1.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug-drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage*
;
Drug Monitoring/methods*
;
Humans
;
Organ Transplantation
;
Immunosuppressive Agents/administration & dosage*
;
Delphi Technique
2.Robot-assisted laparoscopic inferior vena cava segmental resection for renal tumor with tumor thrombus invading the vascular wall
Shuai LIU ; Zhuo LIU ; Yunhe GUAN ; Guoliang WANG ; Xiaojun TIAN ; Hongxian ZHANG ; Lei LIU ; Lulin MA ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):796-802
Objective:To evaluate the safety and oncological outcomes of robot-assisted laparoscopic inferior vena cava(IVC)segmental resection in renal tumor with IVC tumor thrombus(IVCTT).Methods:Clinical data from renal tumor patients undergoing robot-assisted laparoscopic IVC segmental resection at Peking University Third Hospital from Jan.2021 to Feb.2025 were retrospectively analyzed.Data collection included baseline demographics,tumor characteristics,perioperative parameters,and follow-up outcomes.Surgical records and pathological reports were retrieved from the electronic medical record system.Continuous variables were presented as median(P25,P75),and categorical variables as frequency(percentage).Results:Forty-four patients were enrolled.The cohort comprised 31 malesand 13 females,with a median age of 62(55,68)years.Right-sided tumors were observed in 39 cases and left-sided in 5 cases.Median tumor diameter was 8.1(6.1,10.1)cm.Mayo classifications included grade Ⅱ(n=37),Ⅲ(n=6),and Ⅳ(n=1).Neoadjuvant therapy was administered to 23 patients.Seventeen patients were complicated by IVC bland thrombus.Median operative time was 224.0(167.3,303.8)min,with intraoperative blood loss of 500.0(300.0,850.0)mL.Transfusion was administered to 19 patients,with a median blood transfusion of 800.0(400.0,1 200.0)mL.Postoperative complica-tions occurred in 25 cases(56.8%),classified as Clavien-Dindo grade Ⅰ(n=8)and grade Ⅱ(n=17).Procedure-specific complications included deep vein thrombosis(n=6),transfusion-requiring ane-mia(n=5),lower extremity edema(n=2),and pulmonary embolism(n=2),with no procedure-related mortality.Median postoperative serum creatinine was 116.0(86.5,157.5)μmnol/L.Pathological examination identified clear cell renal cell carcinoma as the predominant subtype,observed in 34 cases(77.3%).Pathological staging revealed T3b(n=12),T3c(n=29),and T4(n=3)disease,with nodal involvement(N1)in 8 cases and distant metastasis(M1)in 17.At a median follow-up of 10 months(range:1-49 months),cancer-specific mortality occurred in 3 patients,while 1 succumbed to other causes.Disease progression included pulmonary metastasis(n=5),hepatic metastasis(n=4),and local recurrence(n=4).Adjuvant therapy regimens comprised targeted-immunotherapy combina-tions(n=9)and targeted monotherapy(n=18).Conclusion:Robot-assisted laparoscopic I VC seg-mental resection achieves precise thrombus removal with confirmed short-term efficacy in renal tumor with IVCTT,though vigilance against vascular complications remains critical.
3.Experience summary of robot-assisted laparoscopic transplant nephrectomy
Qiming ZHANG ; Zebo CHEN ; Yu TIAN ; Dameng PAN ; Lei LIU ; Hongxian ZHANG ; Lei ZHAO ; Shudong ZHANG ; Lulin MA ; Xiaofei HOU
Journal of Peking University(Health Sciences) 2025;57(4):666-669
Objective:To review and summarize the experience of robot-assisted laparoscopic trans-plant nephrectomy,share the surgical steps and technical key points,and provide a reference for clinical practice.Methods:A retrospective analysis was conducted on the perioperative data of 5 patients who underwent robot-assisted laparoscopic donor nephrectomy at Peking University Third Hospital from August 2023 to December 2024.The surgical steps and key points were summarized.The continuous variables were described by medians(ranges).Results:A total of 5 patients were included in the analysis,of whom 2 were male and 3 were female.The median age of the patients was 37(31-68)years.The me-dian time from kidney transplantation to donor nephrectomy was 10(3-22)years.The indications for donor nephrectomy included recurrent hematuria,abdominal pain,malignant tumor of the transplanted kidney,and recurrent infection with hydronephrosis of the transplanted kidney.The excised transplanted kidneys from all the 5 patients had a single renal artery and a single renal vein.The median operation time was 212(145-351)min,the median blood loss was 300(20-500)mL,and the median post-operative hospital stay was 7(4-25)days.Only 1 patient experienced intraoperative complications,who experienced an external iliac artery injury during the operation and underwent suture repair.No pa-tient died during the perioperative period.Postoperative pathological results showed that 3 patients had end-stage non-functional kidneys,1 patient had BK virus-associated urothelial carcinoma,and 1 patient had chronic pyelonephritis with renal parenchymal atrophy.Conclusion:Robot-assisted laparoscopic transplant nephrectomy as a new surgical approach is feasible and safe.Compared with traditional open transplant nephrectomy,its advantage lies in the ability to directly observe and prioritize the management of the renal pedicle of the transplanted kidney,while completely freeing and removing the transplanted kidney outside the renal capsule.With the continuous accumulation of experience,this surgical technique is expected to become a powerful alternative to traditional open transplant nephrectomy.
