Dual Immune Checkpoint Inhibition Plus Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Randomized Clinical Trial.

Importance: Immune checkpoint inhibitors (ICIs) show efficacy in treatment of several solid tumors, but microsatellite-stable rectal cancer is largely resistant. Radiotherapy may enhance tumor immunogenicity and thus may make the combination of radiotherapy and ICIs a promising strategy to treat rectal cancer. While anti-programmed cell death protein 1 antibodies in neoadjuvant regimens have been linked to higher complete response rates, the added benefit of including a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor remains unclear.

Differential prognostic roles and clinical implications of mitochondrial and genomic tRNA-derived fragments in colorectal liver metastases.

Background: Colorectal liver metastases (CRLM) are the leading cause of colorectal cancer (CRC)-related mortality. Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNAs (sncRNA), regulate gene expression, stress response, and immune functions in cancer. While increasingly implicated in CRC progression, their prognostic significance in CRLM remains unknown.

High CD36 expression in the tumor microenvironmental vasculature correlates with unfavorable overall survival in high grade serous ovarian cancer.

The scavenger receptor CD36 has gained increasing interest in cancer research, with various functions in cell metabolism, angiogenesis, and immune response. This study aimed to investigate the molecular role of CD36 expression on tumor vasculature of advanced high-grade serous ovarian cancer (HGSOC) tissues and its prognostic implication. Immunohistochemical staining for CD36 was performed on whole tissue slides of 109 patients with advanced HGSOC.

Colorectal cancer peritoneal metastasis is promoted by tissue-specific fibroblasts that can arise in response to various local disorders.

Peritoneal membrane injury induces the activation of local fibroblasts and tissue remodelling, which ultimately can progress to fibrosis. Metastasis of colorectal cancer (CRC) to the abdominal cavity results in such peritoneal damage. Patients with colorectal cancer peritoneal metastasis (CPM) have a particularly poor prognosis, and CPM tumours are characterised by a high infiltration of fibroblasts.

Increased [F]FDG uptake in the infarcted myocardial area displayed by combined PET/CMR correlates with snRNA-seq-detected inflammatory cell invasion.

Combined [F]FDG PET-cardiac MRI imaging (PET/CMR) is a useful tool to assess myocardial viability and cardiac function in patients with acute myocardial infarction (AMI). Here, we evaluated the prognostic value of PET/CMR in a porcine closed-chest reperfused AMI (rAMI) model. Late gadolinium enhancement by PET/CMR imaging displayed tracer uptake defect at the infarction site by 3 days after the rAMI in the majority of the animals (group Match, n = 28).

Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis.

Background: A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial.

Methods: Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL.

Patient reported outcomes of duodenum-preserving pancreatic head resection in chronic pancreatitis: high effectivity is impaired by prolonged non-surgical management.

Background: Chronic pancreatitis (CP) causes suffering and socioeconomic burden. This study evaluated perioperative results and patient-reported outcomes (PRO) in CP patients treated with duodenum-preserving pancreatic head resection (DPPHR).

Methods: Data were analyzed of CP patients undergoing DPPHR between 01/2001-10/2014.

Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer.

Introduction: Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC.

Methods: All patients who underwent resection for PDAC were identified from two prospective institutional databases.

The Revised R Status is an Independent Predictor of Postresection Survival in Pancreatic Cancer After Neoadjuvant Treatment.

Objective: To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1 mm) after neoadjuvant therapy (NAT).

Background: The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1 mm margin clearance after NAT remains controversial.

Methods: Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases.

Pharmacological Inhibition of Lipid Import and Transport Proteins in Ovarian Cancer.

Ovarian cancer (OC) is the most lethal gynecological malignancy with a 5-year survival rate of 49%. This is caused by late diagnosis when cells have already metastasized into the peritoneal cavity and to the omentum. OC progression is dependent on the availability of high-energy lipids/fatty acids (FA) provided by endogenous de novo biosynthesis and/or through import from the microenvironment.

Metabolomics implicate eicosanoids in severe functional mitral regurgitation.

Aims: Secondary, or functional, mitral regurgitation (FMR) was recently recognized as a separate clinical entity, complicating heart failure with reduced ejection fraction (HFrEF) and entailing particularly poor outcome. Currently, there is a lack of targeted therapies for FMR due to the fact that pathomechanisms leading to FMR progression are incompletely understood. In this study, we sought to perform metabolomic profiling of HFrEF patients with severe FMR, comparing results to patients with no or mild FMR.

Corrected Allele Frequency of BRCA1/2 Mutations Is an Independent Prognostic Factor for Treatment Response to PARP-Inhibitors in Ovarian Cancer Patients.

PARP inhibitors (PARPi) have increased treatment options in ovarian cancer, particularly in patients with BRCA1/2 mutations, although there are still marked differences in the duration of patients' response to this targeted therapy. BRCA testing is routinely performed in tumor tissue of ovarian cancer patients. The resulting molecular pathological findings include the genetic nomenclature of the mutation, the frequency of the mutated allele (variant allele frequency, VAF), and the tumor cell content.

