Imperial College London

DrAdamFrampton

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Clinical Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2125a.frampton

 
 
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Location

 

4005Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

193 results found

Wang B, Deng J, Donati V, Merali N, Frampton AE, Giovannetti E, Deng Det al., 2024, The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review., Pathogens, Vol: 13, ISSN: 2076-0817

Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.

Journal article

Julve M, Kennedy O, Frampton AE, Bagwan I, Lythgoe MPet al., 2023, Gene of the month: cancer testis antigen gene 1b (NY-ESO-1)., J Clin Pathol, Vol: 77, Pages: 1-7

Cancer testis antigen gene 1B (CTAG1B) and its associated gene product; New York oesophageal squamous carcinoma 1 (NY-ESO-1), represent a unique and promising target for cancer immunotherapy. As a member of the cancer testis antigen family (CTA), the protein's restricted expression pattern and ability to elicit spontaneous humoural and cellular immune responses has resulted in a plethora of novel modalities and approaches attempting to harness its immunotherapeutic anti-cancer potential. Here, we discuss the structure and function of CTAG1B/NY-ESO-1 in both health and disease, immunohistochemical detection, as well as the most promising advances in the development of associated anti-cancer therapies. From cancer vaccines to engineered cellular therapy approaches, a multitude of immunotherapies targeting CTA's are coming to the forefront of oncology. Although the efficacy of such approaches have yet to provide convincing evidence of durable response, early phase clinical trial data has resulted in some exciting findings which will have significant potential to act as a platform for future practice changing technologies.

Journal article

Mato Prado M, Puik JR, Castellano L, López-Jiménez E, Liu DSK, Meijer LL, Le Large TYS, Rees E, Funel N, Sivakumar S, Pereira SP, Kazemier G, Zonderhuis BM, Erdmann JI, Swijnenburg R-J, Frilling A, Jiao LR, Stebbing J, Giovannetti E, Krell J, Frampton AEet al., 2023, A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease, Experimental Hematology & Oncology, Vol: 12, ISSN: 2162-3619

Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis. As bile flows in close proximity to these lesions, we aimed to establish a bile-based microRNA (miRNA) signature to discriminate between malignant and benign pancreaticobiliary diseases. We performed miRNA discovery by global profiling of 800 miRNAs using the NanoString nCounter platform in prospectively collected bile samples from malignant (n = 43) and benign (n = 14) pancreaticobiliary disease. Differentially expressed miRNAs were validated by RT-qPCR and further assessed in an independent validation cohort of bile from malignant (n = 37) and benign (n = 38) pancreaticobiliary disease. MiR-148a-3p was identified as a discriminatory marker that effectively distinguished malignant from benign pancreaticobiliary disease in the discovery cohort (AUC = 0.797 [95% CI 0.68-0.92]), the validation cohort (AUC = 0.772 [95% CI 0.66-0.88]), and in the combined cohorts (AUC = 0.752 [95% CI 0.67-0.84]). We also established a two-miRNA signature (miR-125b-5p and miR-194-5p) that distinguished PDAC from CCA (validation: AUC = 0.815 [95% CI 0.67-0.96]; and combined cohorts: AUC = 0.814 [95% CI 0.70-0.93]). Our research stands as the largest, multicentric, global profiling study of miRNAs in the bile from patients with pancreaticobiliary disease. We demonstrated their potential as clinically useful diagnostic tools for the detection and differentiation of malignant pancreaticobiliary disease. These bile miRNA biomarkers could be developed to complement c

Journal article

Ciprani D, Frampton A, Amar H, Oppong K, Pandanaboyana S, Aroori Set al., 2023, The role of intraoperative pancreatoscopy in the surgical management of intraductal papillary mucinous neoplasms of the pancreas: a systematic scoping review., Surg Endosc, Vol: 37, Pages: 9043-9051

BACKGROUND: The type and the extent of surgery is still debatable for intraductal papillary mucinous neoplasm (IPMN). Intraoperative pancreatoscopy (IOP) allows the visualization of the main pancreatic duct (MPD) in its entire length and could help determine the extent of MPD involvement and the type and extent of pancreatic resection. However, current guidelines do not advise its routine use as there is a lack of evidence supporting its safety and feasibility. The present study aims to perform a scoping review of published evidence on the safety and feasibility of IOP in IPMN surgical management. METHODS: We systematically searched PubMed, Cochrane, Medline and EMbase to identify studies reporting the use of IOP in IPMN surgical management. The research was completed in June 2023. Data extracted included patient selection criteria, demographics, safety of the procedure, intraoperative findings, impact on surgical strategy, histology results and postoperative outcomes. RESULTS: Four retrospective and one prospective study were included in this scoping review. A total of 142 patients had IOP. The selection criteria for inclusion were heterogenous, with one out of five studies including branch duct (BD), main duct (MD) and mixed type IPMN. Indications for IOP and surgical resection were only reported in two studies. A median of seven outcomes (range 5-8) was described, including the type of surgical resection, additional lesions and change of surgical plan, and complications after IOP. IOP showed additional lesions in 48 patients (34%) and a change of surgical plan in 48(34%). No IOP-related complications were reported. CONCLUSIONS: This scoping review suggests IOP is safe and identifies additional lesions impacting the surgical strategy for IPMN. However, the included studies were small and heterogeneous regarding IPMN definition and indications for surgery and IOP. There is a need for a large multi-centre prospective study to determine the role of IOP and its i

