Safe Criteria for Less Radical Trachelectomy in Patients with Early-Stage Cervical Cancer: A Multicenter Clinicopathologic Study

Background

To determine the safe criteria for less radical trachelectomy to treat patients with early-stage cervical cancer.

Methods

We reviewed medical records and pathologic slides of 65 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA?CIB1 cervical cancer. The safe criteria for less radical trachelectomy were determined by using three factors such as tumor size ??1?cm, stromal invasion ??5?mm, and no lymphovascular space invasion (LVSI) for minimizing parametrial involvement, lymph node metastasis (LNM), and the need of adjuvant radiotherapy. The diagnostic values were investigated by calculating specificity, negative predictive value for no parametrial involvement, no LNM, and no need of adjuvant radiotherapy.

Results

The median age was 32?years (range 22?C44?years), and the median duration of follow-up was 26?months (range 2?C103?months). Among seven single or combined factors for the safe criteria, (1) tumor size ??1?cm, (2) tumor size ??1?cm and stromal invasion ??5?mm, (3) tumor size ??1?cm and no LVSI, (4) tumor size ??1?cm, stromal invasion ??5?mm, and no LVSI did not show parametrial involvement, LNM, and the need of adjuvant radiotherapy. In particular, tumor size ??1?cm showed the highest specificity (28.1?C29.5%) and negative predictive value (100%). In spite of no difference in progression-free survival (PFS) between tumor size ??1?cm and >1?cm (P?=?0.22), tumor size ??1?cm showed better PFS without disease recurrence than tumor size >1?cm (2-year PFS, 100% vs. 90%).

Conclusions

Less radical trachelectomy may be safe in patients with early-stage cervical cancer who have tumor size ??1?cm.     

Transport of N-acetyl-S-(1,2-dichlorovinyl)-l-cysteine, a metabolite of trichloroethylene, by mouse multidrug resistance associated protein 2 (Mrp2)

N-acetyl-S-(1,2-dichlorovinyl)-l-cysteine (Ac-DCVC) and S-(1,2-dichlorovinyl)-l-cysteine (DCVC) are the glutathione conjugation pathway metabolites of a common industrial contaminant and potent nephrotoxicant trichloroethylene (TCE). Ac-DCVC and DCVC are accumulated in the renal proximal tubule where they may be secreted into the urine by an unknown apical transporter(s). In this study, we explored the hypothesis that the apical transport of Ac-DCVC and/or DCVC may be mediated by the multidrug resistance associated protein 2 (Mrp2, ABCC2), which is known to mediate proximal tubular apical ATP-dependent transport of glutathione and numerous xenobiotics and endogenous substances conjugated with glutathione. Transport experiments using membrane vesicles prepared from mouse proximal tubule derived cells expressing mouse Mrp2 utilizing ATPase assay and direct measurements of Ac-DCVC/DCVC using liquid chromatography/tandem mass-spectrometry (LC/MS/MS) demonstrated that mouse Mrp2 mediates ATP-dependent transport of Ac-DCVC. Expression of mouse Mrp2 antisense mRNA significantly inhibited the vectorial basolateral to apical transport of Ac-DCVC but not DCVC in mouse proximal tubule derived cells endogenously expressing mouse Mrp2. The results suggest that Mrp2 may be involved in the renal secretion of Ac-DCVC.