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Approximately 0.2–0.5% of kidney transplant recipients experience renal cell carcinoma (RCC) in their allografts. Recently, nephron-sparing surgery has become widely accepted because of its good survival and low recurrence rates. Methods In this study, we retrospectively evaluated the peri- and postoperative outcomes of RAPN and open partial nephrectomy (OPN) for allograft RCC, including five and six patients who underwent OPN and RAPN from 1998 to 2023, respectively. Results The estimated blood loss was significantly lower in the RAPN group than in the OPN group (6.5 mL [interquartile range (IQR): 1–15] vs. 350 mL [IQR: 139–560], P = 0.006), whereas the operative and renal arterial clamping times were similar. Additionally, perioperative complication rate and its extent were lower in the RAPN group, resulting in a significantly shorter length of postoperative stay than the OPN group (3 days [IQR: 2–5] vs. 10 days [IQR: 8–12], P = 0.01). Postoperative renal function and oncological outcomes were similar between the two groups. Conclusions RAPN for allograft RCC demonstrated some advantages in estimated blood loss and length of postoperative stay as compared with OPN, even though the patients’ backgrounds were not adjusted. Therefore, RAPN may be used for managing T1 allograft tumors. allograft tumor kidney transplantation partial nephrectomy robotic surgery Figures Figure 1 Figure 2 Background Kidney transplantation is associated with improved survival and better quality of life than dialysis [ 1 ]. Although kidney transplantation is the best long-term option for end-stage renal disease (ESRD), immunosuppression increases the risk for developing malignancies, particularly virally driven cancers such as posttransplant lymphoproliferative disorders (Epstein-Barr virus), Kaposi sarcoma (human herpes virus 8), vulvar cancer (human papillomavirus), and skin cancer associated with ultraviolet radiation [ 2 – 4 ]. Overall, kidney transplant recipients have at least a two-fold higher risk for developing or dying from cancer than the general population [ 5 ]. In the case of renal cell carcinoma (RCC), kidney transplant recipients have a 5- to 7-fold increased risk for RCC compared to the general population, accounting for 4.6% of malignancies after kidney transplantation [ 5 , 6 ]. Notably, 90% of RCCs develop in the native kidney, with the remainder occurring in allografts [ 6 – 8 ]. Approximately 0.2–0.5% of kidney transplant recipients experience RCC in their allografts [ 9 , 10 ]. For several years, graftectomy has been considered as an acceptable treatment option for RCC in transplanted kidneys. However, it is a high-risk procedure, particularly in terms of bleeding and vascular risks; morbidity rates range from 20–61%, while mortality rates from 3–11% [ 11 – 14 ]. Nephron-sparing interventions such as partial nephrectomy and ablation therapy, especially in patients with T1aN0M0 RCC in transplanted kidney, have demonstrated favorable oncological outcomes with fewer complications [ 15 , 16 ]. Therefore, graftectomy should be limited to patients with irreversible allograft dysfunction, sarcomatoid-type RCC, multifocal papillary type RCC, RCC greater than 7 centimeters in diameter, locally invasive or metastatic RCC, and infiltrating critical structures [ 17 ]. Nephron-sparing surgery (NSS) is the preferred treatment for patients with localized T1 RCC in native kidneys [ 18 , 19 ]. However, experience in recipients with allograft RCC remains limited, with most cases performed using an open technique [ 10 , 20 – 24 ]. As robot-assisted surgery has become widespread, robot-assisted laparoscopic partial nephrectomy (RAPN) is now being used for allograft RCC [ 25 , 26 ]. Although RAPN for native kidneys shows significant reductions in estimated blood loss, postoperative complications, and length of hospital stay as compared to open partial nephrectomy (OPN) [ 27 ], the effectiveness of RAPN in managing allograft RCC remains unclear. In this study, we aimed to evaluate the short-term functional and surgical outcomes of RAPN and OPN in managing allograft RCC for upholding treatment efficacy and safety. Methods Study design and participants We retrospectively enrolled 11 patients who underwent partial nephrectomy for allograft RCC (OPN, n = 5; RAPN, n = 6) at Tokyo Women’s Medical University Hospital between February 1998 and August 2023. Ethics statements This study was approved by the Health Sciences Institutional Review Board (IRB) of Tokyo Women’s Hospital (approval number: 4460-R) and was conducted in accordance with the ethical standards of the local IRB and the Helsinki Declaration of 1975, as revised in 2013. The requirement for informed consent was waived owing to patient data anonymization. Surgical procedure OPN for allograft RCC was performed through the same incision used for kidney transplantation in the right iliac fossa (Gibson incision) with the patient in the supine position. The anterior rectus sheath and the external oblique muscles were incised. If choosing the retroperitoneal approach, the peritoneum was swept medially to expose the transplanted kidney and iliac vessels. Furthermore, the peritoneum underlining the iliac vessels and the transplanted kidney was incised, thereby exposing the transplanted kidney and renal hilum. The tumor in the transplanted kidney was identified using ultrasonography; a resection line was then marked. The tumor was excised after clamping either the internal or external artery, which was anastomosed with the transplanted kidney artery using a bulldog clamp. An inner running suture, including the repair of the collecting system, was conducted using a braided absorbable suture. Renorrhaphy was performed using a braided absorbable suture after clamping the artery. RAPN for allograft RCC was performed in the Trendelenberg position with da Vinci Xi (Intuitive Surgical, Sunnyvale, CA, USA) using four da Vinci and one 12-mm assistant ports (Fig. 1 ). All RAPNs procedures for allograft RCC were performed using the peritoneal approach. The peritoneum underlying the iliac vessels was incised; the internal or external artery anastomosed with the transplanted kidney artery was identified. The tissue around the tumor was dissected, which was identified using ultrasound; subsequently, a resection line was marked. Similar to the OPN, the tumor was excised after clamping the internal or external artery using a bulldog clamp. An inner running suture was placed using a barbed suture; renorrhaphy was performed using a barbed suture after declamping the artery. Data collection All clinical and laboratory data, including pre-, peri-, and postoperative variables, were extracted from the electronic database and patient medical records of the institution. Estimated glomerular filtration rate (eGFR) was calculated using revised equations for eGFR from serum creatinine in Japan as follows: eGFR (mL/minute/1.73 m 2 ) = 194 × serum creatinine (− 1.094) × age (− 0.287) [× 0.739 (if female)] [ 28 ]. Acute kidney injury (AKI) and its stages were defined as per the Kidney Disease Improving Global Outcomes guidelines. AKI was defined based on one of the following: an increase in serum creatinine by ≥ 0.3 mg/dL within 48 hours; an increase in serum creatinine to ≥ 1.5 times baseline within the previous 7 days; urine volume < 0.5 mL/kg/h for 6 hours). AKI