Kidney Transplantation From Deceased Donors With Bloodstream Infection: A Multicenter Retrospective Study

Background@#The use of organs from donors with infection is limited because of the possibility of transmission. We aimed to investigate the transmission after deceased donor transplantation with bloodstream infection (BSI). @*Methods@#A retrospective study of patients undergoing kidney or pancreas transplantation at five tertiary centers in Korea from January 2009 and November 2019 was performed. We analyzed the outcomes after transplantation from deceased donors with BSI. @*Results@#Eighty-six recipients received transplantation from 69 donors with BSI. The most common isolated pathogens from donors were Gram-positive bacteria (72.0%), followed by Gram-negative bacteria (22.7%), and fungi (5.3%). Appropriate antimicrobial agents were used in 47.8% of donors before transplantation. Transmission occurred only in 1 of 83 recipients (1.2%) from bacteremic donors and 1 of 6 recipients (16.7%) from fungemic donors. One-year patient and graft survival was 97.5%and 96.3%, respectively. There was no significant difference in graft and patient survival between patients who received organs from infected donors and noninfected donors. @*Conclusion@#Using organs from donors with bacteremia seems to be a safe option with low transmission risk. The overall prognosis of using organs from donors with BSI is favorable.

Effects of the Type of Intraoperative Fluid in Living Donor Kidney Transplantation: A Single-Center Retrospective Cohort Study

Purpose@#Perioperative fluid management in kidney transplant recipients is crucial to supporting the fluid, acid-base, and electrolyte balance required for graft perfusion. However, the choice of intraoperative crystalloids in kidney transplantation remains controversial. We conducted a single-center retrospective cohort study to evaluate the impact of intraoperative fluids on acidbase and electrolyte balance and graft outcomes. @*Materials and Methods@#We included 282 living donor kidney transplant recipients from January 2010 to December 2017. Patients were classified into two groups based on the type of intraoperative crystalloids used (157 patients in the half saline group and 125 patients in the balanced crystalloid solutions group, Plasma-lyte). @*Results@#Compared with the half saline group, the Plasma-lyte group showed less metabolic acidosis and hyponatremia during surgery. Hyperkalemia incidence was not significantly different between the two groups. Changes in postoperative graft function assessed by blood urea nitrogen and creatinine were significantly different between the two groups. Patients in the Plasma-lyte group exhibited consistently higher glomerular filtration rates than those in the half saline group at 1 month and 1 year after transplantation after adjusting for demographic differences. @*Conclusion@#Intraoperative Plasma-lyte can lead to more favorable results in terms of acid-base balance during kidney transplantation. Patients who received Plasma-lyte showed superior postoperative graft function at 1 month and 1 year after transplantation.Further studies are needed to evaluate the superiority of intraoperative Plasma-lyte over other types of crystalloids in relation to graft outcomes.

Quantification of the Elastic Property of Normal Thigh Muscles Using MR Elastography:Our Initial Experience

Purpose@#This study aimed to apply MR elastography (MRE) to achieve in vivo evaluation of the elastic properties of thigh muscles and validate the feasibility of quantifying the elasticity of normal thigh muscles using MRE. @*Materials and Methods@#This prospective study included 10 volunteer subjects [mean age, 32.5 years, (range, 23–45 years)] who reported normal activities of daily living and underwent both T2-weighted axial images and MRE of thigh muscles on the same day. A sequence with a motion-encoding gradient was used in the MRE to map the propagating shear waves in the muscle. Elastic properties were quantified as the shear modulus of the following four thigh muscles at rest; the vastus medialis, vastus lateralis, adductor magnus, and biceps femoris. @*Results@#The mean shear modulus was 0.98 ± 0.32 kPa and 1.00 ± 0.33 kPa for the vastus medialis, 1.10 ± 0.46 kPa and 1.07 ± 0.43 kPa for the vastus lateralis, 0.91 ± 0.41 kPa and 0.93 ± 0.47 kPa for the adductor magnus, and 0.99 ± 0.37 kPa and 0.94 ± 0.32 kPa for the biceps femoris, with reader 1 and 2, respectively. No significant difference was observed in the shear modulus based on sex (p < 0.05). Aging consistently showed a statistically significant negative correlation (p < 0.05) with the shear modulus of the thigh muscles, except for the vastus medialis (p = 0.194 for reader 1 and p = 0.355 for reader 2). @*Conclusion@#MRE is a quantitative technique used to measure the elastic properties of individual muscles with excellent inter-observer agreement. Age was consistently significantly negatively correlated with the shear stiffness of muscles, except for the vastus medialis.

