Tristan Wagner

Purpose: Trophoblast cell surface antigen 2 (TROP2) is a glycoprotein expressed on epithelial tumor cells and therefore an established target for antibody-drug conjugates (ADCs). Epstein-Barr virus (EBV)-positive gastric cancer is a molecularly distinct subtype characterized by unique immunological features, including frequent responsiveness to immune checkpoint inhibitors (ICIs). Nevertheless, a subset of these patients fails to benefit from ICI therapy, leaving an unmet need for non-immunotherapeutic treatment options. Tumors lacking TROP2, fail to respond to TROP2-directed ADCs. We therefore assessed the prevalence of TROP2 expression in gastric cancer including the EBV-positive subtype, which has not been characterized to date. Methods: TROP2 expression was evaluated by immunohistochemistry in 525 patients with gastric cancer classified according to TCGA molecular subtypes, representing the largest Caucasian cohort assessed for TROP2 to date. Results: TROP2 expression differed significantly across molecular subtypes (p < 0.01), with EBV-positive tumors showing the highest median expression (H-score 150). Complete absence of TROP2, the expression pattern associated with treatment failure, was observed in only 3.7% of EBV-positive tumors, compared with 18.8% of chromosomal instability, 25.4% of genomically stable, and 36.2% of microsatellite instability tumors. Conclusion: Nearly all EBV-positive gastric cancers therefore express TROP2 at levels compatible with ADC targeting. These findings identify TROP2 as a target in EBV-positive gastric cancer and provide a rationale for clinical investigation of TROP2-directed ADCs in this molecularly defined population, particularly as a non-immunotherapeutic option for patients who fail ICI therapy.

Ischemia-reperfusion injury (IRI) determines early and delayed graft function and long-term allograft survival in solid organ transplantation and is one determinant of outcome that remains modifiable in the operating room. Cell-free heme, a Danger-Associated Molecular Pattern (DAMP), is liberated from hemoproteins as a result of IRI, and overwhelms the haptoglobin, hemopexin scavenging systems. As such, it then intercalates into cell membranes, drives Fenton chemistry, and acts as a DAMP that engages TLR4/MD2, precipitating cell death. Heme also triggers its own clearance through NRF2 and BACH1, which regulate expression of heme oxygenase-1 (HO-1, Hmox1), that degrades heme into the bioactive molecules, carbon monoxide (CO), biliverdin and ferrous iron. CO modulates inflammation, inhibits cell death pathways and preserves the microcirculation. Biliverdin and bilirubin act as potent antioxidants, and ferritin sequesters labile, highly reactive iron. The role of heme and HO-1 has been well-studied in models of kidney transplantation where HO-1 induction and, independently, exogenous CO treatment have been shown to attenuate transplant-induced IRI and chronic rejection. Importantly, human HO-1 is a critical component of the multi-transgenic donor pig organs that are being tested in ongoing clinical trials. This review discusses the current state of HO-1 in transplantation, including mechanisms of action, preclinical modeling, and clinical applications.

Introduction: Kidney transplantation remains the preferred treatment for end-stage renal disease; however, the increasing use of extended-criteria donors has been associated with a higher incidence of postoperative complications. Methods: We retrospectively analyzed 471 kidney transplant recipients at the University of Cologne between 2012 and 2022 to evaluate the incidence, risk factors, clinical outcomes, and surgical management of ureteral stenosis. Results: Ureteral stenosis occurred in 6.37% and was significantly associated with older donor age within the extended-criteria donor range (65 vs. 56 years, p = 0.006), multiple renal arteries (33.3% vs. 10.2%, p < 0.001), and BK virus infection, as reflected by higher rates of BK viruria (26.7% vs. 7.0%, p = 0.002) and BK viraemia (26.7% vs. 8.6%, p = 0.005). Renal function was significantly impaired in recipients with ureteral stenosis at 6 months, 1 year, and 2 years after transplantation. Death-censored graft survival was significantly lower in the stenosis group (79.7% vs. 93.3%, p = 0.01). Discussion: Ureteral transposition and ureteroneocystostomy demonstrated comparable outcomes, long-term renal function and graft survival supporting individualization of surgical technique based on anatomical and patient-specific factors.

BACKGROUND Liver hydatid cysts (LHC) liver requires effective surgical treatment. Open closed total pericystectomy removes the entire echinococcus cyst while preserving healthy liver tissue. AIM To evaluate the outcomes of pericystectomy and its efficacy as a treatment modality for cystic echinococcosis (CE). METHODS Thirty-eight patients were analyzed after open total pericystectomy at the University Hospital of Cologne between January 2006 and January 2024. Demographic, clinical, and laboratory parameters were collected retrospectively. Intraoperative data and postoperative complications were documented and classified using the Clavien-Dindo classification. Throughout the follow-up period, patients underwent regular clinical, serological, and sonographic evaluations both at the outpatient department and by their general physicians. RESULTS Fifty-four cysts were treated with open total pericystectomy. Multiple cysts were found in 42.2% of cases. Singular cysts occurred in 57.8%. The right hepatic lobe was affected in 66.7%. Ectopic cysts occurred in 4 patients in the lung (n = 3) and spleen (n = 1). Median cyst size was 6.78 cm × 5.92 cm (range: 1.4-20.0 cm). The median surgical time of pericystectomy was 189 minutes (range: 78-455 minutes) with a median blood loss of 400 mL (range: 100-1400 mL). The complication rate (Clavien-Dindo > III) was 21.1%. The average hospital stay was 12.5 days. No recurrent disease could be detected after a median follow-up time of 97 months (range: 4-216 months). No recurrent cyst manifestation, postoperative liver failure or death was observed. CONCLUSION The presented surgical procedure known as open total pericystectomy is a safe surgical technique in treatment of cystic echinococcosis.