stages were defined as follows: Stage 1: 1.5–1.9 times baseline or ≥ 0.3 mg/dL increase of serum creatinine; Stage 2: 2.0–2.9 times baseline of serum creatine; Stage 3: 3 times baseline or > 4.0 mg/dL increase of serum creatinine) [ 29 ]. Histological findings were evaluated by one or two pathological specialists. Tumor types were classified according to the World Health Organization classification [ 30 – 33 ]. Additionally, tumor grade was assessed using the Fuhrman grade [ 34 ]. Surgical complications were evaluated using the Clavien-Dindo classification [ 35 ]. Statistical analysis All data of each patient were described, and continuous variables were expressed as median and interquartile range (IQR). Independent continuous variables were analyzed using the Wilcoxon rank-sum (Mann-Whitney) test; categorical variables were analyzed using the Pearson χ-square test. Statistical significance was set at P < 0.05. All analyses were performed using Stata, version 15.1 (Stata Corp. LP, College Station, TX, USA). Results Table 1 presents the background characteristics of the five and six patients in the OPN and RAPN groups, respectively. The median age of patients in the RAPN group was 56 years (IQR: 53–69), which was significantly older than that in the OPN group (42 years [IQR: 38–53]) (P = 0.03), while BMI and sex were similar between the two groups. The donors were all living in the RAPN group; on the other hand, 60% of the donors were deceased while 40% were living in the OPN group. Patients were administered a triple immunosuppressive regimen, including a calcineurin inhibitor, an antiproliferative agent, and a steroid (methylprednisolone at a dose of 2–4 mg). Calcineurin inhibitors (CNI) included cyclosporine and tacrolimus, while antiproliferative agents included azathioprine, mizoribine, and mycophenolic acid (MPA). The median intervals between transplantation and diagnosis were 10.1 years (IQR: 9.4–11.6) in the OPN group and 17.4 years (IQR: 16.0–22.5) in the RAPN group, respectively. The mean preoperative eGFR was similar between two groups, with 38.5 mL/minute/1.73 m 2 (IQR: 36.8–64.9) in the OPN group and with 38.4 mL/minute/1.73 m 2 (IQR: 27.4–42.6) in the RAPN group. The median preoperative diameter of the tumors on images was 24 mm (IQR: 24–29) in the OPN group (four cases with clinical T1a and one with clinical T1b), while that in the RAPN group was 22 mm (IQR: 10–24) (all clinical T1a). While the median total of nephrometry score was not significantly different in the two groups, with 9 (5–9) in the OPN group and 5 (5–6) in the RAPN group, three of five patients in the OPN group had tumors at the middle portion of transplanted kidneys, which could make the procedure more difficult. Table 2 shows peri- and postoperative outcomes. The median times of operative duration and renal arterial clamping were similar between the two groups, with 170 minutes (IQR: 157–186) and 18.0 minutes (IQR: 13.3–28.0) in the OPN group, and 148 minutes (IQR: 109–177) and 14.4 minutes (IQR: 9.0–18.7) in the RAPN group, respectively. However, the median estimated blood loss was significantly lower in the RAPN group, as compared to that in the OPN group (6.5 mL [IQR: 1–15] vs. 350 mL [IQR: 139–560], P = 0.006). Surgical complications occurred in three out of five patients in the OPN group and in one patient in the RAPN group. In the OPN group, patients experienced ileus and urinary infection (grade 2 in the Clavien-Dindo classification) as well as transplant ureteral injury (grade 3). In the RAPN group, one patient experienced subcutaneous emphysema caused by pneumoperitoneum (grade 1 in the Clavien-Dindo classification). The median length of postoperative stay was significantly shorter in the RAPN than in the OPN group (3 days [IQR: 2–5] vs. 10 days [IQR: 8–12], P = 0.01). Postoperative AKI occurred in three patients (60.0%) in the OPN and in four patients (66.7%) in the RAPN groups, with one being classified as stage 3 in the OPN group and the others as stage 1. Figure 2 shows that the decline rates of eGFR after the surgery between the two groups. The median decline rates of eGFR of first postoperative day, second postoperative day, and first postoperative month were similar in the OPN and RAPN groups, with 29.3% (IQR: 19.9–33.8) vs. 23.6% (IQR: 12.4–29.8), 28.3% (IQR: 5.7–38.1) vs. 15.5% (IQR: 5.6–28.1), and 11.9% (IQR: 6.8–12.1) vs. 6.9% (IQR: 5.5–13.1), respectively. There were no significant differences in the decline rate at any point between the two groups. While postoperative renal function recovered at a month after the surgery, one patient in each group returned for hemodialysis, one at 148.8 and another at 4.8 months after the surgery in the OPN and RAPN groups, respectively. Histological findings are shown in Table 3. There was no significant difference in the mean tumor diameter between the two groups; there were no positive surgical margins in either group. One of the five patients was pathological T3a in the OPN group, in which the tumor invaded the renal sinus. All tumors in the RAPN group were pathological stage T1a. The most common histology was clear cell RCC in nine cases (72.7%), followed by papillary RCC in two (18.2%) and clear cell papillary RCC in one (9.1%). Fuhrman nuclear grades were 1 in three cases (27.3%), 2 in six (54.5%), and 3 in three (18.2%). The mean follow-up periods were 124.2 months (IQR: 27.2–151.7) in the OPN and 18.8 months (IQR: 7.2–22.3) in the RAPN groups. During this period, Case 2 in the RAPN group experienced local recurrence at 35.3 months after surgery. None of the patients died during the study period. Discussion RAPN for allograft RCC demonstrated lower estimated blood loss and a shorter length of postoperative stay than OPN. Additionally, the rate and extent of perioperative complications were also lower. There were no positive surgical margins, thereby suggesting the efficacy and safety of RAPN for allograft RCC. Minimally invasive approaches for allograft RCC, including laparoscopic or robot-assisted partial nephrectomy, have been attempted [ 25 , 26 , 36 ]. In our experience, several key points should be considered when performing RAPN for allograft RCC. The first challenging step involves identifying the allograft artery and dissecting it from the surrounding tissues. When the allograft artery was anastomosed to the external iliac artery via end-to-side anastomosis, the latter is first exposed and then carefully dissected distally. Subsequently, the anastomosis site between the allograft and external iliac arteries was identified. In cases where the allograft artery was anastomosed to the internal iliac artery via end-to-end anastomosis, the latter crossing above the external iliac artery was identified through the peritoneum. Dissection between the renal artery and surrounding tissue was then performed to create an arterial clamping space. The second key point involves the approach to the tumor. When a tumor is located on the peritoneal side, it can be easily identified. By contrast, when the tumor is positioned dorsally in the allograft kidney, careful dissection around the renal hilum, including the renal vessels and ureter, is required. Another possible approach is to flip the allograft kidney; however, this carries the risk of damaging the allograft kidney during mobilization owing to its strong adhesion to the surrounding tissue. Although these procedures require more advanced surgical skills, the three-dimensional visualization and seven degrees of freedom with instrument movement provided by the da Vinci robotic system make them possible, thereby contributing to lower complications and blood loss. We presumed that the impact on postoperative renal function was not different between OPN and RAPN. In the OPN group, one patient experienced graft loss approximately 12 years after surgery due to chronic active antibody-mediated rejection. As for the other patient in the RAPN group, the preoperative eGFR was already 19.8 mL/minute/1.73 m 2 , which means the patient had been stage 4 chronic kidney disease at the time of surgery. As predicted, the case gradually worsened the renal function, and lost the graft at 4.8 months after the surgery. A previous report showed that preoperative eGFR < 25 mL/minute/1.73 m 2 was significantly associated with progression to ESRD after partial nephrectomy for native kidney tumors [ 37 ].Taken together, allograft RCC patients whose eGFR were < 25 mL/minute/1.73 m 2 , efforts to achieve shorter clamping time and lower blood loss may be needed. In a previous study, the mean interval between renal transplantation and allograft RCC was reported to be 12.1 ± 8.6 years, which was consistent with our data indicating a mean interval of 14.8 ± 7.6 years [ 7 ]. Interestingly, in a reported series, the mean interval of RCC in the native kidney was 5.8 years, which was relatively earlier than that of allograft RCC [ 7 ]. The predominant rate and earlier interval of RCC in the native kidney could be associated with specific ESRD-related abnormalities such as acquired cystic kidney disease, thereby leading to RCC development [ 38 , 39 ]. In previous reviews, local recurrence rates following partial nephrectomies in transplant kidneys ranged between 3.6-6%, which was comparable to those of partial nephrectomies on native kidneys (3%) [ 21 , 40 ]. However, risk factors for recurrence after nephron-sparing interventions remain uncertain. We experienced one case of local recurrence approximately 3 years after surgery in the RAPN group, with histology showing clear cell pT1a RCC (Fuhrman grade 3). In the transplanted allograft, the incidence of papillary RCC was significantly higher (42.1%) than that in the general population (10–15%); the incidence of clear cell RCC was significantly lower (45.7%) than that in the non-transplant population (75–80%) [ 21 ]. In our series, the most common histology was clear cell RCC (72.7%), followed by papillary (18.2%) and clear cell papillary RCC (9.1%). It is not clear why papillary RCC appears to have a predilection for allograft kidneys as compared to the general population. Currently, there are no formal recommendations on how to manage immunosuppression in patients with posttransplant malignancies; however, the common trend is to reduce CNI and switch from MPA to mammalian target of rapamycin (mTOR) inhibitors, if possible [ 41 ]. In particular, CNIs have been shown to exert their action through indirect inhibition of T cell activation and proliferation by decreasing IL-2 production and upregulating VEGF and TGF-β1 expression, thereby leading to the development of malignancy [ 42 ]. mTOR signaling is primarily involved in cancer growth, angiogenesis, and metastasis formation [ 43 ]. mTOR inhibitors, which suppress these cell-cycle processes, also inhibit T cell activation and proliferation by downregulating IL-2 production, thereby being used for both immunosuppressant and anti-cancer drug. However, detailed data on postoperative immunosuppressive agents were not available for the cancer patients after the kidney transplant. We acknowledge that this study was conducted retrospectively at a single institution and involved only a small cohort, however, the report is still valuable because of a limited number of patients with allograft RCC based on the rarity of the disease. There are few reports that demonstrates technical procedures for performing partial nephrectomy of allograft RCC. In our knowledge, this study is the first report that compares perioperative outcomes between RAPN and OPN for allograft RCC management. Conclusions In conclusion, the perioperative outcomes of RAPN for allograft RCC were better than those of OPN in terms of estimated blood loss, length of postoperative stay, and complications. The postoperative functional and oncological outcomes were comparable. In this era of robotic surgery, RAPN for allograft RCC is feasible and safe. Abbreviations ESRD end-stage renal disease RCC renal cell carcinoma NSS nephron-sparing surgery RAPN robot-assisted laparoscopic partial nephrectomy OPN open partial nephrectomy IRB Institutional Review Board eGFR estimated glomerular filtration rate AKI acute kidney injury IQR interquartile range CNI calcineurin inhibitors MPA mycophenolic acid mTOR mammalian target of rapamycin Declarations Ethics approval and consent to participate This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Tokyo Women’s Medical University (Approval number: 4460-R). The requirement for written informed consent from each patient was waved due to the retrospective design of the study by the Ethics Committee of Tokyo Women’s Medical University (Approval number: 4460-R). Consent for publication The requirement for informed consent was waived owing to patient data anonymization. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors have no relevant financial or nonfinancial interests to disclose. Funding The authors declare that no funds, grants, or other support was received during the preparation of this manuscript. Author Contributions Taro Banno and Toshio Takagi contributed to study conception and design. Yuki Kobari, Hironori Fukuda, Kazuhiko Yoshida, Toshihito Hirai, Kazuya Omoto, Junpei Iizuka, and Tomokazu Shimizu drafted and critically reviewed the manuscript. Hideki Ishida approved the final version of this manuscript. Acknowledgments We thank Toshio Takagi for providing advice on the study design and assistance with data collection. We also thank Yuki Kobari, Hironori Fukuda, Kazuhiko Yoshida, Toshihito Hirai, Kazuya Omoto, Junhti Iizuka, and Tomokazu Shimizu for drafting and reviewing the manuscript. 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Int J Mol Sci. 2012;13(2):1886-918. Tables Tables 1-3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx Table2.xlsx Table3.xlsx Cite Share Download PDF Status: Published Journal Publication published 17 Mar, 2025 Read the published version in BMC Surgery → Version 1 posted Editorial decision: Revision requested 29 Jan, 2025 Reviews received at journal 19 Jan, 2025 Reviewers agreed at journal 11 Jan, 2025 Reviews received at journal 11 Jan, 2025 Reviewers agreed at journal 11 Jan, 2025 Reviewers invited by journal 20 Apr, 2024 Editor assigned by journal 20 Apr, 2024 Editor invited by journal 26 Mar, 2024 Submission checks completed at journal 26 Mar, 2024 First submitted to journal 20 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3972872","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":284123197,"identity":"42524cf0-8346-4fa2-af17-424e4a7d36b4","order_by":0,"name":"Taro Banno","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYBACAziLvfn4jw8VQAYzcwNhLQdABM+xBMkZZ0BaGInVIpFjIM3ZBmIR0GLOfvYA84eae3IMPAcMjBnn1UbztwO1/KjYhlOLZU9eAsOBY8XGDOwNCcmF247nzjjM2MDYc+Y2bocdyDFgOMCWkNjAc+DA4ZnbjuU2ALUwM7bh0XL+DVDLP6AWicTGZt45x3LnE9RyA2jLwTaQlmRmZt6GmtwNhLRYznhjcOBsX4IxG88xNsYZxw7kbgRqOYjPL+b8OYYPKr4lyPGz939j+FBTlzvv/OGDD35U4NYCAgdABBuEfRghQiyoI0XxKBgFo2AUjBAAAN8+Xx2R5XkoAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Taro","middleName":"","lastName":"Banno","suffix":""},{"id":284123198,"identity":"dfa47b5b-b456-4a68-8bbf-12f532ec79b1","order_by":1,"name":"Yuki Kobari","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Kobari","suffix":""},{"id":284123199,"identity":"87617500-6163-4328-aab2-2f64124065e4","order_by":2,"name":"Hironori Fukuda","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hironori","middleName":"","lastName":"Fukuda","suffix":""},{"id":284123200,"identity":"bf8fdff9-2a7f-4dbd-baa6-6256f452f2cf","order_by":3,"name":"Kazuhiko Yoshida","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kazuhiko","middleName":"","lastName":"Yoshida","suffix":""},{"id":284123201,"identity":"7983348d-44c7-4c1a-820b-40a7d3c39aff","order_by":4,"name":"Toshihito Hirai","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Toshihito","middleName":"","lastName":"Hirai","suffix":""},{"id":284123202,"identity":"7df2c23e-06a2-4509-b6ae-81716e4c3130","order_by":5,"name":"Kazuya Omoto","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kazuya","middleName":"","lastName":"Omoto","suffix":""},{"id":284123203,"identity":"ab9237bb-e004-4828-a310-5c2c485beec3","order_by":6,"name":"Junpei Iizuka","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junpei","middleName":"","lastName":"Iizuka","suffix":""},{"id":284123204,"identity":"bfe6f434-6285-40a5-b229-2b4897143c6a","order_by":7,"name":"Tomokazu Shimizu","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomokazu","middleName":"","lastName":"Shimizu","suffix":""},{"id":284123208,"identity":"b81d9102-a72f-4052-bda2-7e0bd487b4df","order_by":8,"name":"Hideki Ishida","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hideki","middleName":"","lastName":"Ishida","suffix":""},{"id":284123210,"identity":"05d0c89d-8b66-44ec-9767-16c7ea9c3809","order_by":9,"name":"Toshio Takagi","email":"","orcid":"","institution":"Department of Urology, Tokyo Women’s Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Toshio","middleName":"","lastName":"Takagi","suffix":""}],"badges":[],"createdAt":"2024-02-20 13:22:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3972872/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3972872/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12893-025-02833-9","type":"published","date":"2025-03-17T15:57:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53752933,"identity":"72ae69fa-64a1-4762-a0fc-3e0d6fc78eda","added_by":"auto","created_at":"2024-03-29 18:52:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":31163,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLocation of robotic and assistant ports.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e●: 8 mm robotic camera port, ▲: 8 mm robotic trocar, ■: 12 mm assistant port.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3972872/v1/556ef9ccb4c1f1b86943974a.png"},{"id":53752936,"identity":"35e5fd8e-379a-4a01-9561-577136b81dab","added_by":"auto","created_at":"2024-03-29 18:52:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":119021,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime course of postoperative decline rate of eGFR.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Postoperative decline rate of eGFR of each patient in the OPN group at first postoperative day, second postoperative day, and first postoperative month; the median decline rate of eGFR were 29.3% (IQR: 19.9–33.8), 28.3% (IQR: 5.7–38.1), and 11.9% (IQR: 6.8–12.1), respectively. (B) Postoperative decline rate of eGFR of each patient in the RAPN group at first postoperative day, second postoperative day, and first postoperative month; the median decline rate of eGFR were 23.6% (IQR: 12.4–29.8), 15.5% (IQR: 5.6–28.1), and 6.9% (IQR: 5.5–13.1), respectively. There were no significant differences in the decline rate at each point between the two groups.\u003c/p\u003e\n\u003cp\u003eeGFR, estimated glomerular filtration rate; POD, postoperative day; POM, postoperative month; OPN, open partial nephrectomy; RAPN, robot-assisted laparoscopic partial nephrectomy; IQR, interquartile range.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3972872/v1/80902d5c1e0e205a33a14a3c.png"},{"id":79120664,"identity":"894464b1-9db7-4606-b123-e24fca6a67d3","added_by":"auto","created_at":"2025-03-24 16:10:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":751807,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3972872/v1/4aaec349-2542-48c5-9ebe-ff5bc5e5f83c.pdf"},{"id":53752934,"identity":"b706cc3d-5d8b-4d4f-9587-a15176764ed8","added_by":"auto","created_at":"2024-03-29 18:52:39","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":14090,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3972872/v1/b8d2b5bdba32b9a6a8a15a87.xlsx"},{"id":53752935,"identity":"722f2061-3f90-4c40-9133-8d8441dd707d","added_by":"auto","created_at":"2024-03-29 18:52:39","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":11006,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3972872/v1/a85dee99388f49e706c3e3e1.xlsx"},{"id":53752938,"identity":"700a78b2-f618-45ff-afed-21bd010182de","added_by":"auto","created_at":"2024-03-29 18:52:39","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10864,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3972872/v1/0cc7fa2cd64411d375267886.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparing surgical outcomes between robot-assisted laparoscopic and open partial nephrectomy for allograft kidney tumors: A retrospective, single-center study","fulltext":[{"header":"Background","content":"\u003cp\u003eKidney transplantation is associated with improved survival and better quality of life than dialysis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Although kidney transplantation is the best long-term option for end-stage renal disease (ESRD), immunosuppression increases the risk for developing malignancies, particularly virally driven cancers such as posttransplant lymphoproliferative disorders (Epstein-Barr virus), Kaposi sarcoma (human herpes virus 8), vulvar cancer (human papillomavirus), and skin cancer associated with ultraviolet radiation [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Overall, kidney transplant recipients have at least a two-fold higher risk for developing or dying from cancer than the general population [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In the case of renal cell carcinoma (RCC), kidney transplant recipients have a 5- to 7-fold increased risk for RCC compared to the general population, accounting for 4.6% of malignancies after kidney transplantation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Notably, 90% of RCCs develop in the native kidney, with the remainder occurring in allografts [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Approximately 0.2\u0026ndash;0.5% of kidney transplant recipients experience RCC in their allografts [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor several years, graftectomy has been considered as an acceptable treatment option for RCC in transplanted kidneys. However, it is a high-risk procedure, particularly in terms of bleeding and vascular risks; morbidity rates range from 20\u0026ndash;61%, while mortality rates from 3\u0026ndash;11% [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Nephron-sparing interventions such as partial nephrectomy and ablation therapy, especially in patients with T1aN0M0 RCC in transplanted kidney, have demonstrated favorable oncological outcomes with fewer complications [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, graftectomy should be limited to patients with irreversible allograft dysfunction, sarcomatoid-type RCC, multifocal papillary type RCC, RCC greater than 7 centimeters in diameter, locally invasive or metastatic RCC, and infiltrating critical structures [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNephron-sparing surgery (NSS) is the preferred treatment for patients with localized T1 RCC in native kidneys [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, experience in recipients with allograft RCC remains limited, with most cases performed using an open technique [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. As robot-assisted surgery has become widespread, robot-assisted laparoscopic partial nephrectomy (RAPN) is now being used for allograft RCC [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Although RAPN for native kidneys shows significant reductions in estimated blood loss, postoperative complications, and length of hospital stay as compared to open partial nephrectomy (OPN) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], the effectiveness of RAPN in managing allograft RCC remains unclear. In this study, we aimed to evaluate the short-term functional and surgical outcomes of RAPN and OPN in managing allograft RCC for upholding treatment efficacy and safety.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eWe retrospectively enrolled 11 patients who underwent partial nephrectomy for allograft RCC (OPN, n\u0026thinsp;=\u0026thinsp;5; RAPN, n\u0026thinsp;=\u0026thinsp;6) at Tokyo Women\u0026rsquo;s Medical University Hospital between February 1998 and August 2023.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEthics statements\u003c/h2\u003e \u003cp\u003e This study was approved by the Health Sciences Institutional Review Board (IRB) of Tokyo Women\u0026rsquo;s Hospital (approval number: 4460-R) and was conducted in accordance with the ethical standards of the local IRB and the Helsinki Declaration of 1975, as revised in 2013. The requirement for informed consent was waived owing to patient data anonymization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSurgical procedure\u003c/h2\u003e \u003cp\u003eOPN for allograft RCC was performed through the same incision used for kidney transplantation in the right iliac fossa (Gibson incision) with the patient in the supine position. The anterior rectus sheath and the external oblique muscles were incised. If choosing the retroperitoneal approach, the peritoneum was swept medially to expose the transplanted kidney and iliac vessels. Furthermore, the peritoneum underlining the iliac vessels and the transplanted kidney was incised, thereby exposing the transplanted kidney and renal hilum. The tumor in the transplanted kidney was identified using ultrasonography; a resection line was then marked. The tumor was excised after clamping either the internal or external artery, which was anastomosed with the transplanted kidney artery using a bulldog clamp. An inner running suture, including the repair of the collecting system, was conducted using a braided absorbable suture. Renorrhaphy was performed using a braided absorbable suture after clamping the artery.\u003c/p\u003e \u003cp\u003eRAPN for allograft RCC was performed in the Trendelenberg position with da Vinci Xi (Intuitive Surgical, Sunnyvale, CA, USA) using four da Vinci and one 12-mm assistant ports (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All RAPNs procedures for allograft RCC were performed using the peritoneal approach. The peritoneum underlying the iliac vessels was incised; the internal or external artery anastomosed with the transplanted kidney artery was identified. The tissue around the tumor was dissected, which was identified using ultrasound; subsequently, a resection line was marked. Similar to the OPN, the tumor was excised after clamping the internal or external artery using a bulldog clamp. An inner running suture was placed using a barbed suture; renorrhaphy was performed using a barbed suture after declamping the artery.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eAll clinical and laboratory data, including pre-, peri-, and postoperative variables, were extracted from the electronic database and patient medical records of the institution. Estimated glomerular filtration rate (eGFR) was calculated using revised equations for eGFR from serum creatinine in Japan as follows: eGFR (mL/minute/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;=\u0026thinsp;194 \u0026times; serum creatinine (\u0026minus;\u0026thinsp;1.094) \u0026times; age (\u0026minus;\u0026thinsp;0.287) [\u0026times; 0.739 (if female)] [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Acute kidney injury (AKI) and its stages were defined as per the Kidney Disease Improving Global Outcomes guidelines. AKI was defined based on one of the following: an increase in serum creatinine by \u0026ge;\u0026thinsp;0.3 mg/dL within 48 hours; an increase in serum creatinine to \u0026ge;\u0026thinsp;1.5 times baseline within the previous 7 days; urine volume\u0026thinsp;\u0026lt;\u0026thinsp;0.5 mL/kg/h for 6 hours). AKI stages were defined as follows: Stage 1: 1.5\u0026ndash;1.9 times baseline or \u0026ge;\u0026thinsp;0.3 mg/dL increase of serum creatinine; Stage 2: 2.0\u0026ndash;2.9 times baseline of serum creatine; Stage 3: 3 times baseline or \u0026gt;\u0026thinsp;4.0 mg/dL increase of serum creatinine) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Histological findings were evaluated by one or two pathological specialists. Tumor types were classified according to the World Health Organization classification [\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Additionally, tumor grade was assessed using the Fuhrman grade [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Surgical complications were evaluated using the Clavien-Dindo classification [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll data of each patient were described, and continuous variables were expressed as median and interquartile range (IQR). Independent continuous variables were analyzed using the Wilcoxon rank-sum (Mann-Whitney) test; categorical variables were analyzed using the Pearson χ-square test. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All analyses were performed using Stata, version 15.1 (Stata Corp. LP, College Station, TX, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;1 presents the background characteristics of the five and six patients in the OPN and RAPN groups, respectively. The median age of patients in the RAPN group was 56 years (IQR: 53\u0026ndash;69), which was significantly older than that in the OPN group (42 years [IQR: 38\u0026ndash;53]) (P\u0026thinsp;=\u0026thinsp;0.03), while BMI and sex were similar between the two groups. The donors were all living in the RAPN group; on the other hand, 60% of the donors were deceased while 40% were living in the OPN group. Patients were administered a triple immunosuppressive regimen, including a calcineurin inhibitor, an antiproliferative agent, and a steroid (methylprednisolone at a dose of 2\u0026ndash;4 mg). Calcineurin inhibitors (CNI) included cyclosporine and tacrolimus, while antiproliferative agents included azathioprine, mizoribine, and mycophenolic acid (MPA). The median intervals between transplantation and diagnosis were 10.1 years (IQR: 9.4\u0026ndash;11.6) in the OPN group and 17.4 years (IQR: 16.0\u0026ndash;22.5) in the RAPN group, respectively. The mean preoperative eGFR was similar between two groups, with 38.5 mL/minute/1.73 m\u003csup\u003e2\u003c/sup\u003e (IQR: 36.8\u0026ndash;64.9) in the OPN group and with 38.4 mL/minute/1.73 m\u003csup\u003e2\u003c/sup\u003e (IQR: 27.4\u0026ndash;42.6) in the RAPN group. The median preoperative diameter of the tumors on images was 24 mm (IQR: 24\u0026ndash;29) in the OPN group (four cases with clinical T1a and one with clinical T1b), while that in the RAPN group was 22 mm (IQR: 10\u0026ndash;24) (all clinical T1a). While the median total of nephrometry score was not significantly different in the two groups, with 9 (5\u0026ndash;9) in the OPN group and 5 (5\u0026ndash;6) in the RAPN group, three of five patients in the OPN group had tumors at the middle portion of transplanted kidneys, which could make the procedure more difficult.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;2 shows peri- and postoperative outcomes. The median times of operative duration and renal arterial clamping were similar between the two groups, with 170 minutes (IQR: 157\u0026ndash;186) and 18.0 minutes (IQR: 13.3\u0026ndash;28.0) in the OPN group, and 148 minutes (IQR: 109\u0026ndash;177) and 14.4 minutes (IQR: 9.0\u0026ndash;18.7) in the RAPN group, respectively. However, the median estimated blood loss was significantly lower in the RAPN group, as compared to that in the OPN group (6.5 mL [IQR: 1\u0026ndash;15] vs. 350 mL [IQR: 139\u0026ndash;560], P\u0026thinsp;=\u0026thinsp;0.006). Surgical complications occurred in three out of five patients in the OPN group and in one patient in the RAPN group. In the OPN group, patients experienced ileus and urinary infection (grade 2 in the Clavien-Dindo classification) as well as transplant ureteral injury (grade 3). In the RAPN group, one patient experienced subcutaneous emphysema caused by pneumoperitoneum (grade 1 in the Clavien-Dindo classification). The median length of postoperative stay was significantly shorter in the RAPN than in the OPN group (3 days [IQR: 2\u0026ndash;5] vs. 10 days [IQR: 8\u0026ndash;12], P\u0026thinsp;=\u0026thinsp;0.01). Postoperative AKI occurred in three patients (60.0%) in the OPN and in four patients (66.7%) in the RAPN groups, with one being classified as stage 3 in the OPN group and the others as stage 1. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows that the decline rates of eGFR after the surgery between the two groups. The median decline rates of eGFR of first postoperative day, second postoperative day, and first postoperative month were similar in the OPN and RAPN groups, with 29.3% (IQR: 19.9\u0026ndash;33.8) vs. 23.6% (IQR: 12.4\u0026ndash;29.8), 28.3% (IQR: 5.7\u0026ndash;38.1) vs. 15.5% (IQR: 5.6\u0026ndash;28.1), and 11.9% (IQR: 6.8\u0026ndash;12.1) vs. 6.9% (IQR: 5.5\u0026ndash;13.1), respectively. There were no significant differences in the decline rate at any point between the two groups. While postoperative renal function recovered at a month after the surgery, one patient in each group returned for hemodialysis, one at 148.8 and another at 4.8 months after the surgery in the OPN and RAPN groups, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistological findings are shown in Table\u0026nbsp;3. There was no significant difference in the mean tumor diameter between the two groups; there were no positive surgical margins in either group. One of the five patients was pathological T3a in the OPN group, in which the tumor invaded the renal sinus. All tumors in the RAPN group were pathological stage T1a. The most common histology was clear cell RCC in nine cases (72.7%), followed by papillary RCC in two (18.2%) and clear cell papillary RCC in one (9.1%). Fuhrman nuclear grades were 1 in three cases (27.3%), 2 in six (54.5%), and 3 in three (18.2%). The mean follow-up periods were 124.2 months (IQR: 27.2\u0026ndash;151.7) in the OPN and 18.8 months (IQR: 7.2\u0026ndash;22.3) in the RAPN groups. During this period, Case 2 in the RAPN group experienced local recurrence at 35.3 months after surgery. None of the patients died during the study period.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRAPN for allograft RCC demonstrated lower estimated blood loss and a shorter length of postoperative stay than OPN. Additionally, the rate and extent of perioperative complications were also lower. There were no positive surgical margins, thereby suggesting the efficacy and safety of RAPN for allograft RCC.\u003c/p\u003e \u003cp\u003eMinimally invasive approaches for allograft RCC, including laparoscopic or robot-assisted partial nephrectomy, have been attempted [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In our experience, several key points should be considered when performing RAPN for allograft RCC. The first challenging step involves identifying the allograft artery and dissecting it from the surrounding tissues. When the allograft artery was anastomosed to the external iliac artery via end-to-side anastomosis, the latter is first exposed and then carefully dissected distally. Subsequently, the anastomosis site between the allograft and external iliac arteries was identified. In cases where the allograft artery was anastomosed to the internal iliac artery via end-to-end anastomosis, the latter crossing above the external iliac artery was identified through the peritoneum. Dissection between the renal artery and surrounding tissue was then performed to create an arterial clamping space. The second key point involves the approach to the tumor. When a tumor is located on the peritoneal side, it can be easily identified. By contrast, when the tumor is positioned dorsally in the allograft kidney, careful dissection around the renal hilum, including the renal vessels and ureter, is required. Another possible approach is to flip the allograft kidney; however, this carries the risk of damaging the allograft kidney during mobilization owing to its strong adhesion to the surrounding tissue. Although these procedures require more advanced surgical skills, the three-dimensional visualization and seven degrees of freedom with instrument movement provided by the da Vinci robotic system make them possible, thereby contributing to lower complications and blood loss.\u003c/p\u003e \u003cp\u003eWe presumed that the impact on postoperative renal function was not different between OPN and RAPN. In the OPN group, one patient experienced graft loss approximately 12 years after surgery due to chronic active antibody-mediated rejection. As for the other patient in the RAPN group, the preoperative eGFR was already 19.8 mL/minute/1.73 m\u003csup\u003e2\u003c/sup\u003e, which means the patient had been stage 4 chronic kidney disease at the time of surgery. As predicted, the case gradually worsened the renal function, and lost the graft at 4.8 months after the surgery. A previous report showed that preoperative eGFR\u0026thinsp;\u0026lt;\u0026thinsp;25 mL/minute/1.73 m\u003csup\u003e2\u003c/sup\u003e was significantly associated with progression to ESRD after partial nephrectomy for native kidney tumors [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].Taken together, allograft RCC patients whose eGFR were \u0026lt;\u0026thinsp;25 mL/minute/1.73 m\u003csup\u003e2\u003c/sup\u003e, efforts to achieve shorter clamping time and lower blood loss may be needed.\u003c/p\u003e \u003cp\u003eIn a previous study, the mean interval between renal transplantation and allograft RCC was reported to be 12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6 years, which was consistent with our data indicating a mean interval of 14.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6 years [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Interestingly, in a reported series, the mean interval of RCC in the native kidney was 5.8 years, which was relatively earlier than that of allograft RCC [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The predominant rate and earlier interval of RCC in the native kidney could be associated with specific ESRD-related abnormalities such as acquired cystic kidney disease, thereby leading to RCC development [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn previous reviews, local recurrence rates following partial nephrectomies in transplant kidneys ranged between 3.6-6%, which was comparable to those of partial nephrectomies on native kidneys (3%) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. However, risk factors for recurrence after nephron-sparing interventions remain uncertain. We experienced one case of local recurrence approximately 3 years after surgery in the RAPN group, with histology showing clear cell pT1a RCC (Fuhrman grade 3). In the transplanted allograft, the incidence of papillary RCC was significantly higher (42.1%) than that in the general population (10\u0026ndash;15%); the incidence of clear cell RCC was significantly lower (45.7%) than that in the non-transplant population (75\u0026ndash;80%) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In our series, the most common histology was clear cell RCC (72.7%), followed by papillary (18.2%) and clear cell papillary RCC (9.1%). It is not clear why papillary RCC appears to have a predilection for allograft kidneys as compared to the general population.\u003c/p\u003e \u003cp\u003eCurrently, there are no formal recommendations on how to manage immunosuppression in patients with posttransplant malignancies; however, the common trend is to reduce CNI and switch from MPA to mammalian target of rapamycin (mTOR) inhibitors, if possible [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In particular, CNIs have been shown to exert their action through indirect inhibition of T cell activation and proliferation by decreasing IL-2 production and upregulating VEGF and TGF-β1 expression, thereby leading to the development of malignancy [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. mTOR signaling is primarily involved in cancer growth, angiogenesis, and metastasis formation [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. mTOR inhibitors, which suppress these cell-cycle processes, also inhibit T cell activation and proliferation by downregulating IL-2 production, thereby being used for both immunosuppressant and anti-cancer drug. However, detailed data on postoperative immunosuppressive agents were not available for the cancer patients after the kidney transplant.\u003c/p\u003e \u003cp\u003eWe acknowledge that this study was conducted retrospectively at a single institution and involved only a small cohort, however, the report is still valuable because of a limited number of patients with allograft RCC based on the rarity of the disease. There are few reports that demonstrates technical procedures for performing partial nephrectomy of allograft RCC. In our knowledge, this study is the first report that compares perioperative outcomes between RAPN and OPN for allograft RCC management.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, the perioperative outcomes of RAPN for allograft RCC were better than those of OPN in terms of estimated blood loss, length of postoperative stay, and complications. The postoperative functional and oncological outcomes were comparable. In this era of robotic surgery, RAPN for allograft RCC is feasible and safe.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESRD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eend-stage renal disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erenal cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enephron-sparing surgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRAPN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erobot-assisted laparoscopic partial nephrectomy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOPN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eopen partial nephrectomy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInstitutional Review Board\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eestimated glomerular filtration rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAKI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute kidney injury\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecalcineurin inhibitors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMPA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emycophenolic acid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emTOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emammalian target of rapamycin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Tokyo Women’s Medical University (Approval number:\u0026nbsp;4460-R). The requirement for written informed consent from each patient was waved due to the retrospective design of the study by the Ethics Committee of Tokyo Women’s Medical University (Approval number:\u0026nbsp;4460-R).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe requirement for informed consent was waived owing to\u0026nbsp;patient data anonymization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting Interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or nonfinancial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support was received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor Contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTaro Banno and Toshio Takagi contributed to study conception and design. Yuki Kobari, Hironori Fukuda, Kazuhiko Yoshida, Toshihito Hirai,\u0026nbsp;Kazuya Omoto, Junpei Iizuka, and Tomokazu Shimizu\u0026nbsp;drafted and critically reviewed the manuscript. Hideki Ishida approved the final version of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgments\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Toshio Takagi for providing advice on the study design and assistance with data collection. We also thank Yuki Kobari, Hironori Fukuda, Kazuhiko Yoshida, Toshihito Hirai, Kazuya Omoto, Junhti Iizuka, and Tomokazu Shimizu for drafting and reviewing the manuscript. Finaly, we thank Hideki Ishida for their supervision.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, et al. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. 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American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2017;17(11):2775-81.\u003c/li\u003e\n\u003cli\u003eDiller R, Senninger N. Treatment options and outcome for renal cell tumors in the transplanted kidney. Int J Artif Organs. 2008;31(10):867-74.\u003c/li\u003e\n\u003cli\u003eChambade D, Meria P, Tariel E, V\u0026eacute;rine J, De Kerviler E, Peraldi MN, et al. Nephron sparing surgery is a feasible and efficient treatment of T1a renal cell carcinoma in kidney transplant: a prospective series from a single center. The Journal of urology. 2008;180(5):2106-9.\u003c/li\u003e\n\u003cli\u003eVarotti G, Bertocchi M, Barabani C, Terulla A, Fontana I. Nephron-sparing surgery for malignancies in kidney allografts. Transplant international : official journal of the European Society for Organ Transplantation. 2015;28(11):1342-4.\u003c/li\u003e\n\u003cli\u003eKaouk JH, Spana G, Hillyer SP, White MA, Haber GP, Goldfarb D. Robotic-assisted laparoscopic partial nephrectomy for a 7-cm mass in a renal allograft. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2011;11(10):2242-6.\u003c/li\u003e\n\u003cli\u003eWatanabe S, Takagi T, Yoshida K, Unagami K, Kanzawa T, Iizuka J, et al. Robot-Assisted Laparoscopic Partial Nephrectomy for Allograft Renal Cell Carcinoma: A Case Report. Transplant Proc. 2021;53(5):1445-9.\u003c/li\u003e\n\u003cli\u003eCalpin GG, Ryan FR, McHugh FT, McGuire BB. Comparing the outcomes of open, laparoscopic and robot-assisted partial nephrectomy: a network meta-analysis. BJU international. 2023;132(4):353-64.\u003c/li\u003e\n\u003cli\u003eMatsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2009;53(6):982-92.\u003c/li\u003e\n\u003cli\u003eKhwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84.\u003c/li\u003e\n\u003cli\u003eKovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, et al. The Heidelberg classification of renal cell tumours. J Pathol. 1997;183(2):131-3.\u003c/li\u003e\n\u003cli\u003eEble J, Sauter G, Epstein J, Sesterhenn I. Pathology and Genetics, Tumors of the Urinary System and Male Genital Organs. Lyon, France: World Health Organization. International Agency for Research on Cancer. 2004.\u003c/li\u003e\n\u003cli\u003eMoch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. European urology. 2016;70(1):93-105.\u003c/li\u003e\n\u003cli\u003eMoch H, Amin MB, Berney DM, Comp\u0026eacute;rat EM, Gill AJ, Hartmann A, et al. The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. European urology. 2022;82(5):458-68.\u003c/li\u003e\n\u003cli\u003eFuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. The American journal of surgical pathology. 1982;6(7):655-63.\u003c/li\u003e\n\u003cli\u003eDindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-13.\u003c/li\u003e\n\u003cli\u003eOzden E, Gulsen M, Mercimek MN, Bostanci Y, Sarikaya S, Yakupoglu YK. Laparoscopic Partial Nephrectomy in Allograft Kidney. Urology. 2020;146:e5-e7.\u003c/li\u003e\n\u003cli\u003eAguilar Palacios D, Li J, Mahmood F, Demirjian S, Abouassaly R, Campbell SC. Partial Nephrectomy for Patients with Severe Chronic Kidney Disease-Is It Worthwhile? The Journal of urology. 2020;204(3):434-41.\u003c/li\u003e\n\u003cli\u003eFarivar-Mohseni H, Perlmutter AE, Wilson S, Shingleton WB, Bigler SA, Fowler JE, Jr. Renal cell carcinoma and end stage renal disease. The Journal of urology. 2006;175(6):2018-20; discussion 21.\u003c/li\u003e\n\u003cli\u003eSchwarz A, Vatandaslar S, Merkel S, Haller H. Renal cell carcinoma in transplant recipients with acquired cystic kidney disease. Clinical journal of the American Society of Nephrology : CJASN. 2007;2(4):750-6.\u003c/li\u003e\n\u003cli\u003eGonz\u0026aacute;lez-L\u0026oacute;pez R, Bueno-Serrano G, V\u0026aacute;zquez-Escuderos JJ, Mayor-De Castro J, Gonz\u0026aacute;lez-Enguita C. [Conservative treatment of renal cell carcinoma in kidney transplantation]. Actas Urol Esp. 2013;37(4):242-8.\u003c/li\u003e\n\u003cli\u003eKrisl JC, Doan VP. Chemotherapy and Transplantation: The Role of Immunosuppression in Malignancy and a Review of Antineoplastic Agents in Solid Organ Transplant Recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2017;17(8):1974-91.\u003c/li\u003e\n\u003cli\u003eMaluccio M, Sharma V, Lagman M, Vyas S, Yang H, Li B, et al. Tacrolimus enhances transforming growth factor-beta1 expression and promotes tumor progression. Transplantation. 2003;76(3):597-602.\u003c/li\u003e\n\u003cli\u003eP\u0026oacute;pulo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci. 2012;13(2):1886-918.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1-3 are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"allograft tumor, kidney transplantation, partial nephrectomy, robotic surgery","lastPublishedDoi":"10.21203/rs.3.rs-3972872/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3972872/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eKidney transplantation is considered the best long-term option for patients with end-stage renal disease; however, immunosuppression increases the risk for malignancies. Approximately 0.2\u0026ndash;0.5% of kidney transplant recipients experience renal cell carcinoma (RCC) in their allografts. Recently, nephron-sparing surgery has become widely accepted because of its good survival and low recurrence rates.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this study, we retrospectively evaluated the peri- and postoperative outcomes of RAPN and open partial nephrectomy (OPN) for allograft RCC, including five and six patients who underwent OPN and RAPN from 1998 to 2023, respectively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe estimated blood loss was significantly lower in the RAPN group than in the OPN group (6.5 mL [interquartile range (IQR): 1\u0026ndash;15] vs. 350 mL [IQR: 139\u0026ndash;560], P\u0026thinsp;=\u0026thinsp;0.006), whereas the operative and renal arterial clamping times were similar. Additionally, perioperative complication rate and its extent were lower in the RAPN group, resulting in a significantly shorter length of postoperative stay than the OPN group (3 days [IQR: 2\u0026ndash;5] vs. 10 days [IQR: 8\u0026ndash;12], P\u0026thinsp;=\u0026thinsp;0.01). Postoperative renal function and oncological outcomes were similar between the two groups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eRAPN for allograft RCC demonstrated some advantages in estimated blood loss and length of postoperative stay as compared with OPN, even though the patients\u0026rsquo; backgrounds were not adjusted. Therefore, RAPN may be used for managing T1 allograft tumors.\u003c/p\u003e","manuscriptTitle":"Comparing surgical outcomes between robot-assisted laparoscopic and open partial nephrectomy for allograft kidney tumors: A retrospective, single-center study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-29 18:52:35","doi":"10.21203/rs.3.rs-3972872/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-29T10:42:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-19T17:18:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286902648419386984625151446744890511536","date":"2025-01-11T18:49:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-11T14:59:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306857870613731661078098863458090182917","date":"2025-01-11T07:44:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-20T09:37:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-20T09:37:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-26T13:52:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-26T13:51:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2024-02-20T13:21:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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