Robot-assisted radical prostatectomy using the novel hinotoriTM surgical robot system: initial experience and operation learning curve at a single institution.

Background: The hinotoriTM surgical robot system (HSRS) is the first made-in-Japan robotic system used for radical prostatectomy. Here, we report initial results and describe our learning curve (skill development) implementing robot-assisted radical prostatectomy using HSRS (h-RARP). Methods: Between November 2021 and December 2022, 97 patients who underwent h-RARP at our institution were enrolled in this study. We retrospectively evaluated the surgical outcomes of the initial cases using h-RARP, comparing those of RARP using da Vinci surgical robot system (d-RARP) in our institution. Furthermore, the learning curves of two surgeons with the highest number of h-RARP were analyzed. Patients treated by each surgeon were categorized into two groups: 1-15 cases (earlier group) and >15 cases (later group). Preoperative patient characteristics, operation parameters, and complication rates were compared between the two groups. Results: In terms of surgical outcome, h-RARP was comparable to d-RARP. The procedures performed by the HSRS were successfully completed in all cases. There was no complication of grade 3 or higher. Comparing the two surgeons, surgeon 1, who had performed 40 d-RARP procedures, had time using robot system of the later group that was significantly shorter than that of the earlier group. However, for surgeon 2 with more than 100 d-RARP procedures, there was no statistically significant difference in time using robot system between groups. Other parameters showed no difference between earlier and later groups for the two surgeons. Conclusions: Our results show that surgical outcomes of h-RARP are comparable to those of d-RARP during the initial experience of clinical application. In addition, the surgeons' learning curves for the total RARP experience suggest that the experience of d-RARP can carry over to performance using the novel HSRS.

A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib.

For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.

A Case Report of Successful Renal Transplantation After Surgically Treated Type A Aortic Dissection.

BACKGROUND: Aortoiliac lesions can influence the results of kidney transplantation and increase technical difficulties during surgery. Aortic dissection (AD) is a rare and infrequently reported event before transplantation, whereas immediate optimal perfusion is paramount for kidney transplantation. Thus, adequate blood flow imposed by the flow from the true lumen must be considered when choosing a target inflow vessel. CASE PRESENTATION: A 67-year-old man on dialysis with end-stage renal disease caused by immunoglobulin A nephropathy was referred for kidney transplantation. He had successfully undergone conventional Stanford type A AD surgery 3 years ago. Pretransplant contrast-enhanced computed tomography angiography revealed termination of the distal intimal flaps within the common iliac arteries. Dilation of the descending aorta was also observed. Based on the meticulous vascular assessment, including consultation with the cardiovascular surgery department, the right internal iliac artery (IIA) was considered usable for anastomosis. He underwent living unrelated kidney transplantation from his 66-year-old wife. The patency and blood flow in the right IIA were also verified using intraoperative findings. Without any special procedure, we used a side-to-end arterial anastomosis between the donor renal artery and recipient IIA. After vascular clamp removal, the allograft was perfused homogeneously and immediately functioned. CONCLUSION: Patients receiving previous surgery for type A AD can successfully undergo kidney transplantation if the patency of the iliac arteries from the true lumen is confirmed by perioperative evaluation, and the artery can be carefully clamped to avoid possible further dissection.

A Case Report of Successful Kidney Transplantation in a Patient With Autosomal Dominant Polycystic Kidney Disease Who Underwent Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with several cardiovascular disorders, including aortic dissection, which preferentially occurs at the thoracic or abdominal level. Because there are few case reports describing surgical repair for aortic dissection followed by renal transplantation in patients with ADPKD, kidney transplantation performed after repair for aortic dissection remains challenging. CASE PRESENTATION: A 34-year-old Japanese man with end-stage renal disease secondary to ADPKD underwent thoracic endovascular aortic repair for complicated acute type B aortic dissection 12 months earlier. A contrast computed tomography scan before transplantation revealed an aortic dissection involving the descending aorta proximal to the common iliac arteries and confirmed multiple large bilateral renal cysts. After simultaneous right native nephrectomy, the patient underwent preemptive living-donor kidney transplantation obtained from his mother. Intraoperatively, we noted that dissection of the external iliac vessels was difficult because of dense adhesions. Arterial clamping was performed immediately below the bifurcation of the internal iliac artery to prevent further aortic dissection of the external iliac artery. After end-to-end anastomosis to the internal iliac artery was completed and the vascular clamp was released, the kidney began to produce urine immediately. CONCLUSION: This case suggests that kidney transplantation in patients undergoing endovascular aortic repair for aortic dissection can be performed by adequately applying a vascular clamp proximal to the internal iliac artery during vascular anastomosis.

