Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials.

Purpose: Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment.

Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML.

Background: Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-molecule inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone.

Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.

Objective: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.

Design: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry.

POLE Score: a comprehensive profiling of programmed death 1 ligand 1 expression in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) being characterized by a pronounced stromal compartment is commonly diagnosed at an advanced stage limiting curative treatment options. Although therapeutical targeting of immune checkpoint regulators like programmed death 1 ligand 1 (PD-L1) represent a promising approach that substantially improved survival of several highly aggressive malignancies, convincing indicators for response prediction are still lacking for PDAC which might be attributed to the insufficient characterization of PD-L1 status. Therefore, we investigated PD-L1 expression by immunohistochemistry in a well characterized cohort of 59 PDAC and 18 peritumoral tissues.

Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.

Objective: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease.

Design: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent.

Persistent Increased Enteric Glial Expression of S100β is Associated With Low-grade Inflammation in Patients With Diverticular Disease.

Background: Diverticular disease (DD) is a common gastrointestinal inflammatory disorder associated with an enteric neuropathy. Although enteric glial cells (EGCs) are essential regulators of intestinal inflammation and motility functions, their contribution to the pathophysiology of DD remains unclear. Therefore, we analyzed the expression of specific EGC markers in patients with DD.

Monitoring and functional characterization of the lymphocytic compartment in pancreatic ductal adenocarcinoma patients.

Background/objectives: Pancreatic ductal adenocarcinoma (PDAC) still has a poor prognosis and current treatments including immunotherapy often fail. This might be due to the pronounced immunosuppressive milieu impairing infiltration and function of immune effector cells. This study aimed at a comprehensive analysis of immune cells in PDAC patients by determining absolute and relative peripheral blood cell numbers of immune cell subsets along with their functional capacity.

L1CAM promotes enrichment of immunosuppressive T cells in human pancreatic cancer correlating with malignant progression.

Regulatory T cell (T-reg) enrichment in the tumor microenvironment is regarded as an important mechanism of tumor immune escape. Hence, the presence of T-regs in highly malignant pancreatic ductal adenocarcinoma (PDAC) is correlated with short survival. Likewise, the adhesion molecule L1CAM is upregulated during PDAC progression in the pancreatic ductal epithelium also being associated with poor prognosis.

Endoscopic therapy of a pancreatic effusion caused by chronic pancreatitis.

A 36-year-old patient was hospitalized because of an extensive right pleural effusion. He complained of increasing dyspnea, moderate weight loss and night sweats. The pleural aspirate was hemorrhagic and, surprisingly, excessively elevated lipase activity (57,000 U/L) was measured.

Effect of physical activity on serum concentrations of digoxin and digitoxin.

Objective: To study the influence of moderate physical activity on serum concentrations of digoxin, digitoxin and albumin.

Methods: Blood samples were drawn from 10 consecutive mobile patients on digoxin and 12 patients on digitoxin therapy before and following a 10-min walking period. Digitalis serum concentrations were determined by radioimmunoassay, and albumin serum concentrations by laser nephelometry.

Detection of atrial fusion systole in patients with dual chamber pacemakers by 24-hour esophagus ECG.

We performed ambulatory 24-hour esophagus ECG in nine patients with dual chamber pacemakers suspect of transient arrhythmias in order to achieve correct and reliable P wave identification during daily life activities. In all patients episodes were observed with varying atrial artifact to left atrial depolarization sequences. These episodes probably reflected presence of atrial fusion systole, an ECG phenomenon which should be taken into account when analyzing ambulatory esophagus ECG.