Expression of the large amino acid transporter SLC7A5/LAT1 on immune cells is enhanced in primary sclerosing cholangitis-associated cholangiocarcinoma and correlates with poor prognosis in cholangiocarcinoma.

Biliary tract cancers (BTC) are rare lethal malignancies arising along the biliary tree. Unfortunately, effective therapeutics are lacking and the prognosis remains dismal even for patients eligible for surgical resection. Therefore, novel therapeutic approaches along with early detection strategies and prognostic markers are urgently needed.

Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-Specific Transcriptome and Molecular Subtype.

Unlabelled: Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping.

[Indications and surgical strategy for bowel resection in mesenteric ischemia : Resection margins considering current guidelines and literature as well as the influence of new technical possibilities].

Acute mesenteric ischemia (AMI) is still a time-critical and life-threatening clinical picture. If exploration of the abdominal cavity is necessary during treatment, an intraoperative assessment of which segments of the intestines have a sufficient potential for recovery must be made. These decisions are mostly based on purely clinical parameters, which are subject to high level of uncertainty.

IL-6-Dependent STAT3 Activation and Induction of Proinflammatory Cytokines in Primary Sclerosing Cholangitis.

Introduction: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with periductal inflammation and fibrosis. Genetic studies suggest inflammatory cytokines and IL-6-dependent activation of transcription factor STAT3 as pivotal steps in PSC pathogenesis. However, details of inflammatory regulation remain unclear.

Significance of Distinct Liquid Biopsy Compartments in Evaluating Somatic Mutations for Targeted Therapy Selection in Cancer of Unknown Primary.

Purpose: Cancer of unknown primary (CUP) accounts for 2-5% of all cancer diagnoses, wherein standard investigations fail to reveal the original tumor site. Basket trials allocate targeted therapeutics based on actionable somatic mutations, independent of tumor entity. These trials, however, mostly rely on variants identified in tissue biopsies.

Single-cell RNA sequencing identifies a population of human liver-type ILC1s.

Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49aCD94CD200R1, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES.

Surgical treatment for pancreatic cystic lesions-implications from the multi-center and prospective German StuDoQ|Pancreas registry.

Purpose: The detection of pancreatic cystic lesions (PCL) causes uncertainty for physicians and patients, and international guidelines are based on low evidence. The extent and perioperative risk of resections of PCL in Germany needs comparison with these guidelines to highlight controversies and derive recommendations.

Methods: Clinical data of 1137 patients who underwent surgery for PCL between 2014 and 2019 were retrieved from the German StuDoQ|Pancreas registry.

Diagnostic Potential of Exosomal microRNAs in Colorectal Cancer.

Background: Despite the significance of colonoscopy for early diagnosis of colorectal adenocarcinoma (CRC), population-wide screening remains challenging, mainly because of low acceptance rates. Herein, exosomal (exo-miR) and free circulating microRNA (c-miR) may be used as liquid biopsies in CRC to identify individuals at risk. Direct comparison of both compartments has shown inconclusive results, which is why we directly compared a panel of 10 microRNAs in this entity.

Overexpression of Parkin in clear cell renal cell carcinoma decreases tumor aggressiveness by regulating CKS2 levels.

Low expression levels of the E3 ubiquitin‑protein ligase Parkin (PARK2) are exhibited in several cancer entities, including clear cell renal cell carcinoma (ccRCC), and are associated with poor prognosis; however, PARK2 can also function as a tumor suppressor gene. The aim of the present study was to thoroughly investigate the effects of PARK2 overexpression in ccRCC cell lines and to determine its effects on malignancy by conducting functional assays such as cell cycle analysis, apoptosis analysis, migration and invasion assays. Furthermore, liquid chromatography‑mass spectrometry was used to decipher potential targets of PARK2 that may influence the behavior of ccRCC tumor cells.

Impact of regular additional endobiliary radiofrequency ablation on survival of patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy.

Prognosis of patients with advanced extrahepatic cholangiocarcinoma (eCCA) is poor. The current standard first-line treatment is systemic chemotherapy (CT) with gemcitabine and a platinum derivate. Additionally, endobiliary radiofrequency ablation (eRFA) can be applied to treat biliary obstructions.

Management of post-operative pancreatic fistulas following Longmire-Traverso pylorus-preserving pancreatoduodenectomy by endoscopic vacuum-assisted closure therapy.

Background: Pylorus-preserving pancreatoduodenectomy (PPPD) with pancreatogastrostomy is a standard surgical procedure for pancreatic head tumors, duodenal tumors and distal cholangiocarcinomas. Post-operative pancreatic fistulas (POPF) are a major complication causing relevant morbidity and mortality. Endoscopic vacuum therapy (EVT) has become a widely used method for the treatment of intestinal perforations and leakages.

A Combined TLR7/TLR9/GATA3 Score Can Predict Prognosis in Biliary Tract Cancer.

Biliary tract cancer (BTC) refers to a heterogenous group of epithelial malignancies arising along the biliary tree. The highly aggressive nature combined with its silent presentation contribute to the dismal prognosis of this tumor. Tumor-infiltrating immune cells (TIICs) are frequently present in BTC and there is growing evidence regarding their role as therapeutic targets.

Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming.

Tumor Infiltrating Neutrophils Are Frequently Found in Adenocarcinomas of the Biliary Tract and Their Precursor Lesions with Possible Impact on Prognosis.

