Impact of different ischemia times on biliary stricture after living donor liver transplantation with biliary atresia.

Biliary atresia (BA) is the most common indication for pediatric liver transplantation, and biliary stricture (BS) remains an Achilles' heel for pediatric living donor liver transplantation (LDLT). We investigated the impact of different ischemia times on BS after LDLT in patients with BA. We retrospectively analyzed patients (<18 y) with BA who underwent LDLT between January 2016 and December 2020. Cases with hepatic artery thrombosis, bile leakage, early BS (<2 wk), and early death (<3 mo) were excluded. In all, 572 cases were included. A total of 26 cases (4.55%, 26/572) developed BS: 25 patients with anastomotic stricture and 1 patient with anastomotic stricture combined with left hepatic duct stricture. In addition, the time to diagnosis of BS ranged from 1.8 to 53.0 months (mean, 13.0 mo and median, 8.2 mo) after transplantation. A multivariate logistic regression analysis showed that arterial ischemia time (AIT), per 10 minutes (OR=1.222, 95% CI: 1.007-1.438, p =0.04) was the only independent risk factor for the development of BS after LDLT in patients with BA. What is more, the 5-year cumulative risk of BS between the AIT ≥40 minutes and AIT <40 minutes groups was 2.79% versus 10.57%. AIT was the only independent risk factor for the development of BS after LDLT with BA, and AIT ≥40 minutes would increase the 5-year cumulative risk of BS in our study. A shorter AIT, especially AIT <40 minutes, should be kept to decrease BS.

Incidence and risk factors of subclinical rejection after pediatric liver transplantation, and impact on allograft fibrosis.

INTRODUCTION: Subclinical rejection (SCR) is a common injury in protocol biopsy after pediatric liver transplantation (pLT), but its effect on the recipient is not clearly understood. We herein investigated the incidence and risk factors involved in SCR and analyzed the relationship between SCR and allograft fibrosis (AF). METHODS: We retrospectively reviewed the biopsy results from 507 children between May 2013 and May 2019, and 352 patients underwent protocol biopsy 2 years after pLT, 203 underwent protocol biopsy 5 years after pLT, and 48 underwent protocol biopsy both 2 and 5 years after pLT. RESULTS: The incidence of SCR in the 5-year group was higher than that in the 2-year group (20.2% vs.13.4%, respectively, p = .033). The number of patients with mild and moderate SCR in the 5-year group was also higher than that in the 2-year group (p = .039). Logistic regression analysis showed that acute rejection before liver biopsy and deceased donor liver transplantation (DDLT) were independent risk factors for SCR in the two groups, and that the incidence and severity of AF in protocol biopsies at both periods in the SCR group were higher than those in the non-SCR group (p < .05). CONCLUSIONS: The incidence and severity of SCR increased with the prolongation of protocol biopsy time. We postulate that acute rejection and DDLT are independent risk factors for SCR after transplantation. As the occurrence of SCR also augmented the incidence and severity of AF.

The value of 18 F-FDG PET/CT quantitative indexes in the diagnosis of nondestructive posttransplant lymphoproliferative disorders after pediatric liver transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication after pediatric liver transplantation (pLT), which may lead to death. 18 F-FDG PET/CT is rarely considered in PTLD after pLT and lacks clear diagnostic guidelines, especially in the differential diagnosis of nondestructive PTLD. The aim of this study was to find a quantifiable 18 F-FDG PET/CT index to identify nondestructive PTLD after pLT. METHODS: This retrospective study collected the data of patients who underwent pLT, postoperative lymph node biopsy, and 18 F-FDG PET/CT at Tianjin First Central Hospital from January 2014 to December 2021. Quantitative indexes were established using lymph node morphology and the maximum standardized uptake value (SUVmax). RESULTS: A total of 83 patients met the inclusion criteria and were included in this retrospective study. To distinguish between PTLD-negative cases and nondestructive PTLD cases, according to the receiver operating characteristic curve, (the shortest diameter of the lymph node at the biopsy site [SDL]/the longest diameter of the lymph node at the biopsy site [LDL])*(SUVmax at the biopsy site [SUVmaxBio]/SUVmax of the tonsils [SUVmaxTon]) had the maximum area under the curve (0.923; 95% confidence interval: 0.834-1.000), and the cutoff value was 0.264 according to the maximum value of Youden's index. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93.6%, 94.7%, 97.8%, 85.7%, and 93.9%, respectively. CONCLUSIONS: (SDL/LDL)*(SUVmaxBio/SUVmaxTon) has good sensitivity, specificity, positive predictive and negative predictive values, and accuracy, and can be used as a good quantitative index for the diagnosis of nondestructive PTLD.