Role of Early Serial Renal Transplant Allograft Protocol Biopsies in Living Kidney Transplantations.

PURPOSE: This study aimed to analyze the incidence of subclinical rejection (SCR) in kidney transplantation patients and risk factors associated with SCR. METHODS: We assessed 80 protocol biopsies taken within 2 years postoperatively in 41 adult patients who underwent living donor kidney transplantation between 2017 and 2020. All patients were on immunosuppressant therapy that included tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The prevalence of Banff Borderline classification at 3, 6, and 12 months after transplantation was 4%, 5%, and 8 %, respectively, whereas none of the biopsies met the Banff criteria for acute T cell-mediated rejection throughout the study period. Active antibody-mediated rejection (ABMR) was only present in 8% of patients at 3 months after transplantation and chronic active ABMR at 6, 12, and 24 months after transplantation was detected in 10%, 13%, and 11% of the patients, respectively. Subgroup analysis revealed that 50% of the 6 patients with preformed anti-donor specific antibodies (DSAs) developed clinical or subclinical active ABMR within 3 months after transplantation, followed by chronic active ABMR according to serial histologic assessment. Conversely, only a small proportion of patients (3%) without preformed DSAs exhibited clinically active ABMR. CONCLUSIONS: SCR occurs too infrequently in patients with low immunologic risk and strong contemporary immunosuppression therapy to justify the diagnostic effort of serial protocol biopsies. However, protocol biopsies remain an indispensable tool in renal transplant monitoring and may be especially important in immunologically high-risk patients with pre-existing DSAs.

Interstitial fibrosis is the critical determinant of impaired renal function in transplant glomerulopathy.

AIM: Transplant glomerulopathy (TG) is a feature of chronic antibody-mediated injury in the glomerular capillaries in renal transplant recipients. TG is generally associated with proteinuria; however, renal function at the diagnosis of TG varies. This study aimed to determine which morphological abnormalities are associated with renal function and proteinuria at the diagnosis of TG. METHODS: A total of 871 renal transplantations were performed at Tokyo Women's Medical University between 2005 and 2013. TG was diagnosed in 127 biopsies from 58 (6.7%) recipients. Renal function was evaluated by the estimated glomerular filtration rate (eGFR). Proteinuria was assessed by a dipstick test: positive for +1 and over. RESULTS: At diagnosis, of 127 biopsies, 72, 37, and 18 had mild, moderate, and severe TG (Banff cg). The severity of TG was not associated with decreased eGFR at the time of biopsy (cg1: 36.1 ± 14.8, cg2-3: 38.8 ± 14.5 mL/min per 1.73 m(2) , P = 0.25), whereas the severity of interstitial fibrosis (IF) (Banff ci) was significantly associated with decreased eGFR (ci0-1: 42.75 ± 13.32, ci2-3: 27.69 ± 11.94 mL/min per 1.73 m(2) , P < 0.0001). The multivariate analysis revealed that IF was the only independent risk factors for decreased eGFR (OR = 4.38, P = 0.0006). Meanwhile, TG was identified as the only independent risk factor for the incidence of proteinuria (OR = 2.67, P = 0.014). CONCLUSION: Interstitial fibrosis was a critical determinant of impaired renal function at the diagnosis of TG. The severity of TG was significantly associated with proteinuria, but did not contribute to renal dysfunction.

Novel CD8 T cell alloreactivities in CCR5-deficient recipients of class II MHC disparate kidney grafts.

Recipient CD4 T regulatory cells inhibit the acute T cell-mediated rejection of renal allografts in wild-type mice. The survival of single class II MHC-disparate H-2(bm12) renal allografts was tested in B6.CCR5(-/-) recipients, which have defects in T regulatory cell activities that constrain alloimmune responses. In contrast to wild-type C57BL/6 recipients, B6.CCR5(-/-) recipients rejected the bm12 renal allografts. However, donor-reactive CD8 T cells rather than CD4 T cells were the primary effector T cells mediating rejection. The CD8 T cells induced to bm12 allografts in CCR5-deficient recipients were reactive to peptides spanning the 3 aa difference in the I-A(bm12) versus I-A(b) ß-chains presented by K(b) and D(b) class I MHC molecules. Allograft-primed CD8 T cells from CCR5-deficient allograft recipients were activated during culture either with proinflammatory cytokine-stimulated wild-type endothelial cells pulsed with the I-A(bm12) peptides or with proinflammatory cytokine-simulated bm12 endothelial cells, indicating their presentation of the I-A(bm12) ß-chain peptide/class I MHC complexes. In addition to induction by bm12 renal allografts, the I-A(bm12) ß-chain-reactive CD8 T cells were induced in CCR5-deficient, but not wild-type C57BL/6, mice by immunization with the peptides. These results reveal novel alloreactive CD8 T cell specificities in CCR5-deficient recipients of single class II MHC renal allografts that mediate rejection of the allografts.

Proliferative glomerulonephritis with monoclonal immunoglobulin A light-chain deposits in the renal allograft.

We herein describe the unique case of a 59-year-old man who underwent living kidney transplantation for IgA nephropathy (IgAN) and developed progressive kidney failure associated with the appearance of proliferative glomerulonephritis. An early protocol biopsy revealed recurrent IgAN with mesangial IgA2 deposits restricted to a single immunoglobulin λ light-chain isotype. Despite treatment with tonsillectomy and rituximab, the patient eventually lost his allograft 31 months after transplantation. Serum electrophoresis showed a monoclonal IgA pattern. This case might share common pathological characteristics with the newly described entity referred to as proliferative glomerulonephritis with monoclonal IgG deposits.

Interleukin-6 receptor signaling disruption prevents cardiac allograft deterioration in mice.

OBJECTIVES: Interleukin-6, a pleiotropic cytokine that functions in both innate and adaptive immune responses, has been implicated in allograft rejection. We analyzed the efficacy of anti interleukin-6 receptor monoclonal antibody in delaying allograft rejection in a murine model of a heart. MATERIALS AND METHODS: To investigate the role of interleukin-6 receptor signal transduction in acute and chronic allograft rejection, we blocked interleukin-6 receptor signaling to suppress the alloimmune response in C57BL/6 recipients of BALB/c cardiac allografts. RESULTS: Administration of a high-dose α-interleukin-6 receptor monoclonal antibody prevented the intragraft infiltration of inflammatory cells and lymphocytes and prolonged allograft survival during the peritransplant period. However, all allografts were rejected by 23.5 days after transplant. In contrast, cardiac allograft recipients treated with a cytotoxic T-lymphocyte antigen 4-immunoglobulin plus continued administration of low-dose α-interleukin-6 receptor monoclonal antibody showed long-term graft survival compared with cytotoxic T-lymphocyte antigen 4-immunoglobulin monotherapy. A histologic analysis revealed that graft fibrosis was prevented in cytotoxic T-lymphocyte antigen 4-immunoglobulin plus high-dose α-interleukin-6 receptor monoclonal antibody group, but not in the cytotoxic T-lymphocyte antigen 4-immunoglobulin alone group. This suggests that deterioration of graft function associated with chronic rejection could be prevented by blocking interleukin-6 receptor signaling. CONCLUSIONS: Disruption of interleukin-6 receptor signaling is an effective strategy for modulating proinflammatory immune responses and preventing chronic rejection.

Mild rhabdomyolysis after renal transplantation.