4.Laparoscopic surgery for kidney grade Ⅳ rupture combined with renal vein thrombosis and liver rupture: a case report
Rui ZHAO ; Ruijian LIU ; Zhiqiang XING ; Wei YAN ; Hongwei WANG ; Ruidong ZHANG ; Lulin MA
Chinese Journal of Urology 2025;46(2):143-144
A 34-year-old male patient was admitted to the hospital on October 6, 2023 due to fall from a high place. Physical examination showed blood pressure 96/53 mmHg (1 mmHg=0.133 kPa), heart rate of 105 beats/min, slight bulge in the right kidney area, and positive percussion pain in the right kidney area. CT examination showed complete rupture of the lower pole of the right kidney, thrombosis of the right renal vein, and contusion and laceration of the right posterior lobe of the liver. According to the American Association for the Surgery of Trauma renal injury classification, he was diagnosed as grade Ⅳ renal rupture. After blood transfusion and fluid infusion, vital signs were stable. Laparoscopic nephrectomy plus renal vein thrombectomy plus liver rupture repair were performed. The operation took 90 minutes, and about 300 ml of blood clots and fresh blood were aspirated during the operation. The patient's vital signs were stable after the operation, and he could get out of bed 3 days after the operation. CT reexamination 1 month after the operation showed right kidney resected and the liver healed well. This operation is feasible if the patient's vital signs are stable, with the advantages of small surgical incision, short operation time, less bleeding, fast postoperative recovery and good surgical effect.
5.Clinical characteristics and influencing factors of extraglandular invasion of prostatic ductal adenocarcinoma.
Xiaoyong YANG ; Fan ZHANG ; Lulin MA ; Cheng LIU
Journal of Peking University(Health Sciences) 2025;57(5):956-960
OBJECTIVE:
To explore the differences in perioperative clinical and pathological characteristics of patients with different pathological types of prostate cancer undergoing radical prostatectomy, and to analyze the influencing factors that may affect the extraglandular invasion of ductal adenocarcinoma of the prostate.
METHODS:
Retrospective collection was made of the radical prostatectomy patients who were admitted to Peking University Third Hospital from December 2011 to April 2021. The patients were screened based on inclusion criteria to obtain basic clinical features and postoperative pathological results. According to the pathological results, the patients were divided into ductal adenocarcinoma group (mixed with ductal adenocarcinoma) and acinar adenocarcinoma group, and a 1 ∶1 propensity score matching was performed to compare the differences in clinical characteristics between the two groups. Univariate and multivariate analyses of the factors related to extraglandular invasion were performed in the matched ductal adenocarcinoma groups.
RESULTS:
A total of 764 patients with prostate cancer were enrolled in this study, of which 62 patients were confirmed to have ductal adenocarcinoma components by postoperative pathology. There was a statistically significant difference in the proportion of the patients with a history of diabetes in baseline characteristics between the two groups before propensity score matching (29.5% vs. 17.7%, P=0.027). A total of 61 patients with simple acinar adenocarcinoma were successfully matched with the patients with ductal adenocarcinoma, and there was no statistically significant difference in baseline characteristics between the two groups after matching (P>0.05). The comparison of perioperative clinical and pathological features showed that International Society of Urology Pathology (ISUP) grade (P=0.003), pT stage (P=0.004), extraglandular invasion rate (P=0.018) and vascular thrombus rate (P=0.019) in ductal adenocarcinoma group were significantly higher than those in simple acinous adenocarcinoma group. Univariate analysis of the influence factors of extraglandular invasion showed that prostate-specific antigen (PSA) level, prostate volume, ISUP grade, seminal vesicle invasion and perineural invasion might be the influencing factors of extraglandular invasion (P < 0.10). Binary Logistic regression analysis showed that perineural invasion was an independent factor of extraglandular invasion (OR=11.78, 95%CI: 1.97-70.56, P=0.007).
CONCLUSION
Prostatic ductal adenocarcinoma has a worse prognosis than simple acinar adenocarcinoma. Perineural invasion is the influencing factor of extraglandular invasion of ductal adenocarcinoma.