Tripartite-motif family genes associated with cancer stem cells affect tumor progression and can assist in the clinical prognosis of kidney renal clear cell carcinoma.

Ubiquitination is presently a hot topic in the field of oncology. The tripartite-motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases, which play an essential role in the ubiquitination of proteins in the body. At the same time, research related to cancer stem cells (CSCs) is increasing in popularity in the field of oncology. CSCs are potentially chemically resistant and can be selectively enriched in patients receiving chemotherapy, ultimately leading to adverse outcomes, such as treatment failure and cancer recurrence. There is a close relationship between multiple TRIM family genes and CSCs. Accumulating evidence suggests that TRIM family proteins are expressed in diverse human cancers and act as regulators of oncoproteins or tumor suppressor proteins. In this study, we used biological information to explore the potential function of TRIM family genes related to CSCs in the development of pan-cancer. Kidney renal clear cell carcinoma (KIRC) is one of the deadliest malignant tumors in the world. Owing to its complex molecular and cellular heterogeneity, the effectiveness of existing KIRC-related risk prediction models is not satisfactory at present. Therefore, we focused on the potential role of these TRIM family genes in KIRC and used seven TRIM family genes to establish a prognostic risk model. This model includes TRIM16, TRIM32, TRIM24, TRIM8, TRIM27, PML, and TRIM11. In conclusion, this study provides further insight into the prognosis of KIRC, which may guide treatment.

Serum CXCL8 Concentration Can Be Used as a Noninvasive Marker of Subclinical Rejection After Pediatric Liver Transplantation.

BACKGROUND: This study aimed to explore whether serum CXCL8 concentration can be used as a noninvasive marker of subclinical rejection (SCR) after pediatric liver transplantation (pLT). METHODS: Firstly, RNA sequencing (RNA-seq) was performed on 22 protocol liver biopsy samples. Secondly, several experimental methods were used to verify the RNA-seq results. Finally, the clinical data and serum samples of 520 LT patients in the Department of Pediatric Transplantation of Tianjin First Central Hospital from January 2018 to December 2019 were collected. RESULTS: RNA-seq results indicated that CXCL8 was significantly increased in the SCR group. The results of the 3 experimental methods were consistent with RNA-seq results. According to the 1:2 propensity score matching, 138 patients were divided into the SCR (n = 46) and non-SCR (n = 92) groups. Serological test results indicated that there was no difference in preoperative CXCL8 concentration between the SCR and non-SCR groups ( P > 0.05). However, during protocol biopsy, CXCL8 in the SCR group was significantly higher than in the non-SCR group ( P < 0.001). In diagnosing SCR, receiver operating characteristic curve analysis showed that the area under the curve of CXCL8 was 0.966 (95% confidence interval, 0.938-0.995), sensitivity was 95%, and specificity was 94.6%. In differentiating nonborderline from borderline rejection, the area under the curve of CXCL8 was 0.853 (95% confidence interval, 0.718-0.988), sensitivity was 86.7%, and specificity was 94.6%. CONCLUSIONS: This study demonstrates that serum CXCL8 concentration has high accuracy for the diagnosis and disease stratification of SCR after pLT.

Nomograms for Predicting the Incidence of Late-Onset Acute Cellular Rejection in Patients After Pediatric Liver Transplantation.

Background: Late-onset acute cellular rejection (LACR) is a special type of acute rejection (AR) only rarely studied after pediatric liver transplantation (pLT). Our study aimed to explore the influencing factors of LACR after pLT and establish a nomogram to provide an individualized prediction of LACR after pLT. Materials and Methods: Data from 640 children who underwent pLT at Tianjin First Central Hospital from January 2016 to December 2019 were collected as part of this retrospective study. The nomogram was then established through the results of the multivariable analysis. Results: Forty-one patients experienced LACR > 1 ≤ 2 years after pLT. Cold ischemia time, donor-specific antibodies (DSAs), and tacrolimus concentration were independent influencing factors, and a nomogram was established with an AUC value of 0.834 (95% confidence interval, 0.755-0.912). Ten-fold cross-validation showed that the accuracy of the nomogram was about 76%. Sixty-three patients experienced LACR > 2 years after pLT. Child-Pugh grade, cold ischemic time, DSAs, early acute cellular rejection, and tacrolimus concentration were independent influencing factors, and a nomogram was established with an AUC value of 0.827 (95% confidence interval, 0.774-0.881). Ten-fold cross-validation showed that the accuracy of the nomogram was about 80.9%. Conclusion: We established nomograms to predict the incidence of LACR > 1 ≤ 2 and > 2 years after pLT, respectively. The verification results showed that nomograms had good accuracy and clinical practicability.