We present a kidney transplantation patient who developed rhabdomyolysis. The patient was initially immunosuppressed with tacrolimus, mycophenolate mofetil, steroids, and chimeric CD25 monoclonal antibody. He complained of severe precordial and appendicular pain on 25th day after the operation. The patient developed rhabdomyolysis manifested as a rise in serum creatine phosphkinase (CPK) and elevation of urinary myoglobulin at approximately the same time as his symptoms. Although he was switched from tacrolimus to cyclosporine (CYA), his muscle pain and levels of serum CPK did not improve. However, dividing the daily total amount of the calcinuerin inhibitors into more frequent doses in order to reach lower serum levels resolved the rhabdomyolysis. Therefore, we conclude that his rhabdomyolysis might be a dose-related problem of calcineurin inhibitor.

Potential role of host effector memory CD8+ T cells in marrow rejection after mixed chimerism induction in cynomolgus monkeys.

Mixed hematopoietic chimerism provides a powerful means of achieving transplantation tolerance. We investigated the efficacy of combined blockade of the CD40/CD154 and CD28/B7 costimulation pathways to induce sustained mixed chimerism in cynomolgus monkeys following major histocompatibility complex-mismatched bone marrow (BM) transplants. A nonmyeloablative conditioning regimen of busulfan, intravenous and intraosseous ifosfamide, and anti-thymocyte globulin was used. BM transplantation was followed by a one-week course of CTLA4-Ig/anti-CD154 monoclonal antibodies. Three recipients achieved a wide range of transient chimerism (10.8-79.8%). A rapid proliferation of host effector memory (CD28(low)CD95(high)) CD8(+) T cells was observed in conditioned animals whether or not they received allogeneic BM, and this expansion occurred concurrently with the loss of chimerism in BM recipients. CD8(+) T cells from the recipients had increased reactivity to donor stimulators vs. third-party stimulators. Additional immunosuppression with tacrolimus or deoxyspergualin after transplantation delayed post-transplant proliferation of effector memory CD8(+) T cells but did not promote chimerism. A one-month course of costimulatory blockade also did not prevent marrow rejection. These studies demonstrate that combined CD40/CD154 and CD28/B7 costimulatory blockade supports transient mixed chimerism induction following nonmyeloablative conditioning in primates, but is insufficient to overcome host immune resistance likely mediated by effector memory CD8(+) T cells.

New-onset diabetes after transplantation in tacrolimus-treated, living kidney transplantation: long-term impact and utility of the pre-transplant OGTT.

BACKGROUND: To evaluate the role of the oral glucose tolerance test (OGTT) before transplantation and to examine the risk factors for new-onset diabetes after transplantation (NODAT) during long-term follow-up of renal transplant recipients receiving FK-based therapy. METHODS: The study evaluated 378 patients pre-transplantation using the OGTT and assigned them to one of three groups: Group 1, normal pattern; Group 2, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) pattern (IFG/IGT); and Group 3, DM pattern. RESULTS: Although the incidence of NODAT was higher in Group 3 than in groups 1 and 2, no significant difference was found between the three groups with regard to graft survival during long-term follow-up. Multivariate analysis showed that only a family history of diabetes was a significant factor determining NODAT progression. CONCLUSIONS: Impaired glucose tolerance appears to be a threshold influencing NODAT; however, it was not a significant factor in graft survival. Careful monitoring and management based on the result of the pre-transplantation OGTT appear to prevent the deterioration of impaired glucose tolerance in renal transplant recipients receiving FK-based therapy, even when a pre-operative OGTT shows impaired glycemic control.

Impact of low-dose rituximab on splenic B cells in ABO-incompatible renal transplant recipients.

The purpose of this study was to assess the effect of a low-dose rituximab (RIT) at < 375 mg/m(2) on B cells in the spleen and peripheral blood. Five renal transplant recipients received a single dose of RIT at 10, 15, 35, 150, or 300 mg/m(2) 3-13 days before transplantation. One patient who received the same immunosuppressive regimen except for RIT was also enrolled as a control. Splenectomy was performed at the time of transplantation in all patients. The B-cell count in the peripheral blood was analysed with a fluorescence-activated cell sorter using anti-CD19 antibodies, and the B cells in the spleen were analysed by immunohistochemistry using anti-CD20 and -CD79a antibodies. All but one dosage (10 mg/m(2)) of RIT completely eliminated B cells from the circulation within 30 days. Immunohistochemical examination of the spleen showed a marked reduction of B cells in the white pulps in all five recipients compared with that in the control patient. The observations in this study indicated that RIT has a potent effect of depleting B cells in the spleen and peripheral blood at low-doses of < 375 mg/m(2).

Differences in humoral immunity between a non-rejection group and a rejection group after ABO-incompatible renal transplantation.

BACKGROUND: Renal transplantation across the blood barrier is a unique model for investigating the humoral response to different carbohydrate antigens. However, in such a renal transplantation, the characteristics of B cells as well as of the antibodies produced by B cells are less well defined. METHODS: In the present study we investigated B cell subsets (i.e., the CD5(+) B-1 and CD5- B-2 subsets) by flow cytometric analysis, and their subclasses of antibody, by ELISA, in patients who had undergone renal transplantation across the blood barrier. The subjects consisted of five recipients with good function (group 1) and five recipients with graft loss (group 2) accompanied by antibody-titer elevation after ABO-incompatible renal transplantation. RESULTS: The B-cell population analysis revealed that CD5(+) B-1 cells temporarily increased in all patients in both groups soon after transplantation, and that CD5- B-2 cells significantly increased 1 month after transplantation only in group 2. The antibody subclasses analysis showed mild elevation of immunoglobulin (Ig) G2 and IgM in group 1 as opposed to remarked elevation of IgG2, IgM and IgG1 in group 2. CONCLUSIONS: The results of this study suggested that CD5(+) B-1 cell T-independent activation usually occurs soon after ABO-incompatible renal transplantation, but that CD5- B-2 cell T-dependent activation occurs only in patients who experience graft rejection.

Lack of correlation between results of ABO-incompatible living kidney transplantation and anti-ABO blood type antibody titers under our current immunosuppression.

In this study, we examined the impact of preoperative anti-A/B antibody titers on the results of ABO-incompatible living kidney transplantation (LKT). In all, 167 recipients underwent ABO-incompatible LKT at our institution between 1989 and 2002. These patients were subdivided into those transplanted under cyclosporine with azathioprine or mizoribine (Group 1, n=78) and those transplanted under tacrolimus or mycophenolate mofetil (Group 2, n=89). Overall patient survival at 5 and 10 years was 93.8% and 88.0%, respectively. Overall graft survival at 5 and 10 years was 76.9% and 55.9%, respectively. Graft survival in the patients with anti-A/B IgG titers over 1:128 was significantly lower in group 1, whereas no significant correlation between the anti-A/B IgG titers and graft survival was found in group 2. In conclusion, no correlation between anti-A/B antibody titers and the results of ABO-incompatible LKT was seen after tacrolimus or mycophenolate mofetil application.

The mechanism responsible for accommodation after living-related kidney transplantations across the blood barrier.

The mechanism responsible for accommodation in renal transplantations across the blood barrier remains unclear. We recently encountered two patients with accommodated status after living-related kidney transplantations across the blood barrier. Both developed elevations of anti-blood-group antibodies to titers over 128x after transplantation, despite excellent renal function. We investigated the serum samples after the establishment of accommodation bound to the erythrocyte membrane of the donors or the third party with the same blood group. After the establishment of accommodation, the serum samples from both accommodated patients demonstrated a significant decrease in binding to the donors' erythrocyte membrane, but did not show any decrease in binding to the erythrocyte membrane of the third party. By contrast, serum samples from patients with graft loss after unsuccessful accommodation showed high anti-blood-type antibody activity directed towards both the donor's and the third party's erythrocytes. The result of this study suggests the difference of quality in antibodies produced by accommodated and nonaccommodated recipients.