and nancial harm to patients, is surgeons' greatest concern and patients' least desire. The primary purpose of this study was to investigate risk factors for severe complications within 30 days after MIRCIC.
CDC is currently the most commonly used complication assessment method, and numerous studies incorporate CDC ≥ into "major complication". A retrospective research of Zhang et al. included 298 cases of MIRC and revealed that the proportion of patients with major complication was 15.1% (45/298) [22] . Su et al. reviewed the clinical data of 126 patients with LRC and 189 patients with RACRC, and found an rate of 7.62% (24/315) about postoperative overall major complications [23] . In contrast, the ratio of patients with CDC ≥ III was higher in our study(23.70% ,64/270). The reason may be that we had an rigorous inclusion criteria for the method of urinary diversion, while 55.7% and 25.7% of other types of diversion were involved in the above two studies, respectively. The occurrence rate of gastrointestinal complications after radical cystectomy was about 29% [24] . Svatek et al.
performed a study involving 283 patients undergoing open radical cystectomy and indicated that the incidence of postoperative paralytic ileus was 15.2% [25] .Furthermore, BMI (95%CI: 1.03-1.17, P =.007) and age (95%CI: 1.02-1.16, P =.008) were independent risk factors of paralytic ileus [25] . In this paper, our results con rmed that the most common major complication was ileus with an rate of 23.70% (64/270), and BMI ≥ 30 kg/m 2 (95% CI: 1.216 5.032, P = 0.012) and estimated blood loss ≥ 400ml (95% CI: 1.367 5.992, P = 0.005) were the independent predictors of CDC ≥ . Increased BMI was associated with higher postoperative complication rates, comprising infection-related diseases, wound-related diseases, acute kidney injury and paralytic ileus [26] . In the article of Lenardis et al., the major complication was de ned as one of the following postoperative events: cardiac or neurological complications, reoperation and death [27] . Patients with BMI ≥ 30kg/m2 were signi cantly more likely to undergo major complications within 30 days after radical cystectomy than those with normal BMI(OR 1.59, 95% CI 1.17-2.16) [27] . Likewise, Arora and colleagues published their study with 2055 patients receiving radical cystectomy, and they suggested that a high BMI was highly correlated with 30-d mortality and morbidity [28] . In minimally invasive surgery, even a small amount of bleeding can seriously impair the clarity of operative visual led due to the magni cation of camera lens. Lin et al. conducted a prospective randomized controlled trial and asserted that the application of minimally invasive tool signi cantly reduced intraoperative blood loss compared to conventional open surgery(215ml vs 510ml,P<0.001) [2] . A latest meta-analysis veri ed that there was no signi cant difference in intraoperative blood loss between LRC and RARC (95%CI: -37.81-258.62, P=0.14) [20] . Wilson and workmates retrospectively analyzed the data of 2934 cases and deemed that perioperative blood transfusion was associated with increased morbidity(OR 1.361, 95% CI 1.131-1.638) [29] . Shen et al. concluded that the need for postoperative blood transfusion, rather than intraoperative blood transfusion, was independently associated with perioperative morbidity [30] . Intraoperative blood transfusion was not associated with the rate of 30-d severe complications but estimated blood loss was an independent predictor of 30-d severe complications(CDC ≥ or CCI > 33.7) in our study(OR 2.862, 95% CI 1.367-5.992; OR 2.904 95% CI 1.497-5.634). Reason may be that intraoperative blood product requirements were closely related to preoperative anaemia [30] , while the degree of anemia was relatively mild before surgery in our research, in which the median HB value was 129g/L(interquartile range: 116-140g/L). Secondly, postoperative blood transfusion may be due to massive intraoperative bleeding or other serious complications such as gastrointestinal bleeding, so, the inclusion of it in multiple logistic regression analysis may lead to greater bias. CCI is a new complication evaluation method developed on the basis of CDC, and it integrates all postoperative complications to obtain the cumulative morbidity, which is conducive to the comprehensive evaluation of patient recovery [15] . CCI values was positively associated with the number and grade of complications, and patients with CCI value exceeding 33.7 accounted for 20% [13] , which was also veri ed in this study. In addition, we further con rmed the feasibility of CCI in evaluating severe complications after radical surgery. BMI ≥ 30kg/m2 (95%CI: 1.411-6.510, P=0.004) and estimated blood loss ≥ 400ml (95%CI: 1.497-5.634, P=0.002) were also independent risk factors for patients with CCI >33.7. Therefore, it is necessary to evaluate and control BMI before MIRCIC, and to minimize the amount of blood loss during the operation.
Admittedly, there were several limitations to this study. Firstly, Our study was a single-center retrospective study with its inherent drawbacks. Secondly, different surgical habits and treatment ideas among the three surgeons may lead to some bias. Thirdly, the present study only included complications occurring within 30 days after MIRCIC. However, it is indubitably crucial to predict longterm procedure-speci c severe complications and survival outcomes. To address these limitations, a multicenter prospective study is necessary. Nevertheless, this study enriches the perioperative data of MIRCIC and provides valuable clinical information for bladder cancer patients and urologists.

Conclusion
BMI ≥ 30kg/m 2 and estimated blood loss ≥ 400ml were found to be independent predictors of 30-

Consent fore publication
A complete informed consent was obtained from the patient and their families before the surgery. Informed consent was signed for all patients.

Availability of date and materials
The datasets used and analysed during the current study are available from the corresponding author on reasonable request Competing interests Xiao Ming, Zhong Zhaohui, Ren Jiannan, Xiong Wei have no con ict of interest to declare.

Funding.
No funding was received.

Authors' contribution
Xiao Ming was responsible for study concepts,study design and the writing of the manuscript. Zhong Zhaohui was responsible for reviewing the article and proposing changes. Ren Jiannan collected and analyzed data. Xiong Wei was responsible for the starring revision of the article and study design. All authors read and approved the nal manuscript.