A Single-Centre Retrospective Analysis of Pregnancies with Placenta Accreta Spectrum (PAS): From One-Step Surgery towards Two-Step Surgical Approach.

Background: Placenta accreta spectrum (PAS) can be the cause of major morbidity and its optimal management is still controversial. The aim of this study was to compare the traditional one-step surgery with a two-step surgical approach in which the placenta is left in situ and the second final operation is delayed to minimise blood loss. Methods: We conducted a single-centre retrospective cohort study including all patients managed for PAS between 2007 and 2023. The number of units of red blood cells (RBCs) needed during surgery was the primary outcome used to compare these two approaches. Results: A total of 43 cases were included in this analysis. Twenty of these were managed with the delayed two-step surgical approach, whereas 23 received one-step surgery. The median estimated blood loss during surgery was 2000 mL and 2800 mL for two-step and one-step surgery, respectively (p = 0.095). In the two-step surgical approach, the median number of RBC units transfused during surgery was significantly lower (p = 0.049) and the odds ratio for needing more than four units of RBCs was 0.28 (95%-CI: 0.08-0.98, p = 0.043). A longer interval between the caesarean section and the second operation showed a trend toward lower blood loss (p = 0.065) and was associated with a significantly lower number of RBC units needed during surgery (p = 0.019). Conclusions: Two-step surgery for the treatment of PAS was safe in our cohort and could lead to a reduction in blood transfusion. Leaving the placenta in situ and delaying the final operation represents a possible alternative to traditional caesarean hysterectomy.

Desmoplasia in cervical cancer is associated with a more aggressive tumor phenotype.

In cancer of the uterine cervix, the role of desmoplasia, i.e., peritumoral stromal remodeling characterized by fibroblast activation and increased extracellular matrix deposition, is not established. We conducted a retrospective cohort study based on data from 438 patients who had undergone surgical treatment for cervical cancer as part of the prospective Leipzig Mesometrial Resection study between 1999 and 2021. Using non-parametric tests, Kaplan-Meier plotting, and Cox regression modeling, we calculated the prognostic impact of desmoplasia and its association with other risk factors. Desmoplasia was present in 80.6% of cases and was associated with a higher frequency of lymphovascular space involvement (76.5 vs. 56.5%, p < 0.001) and venous infiltration (14.4 vs. 2.4%, p < 0.001). Lymph node metastasis (23.0 vs. 11.8%, p < 0.05) and parametrial involvement (47.3 vs. 17.6%, p < 0.0001) were also more common in patients with desmoplasia. The presence of desmoplasia was associated with inferior overall (80.2% vs. 94.5% hazard ratio [HR] 3.8 [95% CI 1.4-10.4], p = 0.002) and recurrence-free survival (75.3% vs. 87.3%, HR 2.3 [95% CI 1.2-4.6], p = 0.008). In addition, desmoplasia was associated with significantly less peritumoral inflammation (rho - 0.43, p < 0.0001). In summary, we link desmoplasia to a more aggressive phenotype of cervical cancer, reduced peritumoral inflammation, and inferior survival.

Multi-Parameter Analysis of Disseminated Tumor Cells (DTCs) in Early Breast Cancer Patients with Hormone-Receptor-Positive Tumors.

BACKGROUND: Patients with hormone-receptor-positive (HR+) breast cancer are at increased risk for late recurrence. One reason might be disseminated tumor cells (DTCs), which split off in the early stages of the disease and metastasize into the bone marrow (BM). METHODS: We developed a novel multi-parameter immunofluorescence staining protocol using releasable and bleachable antibody-fluorochrome-conjugates. This sequential procedure enabled us to analyze six distinct phenotypical and therapy-related markers on the same DTC. We characterized BM aspirates from 29 patients with a HR+ tumor and a known positive DTC status-based on the standardized detection of epithelial cells in BM. RESULTS: Using the immunofluorescence staining, a total of 153 DTCs were detected. Luminal A patients revealed a higher DTC count compared with luminal B. The majority of the detected DTCs were CK-positive (128/153). However, in 16 of 17 luminal A patients we found HER2-positive DTCs. We detected CK-negative DTCs (25/153) in 12 of 29 patients. Of those cells, 76% were Ki67-positive and 68% were HER2-positive. Moreover, we detected DTC clusters consisting of mixed characteristics in 6 of 29 patients. CONCLUSIONS: Using sequential multi-parameter imaging made it possible to identify distinct DTC profiles not solely based on epithelial features. Our findings indicate that characterization rather than quantification of DTCs might be relevant for treatment decisions.

Heterogeneity between Core Needle Biopsy and Synchronous Axillary Lymph Node Metastases in Early Breast Cancer Patients-A Comparison of HER2, Estrogen and Progesterone Receptor Expression Profiles during Primary Treatment Regime.

In breast cancer therapeutic decisions are based on the expression of estrogen (ER), progesterone (PR), the human epidermal growth factor 2 (HER2) receptors and the proliferation marker Ki67. However, only little is known concerning heterogeneity between the primary tumor and axillary lymph node metastases (LNM) in the primary site. We retrospectively analyzed receptor profiles of 215 early breast cancer patients with axillary synchronous LNM. Of our cohort, 69% were therapy naive and did not receive neoadjuvant treatment. Using immunohistochemistry, receptor status and Ki67 were compared between core needle biopsy of the tumor (t-CNB) and axillary LNM obtained during surgery. The discordance rates between t-CNB and axillary LNM were 12% for HER2, 6% for ER and 20% for PR. Receptor discordance appears to already occur at the primary site. Receptor losses might play a role concerning overtreatment concomitant with adverse drug effects, while receptor gains might be an option for additional targeted or endocrine therapy. Hence, not only receptor profiles of the tumor tissue but also of the synchronous axillary LNM should be considered in the choice of treatment.

Intrahepatic cholestasis of pregnancy resistant to both therapeutic plasma exchange and albumin dialysis.

Intrahepatic cholestasis in pregnancy (ICP) represents, depending on its severity, a serious risk for the fetus. Those cases with unusually high bile acid levels may be resistant to pharmaceutical treatment and can be treated with plasma exchange or albumin dialysis. However, the success rate of these therapeutic options and the factors influencing therapeutic response are unknown. Furthermore, if these options fail to improve ICP and serum bile acid levels are very high (>200 µm/L), there are no clear recommendations when delivery should be planned. Here, we report a patient with severe ICP resistant to both therapeutic plasma exchange and albumin dialysis. Caesarean section was performed at 32 weeks of gestation followed by rapid remission of ICP.