Defining Models to Classify between Benign and Malignant Adnexal Masses Using Routine Laboratory Parameters.

Discrimination between benign and malignant adnexal masses is essential for optimal treatment planning, but still remains challenging in a routine clinical setting. In this retrospective study, we aimed to compare albumin as a single parameter to calculate models by analyzing laboratory parameters of 1552 patients with an adnexal mass (epithelial ovarian cancer (EOC): = 294; borderline tumor of the ovary (BTO): = 66; benign adnexal mass: = 1192) undergoing surgery. Models comprising classical laboratory parameters show better accuracies (AUCs 0.

Prostate-Specific Membrane Antigen (PSMA) Expression in Tumor-Associated Neovasculature Is an Independent Prognostic Marker in Patients with Ovarian Cancer.

Prostate-specific membrane antigen (PSMA) is present in the tumor-associated neovasculature of many cancer types. Current data in ovarian cancer are limited and controversial; thus, the aim of this study was to investigate PSMA expression in a larger and homogenous patient cohort. This might lead to further studies investigating the use of imaging and therapeutic modalities targeting PSMA.

PD-1 and PD-L1 expression on TILs in peritoneal metastases compared to ovarian tumor tissues and its associations with clinical outcome.

The therapeutic potential of immune checkpoint inhibitors is currently being investigated in epithelial ovarian cancer (EOC), but immunological effects of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis in EOC still remain poorly understood. The aim of this study was thus to compare infiltration rates of PD-1 and PD-L1 expressing tumor infiltrating leucocytes (TILs) in primary ovarian tumor tissue and metastatic intraperitoneal implants and to investigate its impact on overall survival (OS). Tumor specimens (ovarian tumor tissues and intraperitoneal metastases) of 111 patients were used to investigate the PD-1, PD-L1 and CD8 expression rates on TILs and PD-L1 expression rate of tumor cells.

T cell phenotype in paediatric heart transplant recipients.

Paediatric heart transplantation recipients suffer an increased incidence of infectious, autoimmune and allergic problems. The relative roles of thymus excision and immunosuppressive treatments in contributing to these sequelae are not clear. We compared the immunological phenotypes of 25 heart transplant recipients (Tx), 10 children who underwent thymus excision during non-transplantation cardiac surgery (TE) and 25 age range-matched controls, in two age bands: 1-9 and 10-16 years.

Defining the regenerative effects of native spider silk fibers on primary Schwann cells, sensory neurons, and nerve-associated fibroblasts.

The search for a suitable material to promote regeneration after long-distance peripheral nerve defects turned the spotlight on spider silk. Nerve conduits enriched with native spider silk fibers as internal guiding structures previously demonstrated a regenerative outcome similar to autologous nerve grafts in animal studies. Nevertheless, spider silk is a natural material with associated limitations for clinical use.

Reduced LDL-Cholesterol and Reduced Total Cholesterol as Potential Indicators of Early Cancer in Male Treatment-Naïve Cancer Patients With Pre-cachexia and Cachexia.

Cancer cachexia is characterized by the impairment of glucose and lipid homeostasis, the acceleration of processes promoting the mobilization of energy-rich compounds (e.g., insulin resistance, gluconeogenesis, and lipolysis) and the simultaneous activation of highly energy-demanding processes (e.

A Global Gene Body Methylation Measure Correlates Independently with Overall Survival in Solid Cancer Types.

Epigenetics, CpG methylation of CpG islands (CGI) and gene bodies (GBs), plays an important role in gene regulation and cancer biology, the former established as a transcription regulator. Genome wide CpG methylation, summarized over GBs and CGIs, was analyzed for impact on overall survival (OS) in cancer. The averaged GB and CGI methylation status of each gene was categorized into methylated and unmethylated (defined) or undefined.

The Presence of Active Brown Adipose Tissue Determines Cold-Induced Energy Expenditure and Oxylipin Profiles in Humans.

Background: Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT positive (BATpos) and those without BAT negative (BATneg).

The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray.

Background: T cell density in colorectal cancer (CRC) has proven to be of high prognostic importance. Here, we evaluated the influence of a hyperfractionated preoperative short-term radiation protocol (25 Gy) on immune cell density in tumor samples of rectal cancer (RC) patients and on patient survival. In addition, we assessed spatial tumor heterogeneity by comparison of analogue T cell quantification on full tissue sections with digital T cell quantification on a virtually established tissue microarray (TMA).

Neutrophil Extracellular Trap Formation Correlates with Favorable Overall Survival in High Grade Ovarian Cancer.

It is still a question of debate whether neutrophils, often found in the tumor microenvironment, mediate tumor-promoting or rather tumor-inhibiting activities. The present study focuses on the involvement of neutrophils in high grade serous ovarian cancer (HGSOC). Macroscopic features classify two types of peritoneal tumor spread in HGSOC.