Biliary tract cancer (BTC) is characterized by an intense stromal reaction and a complex landscape of infiltrating immune cells. Evidence is emerging that tumor-infiltrating neutrophils (TINs) have an impact on carcinogenesis and tumor progression. TINs have also been associated with outcomes in various solid malignant tumors but their possible clinical role in BTC is largely unknown.

Open Abdomen Treatment in Acute Pancreatitis.

Severe acute pancreatitis (SAP) is a heterogeneous and life-threatening disease. While recent guidelines recommend a stepwise approach starting with non-surgical techniques, emergency laparotomy remains inevitable in certain situations. Open abdomen treatment (OAT) may follow, potentially resulting in additional risks for severe morbidity.

Induction of cytotoxic effector cells towards cholangiocellular, pancreatic, and colorectal tumor cells by activation of the immune checkpoint CD40/CD40L on dendritic cells.

Introduction: Gastrointestinal (GI) malignancies, such as cholangiocarcinoma, pancreatic carcinoma, and metastatic colorectal carcinoma, have a poor prognosis and effective therapeutic approaches are still challenging. Checkpoint inhibition with PD-1 or PDL-1 antibodies revealed promising results in different tumor entities; however, only few patients with GI tumors can potentially benefit from PD1/PDL1 inhibiting immunotherapy. Further immunotherapeutic strategies for GI malignancies are urgently needed.

Mitophagy-associated genes PINK1 and PARK2 are independent prognostic markers of survival in papillary renal cell carcinoma and associated with aggressive tumor behavior.

The aim of this study was to investigate the mitophagy-related genes PINK1 and PARK2 in papillary renal cell carcinoma and their association with prognosis. In silico data of PINK1 and PARK2 were analyzed in TCGA cohorts of papillary renal cell carcinoma comprising 290 tumors and 33 corresponding non-neoplastic renal tissues. Protein expression data from a cohort of 95 papillary renal cell carcinoma patients were analyzed and associated with clinical-pathological parameters including survival.

Cultivation of Clear Cell Renal Cell Carcinoma Patient-Derived Organoids in an Air-Liquid Interface System as a Tool for Studying Individualized Therapy.

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer accounting for 80% of all renal cancers as well as the majority of renal cancer-associated deaths. During the last decade, the treatment paradigm for ccRCC has radically changed. In particular, the recent development of immune checkpoint inhibitors (ICI) has led to an increased overall survival in the metastatic setting.

Targeting glycolysis with 2-deoxy-D-glucose sensitizes primary cell cultures of renal cell carcinoma to tyrosine kinase inhibitors.

Purpose: To investigate the synergistic effect of glycolysis inhibition on therapy answer to tyrosine kinase inhibitors in renal carcinoma.

Methods: Primary cell cultures from 33 renal tumors including clear cell RCC (ccRCC), papillary RCC and the rare subtype chromophobe RCC as well as two metastases of ccRCC were obtained and cultivated. The patient-derived cells were verified by immunohistochemistry.

[Surgical treatment of primary sclerosing cholangitis : Experiences from 30 years in a single center cohort with 173 consecutive patients].

Background: In recent years substantial progress has been made in the treatment, surveillance and understanding of the pathogenesis of primary sclerosing cholangitis (PSC); however, in most cases liver transplantation (LTX) is still the only curative option for cancer or end-stage liver disease (ELD). In rare cases a partial liver resection is a possible curative treatment of a PSC-associated cholangiocellular carcinoma (CCC). These operations represent a significant additional burden for PSC patients.

Acute mesenteric ischemia (AMI): absence of renal insufficiency and performance of early bowel resection may indicate improved outcomes.

Purpose: Acute mesenteric ischemia (AMI) is still associated with very high morbidity and mortality while the rareness and heterogeneity hamper the establishment of evidence-based guidelines. We sought to help standardize contemporary treatment by a cohort study at our tertiary center in the rising endovascular age.

Methods: A retrospective cohort study was conducted from 2005 to 2015.

Prognostic value of DLGAP5 in colorectal cancer.

Purpose: DLG7 (disc large homolog 7) is a microtubule-associated protein encoded by DLGAP5 (DLG associated protein 5) gene and has an important role during spindle assembly. Spindle assembly deregulation is a well-known cause of genomic instability. The aim of this study was to investigate the influence of DLGAP5 expression on survival and to evaluate its potential use as a biomarker in colorectal cancer (CRC).

Clinicopathological, immune and molecular correlates of methylation in gastric adenocarcinomas.

We investigated the significance of DNA methylation in gastric adenocarcinomas. We analyzed the methylation at different CpG sites within the PD-L2-encoding gene with regard to correlations and associations with gene expression, clinicopathological parameters, molecular features and immune cell infiltrates in two publicly available cohorts (The Cancer Genome Atlas and Singapore cohorts) of a total of 594 gastric adenocarcinoma patients. methylation is significantly associated with transcriptional activity, survival, Epstein-Barr virus infection, gene amplification, CD8 T-cell infiltration, microsatellite instability and high mutational load (tumor mutational burden, hypermutation).

Visceral artery aneurysms: evolving interdisciplinary management and future role of the abdominal surgeon.

Background: Visceral artery aneurysms (VAA) are rare vascular lesions. Clinically silent VAA are increasingly detected by cross-sectional imaging but some lesions are at risk for rupture with severe bleeding. The aim of the present study was to evaluate the trends in the interdisciplinary management at a tertiary center.

Combined photodynamic therapy with systemic chemotherapy for unresectable cholangiocarcinoma.

Background: Chemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma.

Aim: To evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma.