Venous vascular reconstruction of a robotically procured right kidney with two renal veins transplanted into a pediatric recipient.

BACKGROUND: Right versus left kidney donor nephrectomy remains a controversial topic in renal transplantation given the increased incidence of right kidney vascular anomalies and associated venous thrombosis. We present the case of a 3-year-old pediatric recipient with urethral atresia and end-stage kidney disease who received a robotically procured living donor right pelvic kidney with two short same-size renal veins and a short ureter. METHODS: We utilized a completely deceased iliac vein system (common iliac vein with both external and internal veins) to extend the two renal veins. Due to the distance between both renal veins, the external iliac vein was anastomosed to the upper hilum renal vein, and the internal iliac vein was anastomosed to the lower hilum renal vein. The donor's short ureter was anastomosed to the recipient's ureter end-to-side. RESULTS: The patient had immediate graft function and there were no post-operative complications. Renal ultrasound was unremarkable at 48 hours post-transplant. Serum creatinine was 0.5 mg/dL at 3 months post-transplant. CONCLUSION: We demonstrate the successful transplantation of a robotically procured right pelvic donor kidney with two short renal veins using a deceased donor iliac vein system for venous reconstruction without increasing technical complications. This technique of venous reconstruction can be used in right kidneys with similar anatomical variations without affecting graft function.

Renal cell carcinoma with an "uncoiling" tumor thrombus: intraoperative shift from level III to level IV.

BACKGROUND: The gold standard treatment for renal cell carcinoma (RCC) with tumor thrombus (TT) is complete surgical excision. The surgery is complex and challenging to the surgeon, especially with large tumor thrombus extending into the inferior vena cava (IVC) and right atrium. Traditionally, these difficult cases required the use of cardiopulmonary bypass (CPB) with or without deep hypothermic cardiac arrest, but in recent years, different surgical techniques derived from the field of liver transplantation have been used in efforts to avoid CPB. CASE PRESENTATION: We present a case of RCC with TT level IIIc (extending above major hepatic veins) that "uncoiled" intraoperatively into the right atrium after division of the IVC ligament, transforming into a level IV TT. Despite the new TT extension, the surgery was successfully completed exclusively through an abdominal approach without CPB and while using intraoperative transesophageal echocardiography (TEE) monitoring and a cardiothoracic team standby. CONCLUSIONS: This case highlights the need for a multidisciplinary approach and the utility of intraoperative continous TEE monitoring which helped to visualize the change of the TT venous extension, allowing the surgical teamto modify their surgical approach as needed avoiding a catastrophic event.

The importance of avoiding time-dependent bias when testing the prognostic value of an intervening event - Two acute cellular rejection examples in intestinal transplantation.

In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs posttransplant), 3 proper statistical methodologies for testing its prognostic value exist (time-dependent covariate, landmark, and semi-Markov modeling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of first acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR). The (statistically more powerful) time-dependent covariate method in Cox's multivariable model yielded significantly unfavorable effects of first ACR (P < .0001; HR = 2.492) and severe ACR (P < .0001; HR = 4.531). In contrast, when using the time-dependent biased approach, multivariable analysis yielded an incorrect conclusion for the prognostic value of first ACR (P = .31, HR = 0.877, 35.2% of 2.492) and a much smaller estimated effect of severe ACR (P = .0008; HR = 1.589; 35.1% of 4.531). In conclusion, this study demonstrates the importance of avoiding time-dependent bias when testing the prognostic value of an intervening event.

Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation.

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.

Re: Olivero A, et al. Adrenocortical carcinoma with venous tumor invasion: is there a role for mini-invasive surgery?

PURPOSE: The surgical treatment for adrenocortical carcinoma with venous tumor invasion remains a challenge for surgeons. A critical factor in determining the surgical approach is utilizing a classification system that accurately defines the tumor thrombus level. METHODS: Olivero and colleagues report their experience regarding the feasibility of mini-invasive surgery for adrenocortical carcinoma with venous tumor invasion. They studied the outcome of 20 patients from 4 international referral center databases. RESULTS: They describe a classification for adrenal tumor with tumor thrombus into four levels: (1) adrenal vein invasion; (2) renal vein invasion; (3) infra-hepatic inferior vena cava (IVC); and (4) retro-hepatic IVC. CONCLUSIONS: We congratulate the authors for their work and patient outcomes; however, in efforts to avoid confusion in the surgical community, we believe their classification system requires modification compared to our classification system developed in 2004.

Creating a Single Inflow Orifice From Living Donor Kidney Allografts With Multiple Renal Arteries.

Background: Multiple renal arteries (MRA) are often encountered during living-donor kidney transplantation (LDKT), requiring surgeons to pursue complex renovascular reconstructions prior to graft implantation. With improvements in reconstruction and anastomosis techniques, allografts with MRA can be successfully transplanted with similar outcomes to allografts with a single renal artery. Here, we describe in detail various surgical techniques for reconstruction of MRA grafts with the intent of creating a single arterial inflow. Methods: We retrospectively reviewed the medical records of all LDKT recipients with laparoscopically procured MRA kidneys between March 2008 and July 2021. Recipient and donor characteristics, operative data, type of reconstruction, and recipient outcomes were analyzed. The primary outcomes were the incidence of developing delayed graft function (DGF) and/or a vascular or urological complication within 12 months post-transplant. Results: Seventy-three LDKT recipients of MRA donor allografts were evaluated. Two renal arteries (RA) were encountered in 62 allografts (84.9%) and three RA in 11 allografts (15.1%). Renal artery reconstruction was performed in 95.8% (70/73) of patients. Eighteen different reconstruction techniques of MRA were utilized, the most common being side-to-side anastomosis in allografts with two RA (N = 44) and side-to-side-to-side anastomosis in allografts with three RA (N = 4). Interposition grafting was performed in seven cases (9.6%). A single ostium was created in 69 cases (94.5%), and the median warm ischemia time was 27 (range 20-42) minutes. None of the patients developed DGF or post-operative vascular or urological complications. Median creatinine at 3, 6, and 12 months post-transplant remained stable at 1.1 mg/dl. With a median follow-up of 30.4 months post-transplant, only one graft failure has been observed-death-censored graft survival was 98.6%. Conclusion: Complex reconstruction techniques to create a single renal artery ostium for graft implantation anastomosis in allografts with MRA show acceptable warm ischemic times, with no increased risk of post-operative vascular or urological complications.

Surgical modifications to the conventional kidney transplant technique: the Miami Transplant Institute approach in a retrospective cohort study.

BACKGROUND: At our center, surgical modifications to the conventional kidney transplant technique were developed with two goals in mind: to minimize the risk of developing post-transplant urologic/vascular/other surgical complications, and to simultaneously eliminate the need for initial ureteral stent placement and surgical drainage. METHODS: Here, the authors describe these modifications along with (what we believe are) their advantages over the conventional technique: creating an abdominal flap for easier abdominal closure (reflecting the parietal peritoneum from the abdominal wall), mobilizing the bladder before transplant (creating more space for bladder dissection, allowing it to move upward during abdominal wall closure), minimizing the dissection of iliac vessels to only anterior lymphatic tissue (attempting to minimize the incidence of fluid collections), using plastic arterial vascular bulldog clamps (causing less trauma to the iliac artery), performing vascular anastomosis of the renal artery first (making it easier for the surgeon to perform the anastomoses), creating longer ureteral spatulation, and inclusion of bladder mucosa along with some detrusor muscle layer in performing the ureteral anastomosis (attempting to minimize the incidence of urologic complications). Of note, no initial ureteral stent placement or surgical drainage was used. The authors report our experience during the first 12 months post-transplant of a single transplant surgeon who used each of these modifications among 707 consecutive recipients of kidney-alone transplants at our center since 2014. RESULTS: During the first 12 months post-transplant, 2.3% (16/707) of patients developed a urologic complication; only 1.0% (7/707) required surgical repair of their original ureteroneocystostomy. Additionally, 2.7% (19/707) developed a vascular complication; 8.8% (62/707) developed some other type of surgical complication (wound complication, lymphocele development, or development of a peri-renal hematoma or peri-renal collection). These overall results were advantageous when compared with other studies. CONCLUSION: The authors believe that this modified kidney transplant technique clearly helped in reducing post-transplant risks of developing urologic/vascular/other surgical complications. Importantly, these results were achieved without initial ureteral stent placement or surgical drainage.

Optimizing the kidney donor pool: transplanting donor kidneys after partial nephrectomy of masses or cysts.

Background: A limiting factor in expanding the kidney donor pool is donor kidneys with renal tumors or cysts. Partial nephrectomy (PN) to remove these lesions prior to transplantation may help optimize organ usage without recurrence of malignancy or increased risk of complications. Methods: We retrospectively analyzed all recipients of a living or deceased donor graft between February 2009 and October 2022 in which a PN was performed prior to transplant due to the presence of one or more concerning growths. Donor and recipient demographics, perioperative data, donor allograft pathology, and recipient outcomes were obtained. Results: Thirty-six recipients received a graft in which a PN was performed to remove suspicious masses or cysts prior to transplant. Majority of pathologies turned out to be a simple renal cyst (65%), followed by renal cell carcinoma (15%), benign multilocular cystic renal neoplasm (7.5%), angiomyolipoma (5%), benign renal tissue (5%), and papillary adenoma (2.5%). No renal malignancy recurrences were observed during the study period (median follow-up: 67.2 months). Fourteen complications occurred among 11 patients (30.6% overall) during the first 6mo post-transplant. Mean eGFR (± standard error) at 36 months post-transplant was 51.9 ± 4.2 ml/min/1.73 m2 (N = 23). Three death-censored graft losses and four deaths with a functioning graft and were observed. Conclusion: PN of renal grafts with suspicious looking masses or cysts is a safe option to optimize organ usage and decrease the kidney non-use rate, with no observed recurrence of malignancy or increased risk of complications.

Competing Risks Analysis of Kidney Transplant Waitlist Outcomes: Two Important Statistical Perspectives.

Modern competing risks analysis has 2 primary goals in clinical epidemiology as follows: (i) to maximize the clinician's knowledge of etiologic associations existing between potential predictor variables and various cause-specific outcomes via cause-specific hazard models, and (ii) to maximize the clinician's knowledge of noteworthy differences existing in cause-specific patient risk via cause-specific subdistribution hazard models (cumulative incidence functions [CIFs]). A perfect application exists in analyzing the following 4 distinct outcomes after listing for a deceased donor kidney transplant (DDKT): (i) receiving a DDKT, (ii) receiving a living donor kidney transplant (LDKT), (iii) waitlist removal due to patient mortality or a deteriorating medical condition, and (iv) waitlist removal due to other reasons. It is important to realize that obtaining a complete understanding of subdistribution hazard ratios (HRs) is simply not possible without first having knowledge of the multivariable relationships existing between the potential predictor variables and the cause-specific hazards (perspective #1), because the cause-specific hazards form the "building blocks" of CIFs. In addition, though we believe that a worthy and practical alternative to estimating the median waiting-time-to DDKT is to ask, "what is the conditional probability of the patient receiving a DDKT, given that he or she would not previously experience one of the competing events (known as the cause-specific conditional failure probability)," only an appropriate estimator of this conditional type of cumulative incidence should be used (perspective #2). One suggested estimator, the well-known "one minus Kaplan-Meier" approach (censoring competing events), simply does not represent any probability in the presence of competing risks and will almost always produce biased estimates (thus, it should never be used).

Current Approaches in Surgical and Immunotherapy-Based Management of Renal Cell Carcinoma with Tumor Thrombus.

Renal cell carcinoma (RCC) accounts for 2-3% of all malignant disease in adults, with 30% of RCC diagnosed at locally advanced or metastatic stages of disease. A form of locally advanced disease is the tumor thrombus (TT), which commonly grows from the intrarenal veins, through the main renal vein, and up the inferior vena cava (IVC), and rarely, into the right cardiac chambers. Advances in all areas of medicine have allowed increased understanding of the underlying biology of these tumors and improved preoperative staging. Although the development of several novel system agents, including several clinical trials utilizing immune checkpoint inhibitors and combination therapies, has been shown to lower perioperative morbidity and increase post-operative recurrence-free and progression-free survival, surgery remains the mainstay of therapy to achieve a cure. In this review, we provide a description of specific surgical approaches and techniques used to minimize intra- and post-operative complications during radical nephrectomy and tumor thrombectomy of RCC with TT extension of various levels. Additionally, we provide an in-depth review of the major developments in neoadjuvant and adjuvant immunotherapy-based treatment and the impact of ongoing and recently completed clinical trials on the surgical treatment of advanced RCC.

The surgical evolution of radical nephrectomy and tumor thrombectomy: a narrative review.

Background and Objective: Renal cell carcinoma (RCC) accounts for 2-3% of all malignant disease in adults. RCC propagates into the renal vein and inferior vena cava (IVC) in up to 25% of patients with RCC. Despite advances in medical management such as immunotherapy, surgical resection remains the gold standard treatment of RCC with venous tumor thrombus (TT) extension. Surgical innovation has revolutionized the management of RCC with TT, reducing morbidity and mortality through advanced surgical techniques and minimally invasive approaches. The aim of this review is to summarize the evolving developments in the surgical treatment of RCC with venous TT. Methods: We performed an advanced search on PubMed between the inception of the database and April 2022 to summarize the evolution of the surgical management of RCC with venous TT, focusing on the reports of key historical, current, and recent studies. Key Content and Findings: Implementation of entirely intraabdominal liver transplant-based approaches have allowed for successful surgical excision of higher-level tumor thrombi, obviating the need for sternotomy or cardiopulmonary bypass (CPB). Recent advances in robotic surgery provide a promising approach for minimally invasive management of RCC with venous TT extension. Conclusions: Surgical innovation has revolutionized the management of RCC with TT, reducing morbidity and mortality through minimally invasive techniques with preserved oncologic effectiveness.

Unresectable leiomyosarcoma of the inferior vena cava with right atrium tumor thrombus: when to deem this tumor inoperable? A case report and literature review.

Leiomyosarcomas (LMS) of the inferior vena cava (IVC) are a rare form of retroperitoneal malignancy, and their venous extension to the right atrium is an even rarer event. These tumors pose a unique surgical challenge and often require a multidisciplinary team-based approach for their surgical treatment. We present a case of a 68-year-old man with primary LMS of the IVC with a tumor thrombus extending into the right atrium that was initially deemed inoperable. After extensive neoadjuvant chemo-radiation with minimal tumor effect, the patient underwent en bloc surgical resection of the tumor along with removal of the infrarenal IVC and right kidney and adrenal without the need for cardiopulmonary bypass. This case demonstrates the successful management of a primary LMS of the IVC with right atrial extension using a multimodal approach of neoadjuvant chemo-radiation and en bloc surgical resection without cardiopulmonary bypass. This strategy may offer a curative option for selected patients with these rare and aggressive tumors, improving their survival and quality of life.

Long-term effects of average calcineurin inhibitor trough levels (over time) on renal function in a prospectively followed cohort of 150 kidney transplant recipients.

More favorable clinical outcomes with medium-term follow-up have been reported among kidney transplant recipients receiving maintenance therapy consisting of "reduced-tacrolimus (TAC) dosing," mycophenolate mofetil (MMF), and low-dose corticosteroids. However, it is not clear whether long-term maintenance therapy with reduced-calcineurin inhibitor (CNI) dosing still leads to reduced renal function. A prospectively followed cohort of 150 kidney transplant recipients randomized to receive TAC/sirolimus (SRL) versus TAC/MMF versus cyclosporine microemulsion (CSA)/SRL, plus low-dose maintenance corticosteroids, now has 20 years of post-transplant follow-up. Average CNI trough levels over time among patients who were still alive with functioning grafts at 60, 120, and 180 months post-transplant were determined and ranked from smallest-to-largest for both TAC and CSA. Stepwise linear regression was used to determine whether these ranked average trough levels were associated with the patient's estimated glomerular filtration rate (eGFR) at those times, particularly after controlling for other significant multivariable predictors. Experiencing biopsy-proven acute rejection (BPAR) and older donor age were the two most significant multivariable predictors of poorer eGFR at 60, 120, and 180 months post-transplant (p < 000001 and 0.000003 for older donor age at 60 and 120 months; p = 0.00008 and <0.000001 for previous BPAR at 60 and 120 months). Assignment to CSA also implied a significantly poorer eGFR (but with less magnitudes of effect) in multivariable analysis at 60 and 120 months (p = 0.01 and 0.002). Higher ranked average CNI trough levels had no association with eGFR at any timepoint in either univariable or multivariable analysis (p > 0.70). Long-term maintenance therapy with reduced-CNI dosing does not appear to cause reduced renal function.

Retroperitoneal kidney transplantation with liver and native kidney mobilization: a safe technique for pediatric recipients.

BACKGROUND: Pediatric kidney transplant (KT) using larger, deceased or living donor adult kidneys can be challenging in the pediatric population due to limited space in the retroperitoneum. Liver and native kidney (L/NK) mobilization techniques can be used in smaller and younger transplant recipients to aid in retroperitoneal placement of the renal allograft. Here, we compare the clinical outcomes of pediatric retroperitoneal KT with and without L/NK mobilization. METHODS: We retrospectively analyzed pediatric renal transplant recipients treated between January 2015 and May 2021. Donor and recipient demographics, intraoperative data, and recipient outcomes were included. Recipients were divided into two groups according to the surgical technique utilized: with L/NK mobilization (Group 1) and without L/NK mobilization (Group 2). Baseline variables were described using frequency distributions for categorical variables and means and standard errors for continuous variables. Tests of association with the likelihood of using L/NK mobilization were performed using standard χ2 tests, t tests, and the log-rank test. RESULTS: Forty-six pediatric recipients were evaluated and categorized into Group 1 (n = 26) and Group 2 (n = 20). Recipients in Group 1 were younger (6.7 ± 0.8 years vs. 15. 3 ± 0.7, P < 0.001), shorter (109.5 ± 3.7 vs. 154.2 ± 3.8 cm, P < 0.001) and weighed less (21.4 ± 2.0 vs. 48.6 ± 3.4 kg, P < 0.001) than those in Group 2. Other baseline characteristics did not differ between Groups 1 and 2. One urologic complication was encountered in Group 2; no vascular or surgical complications were observed in either group. Additionally, no stents or drains were used in any of the patients. There were no cases of delayed graft function or graft primary nonfunction. The median follow-up of the study was 24.6 months post-transplant. Two patients developed death-censored graft failure (both in Group 2, P = 0.22), and there was one death with a functioning graft (in Group 2, P = 0.21). CONCLUSIONS: Retroperitoneal liver/kidney mobilization is a feasible and safe technique that facilitates implantation of adult kidney allografts into pediatric transplant recipients with no increased risk of developing post-operative complications, graft loss, or mortality.

