Application of three-dimensional reconstruction in partial nephrectomy, a systematic review and meta‑analysis

doi:10.21203/rs.3.rs-2630173/v1

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Application of three-dimensional reconstruction in partial nephrectomy, a systematic review and meta‑analysis

https://doi.org/10.21203/rs.3.rs-2630173/v1

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Three dimensional (3D) reconstruction is widely used in complicated renal surgery. This article focus on investigating the role of three-dimensional reconstruction participated in partial nephrectomy (PN) from a systematic review and meta-analysis. We searched the published studies that reported the relationship between 3D reconstruction and PN using PubMed, Embase and medline up to December 8, 2022. STATA version 12.0 was used to conduct all analyses. studies were finally progressed to data extraction, Meta-analysis indicated a significant reduction in operation time ([SMD] =-0.34; confidence interval [CI]: -0.59 to -0.09), global ischemia time ([SMD] =-0.42; CI: -0.64 to -0.21) and opening collecting system rate (OR 0.26, 95% CI 0.14 to 0.47). Estimated blood loss, GFR change, positive surgical margin, length of hospital stay, intraoperative complication were no statistically significant differences between 3d reconstruction assisted PN and 2D control group. Our study provides evidence that 3D reconstruction played an important role in PN, especially for complex renal tumors. However, more high-quality, larger sample size and more rigorous design randomized controlled trials which report this topic are still needed to support our conclusions.

Health sciences/Diseases/Kidney diseases/Renal cancer

Health sciences/Urology/Urogenital diseases/Renal cancer

Three dimensional (3D) reconstruction

Partial nephrectomy

Kidney cancer

Meta-analysis

Cancer, an incurable disease posed great threat to human, is characterized by uncontrolled proliferation of abnormal cells and aberrant recognition of the immune system. Kidney cancer is the cause of 5% of malignancies and is the sixth most common cancer in men. It is also the cause of 3% of malignancies and the tenth most common cancer in women¹. Renal cell carcinoma (RCC), the most common type, is divided into a number of different histological types. Clear cell (70–90%), papillary (10–15%) and chromophobe RCCs(3–5%)². The risk factors include age, gender³, location, ethnicity⁴, history of smoking⁵, etc. Despite the advances in diagnosis and treatment of kidney cancer, surgical treatment is still critical to the prognosis of it so far. How to resect tumor completely and protect renal function to the maximum extent has became a challenge.

PN is an important way to remove tumor and protect renal function. It recommend as the standard surgical treatment for clinical T1a renal tumors⁶. Also for larger renal tumors (T1b, T2) it provides equivalent cancer control and better preservation of renal function, with potential for better long-term survival⁷. So when technically feasible PN represents the standard of care for clinically T1 and T2 renal tumors. It has demonstrated that PN cause higher complications odds, including Bleeding, infection, atrophy, etc. The most serious complication is positive surgical margin. Therefore the crucial point is how to minimize the complications of PN. Conventional PN possesses some inherent disadvantages. Along with the development of imaging technology, especially the application of three-dimensional reconstruction technology, it provides hyper accurate vision, and greatly assists judgment of distance and visualization of anatomical layers and microstructures. The application of three-dimensional reconstruction may reduce the complication rates of PN.

Traditional computed tomography (CT) or magnetic resonance imaging (MRI) images were weak in describing anatomic structure for some complex tumors, such as renal hilar tumor and renal endophytic tumor. three-dimensional models based on CT or MRI facilitate the understanding of renal anatomy^8,9and are more accurate to assess with higher accuracy surgical complexity of renal masses^10,11. Whether three-dimensional reconstruction technology could become the standard evaluation method for PN of complex renal tumors, hence, we conducted a meta-analysis of the relevant studies by combining the results from the published studies to assess the application of three-dimensional reconstruction in PN.

Search strategy

We performed a systematic literature review up to December 2022 using PubMed and Embase, published studies that reported were used to identify application of three-dimensional reconstruction in PN.

Separate searches were performed as follows: Three-dimensional, 3D, 3D model, three-dimensional visualization, three-dimensional reconstruction, three-dimensional printing, partial nephrectomy, robot-assisted partial nephrectomy, laparoscopic partial nephrectomy.

Inclusion criteria

The studies that met the following criteria could be included: 1. a prospective cohort or retrospective study design; 2. present the comparison of Three-dimensional VS traditional 2D imageological examination (CT or MRI); 3. The outcome was based on operation time, ischemic time, estimated blood loss, decline in eGFR, length of stay, opening collecting system, positive surgical margin and complication. Exclusion criteria included the following items: basic research, without control group，without full text available， without relevant outcomes， without relevant operation mode. Two authors(Li Jia, Yang Xinliang) independently conducted this step, selecting studies that met the inclusion and exclusion criteria. Data extraction and quality assessment were conducted for the included studies. Disagreement on whether or not an article should be included was resolved using a third reviewer (Fang Zhenqiang).