Journal article

Halle-Smith JM, Hall LA, Powell-Brett SF, Merali N, Frampton A, Roberts KJet al., 2023, Realising the therapeutic potential of the human microbiota in metastatic pancreatic ductal adenocarcinoma, Clinical Surgical Oncology, Vol: 2, Pages: 100020-100020, ISSN: 2773-160X

Journal article

Merali N, Chouari T, Terroire J, Jessel M-D, Liu DSK, Smith J-H, Wooldridge T, Dhillon T, Jiménez JI, Krell J, Roberts KJ, Rockall TA, Velliou E, Sivakumar S, Giovannetti E, Demirkan A, Annels NE, Frampton AEet al., 2023, Bile microbiome signatures associated with pancreatic ductal adenocarcinoma compared to benign disease: a UK pilot study, International Journal of Molecular Sciences, Vol: 24, ISSN: 1422-0067

Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance and, therefore, patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3-V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova p = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (FDR = 0.033) was found to be of increased abundance in the PDAC group. We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.

Journal article

Phillips ME, Zekavica J, Kumar R, Lahiri R, Kirk-Bayley J, Patel A, Frampton AEet al., 2023, Bedside naso-jejunal placement is more difficult, but successful in patients with COVID-19 in critical care: A retrospective service evaluation of a dietitian-led service, Journal of the Intensive Care Society, Vol: 24, Pages: 435-437, ISSN: 1751-1437

The COVID-19 pandemic presented clinical and logistical challenges in the delivery of adequate nutrition in the critical care setting. The use of neuromuscular-blocking drugs, presence of maxilla-facial oedema, strict infection control procedures, and patients placed in a prone position complicated feeding tube placement. We audited the outcomes of dietitian-led naso-jejunal tube (NJT) insertions using the IRIS® (Kangaroo, USA) device, before and during the COVID-19 pandemic. NJT placement was successful in 78% of all cases (n = 50), and 87% of COVID-19 cases. Anaesthetic support was only required in COVID-19 patients (53%). NJT placement using IRIS was more difficult but achievable in patients with COVID-19.

Journal article

Halle-Smith JM, Hall LA, Powell-Brett SF, Merali N, Frampton AE, Beggs AD, Moss P, Roberts KJet al., 2023, Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies?, Cancers (Basel), Vol: 15, ISSN: 2072-6694

Pancreatic exocrine insufficiency (PEI) is common amongst pancreatic cancer patients and is associated with poorer treatment outcomes. Pancreatic enzyme replacement therapy (PERT) is known to improve outcomes in pancreatic cancer, but the mechanisms are not fully understood. The aim of this narrative literature review is to summarise the current evidence linking PEI with microbiome dysbiosis, assess how microbiome composition may be impacted by PERT treatment, and look towards possible future diagnostic and therapeutic targets in this area. Early evidence in the literature reveals that there are complex mechanisms by which pancreatic secretions modulate the gut microbiome, so when these are disturbed, as in PEI, gut microbiome dysbiosis occurs. PERT has been shown to return the gut microbiome towards normal, so called rebiosis, in animal studies. Gut microbiome dysbiosis has multiple downstream effects in pancreatic cancer such as modulation of the immune response and the response to chemotherapeutic agents. It therefore represents a possible future target for future therapies. In conclusion, it is likely that the gut microbiome of pancreatic cancer patients with PEI exhibits dysbiosis and that this may potentially be reversible with PERT. However, further human studies are required to determine if this is indeed the case.

Journal article

Chouari T, Merali N, La Costa F, Santol J, Chapman S, Horton A, Aroori S, Connell J, Rockall TA, Mole D, Starlinger P, Welsh F, Rees M, Frampton AEet al., 2023, The Role of the Multiparametric MRI LiverMultiScan™ in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis, CANCERS, Vol: 15

Journal article

Primavesi F, Maglione M, Cipriani F, Denecke T, Oberkofler CE, Starlinger P, Dasari BVM, Heil J, Sgarbura O, Søreide K, Diaz-Nieto R, Fondevila C, Frampton AE, Geisel D, Henninger B, Hessheimer AJ, Lesurtel M, Mole D, Öllinger R, Olthof P, Reiberger T, Schnitzbauer AA, Schwarz C, Sparrelid E, Stockmann M, Truant S, Aldrighetti L, Braunwarth E, D'Hondt M, DeOliveira ML, Erdmann J, Fuks D, Gruenberger T, Kaczirek K, Malik H, Öfner D, Rahbari NN, Göbel G, Siriwardena AK, Stättner Set al., 2023, E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy., Br J Surg, Vol: 110, Pages: 1331-1347

