Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study

Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design: RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Results: Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5–7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion: Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required

Peripheral blood immune profile in patients with pancreatic cancer

Aims Evaluate the T cell phenotypic subsets and functional responses in paired blood samples from patients undergoing surgical debulking for pancreatic adenocarcinoma (PDAC). Methods Preoperative and postoperative samples from patients with PDAC provided by the PCRFTB (2019/09/QM/HK/P/Blood) after ethical approval for the processing and handling of human tissue samples with the informed consent of the participants. Specimens have been collected at Barts Health NHS trust. T cells were stained with fluorescent antibodies to characterise memory subsets (CD45RA, CCR7), inhibitory receptors (PD-1, TIM3) and the functional transcription factor TCF1. T cells were also stimulated in vitro with CD3/CD28 beads (Dynabeads, Gibco) to assess phenotypic changes and functional responses under T cell receptor (TCR) stimulatory conditions. The samples were acquired using a spectral flow cytometer (Cytek Aurora) and part of the samples was used for bulk transcriptomics analysis. The analysis of the flow cytometry acquisition panels was performed using FCS Express (DeNovo Software 7th edition). Descriptive statistics were performed using GraphPad Prism (8th edition). Transcriptomics analysis was performed using PartekFlow. Results There is no percentage difference in the memory subsets of T cells or the expression of inhibitory receptors at rest. After TCR stimulation we observe a divergence to effector subsets in the preoperative samples compared to the postoperative samples which maintain a better equilibrium amongst all memory subsets. Similarly, there is no percentage difference in the expression of inhibitory receptors (PD1, TIM3) at rest but under stimulatory conditions TIM3 expression is increasing in postoperative samples. Finally, we can see high upregulation of TCF1 in the postoperative samples after stimulation which can explain the equilibrium maintenance in the postoperative samples. Similarly, divergent stimulatory response has been observed in the transcriptomic analysis supporting the expression of less effector phenotype. Conclusions This study shows divergent functionality of T cells associated with surgical debulking of PDAC with increased expression of TCF1. Although our results cannot support causality related to the presence of PDAC, they support the presence of offsite effects in T cells by PDAC which are altered by surgical debulking. These observations may partially explain the higher survival observed in the operated population and might support the use of adjuvant immunotherapies targeted at T cells in the perioperative period

Temporality of clinical factors associated with pancreatic cancer: a case-control study using linked electronic health records

Abstract Background Pancreatic cancer risk is poorly quantified in relation to the temporal presentation of medical comorbidities and lifestyle. This study aimed to examine this aspect, with possible influence of demographics. Methods We conducted a retrospective case-control study on the ethnically-diverse population of East London, UK, using linked electronic health records. We evaluated the independent and two-way interaction effects of 19 clinico-demographic factors in patients with pancreatic cancer (N = 965), compared with non-malignant pancreatic conditions (N = 3963) or hernia (control; N = 4355), reported between April 1, 2008 and March 6, 2020. Risks were quantified by odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models. Results We observed increased odds of pancreatic cancer incidence associated with recent-onset diabetes occurring within 6 months to 3 years before cancer diagnosis (OR 1.95, 95% CI 1.25-3.03), long-standing diabetes for over 3 years (OR 1.74, 95% CI 1.32-2.29), recent smoking (OR 1.81, 95% CI 1.36-2.4) and drinking (OR 1.76, 95% CI 1.31-2.35), as compared to controls but not non-malignant pancreatic conditions. Pancreatic cancer odds was highest for chronic pancreatic disease patients (recent-onset: OR 4.76, 95% CI 2.19-10.3, long-standing: OR 5.1, 95% CI 2.18-11.9), amplified by comorbidities or harmful lifestyle. Concomitant diagnosis of diabetes, upper gastrointestinal or chronic pancreatic conditions followed by a pancreatic cancer diagnosis within 6 months were common, particularly in South Asians. Long-standing cardiovascular, respiratory and hepatobiliary conditions were associated with lower odds of pancreatic cancer. Conclusions Several factors are, independently or via effect modifications, associated with higher incidence of pancreatic cancer, but some established risk factors demonstrate similar magnitude of risk measures of developing non-malignant pancreatic conditions. The findings may inform refined risk-stratification strategies and better surveillance for high-risk individuals, and also provide a means for systematic identification of target population for prospective cohort-based early detection research initiatives

Percutaneous endoscopic gastrostomy tube replacement unexpected serious events

Percutaneous endoscopic gastrostomy tubes are replaced due to clogging, breaking, and dislodgement. There are potential complications associated with these procedures, including intraperitoneal placement of the tube and peritonitis, which can occur even in the presence of a well established stoma site. Herein we present a case series of 3 patients with mature gastrocutaneous tracks, who developed peritonitis following tube replacement. In the absence of a consensus or international guidelines regarding the management of patients requiring percoutaneous endoscopic gastrostomy tube replacement, emphasis should be given on prevention of severe adverse events and on early anticipation of their occurrence. Clinical experience indicates that recognition of high-risk procedures, selection of the appropriate replacement method and confirmation of correct tube placement can improve patients' safety and reduce the complications rate. © 2013 American Society for Parenteral and Enteral Nutrition

Ecohydrological gradients affecting the abundance and biodiversity of macro-invertebrates in the estuarine system of Sperchios River, Central Greece

The factors affecting the abundance and biodiversity of the macro- invertebrates in relation to the quality of substrate and vegetation of the estuarine system of Sperchios River, Central Greece, were examined. The reason why only the two specific seasons of winter and summer were chosen is because extreme weather phenomena take place during both seasons that affect the factors of abundance and biodiversity. Of the nine identified taxa, the main contributor to macro-invertebrate abundance in August 2001 was Hediste diversicolor, while Cerastoderma glaucum was the principal one in January 2002. The Spearman coefficient showed a positive correlation of biomass (A') with water temperature (0.39) in January, the concentration of nitrates (0.69), the clay (0.66), and the organic matter of the sediment (0.47-0.53). A positive correlation (Spearman) has also been shown between biodiversity, the percentage of sand in the sediment, and the concentrations of ammonia and nitrates. As species abundance (A) has been positively correlated (Spearman coefficient = 0.21-0.72) with sediment organic matter, vegetation in the lower inter-tidal zone seems to have affected A positively. The analyses of the used indices (A, A', Margalef, Shannon-Wiener, Pielou's evenness, Sorensen similarity) indicated a negative influence on the diversity of benthic macroinvertebrates, and a possibly causal relationship between agricultural wastes drained to the estuarine Sperchios system and its sediment quality