Interdisciplinary evidence-based tumor board simulation training in surgical medical education.

Purpose: Evidence-based medicine (EBM), precision medicine and interdisciplinarity are becoming increasingly important in medical education. The purposeful connection between EBM and interdisciplinary work is given in the context of a tumor board, since therapy decisions are discussed here in an interdisciplinary team based on current evidence-based guidelines. To date, there has been little focus on either topic.

Reconsidering palliative radiotherapy in addition to PD-1 blockade for non-small cell lung cancer: results from the FORCE phase II trial (AIO/YMO-TRK-0415).

Introduction of immune checkpoint inhibitors (ICI) has improved overall survival (OS) for advanced non-small cell lung cancer (NSCLC). However, responses differ greatly amongst patients. Additional radiotherapy (RT) may promote tumor-specific immunity and synergize with ICI to improve tumor control.

Selective neoadjuvant therapy of rectal cancer patients (SELREC): study protocol for a European randomised controlled, open, multicentre non-inferiority trial.

Introduction: Neoadjuvant (chemo)radiotherapy (n(C)RT) followed by resection with total mesorectal excision (TME) constitutes the standard treatment for patients with locally advanced rectal cancer of the middle and lower third. However, n(C)RT has demonstrated no significant impact on overall survival but is associated with adverse effects, including impaired sphincter and sexual function. We hypothesise that omitting n(C)RT in selected patients with a clear circumferential resection margin (CRM) >1 mm as determined through preoperative MRI is not inferior regarding local recurrence rate within 3 years after surgery.

Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer.

Background: Prostate cancer (PCa) is a highly heterogeneous disease, ranging from indolent to highly aggressive forms. Ongoing research focuses on identifying new biomarkers to improve early risk stratification in PCa, addressing current limitations to accurately evaluate disease progression. A promising new approach to aid PCa risk stratification is digital spatial profiling (DSP) of PCa tissue.

Integrated 3D imaging of FFPE lung tissue combining microCT, light and electron microscopy allows for contextualized ultrastructural and histological analysis.

Classical histopathology of formalin fixed and paraffin embedded (FFPE) tissue using light microscopy (LM) remains the undisputed gold standard in biomedical microstructural lung tissue analysis. To extend this method, we developed an integrative imaging and processing pipeline which adds 3D context and screening capabilities by microCT (µCT) imaging of the entire paraffin block and adds ultrastructural information by correlative same-slide scanning electron microscopy (SEM). The different modalities are integrated by elastic registration to provide hybrid image datasets.

Extensive genotype-phenotype heterogeneity in renal cell carcinoma - a proof-of-concept study.

Background: Renal cell carcinoma (RCC) is characterized by a high degree of genomic but also functional intratumoral heterogeneity (ITH). Mutations in , chromatin remodeling genes such as and genes that regulate the PI3K/AKT/mTOR pathway have been identified as recurrent drivers despite genomic ITH. Whether and to what extent these mutations shape functional ITH including the formation of spatial niches is incompletely understood.

Presenting the framework of the whole slide image file Babel fish: An OCR-based file labeling tool.

Introduction: Metadata extraction from digitized slides or whole slide image files is a frequent, laborious, and tedious task. In this work, we present a tool to automatically extract all relevant slide information, such as case number, year, slide number, block number, and staining from the macro-images of the scanned slide.We named the tool Babel fish as it helps translate relevant information printed on the slide.

Enhancing the diagnostic capacity of [F]PSMA-1007 PET/MRI in primary prostate cancer staging with artificial intelligence and semi-quantitative DCE: an exploratory study.

Background: To investigate the ability of artificial intelligence (AI)-based and semi-quantitative dynamic contrast enhanced (DCE) multiparametric MRI (mpMRI), performed within [F]-PSMA-1007 PET/MRI, in differentiating benign from malignant prostate tissues in patients with primary prostate cancer (PC).

Results: A total of seven patients underwent whole-body [F]-PSMA-1007 PET/MRI examinations including a pelvic mpMRI protocol with T2w, diffusion weighted imaging (DWI) and DCE image series. Conventional analysis included visual reading of PET/MRI images and Prostate Imaging Reporting & Data System (PI-RADS) scoring of the prostate.

Tumour mutational burden: clinical utility, challenges and emerging improvements.

