Purpose: There are increased therapeutic usages of rituximab in kidney transplantation (KT). However, few studies have evaluated the effect of rituximab on cancer development following KT. This study aimed to evaluate the effect of rituximab on the cancer occurrence and mortality rate according to each type of cancer. Methods: Five thousand consecutive recipients who underwent KT at our center were divided into era1 (1990–2007) and era2-rit– (2008–2018), and era2-rit+ (2008–2018) groups. The era2-rit+ group included patients who received single-dose rituximab (200–500 mg) as a desensitization treatment 1–2 weeks before KT. Results: The 5-year incidence rates of malignant tumors after KT were 3.1%, 4.3%, and 3.5% in the era1, era2-rit–, and era2-rit+ group, respectively. The overall incidence rate of cancer after transplantation among the 3 study groups showed no significant difference (P = 0.340). The overall cancer-related mortality rate was 17.1% (53 of 310). Hepatocellular carcinoma (HCC) had the highest mortality rate (61.5%) and relative risk of cancer-related death (hazard ratio, 8.29; 95% confidence interval, 2.40–28.69; P = 0.001). However, we found no significant association between rituximab and the incidence of any malignancy. Conclusion Our results suggest that single-dose rituximab for desensitization may not increase the risk of malignant disease or cancer-related mortality in KT recipients. HCC was associated with the highest risk of cancer-related mortality in an endemic area of HBV infection.

Hyperparathyroidism is common in patients with chronic kidney disease with reduced renal function and has been observed after kidney transplantation. The optimal treatment for cases in which hyperparathyroidism persists after kidney transplantation has not been determined. Methods: This retrospective study included 83 patients with tertiary hyperparathyroidism who underwent kidney transplantation between 2000 and 2018 at a single tertiary center in Korea. Sixty-four patients underwent parathyroidectomy and 19 patients were treated with cinacalcet following renal transplantation. Biochemical parameters and clinical outcomes were compared between the two groups. Results: Serum calcium and parathyroid hormone (PTH) levels improved in both the parathyroidectomy and cinacalcet groups. One year after treatment, parathyroidectomy resulted in a lower mean serum calcium level than cinacalcet (9.7 ± 0.7 mg/dL vs. 10.5 ± 0.7 mg/dL, p = 0.001). Regarding serum PTH, the parathyroidectomy group showed a significantly lower PTH level than the cinacalcet group at 6 months (129.1 ± 80.3 pg/mL vs. 219.2 ± 92.5 pg/mL, p = 0.002) and 1 year (118.8 ± 75.5 pg/mL vs. 250.6 ± 94.5 pg/ mL, p < 0.001). There was no statistically significant difference in the incidence of kidney transplant rejection, graft failure, cardiovascular events, fracture risk, or bone mineral density changes between the two groups. Conclusion: Parathyroidectomy appears to reduce PTH and calcium levels effectively in tertiary hyperparathyroidism. However, creatinine level and allograft rejection should be monitored closely.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels and enhance the function of pancreatic βcells. Yet, it is unknown whether posttransplant administration of DPP4 inhibitors is beneficial for pancreas transplant recipients. Methods: We thus retrospectively analyzed the records of 312 patients who underwent pancreas transplantation between 2000 and 2018 at Asan Medical Center (Seoul, Korea) and compared the metabolic and survival outcomes according to DPP-4 inhibitor treatment. Results: The patients were divided into the no DPP-4 inhibitor group (n = 165; no treatment with DPP-4 inhibitors or treated for <1 month) and the DPP-4 inhibitor group (n = 147; treated with DPP-4 inhibitors for ≥1 month). There were no significant differences in levels of glucose, hemoglobin A1c, and insulin between the 2 groups during 36 months of follow-up. However, the level of C-peptide was significantly higher in the DPP-4 inhibitor group at 1, 6, and 24 months posttransplant (all P < 0.05). Moreover, the DPP-4 inhibitor group had significantly higher rates of overall (log-rank test, P = 0.009) and death-censored (log-rank test, P = 0.036) graft survival during a 15-year follow-up. Conclusion Posttransplant DPP-4 inhibitor administration may help improve the clinical outcomes including β cell function after pancreas transplantation.