Systemic Immunomodulatory Effects of Combinatorial Treatment of Thalidomide and Dexamethasone on T Cells and Other Immune Cells

Purpose@#In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. @*Materials and Methods@#Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. @*Results@#CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. @*Conclusion@#Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.

Complications and outcomes following inguinal lymphadenectomy for malignant melanoma in an Asian population

Purpose@#Melanoma is a potentially fatal cutaneous malignancy and regional lymph node (LN) metastases are the most important predictors of mortality. This study aimed to analyze clinical features and risk factors of complications associated with inguinal LN dissection (LND) to establish treatment protocols. @*Methods@#This single-center retrospective study (2000 to 2018) consisted of patients who underwent inguinal area sentinel LN biopsy (SLNB) or LND due to malignant melanoma. Risk factors and outcomes were analyzed. @*Results@#One hundred patients underwent SLNB alone (n=67; patients with negative SLNB), complete LND (CLND) after positive SLNB (n=19), or radical LND without SLNB (n=14). Five-year overall survival and disease-free survival rates among these groups were 87.3%, 57.4%, and 61.9%, and 59.0%, 22.7%, and 28.1%, respectively. The complication rate in the SLNB alone group was lower than the other groups (22.4% vs. 47.4% and 35.7%, respectively; P=0.048). Seroma was the most common complication in the SLNB alone group (15.0%); lymphedema was most common in the CLND after SLNB group (21.1%). Multivariate analysis of risk factors for postoperative complications found the hazard ratio for body mass index >28 kg/m2 was 4.376 (95% confidence interval [CI], 1.243–15.401; P=0.022). The hazard ratio for LND (including CLND after SLNB and radical LND without SLNB) was 3.263 (95% CI, 1.248–8.529; P=0.016). @*Conclusion@#Inguinal LND is a higher risk procedure compared to SLNB and other sites for postoperative complications, irrespective of meticulous surgical techniques. More studies are needed to establish treatment protocols (e.g., observation vs. CLND after a positive SLNB result) and the risks and benefits in Asian populations.

Complications and outcomes following inguinal lymphadenectomy for malignant melanoma in an Asian population

Purpose@#Melanoma is a potentially fatal cutaneous malignancy and regional lymph node (LN) metastases are the most important predictors of mortality. This study aimed to analyze clinical features and risk factors of complications associated with inguinal LN dissection (LND) to establish treatment protocols. @*Methods@#This single-center retrospective study (2000 to 2018) consisted of patients who underwent inguinal area sentinel LN biopsy (SLNB) or LND due to malignant melanoma. Risk factors and outcomes were analyzed. @*Results@#One hundred patients underwent SLNB alone (n=67; patients with negative SLNB), complete LND (CLND) after positive SLNB (n=19), or radical LND without SLNB (n=14). Five-year overall survival and disease-free survival rates among these groups were 87.3%, 57.4%, and 61.9%, and 59.0%, 22.7%, and 28.1%, respectively. The complication rate in the SLNB alone group was lower than the other groups (22.4% vs. 47.4% and 35.7%, respectively; P=0.048). Seroma was the most common complication in the SLNB alone group (15.0%); lymphedema was most common in the CLND after SLNB group (21.1%). Multivariate analysis of risk factors for postoperative complications found the hazard ratio for body mass index >28 kg/m2 was 4.376 (95% confidence interval [CI], 1.243–15.401; P=0.022). The hazard ratio for LND (including CLND after SLNB and radical LND without SLNB) was 3.263 (95% CI, 1.248–8.529; P=0.016). @*Conclusion@#Inguinal LND is a higher risk procedure compared to SLNB and other sites for postoperative complications, irrespective of meticulous surgical techniques. More studies are needed to establish treatment protocols (e.g., observation vs. CLND after a positive SLNB result) and the risks and benefits in Asian populations.