Data extraction

For data extraction, the following information was extracted: author, publication year, Study period, Country, age, body mass index (BMI), sample size, operation time, ischemic time, estimated blood loss, decline in eGFR, length of stay, opening collecting system, positive surgical margin and complication.

Quality evaluation

Based on the evidence of each study, the quality of each study was determined using the Jadad scale¹² and NOS scoring rules¹³ for randomized controlled studies and non-randomized controlled studies. The total score of the Jadad scale is seven points. The score lower than four should be considered as a low-quality study,

it should be considered a high-quality study when the score higher than four. The total score of the NOS scale is nine stars, more than six stars should be considered as high-quality research.

Statistical analysis

STATA version 12.0 was used to conducted all analyses. Based on a random-effects model, the weighted mean difference (WMD) 95% confidence intervals was used as a summary measure for continuous outcomes, if the data was not available, the validated mathematical model was used for transforming the median, interquartile range (IQR), and range to mean (standard deviation)¹⁴. For binary variables, the odds ratio (OR) with 95% confidence interval (CI) was calculated. Statistical heterogeneity was defined based on the Cochrane Q p value or I2 statistic. All statistical tests were two-sided and P < 0.05 was considered statistically significant, except where otherwise specified.

Study characteristics

We initially identified 666 potential articles from Pubmed and Embase. After duplicated records excluded, 67 studies left then we Screened the titles, abstracts and topics. The full-texts were evaluated by the excluding criteria, a final 17 studies^15-31 embracing 714 cases and 801 controls were included for extracting data. The literature search and selection process as the flow chart is shown in Fig. 1. We show the included studies in Table 1, these studies were published from 2014 to 2022. Among them, 11 studies were retrospectively designed and the others were prospectively designed. All studies were based on Asia, Europe, and USA. The baseline data including publication year, Study period, Country, age, body mass index (BMI), operation mode, sample size. Also we have exhibited the final study quality scores based on Jadad scale and NOS scoring rules in Table 1.

Operative time

All the including studies have reported the results of the operative time in 3D (n=714) and non-3D group (n=801). A random effect model was used because the heterogeneity among studies is high (I2>50%). The final meta-analysis showed the operative time of Patients undergoing PN with 3D assisted was shorter than Patients undergoing PN without 3D (SMD -0.24, 95% CI –0.59 to –0.09; p < 0.001)( Fig. 2).

Ischemic time

There were 14 studies^{15,17-19,21-22,24-31} have reported the results of Ischemic time in 3D (n=633) and non-3D group (n=727). The heterogeneity among studies is high (I2 >50%), then a random effect model was used. The final meta-analysis showed the ischemic time of Patients undergoing PN with 3D assisted was shorter than Patients undergoing PN without 3D (SMD -0.42, 95% CI –0.64 to –0.21; p < 0.001) ( Fig. 3).

Estimated blood loss

There were 15 studies^{15,17-24,26-31} have showed the results of estimated blood loss in 3D (n=669) and non-3D group (n=756). The heterogeneity among studies is high (I2 >50%), then a random effect model was used. The result showed there was no significant difference of estimated blood loss of patients undergoing PN with or without 3D assisted (SMD -0.16, 95% CI –0.37 to 0.05; p < 0.001) (Fig. 4).

Decline in eGFR

There were 8 studies^{15,17-18,20,22,24,28,30} have showed the results of declining of eGFR in 3D (n=366) and non-3D group (n=433). The eGFR declining in patients undergoing PN with 3D or without 3D assisted was showed no significant difference (SMD -0.05, 95% CI –0.34 to 0.23; p < 0.001) (Fig. 5).

Length of hospital stay

The results of length of hospital stay including in 8 studies^{17, 18, 23, 26-30}. The final meta-analysis showed there was no significant difference of hospital stay length between 3D (n=441) and non-3D group (n=496) (SMD -0.03, 95% CI –0.82 to 0.77; p < 0.001). A random effect model was used because the heterogeneity among studies is high (I2 >50%) (Fig. 6).

Opening collecting system

Four studies compared PN with 3D (n = 169) to without 3D (n = 231) in the case opening collecting system^17,22-23,31. The heterogeneity among studies is low (I2 <50%), then a fixed effect model was used. The likelihood of opening collecting system was lower for PN with 3D (OR 0.26, 95% CI 0.14–0.47; p = 0.391) (Fig. 7).

