الملخص
Objective:To investigate the effects of preoperative mammalian target of rapamycin(mTOR )inhibitor on partial nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML).Methods:A retrospective analysis was conducted on clinical data from 13 patients who were diagnosed with TSC-RAML and treated at Peking Union Medical College Hospital between August 2019 and July 2022. This cohort included 4 males and 9 females, with ages ranging from 22 to 66 years. All patients underwent partial nephrectomy, with 2 patients requiring two-stage surgeries due to bilateral RAMLs, resulting in a total of 15 surgeries being performed. Preoperative mTOR inhibitors, specifically everolimus (10 mg/d) or sirolimus (2 mg/d), were administered orally for at least 3 months prior to 7 of the surgeries. The effects of mTOR inhibitors on tumor size, tumor computed tomography attenuation value (CT value), and tumor CT enhancement were evaluated. The comparison of surgery-related clinical parameters was conducted between patients who received preoperative mTOR inhibitors and those who did not to assess the influences of mTOR inhibitors on surgery.Results:Compared to the baseline tumor, there was a significant reduction in tumor diameter after mTOR treatment [(6.4±3.1) cm vs. (8.7±3.9)cm], as well as in the CT value in both the unenhanced phase[(-18.63±48.73)HU vs. (-2.13±51.58)HU] and corticomedullary phase[(13.25±64.01)HU vs. (47.25±66.99)HU]. Additionally, tumor CT enhancement also decreased as compared with that before treatment [(31.88±18.20)HU vs. (49.38±20.63)HU]. Patients who received preoperative mTOR inhibitor showed a trend towards shorter operative time for removing per milliliter of tumor compared to those without preoperative mTOR inhibitor [1.06(0.18, 2.40) min/ml vs. 1.98(0.39, 5.03) min/ml] and so was the renal artery clamping time [0.17(0.03, 0.79) min/ml vs. 0.34(0.10, 1.71) min/ml]. Additionally, the amount of intraoperative bleeding for removing per milliliter of tumor was lower in patients with preoperative mTOR inhibitors compared to those without [0.72(0.19, 0.88) ml/ml vs. 1.69(0.59, 4.54) ml/ml].Conclusions:The administration of mTOR inhibitors before partial nephrectomy in patients with TSC-RAM have the potential to reduce tumor size and blood supply, as well as operative time, renal artery clamping time and intraoperative bleeding, which might contribute to surgery safety and preservation of renal function.
الملخص
Objective:To investigate the predictive effect of adjusted Utrecht staging criteria on efficacy of mammalian target of rapamycin (mTOR) inhibitors in patients with tuberous sclerosis-associated renal angiomyolipoma (TSC-AML).Methods:In this study, 39 adult patients with TSC-AML who attended the Peking Union Medical College Hospital from December, 2014 to December, 2020 were retrospectively analyzed, and were divided into 4 groups based on Utrecht staging criteria: Group 1, Utrecht staging ≤ stage 5, all AMLs <5 cm( n=6); Group 2, stage 6 with at least one AML ≥5 cm and normal renal anatomy( n=14); Group 3, stage 6 with at least one AML ≥5 cm and recognizable renal anatomy( n=10); Group 4, stage with at least one AML ≥5 cm and unrecognizable renal anatomy ( n=9). The mean age of patients in the 4 groups were 27.33±7.84, 28.64±12.36, 31.10±5.88 and 29.11±7.15 ( P=0.869). No statistic difference in gender was found among the different groups ( P=0.233). The mean maximum diameters of AML in the four groups were (3.54±0.52)cm, (8.11±2.08)cm, (11.58±4.60)cm and (17.08±3.61)cm, respectively( P<0.01). The mean levels of creatinine were (80.17±16.01)μmol/L, (76.36±18.72)μmol/L, (76.10±27.61)μmol/L and (71.89±18.66)μmol/L in the four groups( P=0.900). The numbers of patients with positive urine protein were 2, 3, 8 and 2 ( P=0.023). All the patients took Everolimus 10mg orally per day for at least 3 months. Differences in maximum AML shrinkage rate, creatinine level, severity of urine protein and microscopic hematuria were compared between the groups. Results:As AML severity increased, the shrinkage rates decreased significantly in turn [Group 1: (76.06±13.16)%, Group 2: (64.92±16.33)%, Group 3: (55.30±20.49)%, Group 4: (43.73±20.61)%, P=0.009]. After treatment, creatinine levels increased in all groups[Group 1: (8.50±7.61)μmol/L, Group 2: (5.71±8.54)μmol/L, Group 3: (7.70±7.18)μmol/L, Group 4: (6.11±7.04)μmol/L], but there was no significant difference among groups (P=0.856). Moreover the increase in urine protein worsened with the degree of severity (Group 1∶3, Group 2∶4, Group 3∶6, Group 4∶9, P=0.014). Conclusions:The adjusted Utrecht staging criteria could predict the maximum AML shrinkage rate and urine protein increase in TSC-AML patients with treatment of mTOR inhibitors.