Tumour mutational burden (TMB), defined as the total number of somatic non-synonymous mutations present within the cancer genome, varies across and within cancer types. A first wave of retrospective and prospective research identified TMB as a predictive biomarker of response to immune-checkpoint inhibitors and culminated in the disease-agnostic approval of pembrolizumab for patients with TMB-high tumours based on data from the Keynote-158 trial. Although the applicability of outcomes from this trial to all cancer types and the optimal thresholds for TMB are yet to be ascertained, research into TMB is advancing along three principal avenues: enhancement of TMB assessments through rigorous quality control measures within the laboratory process, including the mitigation of confounding factors such as limited panel scope and low tumour purity; refinement of the traditional TMB framework through the incorporation of innovative concepts such as clonal, persistent or HLA-corrected TMB, tumour neoantigen load and mutational signatures; and integration of TMB with established and emerging biomarkers such as PD-L1 expression, microsatellite instability, immune gene expression profiles and the tumour immune contexture.

Prospective Validation of the Pancreatic Fistula Risk Classification by the International Study Group for Pancreatic Surgery (PARIS trial).

Objective: The aim of this study was a prospective validation of the recently established ISGPS pancreas classification as a parenchymal risk classification system for pancreatic fistula after pancreatoduodenectomy.

Summary Background Data: Postoperative pancreatic fistula (POPF) is the major driver for complications after partial pancreatoduodenectomy (PD). Recently, the International Study Group for Pancreatic Surgery (ISGPS) published a pancreas classification containing the parameters main pancreatic duct diameter (MPD) and pancreatic texture to help assess the risk of POPF development following pancreatoduodenectomy.

Immune landscape of renal cell carcinoma with metastasis to the pancreas.

Introduction: Clear cell Renal Cell Carcinoma (ccRCC) has a poor prognosis once metastatic. However, certain metastatic sites have been reported to have a different impact on the patient prognosis. For example, patients with pancreatic metastases have a much more favorable prognosis than those with metastases to other organs.

Clinical Relevance of Pathological Diagnosis of Hirschsprung's Disease with Acetylcholine-Esterase Histochemistry or Calretinin Immunohistochemistry.

Introduction: Hirschsprung disease (HD) manifests as a developmental anomaly affecting the enteric nervous system, where there is an absence of ganglion cells in the lower part of the intestine. This deficiency leads to functional blockages within the intestines. HD is usually confirmed or ruled out through rectal biopsy.

Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.

Purpose: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. is located on chromosome 1q23.

PD-L1 as a Urine Biomarker in Renal Cell Carcinoma-A Case Series and Proof-of-Concept Study.

Background: Renal cell carcinoma (RCC) is among the most lethal urologic malignancies once metastatic. Current treatment approaches for metastatic RCC (mRCC) involve immune checkpoint inhibitors (ICIs) that target the PD-L1/PD-1 axis. High PD-L1 expression in tumor tissue has been identified as a negative prognostic factor in RCC.

Knock-out of dipeptidase CN2 in human proximal tubular cells disrupts dipeptide and amino acid homeostasis and para- and transcellular solute transport.

Aim: Although of potential biomedical relevance, dipeptide metabolism has hardly been studied. We found the dipeptidase carnosinase-2 (CN2) to be abundant in human proximal tubules, which regulate water and solute homeostasis. We therefore hypothesized, that CN2 has a key metabolic role, impacting proximal tubular transport function.

Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy-Results of a Prospective Single-Center Trial.

Donor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. In this prospective study, 106 kidney transplant recipients with 108 clinically indicated biopsies were enrolled at Heidelberg University Hospital between November 2020 and December 2022 to validate the clinical value of dd-cfDNA in a cohort of German patients. dd-cfDNA was quantified at biopsy and correlated to histopathology.

Digital Spatial Profiling Identifies the Tumor Periphery as a Highly Active Biological Niche in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by a high degree of intratumoral heterogeneity (ITH). Besides genomic ITH, there is considerable functional ITH, which encompasses spatial niches with distinct proliferative and signaling activities. The full extent of functional spatial heterogeneity in ccRCC is incompletely understood.

Application of a validated prostate MRI deep learning system to independent same-vendor multi-institutional data: demonstration of transferability.

Objectives: To evaluate a fully automatic deep learning system to detect and segment clinically significant prostate cancer (csPCa) on same-vendor prostate MRI from two different institutions not contributing to training of the system.

Materials And Methods: In this retrospective study, a previously bi-institutionally validated deep learning system (UNETM) was applied to bi-parametric prostate MRI data from one external institution (A), a PI-RADS distribution-matched internal cohort (B), and a csPCa stratified subset of single-institution external public challenge data (C). csPCa was defined as ISUP Grade Group ≥ 2 determined from combined targeted and extended systematic MRI/transrectal US-fusion biopsy.