Humans
;
Male
;
Prostatic Neoplasms/surgery*
;
Retrospective Studies
;
Prostatectomy
;
Neoplasm Invasiveness
;
Middle Aged
;
Aged
;
Carcinoma, Ductal/surgery*
;
Propensity Score
;
Adenocarcinoma/surgery*
6.Robot-assisted laparoscopic inferior vena cava segmental resection for renal tumor with tumor thrombus invading the vascular wall
Shuai LIU ; Zhuo LIU ; Yunhe GUAN ; Guoliang WANG ; Xiaojun TIAN ; Hongxian ZHANG ; Lei LIU ; Lulin MA ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):796-802
Objective:To evaluate the safety and oncological outcomes of robot-assisted laparoscopic inferior vena cava(IVC)segmental resection in renal tumor with IVC tumor thrombus(IVCTT).Methods:Clinical data from renal tumor patients undergoing robot-assisted laparoscopic IVC segmental resection at Peking University Third Hospital from Jan.2021 to Feb.2025 were retrospectively analyzed.Data collection included baseline demographics,tumor characteristics,perioperative parameters,and follow-up outcomes.Surgical records and pathological reports were retrieved from the electronic medical record system.Continuous variables were presented as median(P25,P75),and categorical variables as frequency(percentage).Results:Forty-four patients were enrolled.The cohort comprised 31 malesand 13 females,with a median age of 62(55,68)years.Right-sided tumors were observed in 39 cases and left-sided in 5 cases.Median tumor diameter was 8.1(6.1,10.1)cm.Mayo classifications included grade Ⅱ(n=37),Ⅲ(n=6),and Ⅳ(n=1).Neoadjuvant therapy was administered to 23 patients.Seventeen patients were complicated by IVC bland thrombus.Median operative time was 224.0(167.3,303.8)min,with intraoperative blood loss of 500.0(300.0,850.0)mL.Transfusion was administered to 19 patients,with a median blood transfusion of 800.0(400.0,1 200.0)mL.Postoperative complica-tions occurred in 25 cases(56.8%),classified as Clavien-Dindo grade Ⅰ(n=8)and grade Ⅱ(n=17).Procedure-specific complications included deep vein thrombosis(n=6),transfusion-requiring ane-mia(n=5),lower extremity edema(n=2),and pulmonary embolism(n=2),with no procedure-related mortality.Median postoperative serum creatinine was 116.0(86.5,157.5)μmnol/L.Pathological examination identified clear cell renal cell carcinoma as the predominant subtype,observed in 34 cases(77.3%).Pathological staging revealed T3b(n=12),T3c(n=29),and T4(n=3)disease,with nodal involvement(N1)in 8 cases and distant metastasis(M1)in 17.At a median follow-up of 10 months(range:1-49 months),cancer-specific mortality occurred in 3 patients,while 1 succumbed to other causes.Disease progression included pulmonary metastasis(n=5),hepatic metastasis(n=4),and local recurrence(n=4).Adjuvant therapy regimens comprised targeted-immunotherapy combina-tions(n=9)and targeted monotherapy(n=18).Conclusion:Robot-assisted laparoscopic I VC seg-mental resection achieves precise thrombus removal with confirmed short-term efficacy in renal tumor with IVCTT,though vigilance against vascular complications remains critical.
7.Experience summary of robot-assisted laparoscopic transplant nephrectomy
Qiming ZHANG ; Zebo CHEN ; Yu TIAN ; Dameng PAN ; Lei LIU ; Hongxian ZHANG ; Lei ZHAO ; Shudong ZHANG ; Lulin MA ; Xiaofei HOU
Journal of Peking University(Health Sciences) 2025;57(4):666-669
Objective:To review and summarize the experience of robot-assisted laparoscopic trans-plant nephrectomy,share the surgical steps and technical key points,and provide a reference for clinical practice.Methods:A retrospective analysis was conducted on the perioperative data of 5 patients who underwent robot-assisted laparoscopic donor nephrectomy at Peking University Third Hospital from August 2023 to December 2024.The surgical steps and key points were summarized.The continuous variables were described by medians(ranges).Results:A total of 5 patients were included in the analysis,of whom 2 were male and 3 were female.The median age of the patients was 37(31-68)years.The me-dian time from kidney transplantation to donor nephrectomy was 10(3-22)years.The indications for donor nephrectomy included recurrent hematuria,abdominal pain,malignant tumor of the transplanted kidney,and recurrent infection with hydronephrosis of the transplanted kidney.The excised transplanted kidneys from all the 5 patients had a single renal artery and a single renal vein.The median operation time was 212(145-351)min,the median blood loss was 300(20-500)mL,and the median post-operative hospital stay was 7(4-25)days.Only 1 patient experienced intraoperative complications,who experienced an external iliac artery injury during the operation and underwent suture repair.No pa-tient died during the perioperative period.Postoperative pathological results showed that 3 patients had end-stage non-functional kidneys,1 patient had BK virus-associated urothelial carcinoma,and 1 patient had chronic pyelonephritis with renal parenchymal atrophy.Conclusion:Robot-assisted laparoscopic transplant nephrectomy as a new surgical approach is feasible and safe.Compared with traditional open transplant nephrectomy,its advantage lies in the ability to directly observe and prioritize the management of the renal pedicle of the transplanted kidney,while completely freeing and removing the transplanted kidney outside the renal capsule.With the continuous accumulation of experience,this surgical technique is expected to become a powerful alternative to traditional open transplant nephrectomy.
8.Laparoscopic surgery for kidney grade Ⅳ rupture combined with renal vein thrombosis and liver rupture: a case report
Rui ZHAO ; Ruijian LIU ; Zhiqiang XING ; Wei YAN ; Hongwei WANG ; Ruidong ZHANG ; Lulin MA
Chinese Journal of Urology 2025;46(2):143-144
A 34-year-old male patient was admitted to the hospital on October 6, 2023 due to fall from a high place. Physical examination showed blood pressure 96/53 mmHg (1 mmHg=0.133 kPa), heart rate of 105 beats/min, slight bulge in the right kidney area, and positive percussion pain in the right kidney area. CT examination showed complete rupture of the lower pole of the right kidney, thrombosis of the right renal vein, and contusion and laceration of the right posterior lobe of the liver. According to the American Association for the Surgery of Trauma renal injury classification, he was diagnosed as grade Ⅳ renal rupture. After blood transfusion and fluid infusion, vital signs were stable. Laparoscopic nephrectomy plus renal vein thrombectomy plus liver rupture repair were performed. The operation took 90 minutes, and about 300 ml of blood clots and fresh blood were aspirated during the operation. The patient's vital signs were stable after the operation, and he could get out of bed 3 days after the operation. CT reexamination 1 month after the operation showed right kidney resected and the liver healed well. This operation is feasible if the patient's vital signs are stable, with the advantages of small surgical incision, short operation time, less bleeding, fast postoperative recovery and good surgical effect.
9.Discussion on the surgical timing of rupture and hemorrhage of renal angiomyoli-poma
Kewei CHEN ; Shaohui DENG ; Zhuo LIU ; Hongxian ZHANG ; Lulin MA ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2024;56(2):326-331
Objective:To investigate the effect of different surgical timing on the surgical treatment of renal angiomyolipoma(RAML)with rupture and hemorrhage.Methods:The demographic data and peri-operative data of 31 patients with rupture and hemorrhage of RAML admitted to our medical center from June 2013 to February 2023 were collected.The surgery within 7 days after hemorrhage was defined as a short-term surgery group,the surgery between 7 days and 6 months after hemorrhage was defined as a me-dium-term surgery group,and the surgery beyond 6 months after hemorrhage was defined as a long-term surgery group.The perioperative related indicators among the three groups were compared.Results:This study collected 31 patients who underwent surgical treatment for RAML rupture and hemorrhage,of whom 13 were males and 18 were females,with an average age of(46.2±11.3)years.The short-term surgery group included 7 patients,the medium-term surgery group included 12 patients and the long-term surgery group included 12 patients.In terms of tumor diameter,the patients in the long-term surgery group were significantly lower than those in the recent surgery group[(6.6±2.4)cmvs.(10.0±3.0)cm,P=0.039].In terms of operation time,the long-term surgery group was significantly shorter than the mid-term surgery group[(157.5±56.8)min vs.(254.8±80.1)min,P=0.006],and there was no sig-nificant difference between other groups.In terms of estimated blood loss during surgery,the long-term surgery group was significantly lower than the mid-term surgery group[35(10,100)mL vs.650(300,1 200)mL,P<0.001],and there was no significant difference between other groups.In terms of intraoperative blood transfusion,the long-term surgery group was significantly lower than the mid-term surgery group[0(0,0)mL vs.200(0,700)mL,P=0.014],and there was no significant difference between other groups.In terms of postoperative hospitalization days,the long-term surgery group was sig-nificantly lower than the mid-term surgery group[5(4,7)d vs.7(6,10)d,P=0.011],and there was no significant difference between other groups.Conclusion:We believe that for patients with RAML rupture and hemorrhage,reoperation for more than 6 months is a relatively safe time range,with minimal intraoperative bleeding.Therefore,it is more recommended to undergo surgical treatment after the hema-toma is systematized through conservative treatment.
10.Sodium butyrate and sorafenib synergistically inhibit hepatocellular carcinoma cells possibly by inducing ferroptosis through inhibiting YAP
Huaxing HE ; Lulin LIU ; Yingyin LIU ; Nachuan CHEN ; Suxia SUN
Journal of Southern Medical University 2024;44(7):1425-1430
Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Result Analysis
Print
Save
E-mail