Positive surgical margins and intraoperative complication

We extracted data on positive surgical margins from 8 studies^{17,19,22,25-26,29-31} (n(3D)=416,n(non-3D)=488) and intraoperative complications from 10 studies(17-18,22,24-26,28-31) (n(3D)=478,n(non-3D)=545). Fixed effect models were used based on the heterogeneity test. The final results indicated that there was no significant difference in positive surgical margin rate (OR 0.56, 95% CI 0.25–1.23; p = 0.958) and intraoperative complication rate (OR 0.75, 95% CI 0.45–1.26; p = 0.958) (Fig. 8.9).

With the attention to the treatment of protecting renal function for renal tumor, greater recognition of the importance of preservation of renal function alongside cancer control. By development and increasing use of minimally invasive techniques, those patients previously considered too complex or technically difficult became easy to approach. PN is now considered as the standard treatment for T1 tumors. Even for T2 tumors, PN provides equivalent cancer control and better preservation of renal function, with potential for better long-term survival³². However, PN has a higher incidence of complications.

Three dimensional reconstruction technology in amount of surgeries has become a reliable resource based on preoperative CT/MRI images of the patient. It also emerged as a technological tool with great potential to facilitate the performance of PN. This technique helps PN planning, predicting and anticipating difficulties, and finally increasing the success rate. However, this technology also has some controversial aspects. Some studies indicated that the operation time of PN with 3D assisted was longer than that in the without 3D group^{15, 16}. For ischemic time, some studies demonstrated that the time was longer in 3D group^{15, 24}. We conducted this meta-analysis including 17 studies to estimate PN with 3D assisted would be more secure.

For operation time, the pooled result of our meta-analysis including 17 studies showed that there was significant reduction in 3D group. Partial nephrectomy is a complex operation, before operation many decision points should be made according to the patient’s anatomy. 3D reconstruction could describe these anatomic structures vividly and realistically. Better decisions could be include, for example, selection of blood vessels for clamping, identification of appropriate vessels to ligate, and tumor resection margin and depth²¹. It was the main reason for shorter operation time in 3D group. In terms of global ischemia time, it was also shorter in PN with 3D assisted than in PN without 3D assisted. 3D models could visualize the arterial vasculature within the hilum, guiding in choosing the appropriate hilar approach and intraoperative target orientation during segmental artery clamping³³.

There was no significant difference of estimated blood loss between the two groups. Professor Yuan Ruan indicated that more blood loss was found in 3D-PN group in comparison with the control group²⁰. This technique of 3D-PN showed better arterial vasculature, so choosing segmental renal artery to clamp may slightly increase intraoperative blood loss compared with conventional PN. On the other hand, different of urinary drainage, tumor size, tumor location and surgical proficiency of the surgeon operating are also issues that cause this final result. For the decline of eGFR, there was also no significant difference between the two groups. eGFR changing based on the tumor size, tumor location, resection range. Patients undergoing PN with 3D or without 3D from each study were similar tumor size, R.E.N.A.L. score, all these may lead to this conclusion.

In terms of opening collecting system rate，there was significant reduction in 3D group. The merits of the 3D system including better hand–eye coordination, better depth perception, and more precise localization³⁴, so it facilitates surgical orientation and the surgeon’s decision-making, that may be the main reason of lower opening collecting system rate in 3D group. Nevertheless, our final result reveal that there was no significant difference of hospital stay length, positive surgical margin rate and intraoperative complication rate within the two groups. Traditionally, a 1-cm margin of healthy tissue was suggested to achieve optimal cancer control^{35, 36}. Furthermore, wider margins of resection are associated with greater loss of normal renal parenchyma volume and subsequent renal functional decline³⁷. Within the standard resection range, different tumor properties may cause microscopic extension of malignancy at the resection margin. Even though 3D recognition provided vivid tumor margin, it could not completely eliminate the positive surgical margin. On account of operator’s operating skills become proficient and the patient’s different preoperative condition, there was no significant difference of hospital stay length and intraoperative complication rate with or without 3D assisted.

Another advantage of 3D reconstruction is surgical training, which allows the creation of application-specific models with low associated high cost^{38, 39}. 3D models may also enhance the patients’ understanding of their tumors and the available treatment options⁴⁰. 3D reconstruction provided better insight on tumor’s depth and its relation with the surrounding structure, so it could enhance the predictive performance^{41, 42}. 3D surgical planning provided a patient-specific virtual or physical model, which could be used to guide the decision-making process, and increase the complex renal tumor treating confidence^{43, 44}. Combining with our study 3D reconstruction may become the standard examination of pre-PN.

Some limitations of our present study should be considered. First, the present findings were mainly based on non-randomized controlled studies, leading to insufficient levels of evidence. Second, the patients were mainly from Asia population, so it is not convincing to apply it on a large scale. Third, this study included many types of the 3D reconstruction mode, which one is better need more high-quality randomized controlled trials.