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Journal article

Russell TB, Labib PL, Ausania F, Pando E, Roberts KJ, Kausar A, Mavroeidis VK, Marangoni G, Thomasset SC, Frampton AE, Lykoudis P, Maglione M, Alhaboob N, Bari H, Smith AM, Spalding D, Srinivasan P, Davidson BR, Bhogal RH, Croagh D, Dominguez I, Thakkar R, Gomez D, Silva MA, Lapolla P, Mingoli A, Porcu A, Shah NS, Hamady ZZR, Al-Sarrieh B, RAW Study collaborators S, Aroori Set al., 2023, Serious complications of pancreatoduodenectomy correlate with lower rates of adjuvant chemotherapy: Results from the recurrence after Whipple's (RAW) study, EJSO, Vol: 49, ISSN: 0748-7983

Journal article

Chouari T, La Costa FS, Merali N, Jessel M-D, Sivakumar S, Annels N, Frampton AEet al., 2023, Advances in Immunotherapeutics in Pancreatic Ductal Adenocarcinoma, CANCERS, Vol: 15

Journal article

Patel BY, Bhome R, Liu DSK, Giovannetti E, Merali N, Primrose JN, Mirnezami AH, Rockall TA, Annels N, Frampton AEet al., 2023, Cancer cell-derived extracellular vesicles activate hepatic stellate cells in colorectal cancer, EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, ISSN: 1473-7159

Journal article

Siriwardena AK, Serrablo A, Fretland ÅA, Wigmore SJ, Ramia-Angel JM, Malik HZ, Stättner S, Søreide K, Zmora O, Meijerink M, Kartalis N, Lesurtel M, Verhoef K, Balakrishnan A, Gruenberger T, Jonas E, Devar J, Jamdar S, Jones R, Hilal MA, Andersson B, Boudjema K, Mullamitha S, Stassen L, Dasari BVM, Frampton AE, Aldrighetti L, Pellino G, Buchwald P, Gürses B, Wasserberg N, Gruenberger B, Spiers HVM, Jarnagin W, Vauthey J-N, Kokudo N, Tejpar S, Valdivieso A, Adam Ret al., 2023, Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE., Br J Surg, Vol: 110, Pages: 1161-1170

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Journal article

Lemanska A, Andrews C, Fisher L, Bacon S, Frampton AE, Mehrkar A, Inglesby P, Davy S, Roberts K, Patalay P, Goldacre B, MacKenna B, OpenSAFELY Collaborative, Walker AJet al., 2023, Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: A cohort study using OpenSAFELY-TPP., Elife, Vol: 12

BACKGROUND: Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic. METHODS: With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. RESULTS: The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (±11 SD), 48% of people were female, 95% were of White ethnicity, and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25-28% during the pandemic. In addition, 20%, 10%, and 4% fewer people received body mass index, glycated haemoglobin, and liver function tests, respectively, before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1-2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within 12 months into the pandemic. Emergency department visits, hospital a

Journal article

Yin T, Xu L, Gil B, Merali N, Sokolikova MSS, Gaboriau DCA, Liu DSK, Muhammad Mustafa AN, Alodan S, Chen M, Txoperena O, Arrastua M, Gomez JM, Ontoso N, Elicegui M, Torres E, Li D, Mattevi C, Frampton AEE, Jiao LRR, Ramadan S, Klein Net al., 2023, Graphene sensor arrays for rapid and accurate detection of pancreatic cancer exosomes in patients' blood plasma samples, ACS Nano, Vol: 17, Pages: 14619-14631, ISSN: 1936-0851

Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients’ plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.

Journal article

Boyd LNC, Ali M, Comandatore A, Garajova I, Kam L, Puik JR, Fraga Rodrigues SM, Meijer LL, Le Large TYS, Besselink MG, Morelli L, Frampton A, van Laarhoven HWM, Giovannetti E, Kazemier Get al., 2023, Prediction Model for Early-Stage Pancreatic Cancer Using Routinely Measured Blood Biomarkers., JAMA Netw Open, Vol: 6

