Krukenberg Progression of Gastric Carcinoma in Pregnancy: Is Early Diagnosis Possible? Case Report and Review of the Literature.

Krukenberg tumors are metastatic tumors of the ovaries, associated with poor outcomes. Most commonly, these tumors are of gastric origin. The diagnosis of Krukenberg tumors in pregnant patients is extremely rare and poses specific difficulties for clinicians. We report a case of a pregnant woman presenting with an unknown abdominal tumor. Through the use of magnetic resonance imaging, multiple differential diagnoses were proposed, including a malignant ovarian tumor. A cesarean section and explorative laparotomy were conducted, revealing Krukenberg metastases of a gastric tumor, discovered during intraoperative gastroscopy. Tumor resection with concomitant chemotherapy was conducted. The main aim of this paper was to evaluate whether earlier diagnosis seems possible in such cases. A thorough literature review was conducted, unfortunately revealing no reliable method for early detection. Furthermore, no consensus regarding diagnostics or therapy exists to date. Thus, more research should be conducted regarding this rare condition to offer recommendations regarding early detection, diagnostics, and therapeutic approaches.

Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma.

The most prevalent histological type of non-small cell lung cancer (NSCLC) is adenocarcinoma. The WHO classifies this tumor into subtypes according to the predominant growth pattern such as lepidic, acinar, papillary, solid or micropapillary, each harboring specific molecular features. NSCLC adenocarcinoma heterogeneity is discussed to be a reason for therapy failure using targeted therapy or immune checkpoint inhibitors. For successful therapy of immune checkpoint inhibitors the expression and distribution of the involved immune checkpoint proteins is essential. Therefore, we aimed to investigate the distribution of five prominent immune checkpoint proteins in regard of the histological growth patterns of lung adenocarcinoma. We performed immunohistochemical staining of 84 tumor segments from 22 resected tumor samples to evaluate the expression of PD-L1, PD-1, Nectin-2, PVR, and TIGIT in distinct growth patterns of lung adenocarcinoma. We determined a distinct heterogeneity between and within different tumor segments regarding morphological growth patterns. Furthermore, expression of immune checkpoint proteins varied between different growth pattern areas as well as within one distinct growth pattern. Expression of PVR was significantly higher in solid compared to acinar growth pattern (p= 0.00736). Of note, we detected TIGIT not only on tumor infiltrating lymphocytes but also on tumor cells, whereas non-neoplastic lung tissue was consistently TIGIT-negative. The immune checkpoint protein distribution in histologic subtypes of pulmonary adenocarcinoma displays an considerable intra- and intertumoral heterogeneity implying the requirement of either a multiregion or an adjusted analysis when determining the expression status of PD-1:PD-L1 and the TIGIT:PVR/Nectin-2 checkpoint proteins as predictive markers.

Simulation-Based Interpretation of Therapeutically Monitored Cabozantinib Plasma Concentration in Advanced Adrenocortical Carcinoma with Hemodialysis.

BACKGROUND: Adrenocortical carcinoma is an orphan but aggressive malignancy with limited treatment options. Cabozantinib (CAB), a tyrosine kinase inhibitor, has emerged as a new potential treatment. However, no data are available on whether and how CAB can be administered to patients undergoing hemodialysis. METHODS: An liquid chromatography with tandem mass spectrometry detection method was developed and validated according to the European Medicines Agency and United States Food and Drug Administration guidelines for bioanalytical method validation. The samples were prepared using protein precipitation and online solid-phase extraction. The method was applied to clinical samples of an adrenocortical carcinoma patient receiving CAB treatment (80 mg daily). During the 10 days of observation, the patient received periodic hemodialysis on 7 days. Pharmacokinetic (PK) simulations were performed using Bayesian forecasting according to an existing population PK model for CAB. RESULTS: Based on the PK simulation, a mean plasma trough concentration of 1375 ng/mL [90% prediction interval (PI), 601-2602 ng/mL] in the steady state at a daily dose of 80 mg was expected for CAB. However, an individual simulation involving the measured plasma levels of the patient resulted in a mean trough concentration of 348 ng/mL (90% PI, 278-430 ng/mL). The model based on individual PK parameters estimated accessible plasma levels of 521, 625, and 834 ng/mL by dose adjustment to 100, 120, and 160 mg, respectively. CONCLUSIONS: After establishing an liquid chromatography with tandem mass spectrometry detection method for therapeutic drug monitoring of CAB, our analyses involving a single patient undergoing hemodialysis indicated that higher than expected doses of CAB were required to achieve reasonable plasma concentrations. Our study demonstrates the usefulness of therapeutic drug monitoring for the evaluation of "new" drugs in patients with renal impairment.

Rescue of Non-Informative Circulating Tumor DNA to Monitor the Mutational Landscape in NSCLC.

In non-small cell lung cancer (NSCLC) the usage of plasma-derived circulating tumor DNA (ctDNA) have come into focus to obtain a comprehensive genetic profile of a given lung cancer. Despite the usage of specific sampling tubes, archived plasma samples as well as inappropriately treated blood samples still cause a loss of information due to cell lysis and contamination with cellular DNA. Our aim was to establish a reliable protocol to rescue ctDNA from such non-informative samples to monitor the mutational landscape in NSCLC. As a proof-of-concept study we used archived plasma samples derived from whole blood EDTA samples of 51 patients suffering from NSCLC. Analysis of the isolated plasma DNA determined only a small fraction of ctDNA in a range of 90-250 bp. By applying a specific purification procedure, we were able to increase the informative ctDNA content and improve in a cohort of 42 patients the detection of driver mutations from 32% to 79% of the mutations found in tissue biopsies. Thus, we present here an easy to perform, time and cost effective procedure to rescue non-informative ctDNA samples, which is sufficient to detect oncogenic mutations in NGS approaches and is therefore a valuable technical improvement for laboratories handling liquid biopsy samples.

Comparison of actual hospital costs versus DRG revenues for in-patient treatment of febrile neutropenia during adjuvant anthracycline plus/minus taxane-based chemotherapy for primary breast cancer.

BACKGROUND: In flat-rate reimbursement systems, the hospital's own costs should not exceed its revenues. In a cohort of primary breast cancer (pBC) patients, costs and reimbursement for febrile neutropenia (FN) were compared to verify cost coverage. METHODS: A prospective, observational study in pBC patients receiving adjuvant anthracycline ± taxane-based chemotherapy calculated the costs per in-patient FN episode. The correlating revenues were retrospectively analyzed from diagnosis-related group (DRG) invoices. The actual costs of the therapies were compared to the individual DRG revenues, and the results are presented from the provider's perspective. RESULTS: In 50 patients, n = 11 patients were treated for FN as in-patients. The hospital's overall treatment costs were € 18,288, on average (Ø) € 1663 per case (range € 1139-2344); the overall DRG revenues were € 23,593, Ø € 2145 per case (range € 1266-2660). In n = 8 cases, the DRGs were cost covering, and in n = 3 cases, a loss was observed, but overall resulting in a gain of Ø € 482 per case and thus being cost covering for the provider. Inadequate DRG coding (n = 4/11; 36.4%) resulted in a preventable loss of Ø € 1069/case. CONCLUSIONS: The costs of FN treatment vary substantially and DRG reimbursements do not necessarily reflect the provider's costs. Surprisingly, the in-patient treatment of FN here is overall more than cost covering if adequately coded. The main reasons are asymmetrical costs for this FN low-risk pBC group. These results emphasize the importance of correct medical coding to avoid potential losses.