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels and enhance the function of pancreatic βcells. Yet, it is unknown whether posttransplant administration of DPP4 inhibitors is beneficial for pancreas transplant recipients. Methods: We thus retrospectively analyzed the records of 312 patients who underwent pancreas transplantation between 2000 and 2018 at Asan Medical Center (Seoul, Korea) and compared the metabolic and survival outcomes according to DPP-4 inhibitor treatment. Results: The patients were divided into the no DPP-4 inhibitor group (n = 165; no treatment with DPP-4 inhibitors or treated for <1 month) and the DPP-4 inhibitor group (n = 147; treated with DPP-4 inhibitors for ≥1 month). There were no significant differences in levels of glucose, hemoglobin A1c, and insulin between the 2 groups during 36 months of follow-up. However, the level of C-peptide was significantly higher in the DPP-4 inhibitor group at 1, 6, and 24 months posttransplant (all P < 0.05). Moreover, the DPP-4 inhibitor group had significantly higher rates of overall (log-rank test, P = 0.009) and death-censored (log-rank test, P = 0.036) graft survival during a 15-year follow-up. Conclusion Posttransplant DPP-4 inhibitor administration may help improve the clinical outcomes including β cell function after pancreas transplantation.

Blood perfusion of skeletal muscle and callus was evaluated using contrast-enhanced ultrasonography (CEUS) in a canine osteotomy model to determine the applicability of CEUS in the assessment of neovascularization during fracture healing and to compare the vascular signals on CEUS between external skeletal fixation and cast-applied dogs. In 6 Beagle dogs, a simple transverse osteotomy was performed at the left tibial shaft and external skeletal fixation (n = 3) or a cast (n = 3) was applied. Radiography, power Doppler ultrasonography (power Doppler), and CEUS were performed until complete union was achieved. On CEUS, vascular changes were quantitatively evaluated by measuring peak intensity (PI) and time to PI in the soft tissue and callus and by counting the vascular signals. Vascular signals from the soft tissue were detected on power Doppler and CEUS on day 2. Significantly more vascular signals were detected by CEUS than by power Doppler. On CEUS, PI in the surrounding soft tissue was markedly increased after the fracture line appeared indistinctively changed on radiography in all dogs. In the cast-applied dogs, vascular signals from the periosteal and endosteal callus were detected on CEUS before mineralized callus was observed on radiography. CEUS was useful in assessing the vascularity of soft tissue and callus, particularly in indirect fracture healing, and provided indications of a normally healing fracture.

Blood perfusion of skeletal muscle and callus was evaluated using contrast-enhanced ultrasonography (CEUS) in a canine osteotomy model to determine the applicability of CEUS in the assessment of neovascularization during fracture healing and to compare the vascular signals on CEUS between external skeletal fixation and cast-applied dogs. In 6 Beagle dogs, a simple transverse osteotomy was performed at the left tibial shaft and external skeletal fixation (n = 3) or a cast (n = 3) was applied. Radiography, power Doppler ultrasonography (power Doppler), and CEUS were performed until complete union was achieved. On CEUS, vascular changes were quantitatively evaluated by measuring peak intensity (PI) and time to PI in the soft tissue and callus and by counting the vascular signals. Vascular signals from the soft tissue were detected on power Doppler and CEUS on day 2. Significantly more vascular signals were detected by CEUS than by power Doppler. On CEUS, PI in the surrounding soft tissue was markedly increased after the fracture line appeared indistinctively changed on radiography in all dogs. In the cast-applied dogs, vascular signals from the periosteal and endosteal callus were detected on CEUS before mineralized callus was observed on radiography. CEUS was useful in assessing the vascularity of soft tissue and callus, particularly in indirect fracture healing, and provided indications of a normally healing fracture.