In conclusion, our meta-analysis shows that three-dimensional reconstruction could reduce operation time, global ischemia time and opening collecting system rate, it played an important role in PN, especially for complex renal tumors. However, our conclusion was not based on enough high-quality studies. More larger sample size randomized controlled trials which report this topic are still needed to support our conclusions.

Acknowledgements Not applicable.

Authors’ contribution Conceived and designed the experiments: Li Jia and Yang Xingliang. Analyzed the data: Zhu Jingzhen, Liu Xiaobing, Zhao Jiang. Contributed reagents/materials/analysis: Li Jia, Yang Xingliang, Sun Bishao, Luo Xing. Wrote the manuscript: Li Jia，Zheng Ji and Fang Zhenqiang. All authors have read and approved the final manuscript.

Funding None

Availability of data and materials The data we used can be found in the references listed.

Ethics approval and consent to participate Not applicable

Competing interests The authors declare that they have no competing interests.

Human and animals rights Not applicable.

Consent for publication The manuscript is approved by all authors for publication. All the authors listed have approved the manuscript that is enclosed.

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Table 1: Overall characteristics of the included studies.

Study	Year	Study period	Country	Study design	Age		BMI		Operati-on mode	Sampl-e size (3D/C)	SQ
					3D	C^e	3D	C
Zhi Wang	2017	2015-2016	China	retrospective	53.9±8.6^a	56.8±7.6	22.1±1.6	22.0±1.8	LPN	49/45	7*
Haijie Zhang	2021	2018-2019	China	Prospective	52.4±11.8^a	50.5±10.2	N	N	LPN	15/15	3^#
Daniele Amparore	2022	2017-2021	Italy, Netherlands	retrospective	60 (51-72)^b	61 (52-72)	25.5 (22.9-26.2)	25.7 (24.8-26.0)	L,RPN	79/143	8*
Xiaorong Wu	2020	2017-2018	China	retrospective	57.6±11.7^a	56.4±9.8	25.2±2.8	24.9±2.5	LPN	30/30	6*
Jipeng Wang	2019	2017-2018	China	retrospective	56 (45-68)^b	60 (48-72)	23 (19-28)	24 (21-28)	LPN	21/28	7*
Yuan Ruan	2015	2012-2014	China	Prospective	60.4 ±2.7^a	58.7 ±3.2	N	N	LPN	45/45	3^#
JosephD.Shirk	2019	2018-2019	USA	Prospective	64.6 ±9.7^a	57.6 ±12.3	n	n	RPN	44/48	8*
Francesco Porpiglia	2017	2016-2017	Italy	retrospective	60.8 ±12.3^a	59.5 ±10.6	24 (23.5; 25.5)	25 (23.5; 25)	RPN	21/31	8*
Dongwen Wang	2014	2012-2014	China	retrospective	58.5 (48, 73)^b	62.1 (47, 80)	26.2 (22.5,30.2)	25.2 (23.0, 26.9)	LPN	21/14	7*
Akari Komatsuda	2016	2009-2014	Japan	retrospective	53.0±11.4^a	57.3±13.0	27.1±0.7	24.8±0.8	LPN	11/20	7*
Shirk, Joseph D	2019	N	USA	Prospective	63.4 ±13.0^a	60.9 ±15.0	N	N	RPN	30/30	3^#
Gang Fan	2019	2016-2018	China	retrospective	48.0±11.9^a	50.0±11.4	23.7±3.0	23.2±4.4	LPN	69/58	6*
Yinzhao Wang	2022	2019-2020	China	retrospective	54(46.0, 62.0)^a	52(43.8, 63.3)	25.9(22.5, 30.7)	26.9(22.3, 30.0)	LPN	52/62	7*
Maomao Li	2020	2017-2020	China	retrospective	54.6± 12.2^a	54.8±13.2	24.9± 1.3	24.7±1.2	LPN	42/34	7*
Mingqiu Hu	2019	2014-2018	China	retrospective	58 (48,73)^b	58 (50,71)	23.8 (21.5, 28.7)	23.5 (21.5,27.2)	LPN	48/60	7*
Lorenzo Bianchi	2022	2018-2021	Italy	prospective	65 (58-70)^b	66 (54-72)	26.4 (24-29.5)	26.2 (23.9-29)	O/L/RPN	100/95	7*
Francesco Porpiglia	2019	2017-2019	Italy	prospective	62 ±15^a	58 ±9.8	24.1±3.7	25.9±3.8	RPN	48/43	8*

a: mean±SD; ^b: median (IQR) ; SQ: study quality according to ^*NOS and ^#jadad; ^e: control standard 2D group.

No competing interests reported.

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