RNASEH2B loss and PARP inhibition in advanced prostate cancer.

BACKGROUNDClinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome, and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial.

Multiparametric bone MRI targeting aides lesion selection for CT-guided sclerotic bone biopsies in metastatic castrate resistant prostate cancer.

Background: Bone biopsies in metastatic castrate-resistant prostate cancer (mCRPC) patients can be challenging. This study's objective was to prospectively validate a multiparametric bone MRI (mpBMRI) algorithm to facilitate target lesion selection in mCRPC patients with sclerotic bone disease for subsequent CT-guided bone biopsies.

Methods: 20 CT-guided bone biopsies were prospectively performed between 02/2021 and 11/2021 in 17 mCRPC patients with only sclerotic bone disease.

Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance.

Inflammation is a hallmark of cancer. In patients with cancer, peripheral blood myeloid expansion, indicated by a high neutrophil-to-lymphocyte ratio, associates with shorter survival and treatment resistance across malignancies and therapeutic modalities. Whether myeloid inflammation drives progression of prostate cancer in humans remain unclear.

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion.

Optimising CT-guided biopsies of sclerotic bone lesions in cancer patients.

Objectives: Investigate the laboratory, imaging and procedural factors that are associated with a tumour-positive and/or NGS-feasible CT-guided sclerotic bone lesion biopsy result in cancer patients.

Methods: In total, 113 CT-guided bone biopsies performed in cancer patients by an interventional radiologist in one institution were retrospectively reviewed. Sixty-five sclerotic bone biopsies were eventually included and routine blood parameters and tumour marker levels were recorded.

Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer.

Background: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited.

Objective: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS).

Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer.

Despite major improvements in the management of advanced prostate cancer over the last 20 years, the disease remains invariably fatal, and new effective therapies are required. The development of novel hormonal agents and taxane chemotherapy has improved outcomes, although primary and acquired resistance remains problematic. Inducing cancer cell death via apoptosis has long been an attractive goal in the treatment of cancer.

A New Old Target: Androgen Receptor Signaling and Advanced Prostate Cancer.

Owing to the development of multiple novel therapies, there has been major progress in the treatment of advanced prostate cancer over the last two decades; however, the disease remains invariably fatal. Androgens and the androgen receptor (AR) play a critical role in prostate carcinogenesis, and targeting the AR signaling axis with abiraterone, enzalutamide, darolutamide, and apalutamide has improved outcomes for men with this lethal disease. Targeting the AR and elucidating mechanisms of resistance to these agents remain central to drug development efforts.

Beyond the Androgen Receptor: The Sequence, the Mutants, and New Avengers in the Treatment of Castrate-Resistant Metastatic Prostate Cancer.

Targeting the androgen receptor by depriving testosterone with gonadotropin-releasing hormone agonists or antagonists, or surgical castration, has been the backbone of metastatic prostate cancer treatment. Although most prostate cancers initially respond to androgen deprivation, metastatic castration-resistant prostate cancer evolves into a heterogeneous disease with diverse drivers of progression and mechanisms of therapeutic resistance. Development of castrate resistance phenotype is associated with lethality despite the recent noteworthy strides gained via increase in therapeutic options.

The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study.

Objective: Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk factors for progressive disease.

Methods: A longitudinal population-based cohort study was conducted.

Short and long-term post-operative outcomes of duodenum preserving pancreatic head resection for chronic pancreatitis affecting the head of pancreas: a systematic review and meta-analysis.

Background: To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis.

Methods: A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function).

Results: Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure.

Surgery remains the best option for the management of pain in patients with chronic pancreatitis: A systematic review and meta-analysis.

Controversy related to endoscopic or surgical management of pain in patients with chronic pancreatitis remains. Despite improvement in endoscopic treatments, surgery remains the best option for pain management in these patients.

Analysis of Endoscopic Radiofrequency Ablation of Biliary Malignant Strictures in Pancreatic Cancer Suggests Potential Survival Benefit.

Background: Pancreatic carcinoma is often inoperable, carries a poor prognosis, and is commonly complicated by malignant biliary obstruction. Phase I/II studies have demonstrated good safety and early stent patency using endoscopic biliary radiofrequency ablation (RFA) as an adjunct to self-expanding metal stent (SEMS) insertion for biliary decompression.

Aim: To analyze the clinical efficacy of endobiliary RFA.

Diagnostic utility of single-user peroral cholangioscopy in sclerosing cholangitis.

Objective: To evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) in patients with sclerosing cholangitis.

Methods: All patients with sclerosing cholangitis who underwent SOC procedures due to suspicious biliary strictures, in one Swedish and four UK tertiary centers in 2008-2012, were retrospectively enrolled. For each SOC procedure in sclerosing cholangitis, another one attempted due to a single biliary stricture in the same center and calendar year was randomly selected as control.

Endoscopic radiofrequency ablation for cholangiocarcinoma.

Purpose Of Review: To describe the use of endobiliary radiofrequency ablation (RFA) in the treatment of malignant disease of the bile duct and offer a comprehensive review of the emerging evidence on the safety and effectiveness of this new technique.

Recent Findings: Ex-vivo and in-vivo porcine studies have been reported, confirming the feasibility of the technique, gathering preliminary safety data and defining appropriate power settings for human studies. Moderate-sized case series have now reported the use of RFA in mixed cohorts of human individuals with pancreatic cancer, cholangiocarcinoma and other malignant diseases of the bile duct.

The palliation of cholangiocarcinoma.

Purpose Of Review: Cholangiocarcinoma is the second most common primary liver tumour, worldwide. Its incidence and mortality are rising, the cause of which is unclear. Cholangiocarcinoma usually presents late, with obstructive jaundice, malaise, weight loss and discomfort.

Has increased clinical experience with methotrexate reduced the direct costs of medical management of ectopic pregnancy compared to surgery?

Background: There is a debate about the cost-efficiency of methotrexate for the management of ectopic pregnancy (EP), especially for patients presenting with serum human chorionic gonadotrophin levels of >1500 IU/L. We hypothesised that further experience with methotrexate, and increased use of guideline-based protocols, has reduced the direct costs of management with methotrexate.

Methods: We conducted a retrospective cost analysis on women treated for EP in a large UK teaching hospital to (1) investigate whether the cost of medical management is less expensive than surgical management for those patients eligible for both treatments and (2) to compare the cost of medical management for women with hCG concentrations 1500-3000 IU/L against those with similar hCG concentrations that elected for surgery.

Diagnostic and therapeutic utility of single-operator peroral cholangioscopy for indeterminate biliary lesions and bile duct stones.

Background And Aim: We aimed to evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) for indeterminate biliary lesions and its usefulness in electrohydraulic lithotripsy (EHL) of biliary stones not amenable to conventional endoscopic therapy.

Patients And Methods: All patients undergoing SpyGlass SOC in four UK tertiary centres between 2008 and 2010 were retrospectively enrolled. Patients were followed up until death or the last clinic visit until May 2011.

National survey evaluating service provision for percutaneous endoscopic gastrostomy within the UK.

Objectives: Percutaneous endoscopic gastrostomy (PEG) feeding has a significant morbidity and mortality associated with the procedure. Patient selection, procedural volume, timing of insertion and aftercare may have a direct bearing on mortality. We aimed to establish whether variation in PEG practice exists within the UK.

Elevated levels of neutrophil gelatinase-associated lipocalin in bile from patients with malignant pancreatobiliary disease.

Objectives: Accurate differentiation between benign and malignant causes of biliary obstruction remains challenging and reliable biomarkers are urgently needed. Bile is a potential source of such biomarkers. Our aim was to apply a proteomic approach to identify a potential biomarker in bile that differentiates between malignant and benign disease, and to assess its diagnostic accuracy.