Sirolimus Combination with Tacrolimus in Kidney Transplant Recipients at High Immunological Risk: Observational Results 3 Years after Transplantation / 대한이식학회지

BACKGROUND: The optimal immunosuppressive strategy for renal transplant recipients at high immunological risk requires clarification. We compared the 3 year outcomes of a sirolimus group (tacrolimus plus sirolimus) to those of a control group (tacrolimus plus mycophenolate mofetil). METHODS: This observational study was an extension of a prospective pilot study. We assessed acute rejection, glomerular filtration rate, adverse events, graft, and patient survival. RESULTS: Overall, 43% of the sirolimus group versus 78% of the control group were still on the initial immunosuppressive regimen at 3 years (P=0.005), and most discontinuations in each group were due to adverse events. No differences were observed between two groups with respect to acute rejection. The mean glomerular filtration rate at 36 months was greater in the sirolimus group than in the control group, but this was not statistically significant (64.0±6.8 mL/min/1.73 m² vs. 61.8±17.1 mL/min/1.73 m², P=0.576). Graft and patient survival were similar in both groups. Importantly, mean tacrolimus through levels were significantly lower in the sirolimus group than in the control group at each time point. No neoplasm was reported in the sirolimus group. In the control group, three cases of neoplasms developed during the study period. CONCLUSIONS: The sirolimus group had a greater number of discontinuations, particularly related to adverse events. Nevertheless, optimal concentration of sirolimus allowed reduced calcineurin inhibitor exposure in high immunologic risk patients, without increasing the risk of acute rejection and graft failure.

A 12-Month Single Arm Pilot Study to Evaluate the Efficacy and Safety of Sirolimus in Combination with Tacrolimus in Kidney Transplant Recipients at High Immunologic Risk

The optimal immunosuppressive strategy for renal transplant recipients at high immunologic risk remains a topic of investigation. This prospective single arm pilot study was undertaken to evaluate the safety and efficacy of a combined tacrolimus and sirolimus regimen in recipients at immunological high risk and to compare outcomes with a contemporaneous control group received tacrolimus and mycophenolate mofetil. Patients that received a renal allograft between 2010 and 2011 at high risk (defined as panel reactive antibodies > 50%, 4 or more human leukocyte antigen mismatches, or retransplantation) were enrolled. All patients received basiliximab induction and corticosteroids. A total of 28 recipients treated with tacrolimus and sirolimus were enrolled in this study and 69 recipients were retrospectively reviewed as a control group. The sirolimus group showed a higher, but not statistically significant, incidence of biopsy proven acute rejection and a lower glomerular filtration rate than the control group. Furthermore, sirolimus group was associated with significant increases in BKV infection (P = 0.031), dyslipidemia (P = 0.004), and lymphocele (P = 0.020). The study was terminated prematurely due to a high incidence of adverse events. A de novo tacrolimus/sirolimus combination regimen may not be an ideal choice for recipients at high immunological risk.

Adult Kidney Transplantation of Pediatric En bloc Kidneys Using a Partial Bladder Wall / 대한이식학회지

Kidney transplantation is a treatment of choice which improves survival and quality of life for patients with end-stage renal disease. Due to the growing waiting list for kidney transplantation, expansion of the donor pool to use of deceased pediatric kidneys is of critical importance. However, the use of pediatric kidneys has been limited due to concerns about early graft failure, hyperfiltration injury, and technical difficulties. Performing ureteroneocystostomy using small pediatric en bloc kidneys is sometimes difficult due to the small diameter and short length of the ureter in the adult kidney recipient. We hereby report on a partial bladder wall transplantation using pediatric en bloc kidneys. Pediatric en bloc kidneys and partial bladder wall from a 12-month-old female donor who weighed 9.13 kg was transplanted into a 49-year-old male recipient. The urinary tract was reconstructed with a partial bladder wall of the donor. At 12 months post-transplantation, Doppler ultrasonograpy and renogram showed stable graft renal function without urological complications. Pediatric en bloc kidney transplantation with a partial bladder wall can be a safe and feasible surgical technique to reduce urological complications.

Effect of donor-specific antibodies and panel reactive antibodies in living donor liver transplant recipients

PURPOSE: Preformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT). METHODS: We retrospectively reviewed 219 LDLT patients' records treated at our center. RESULTS: Of the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (-). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (-) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (-) group. CONCLUSION: In LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT.

The Effect of Bortezomib on Antibody-Mediated Rejection after Kidney Transplantation

PURPOSE: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR. MATERIALS AND METHODS: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11. RESULTS: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91+/-22.15 mL/min/1.73 m2) versus eGFR at time of AMR diagnosis (17.00+/-9.25 mL/min/1.73 m2; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function. CONCLUSION: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.

Laparoscopic Total Gastrectomy in a Gastric Cancer Patient with Intestinal Malrotation

As the incidence of early gastric cancer increases, laparoscopic surgery has become one of the treatments of choice for gastric cancer. With the increase of laparoscopic surgery, the chance of discovering aberrant anatomy during the operation also increases. We present a case of laparoscopic total gastrectomy in gastric cancer patients with intestinal malrotation. Intestinal malrotation occurs in one in every 500 births. We found that laparoscopic total gastrectomy in such patients can be performed successfully when it is performed with a proper Roux limb orientation through an alternative minilaparotomy.

Laparoscopic Total Gastrectomy in a Gastric Cancer Patient with Intestinal Malrotation

As the incidence of early gastric cancer increases, laparoscopic surgery has become one of the treatments of choice for gastric cancer. With the increase of laparoscopic surgery, the chance of discovering aberrant anatomy during the operation also increases. We present a case of laparoscopic total gastrectomy in gastric cancer patients with intestinal malrotation. Intestinal malrotation occurs in one in every 500 births. We found that laparoscopic total gastrectomy in such patients can be performed successfully when it is performed with a proper Roux limb orientation through an alternative minilaparotomy.

Duodenum-preserving pancreatic head resection in benign and low-grade malignant pancreatic tumors

BACKGROUNDS/AIMS: With development of imaging techniques, pancreatic tumors are being diagnosed more frequently. Applying the standard surgical procedures for pancreatic head tumors, such as pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy may seem too extensive for benign or low-grade malignant pancreas head tumors. Duodenum-preserving pancreatic head resection (DPPHR) has been safely performed in patients with chronic pancreatitis. Recently, DPPHR has been used as a limited surgical procedure to remove benign or low-grade malignant pancreatic head lesions. This study is aimed to evaluate the results of DPPHR in benign or low-grade malignant tumors. METHODS: Between 2004 and 2012, six patients underwent DPPHR due to benign or low-grade malignant pancreas tumor. We performed this retrospective analysis based on the medical records. RESULTS: Five of six patients were diagnosed as intraductal papillary mucinous neoplasms. Remaining one patient was diagnosed as solid pseudopapillary neoplasm. The median age of patients was 60.3 (27-75) years, and the median follow-up period was 24 months. The operation time, blood loss and length of stay were 442.5 minutes, 680 ml and 19.2 days, respectively. There was no mortality. Five patients experienced complications including 1 delayed gastric empting, 2 bile duct strictures, 1 pancreatic fistula and 1 duodenal stricture. No recurrence or metastasis was found during follow-up. CONCLUSIONS: In benign and low-grade malignant lesions of pancreatic head, DPPHR could be alternative to traditional surgery. For applying DPPHR in pancreas tumor, a thorough preoperative examination and utilization of frozen section for sufficient resection margin are required.