Impact of an enhanced recovery protocol in frail patients after intracorporeal urinary diversion.

OBJECTIVE: To determine whether an enhanced recovery after surgery (ERAS) protocol enhances bowel recovery and reduces postoperative ileus (POI) in both non-frail and frail patients after robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: This retrospective cohort study included 186 patients (104 with and 82 without ERAS) who underwent iRARC between 2012 and 2023. 'Frail' patients was defined as those with a low Geriatric-8 questionnaire score (≤13). The primary outcomes were postoperative bowel recovery and the incidence of POI. Secondary outcomes included length of stay (LOS), 30- and 90-day complications, 90-day readmission rate, and POI predictors. RESULTS: The ERAS group exhibited a significantly shorter LOS, early bowel recovery, a lower POI rate, fewer 90-day high-grade complications, and fewer 90-day readmissions than the non-ERAS group in the entire cohort. Non-frail patients in the ERAS group had a lower rate of POI (7.1% vs. 22.1%; P = 0.008), whereas ERAS did not reduce POI in frail patients (44.1% vs. 36.6%; P = 0.50). In the multivariate analysis, ERAS was associated with a reduced risk of POI in both the entire cohort (odds ratio [OR] 0.39, P = 0.01) and in non-frail patients (OR 0.24, P = 0.01), whereas ERAS was not likely to reduce POI (OR 1.14, P = 0.70) in frail patients. Prehabilitation was identified as a favourable predictor of POI. CONCLUSIONS: The ERAS protocol did not reduce POI in frail patients after iRARC, although it enhanced bowel recovery and reduced POI in non-frail patients. Prehabilitation for frail patients might reduce POI.

Total Cell-Free DNA as a Noninvasive Biomarker of a Delayed Graft Function After Kidney Transplantation From Donors After Cardiac Death.

BACKGROUND: Because of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx. STUDY DESIGN AND METHOD: Consecutive patients from living donors (LDs; n = 9), BDs (n = 8), or DCD donors (n = 13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program. RESULTS: The tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r = 0.5825, P < .05). CONCLUSION: Although the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx.

Robotic surgery for pelvic organ prolapse with complete bladder eversion.

Introduction: Pelvic organ prolapse with complete bladder eversion is extremely rare. Case presentation: An 82-year-old woman was diagnosed with uterine prolapse 3 years ago and underwent occasional urethral catheter placement for difficulty in micturition. She presented with vulvar bleeding and prolapsed uterus from the vagina. Pelvic examination revealed uterine prolapse and a 65 × 65-mm red mass ventrally with urinary outflow. Contrast medium leakage from the vulvar mass and guidewire observed on antegrade pyeloureterography indicated pelvic organ prolapse with complete bladder eversion. Manual reduction of the everted bladder, robotic sacrocolpopexy, and bladder neck reconstruction was performed. However, eversion recurred 10 months postoperatively. Subsequently, robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed. There was no recurrence postoperatively. Conclusion: Robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed for complete bladder eversion.

The Effects of Using Pancreases Obtained from Brain-Dead Donors for Clinical Islet Transplantation in Japan.

BACKGROUND: The pool of brain-dead donors (BDDs) was increased with the revision to the relevant law in 2010, and islet transplantation from BDDs was started in 2013. The present study assessed the influence of using pancreases from BDDs on islet transplantation in Japan. METHODS: The donor information registered with the secretariat of islet transplants from 2012 was reviewed, and the results of 86 clinical islet isolations performed in Japan between 2003 and 2018 with non-heart-beating donors (NHBDs) (n = 71) and BDDs (n = 15) were investigated. RESULTS: The number of cases for which donor information was registered with the secretariat of islet transplants increased to 1.84 cases/month from 2013 to 2018 in comparison to 1.44/month in 2012, when only NHBDs were used. The median pancreatic islet yield was 275,550 IEQ (Islet equivalents) in the NHBD group but 3,627,000 in the BDD group, which amounted to a statistically significant difference (p = 0.02). As a result, 38/71 cases (53.5%) were achieved successful islet isolation (>5000 IEQ per recipient weight (kg)) was achieved in 38/71 cases (53.5%) in the NHBD group, and 12/15 cases (80.0%) in the BDD group; thus, the rate of successful islet transplantation was higher in the BDD group. CONCLUSION: The use of pancreases from BDDs has increased the overall number of cases for which donor information is registered with the secretariat of islet transplants and has improved the performance of islet isolation, thereby increasing the probability of successfully achieving islet transplantation.

The Outcomes of Pancreatic Transplantation from Pediatric Donors-A Single Institution Experience.

OBJECTIVES: The aim of this study was to compare the outcomes of pancreatic transplantation from pediatric donors younger than 15 years of age to the outcomes of pancreatic transplantation from adult donors. METHODS: Sixty patients underwent pancreatic transplantation in our facility from August 2012 to June 2019. These patients were divided into two groups according to the age of the donor: Cases in which the donor was younger than 15 years of age were classified into the PD group (n = 7), while those in which the donor was older than 15 years of age were classified into the AD group (n = 53). The outcomes of pancreas transplantation were retrospectively compared between the two groups. RESULTS: Pancreatic graft survival did not differ between the PD and AD groups. Furthermore, there were no differences in the HbA1c and serum creatinine levels at three months, with good values maintained in both groups. The results of oral glucose tolerance tests (OGTTs) revealed that the blood glucose concentration did not differ between the two groups. However, the serum insulin concentration at 30 min after 75 g glucose loading was significantly higher in the PD group. CONCLUSION: The outcomes of pancreatic transplantation from pediatric donors may be comparable to those of pancreatic transplantation from adult donors and the insulin secretion ability after transplantation may be better.

Warm ischemic time as a critical risk factor of graft failure from donors after cardiac death: A single-center experience over three decades in the Kidney Donor Profile Index/Kidney Donor Risk Index era in Japan.

OBJECTIVES: To evaluate the prognostic value of the warm ischemic time and the validity of the Kidney Donor Profile Index/Kidney Donor Risk Index for predicting the survival of donors after cardiac death grafts. METHODS: We retrospectively assessed 315 kidneys retrieved from donors after cardiac death at Fujita Health University Hospital, Toyoake, Aichi, Japan. The Kidney Donor Profile Index/Kidney Donor Risk Index was calculated and the grafts were enrolled. RESULTS: The median follow-up period was 11.9 years. The Kidney Donor Profile Index had a markedly asymmetric distribution (median 94%), and the Kidney Donor Risk Index had high index rates (0.79-2.94, median 1.70). The overall 5-, 10- and 15-year graft survival rates were 67.5%, 52.1% and 38.9%, respectively. The Kidney Donor Profile Index correlated with graft survival. The 5-, 10- and 15-year graft survival rates for the Kidney Donor Profile Index <1.2 were 87.7%, 73.5% and 59.2%; those for the Kidney Donor Risk Index >2.0 were 55.0%, 34.7% and 22.1%, respectively. A Cox multivariate analysis identified the Kidney Donor Risk Index (hazard ratio 2.06, 95% confidence interval 1.48-2.86, P < 0.0001) and warm ischemic time (hazard ratio 1.21, 95% confidence interval 1.09-1.34, P = 0.0010) as independent risk factors for graft loss. The addition of warm ischemic time >30 min had a significant effect, as measured by the C-index (0.708-0.731, P = 0.032), improving the net reclassification improvement score (0.256, P = 0.0039) and integrated discrimination improvement score (0.042, P = 0.0022). CONCLUSIONS: The Kidney Donor Profile Index/Kidney Donor Risk Index is a good prognostic tool for determining the outcomes of donors after cardiac death grafts. However, the warm ischemic time should also be included in the allocation system for donors after cardiac death grafts.

Prediction of Insulin Secretion Ability With Microcirculation Evaluated by Contrast-enhanced Ultrasonography in Pancreas Transplantation.

OBJECTIVES: Contrast-enhanced ultrasonography can evaluate microcirculation. Thus, we used contrast-enhanced ultrasonography in evaluating pancreas graft perfusion and examined the relationship between graft circulation and function. METHODS: Contrast-enhanced ultrasonography was performed in 17 cases within 24 hours and at 1, 3, 5, 7, 14, 21, and 28 days after transplantation (Tx). The time between the time to peak intensity in the parenchyma and that in the vein was defined as delta-Tp(P-V). Graft function was evaluated with oral glucose tolerance test (OGTT) at 1 and 3 months after Tx, and glucagon stimulation test at 1 month after Tx. RESULTS: Differences in delta-Tp(P-V) between individual cases were more significant early after Tx, and delta-Tp(P-V) within 24 hours (delta-Tp[P-V]24h) was used in the subsequent analysis. Delta-Tp(P-V)24 hours showed a negative correlation with C-peptide increment in the glucagon stimulation test and the area under the curve of insulin level in oral glucose tolerance test. The cases were divided into the following 2 groups: the standard group (delta-Tp[P-V]24h ≤6.10 seconds) and the delayed group (>6.10 seconds). The area under the curve of insulin level increased significantly from 1 to 3 months after Tx in the standard group only. CONCLUSIONS: These results suggest that delta-Tp(P-V)24 hours affects insulin secretion after Tx. Contrast-enhanced ultrasonography is useful in predicting endocrine function of the graft.

Effects of carbon monoxide on early dysfunction and microangiopathy following GalT-KO porcine pulmonary xenotransplantation in cynomolgus monkeys.

BACKGROUND: Despite progress in the current genetic manipulation of donor pigs, most non-human primates were lost within a day of receiving porcine lung transplants. We previously reported that carbon monoxide (CO) treatment improved pulmonary function in an allogeneic lung transplant (LTx) model using miniature swine. In this study, we evaluated whether the perioperative treatment with low-dose inhalation of CO has beneficial effects on porcine lung xenografts in cynomolgus monkeys (cynos). METHODS: Eight cynos received orthotopic left LTx using either α-1,3-galactosyltransferase knockout (GalT-KO; n = 2) or GalT-KO with human decay accelerating factor (hDAF) (GalT-KO/hDAF; n = 6) swine donors. These eight animals were divided into three groups. In Group 1 (n = 2), neither donor nor recipients received CO therapy. In Group 2 (n = 4), donors were treated with inhaled CO for 180-minute. In Group 3 (n = 2), both donors and recipients were treated with CO (donor: 180-minute; recipient: 360-minute). Concentration of inhaled CO was adjusted based on measured levels of carboxyhemoglobin in the blood (15%-20%). RESULTS: Two recipients survived for 3 days; 75 hours (no-CO) and 80 hours (CO in both the donor and the recipient), respectively. Histology showed less inflammatory cell infiltrates, intravascular thrombi, and hemorrhage in the 80-hour survivor with the CO treatment than the 75-hours non-CO treatment. Anti-non-Gal cytotoxicity levels did not affect the early loss of the grafts. Although CO treatment did not prolong overall xeno lung graft survival, the recipient/donor CO treatment helped to maintain platelet counts and inhibit TNF-α and IL-6 secretion at 2 hours after revascularization of grafts. In addition, lung xenografts that were received recipient/donor CO therapy demonstrated fewer macrophage and neutrophil infiltrates. Infiltrating macrophages as well as alveolar epithelial cells in the CO-treated graft expressed heme oxygenase-1. CONCLUSION: Although further investigation is required, CO treatment may provide a beneficial strategy for pulmonary xenografts.

Protective effect of neutralization of the extracellular high-mobility group box 1 on renal ischemia-reperfusion injury in miniature swine.

BACKGROUND: Strategies that reduce ischemia-reperfusion injury (IRI) have the potential to expand the numbers of available organs for transplantation. Recent reports in rodent models have demonstrated that high-mobility group box 1 (HMGB1) acts as an alarm in initiating the inflammatory response resulting from ischemic injury. The aim of this study was to evaluate the cytoprotective effects of anti-HMGB1 antibodies on renal IRI in preclinical large animals. METHODS: One hundred twenty minutes of warm and 60 min of cold renal ischemia were induced in 8 CLAWN miniature swine. Three of eight animals received intravenous anti-HMGB1 antibody at 1 mg/kg just before the reperfusion of renal blood flow. Renal function was assessed by serum creatinine and renal biopsy. Serum levels of interleukin (IL)-1ß, IL-6, and HMGB1 were measured. RESULTS: The concentration of HMGB1 increased as early as 30 min after reperfusion and before the elevation of IL-1ß and IL-6. Serum creatinine levels were markedly elevated, peaking at a median of 5 days (peak creatinine levels: 11.6 ± 1.6 mg/dL) and recovering by day 14. Anti-HMGB1 antibody injection dramatically decreased renal damage as well as serum levels of HMGB1 associated with IRI. Renal function returned to near normal by day 9, and peak creatinine levels were markedly lower (7.4 ± 0.2 mg/dL), and biopsies possessed fewer pathologic changes when compared to the control group. CONCLUSION: In this study, we demonstrated the beneficial effects of perioperative administration of anti-HMGB1 antibody in reducing renal IRI in a clinically relevant, large animal model.

Serum liver-type fatty acid-binding protein predicts recovery of graft function after kidney transplantation from donors after cardiac death.

Kidneys procured by donation after cardiac death (DCD) may increase the donor pool but are associated with high incidence of delayed graft function (DGF). Urinary liver-type fatty acid-binding protein (L-FABP) level is an early biomarker of renal injury after kidney transplantation (KTx); however, its utility is limited in DGF cases owing to urine sample unavailability. We examined whether serum L-FABP level predicts functional recovery of transplanted DCD kidneys. Consecutive patients undergoing KTx from living related donors (LD), brain-dead donors (BD), or DCD were retrospectively enrolled. Serum L-FABP levels were measured from samples collected before and after KTx. Serum L-FABP decreased rapidly in patients with immediate function, slowly in DGF patients, and somewhat increased in DGF patients requiring hemodialysis (HD) for >1 wk. Receiver-operating characteristic curve analysis demonstrated that DGF was predicted with 84% sensitivity (SE) and 86% specificity (SP) at cutoff of 9.0 ng/mL on post-operative day (POD) 1 and 68% SE and 90% SP at 6.0 on POD 2. DGF >7 d was predicted with 83% SE and 78% SP at 11.0 on POD 1 and 67% SE and 78% SP at 6.5 on POD 2. Serum L-FABP levels may predict graft recovery and need for HD after DCD KTx.

Geraniol, E-3,7-dimethyl-2,6-octadien-1-ol, as the alarm pheromone of the sycamore lace bug Corythucha ciliata (Say).

Although adult sycamore lace bugs Corythucha ciliata (Say) show no sign of aggregation, nymphs at all developing stages are gregarious. When an individual nymph in the center of a colony was squashed with a needlepoint, proximate nymphs showed evasive behavior. The same evasive reaction was produced by exposing aggregated nymphs to nymph hexane extract. The active component, E-3,7-dimethyl-2,6-octadien-1-ol, geraniol, was responsible for the evasive behavior, and identified as the alarm pheromone. One nanogram of the alarm pheromone elicited activity similar to that in a third instar nymph. Presence of 2-acylcyclohexane-1,3-diones and their 4-hydroxy analogues are reconfirmed as nymph-specific components, though their biological significance remains unknown.