Animals ; Bony Callus ; Diagnostic Imaging ; Dogs ; Fracture Fixation ; Fracture Healing ; Microbubbles ; Miners ; Muscle, Skeletal ; Osteotomy ; Perfusion ; Radiography ; Ultrasonography ; Ultrasonography, Doppler

PURPOSE: We aimed to compare clinical outcomes after carotid endarterectomy (CEA) between Korean patients with and without severe contralateral extracranial carotid stenosis or occlusion (SCSO). METHODS: Between January 2004 and December 2014, a total of 661 patients who underwent 731 CEAs were stratified by SCSO (non-SCSO and SCSO groups) and analyzed retrospectively. The study outcomes included the occurrence of major adverse cardiovascular events (MACE), defined as stroke or myocardial infarction, and all-cause mortality during the perioperative period and within 4 years after CEA. RESULTS: There were no significant differences in the incidence of MACE or any individual MACE manifestations between the 2 groups during the perioperative period or within 4 years after CEA. On multivariate analysis to identify clinical variables associated with long-term study outcomes, older age (hazard ratios [HRs], 1.06; 95% confidence intervals [CIs], 1.03–1.09; P < 0.001) and diabetes mellitus (HR, 1.71; 95% CI, 1.14–2.57; P = 0.010) were significantly associated with an increased risk of MACE occurrence, while preexisting SCSO was not associated with long-term incidence of MACE and individual MACE components. Kaplan-Meier survival analysis showed similar MACE-free (P = 0.509), overall (P = 0.642), and stroke-free (P = 0.650) survival rates in the 2 groups. CONCLUSION: There were no significant differences in MACE incidence after CEA between the non-SCSO and SCSO groups, and preexisting SCSO was not associated with an increased risk of perioperative or long-term MACE occurrence.
Carotid Stenosis ; Diabetes Mellitus ; Endarterectomy, Carotid ; Humans ; Incidence ; Mortality ; Multivariate Analysis ; Myocardial Infarction ; Perioperative Period ; Retrospective Studies ; Stroke ; Survival Rate

BACKGROUND: Risk factors for bone avascular necrosis (AVN), a common late complication after kidney transplantation (KT), are not well known. METHODS: Patients that underwent living-donor KT at Asan Medical Center between January 2009 and July 2016 were included in this retrospective study to determine the incidence and risk factors for AVN after KT. RESULTS: Among 1,570 patients that underwent living-donor KT, 33 (2.1%) developed AVN during a mean follow-up of 49.8±25.0months. Additionally, AVN was diagnosed at a mean of 13.9±6.6 months after KT. The mean cumulative corticosteroid dose during the last follow-up in patients without AVN (9,108±3,400 mg) was higher than that that in patients with AVN (4,483±1,114 mg) until AVN development (P < 0.01). More patients among those with AVN (n=4, 12.1%) underwent steroid pulse treatment because of biopsy-proven rejections during the first 6 months after KT than patients without AVN (n=68, 4.4%; P=0.04). Female (hazard ratio [HR], 2.29; P=0.04) and steroid pulse treatment during the first 6 months (HR, 2.31; P=0.02) were significant AVN risk factors as revealed by the Cox proportional multivariate analysis. However, no significant differences in rejection-free graft survival rates were observed between the two groups (P=0.67). CONCLUSIONS: Steroid pulse treatment within 6 months of KT and being female were independent risk factors for AVN development.
Chungcheongnam-do ; Female ; Follow-Up Studies ; Graft Survival ; Humans ; Immunosuppression ; Incidence ; Kidney Transplantation* ; Kidney* ; Multivariate Analysis ; Necrosis* ; Osteonecrosis ; Retrospective Studies ; Risk Factors