IMPORTANCE: Accurate risk prediction models using routinely measured biomarkers-eg, carbohydrate antigen 19-9 (CA19-9) and bilirubin serum levels-for pancreatic cancer could facilitate early detection of pancreatic cancer and prevent potentially unnecessary diagnostic tests for patients at low risk. An externally validated model using CA19-9 and bilirubin serum levels in a larger cohort of patients with pancreatic cancer or benign periampullary diseases is needed. OBJECTIVE: To assess the discrimination, calibration, and clinical utility of a prediction model using readily available blood biomarkers (carbohydrate antigen 19-9 [CA19-9] and bilirubin) to distinguish early-stage pancreatic cancer from benign periampullary diseases. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study used data from 4 academic hospitals in Italy, the Netherlands, and the UK on adult patients with pancreatic cancer or benign periampullary disease treated from 2014 to 2022. Analyses were conducted from September 2022 to February 2023. EXPOSURES: Serum levels of CA19-9 and bilirubin from samples collected at diagnosis and before start of any medical intervention. MAIN OUTCOMES AND MEASURES: Discrimination (measured by the area under the curve [AUC]), calibration, and clinical utility of the prediction model and the biomarkers, separately. RESULTS: The study sample comprised 249 patients in the development cohort (mean [SD] age at diagnosis, 67 [11] years; 112 [45%] female individuals), and 296 patients in the validation cohort (mean [SD] age at diagnosis, 68 [12] years; 157 [53%] female individuals). At external validation, the prediction model showed an AUC of 0.89 (95% CI, 0.84-0.93) for early-stage pancreatic cancer vs benign periampullary diseases, and outperformed CA19-9 (difference in AUC [ΔAUC], 0.10; 95% CI, 0.06-0.14; P < .001) and bilirubin (∆AUC, 0.07; 95% CI, 0.02-0.12; P = .004). In the subset of patients without elevated tumor marker l

Journal article

Papadakos SP, Machairas N, Stergiou IE, Arvanitakis K, Germanidis G, Frampton AE, Theocharis Set al., 2023, Unveiling the Yin-Yang Balance of M1 and M2 Macrophages in Hepatocellular Carcinoma: Role of Exosomes in Tumor Microenvironment and Immune Modulation, CELLS, Vol: 12

Journal article

Mcdonnell D, Cheang AWE, Wilding S, Wild SH, Frampton AE, Byrne CD, Hamady ZZet al., 2023, Elevated Glycated Haemoglobin (HbA1c) Is Associated with an Increased Risk of Pancreatic Ductal Adenocarcinoma: A UK Biobank Cohort Study, CANCERS, Vol: 15

Journal article

Russell TB, Labib PL, Denson J, Ausania F, Pando E, Roberts KJ, Kausar A, Mavroeidis VK, Marangoni G, Thomasset SC, Frampton AE, Lykoudis P, Maglione M, Alhaboob N, Bari H, Smith AM, Spalding D, Srinivasan P, Davidson BR, Bhogal RH, Croagh D, Dominguez I, Thakkar R, Gomez D, Silva MA, Lapolla P, Mingoli A, Porcu A, Shah NS, Hamady ZZR, Al-Sarrieh B, Serrablo A, Aroori Set al., 2023, Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study, HPB, Vol: 25, Pages: 788-797, ISSN: 1365-182X

Journal article

Kosti A, Borakati A, Varma A, Gupta A, Mustafa A, Hakeem A, Quddus A, Bin Sahl A, Beniwal A, Adesuyi A, Krzak AM, Brooks A, Frampton A, Gadhvi A, Talbot A, Elnogoomi A, Mahgoub A, Naqvi A, Pervez A, Bodla AS, Taha A, Tawfik A, Prabhu A, Puri A, Belgaumkar A, Gupta A, McCrorie A, Findlay A, Healey A, De Prendergast A, Farrugia A, Dosis A, Adiamah A, Sallam A, Wong A, Bradley A, Martin A, Collins A, Awan A, Bond A, Koh A, Kourdouli A, Patel AG, Dhannoon A, Khalil A, Banerjee A, Khan A, Elserafy A, Alamassi A, Owen A, Benjafield A, Zuccarrelli A, Luhmann A, Jones A, Kennedy-Dalby A, Smith AM, Kaul A, Kumar A, White A, Baker A, Minicozzi A, Bardoli A, Golpe AL, Manzelli A, Sivakumar A, Saha A, Shajpal A, Lango A, Cotton A, Nair A, Brown A, Menon A, Tandon A, Afza A, Hassan A, Shamali A, Khalid A, Regan A, Piramanayagam B, Oyewole B, Ibrahim B, Murphy B, Clayton B, Jenkins B, Kumar B, Rybinski B, Khor BY, Davidson BR, Lees B, Blacklock C, Johnstone C, Salinas CH, Boven C, Wolstenholme C, Chin C, Gilmore C, Sharp C, Walker C, Harris C, Khanna Cet al., 2023, PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK, BJS Open, Vol: 7

Background: Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods: All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results: A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion: Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions.

Journal article

Lythgoe M, Dama P, Frampton AE, Pickford E, Tookman L, Cunnea P, Fotopoulou C, Liu D, Clark J, