PubMed Health⌕ Search

Biomedical subjects

Christian Bolenz

Publications and source records attributed to Christian Bolenz.

3 recordsLinked to original sources

Integrating NECTIN4 Amplification With Membranous Nectin-4 Expression to Develop a Scoring System for Predicting Enfortumab Vedotin Response in Urothelial Carcinoma.

PURPOSE: Enfortumab vedotin (EV) is standard therapy for metastatic urothelial carcinoma (mUC), yet the predictive relevance of NECTIN4 expression-especially membranous versus cytoplasmic-remains unclear. Here, we sought to extend previous findings on NECTIN4 gene amplification in parallel with a systematic subcellular evaluation of NECTIN4 expression. EXPERIMENTAL DESIGN: We retrospectively analyzed 179 EV-treated mUC patients. NECTIN4 amplification was assessed by FISH and NECTIN4 protein levels by IHC. A four-tier membranous scoring algorithm (0,1+,2+,3+) adapted from CAP HER2 gastric guidelines was benchmarked against H-score. We integrated amplification status with membranous staining to refine predictive stratification and compared associations with objective response rate (ORR) to EV-301 data. RESULTS: Combining membranous and cytoplasmic compartments resulted in a median composite H-score of 260 (78.2% &#x2265;150), closely matching NECTIN4 expression prevalence reported in EV-301 (median 250; 82.6% &#x2265; 150). A &#x2265;150 cut-off enriched for EV responders in both cohorts; in EV-301 with ORR of 45.8% vs. 20% (P = 0.001). High membranous expression based on the scoring (2+/3+) predicted response (ORR 55.1% vs. 25.5%; P < 0.001), with longer PFS (7.1 vs. 2.9 months; HR 0.45) and OS (12.3 vs. 6.9 months; HR 0.57), whereas cytoplasmic expression lacked predictive value. NECTIN4-amplified tumors showed particularly favorable outcomes (PFS 12.2 months; OS 30.1 months). An integrated three-tier model-amplified, non-amplified/high-membranous, and non-amplified/low-membranous-yielded ORRs of 77.2%, 42.9%, and 26.1% and separated survival outcomes. CONCLUSIONS: Our NECTIN4 scoring system integrating NECTIN4 amplification with membranous NECTIN4 expression accurately predicts outcomes, supporting combined genomic and membranous assessment as complementary biomarkers for optimizing EV selection.

Journal Article↗

Late results after extended pulmonary artery reconstruction in the arterial switch operation.

BACKGROUND: Pulmonary artery stenosis remains the most frequent late complication and cause of reintervention after the arterial switch operation for transposition of the great arteries. We investigated the influence of an extended pericardial patch augmentation of the neopulmonary root and pulmonary artery on late pulmonary artery stenosis development. METHODS: Augmentation of the neopulmonary root and pulmonary artery was achieved by reconstructing the posterior wall using a large glutaraldehyde-treated autologous pericardial patch. Reviewed were regular follow-up echocardiograms from 58 out of 87 patients undergoing the arterial switch operation who presented a follow-up period of at least 5 years. An actual follow-up echocardiographic evaluation focusing on the maximal instantaneous transpulmonary continuous-wave (cw)-Doppler gradient was performed, followed by cardiac catheterization when indicated (peak cw-Doppler gradient > 40 mm Hg). RESULTS: Follow-up was 8.9 [5 to 15] years. There was no reintervention due to residual pulmonary artery stenosis. Actual Doppler examination revealed a transpulmonary peak gradient of 19.5 [0 to 56] mm Hg, compared with 20 [0 to 60] mm Hg at discharge. Forty-three patients (74.1%) had no or only trivial pulmonary artery stenosis (pressure gradient < 25 mm Hg), 14 patients (24.2%) had mild stenosis (25 to 49 mm Hg), and 1 patient (1.7%) had moderate stenosis (50 to 79 mm Hg). CONCLUSIONS: Compared with the majority of literature data, we could demonstrate a low incidence of late pulmonary artery stenosis after the arterial switch operation by employing an extended pericardial patch reconstruction technique with augmentation of the neopulmonary root and pulmonary artery.

Bioprosthesis↗

Intravesical mitomycin C for superficial transitional cell carcinoma.

Intravesical instillation of mitomycin C after a transurethral resection of a bladder tumor constitutes a standard treatment modality in the management of superficial transitional cell carcinoma in the urinary bladder. An immediate instillation of mitomycin C after transurethral resection has been shown to reduce the recurrence rate of superficial transitional cell carcinoma. Intravesical mitomycin C is generally considered to be a safe treatment option, but the past few years have seen the publication of a number of case reports on severe complications following mitomycin C instillation. This article reports on the mode of action, as well as the intravesical effects and current indications for mitomycin C instillation. This review will summarize the oncological benefits of mitomycin C in comparison with other intravesical treatments, such as bacillus Calmette-Guérin, and elucidate the incidence and types of possible complications associated with intravesical mitomycin C chemotherapy.

Administration, Intravesical↗