Renal cell carcinoma with right atrium tumor thrombus treated with radical nephrectomy and tumor thrombectomy in a patient with previous coronary artery bypass graft: a case report.

Renal cell carcinoma (RCC) with inferior vena cava (IVC) and right atrium (RA) tumor thrombus (TT) is a rare occurrence and its resection is surgical challenge. Management becomes even more difficult when the TT causes hepatic vein obstruction and leads to Budd-Chiari syndrome. We report a case of 68-year-old male with right RCC with IVC and RA TT with associated Budd-Chiari syndrome. Surgical management was performed without cardiopulmonary bypass (CPB) and re-sternotomy due to the patient's previous history of coronary artery bypass grafting (CABG) for 3 vessel coronary artery disease. Through a transabdominal approach, the diaphragm was dissected off the IVC and the RA was gently pulled into the abdomen and clamped under transesophageal echocardiogram (TEE) control. As use of CPB in these surgeries is associated with increased morbidity and mortality, this organ transplant-based approach is encouraged for patients requiring resection of RCC with supradiaphragmatic TT.

Renal cell carcinoma with inferior vena cava tumor thrombus initially misdiagnosed as bland thrombus due to hypercoagulable state.

Renal cell carcinoma with inferior vena cava tumor thrombus can be misdiagnosed as an inferior vena cava thrombosis if not evaluated carefully with imaging. We describe a case of renal cell carcinoma with inferior vena cava tumor thrombus that was initially misdiagnosed as an inferior vena cava thrombosis due to a possible hypercoagulable state. After 7 months of anticoagulation therapy with no improvement, a right radical nephrectomy and thrombectomy was performed without cardiopulmonary bypass, and a diagnosis of papillary renal cell carcinoma with a level-IIId tumor thrombus was confirmed with no presence of a bland thrombus. We demonstrate the complexity of identifying and treating renal cell carcinoma with venous tumor thrombus and the importance of differentiating between a malignant thrombus and a bland thrombus.

Renal Cell Carcinoma with Supradiaphragmatic Tumor Thrombus: Avoiding Sternotomy and Cardiopulmonary Bypass.

Renal cell carcinoma (RCC) accounts for 2-3% of all malignant disease in adults and has a propensity to infiltrate the surrounding adjacent structures with a biologic predisposition for vascular invasion. This tropism for the venous system facilitates propagation into the renal vein and inferior vena cava (IVC) in up to 25% of patients with RCC. Surgical resection remains the mainstay treatment for RCC with venous tumor thrombus (TT) extension and the only hope for a potential cure. Higher thrombus levels correlate with more advanced stages of disease and thus poorer survival rates. Although CPB with circulatory arrest has been successfully performed during resection of these tumors, its use remains controversial due to the risk of coagulopathy, platelet dysfunction, and central nervous system complications. Complete intraabdominal surgical excision of level III thrombi can be achieved without sternotomy and CPB by utilizing hepatic mobilization maneuvers. The purpose of this review is to provide an update on the surgical management of these difficult cases of RCC with supradiaphragmatic tumor thrombi, including a description of transplant-based techniques that avoid sternotomy and cardiopulmonary bypass (CPB), minimizing intra- and post-operative complications.

Complex Vascular Reconstruction of an En Bloc Pediatric Kidney Damaged during Organ Procurement.

En bloc pediatric kidney (EBPK) allografts are a potential solution to expand the organ donor pool; however, EBPK transplantation has been traditionally considered suboptimal due to concerns of perioperative vascular and urologic complications. Accidental organ or vasculature injury during harvest is not uncommon; however, this does not necessarily mean that the organ should be discarded. Careful vascular reconstruction can be performed using donor vascular grafts, salvaging the organ without stenosis or thrombosis of the vessels. We report an extensive vascular reconstruction of the right renal artery, aorta, and inferior vena cava of a damaged EBPK allograft using a donor pediatric aorta vascular patch with the goal of avoiding postoperative vascular complications.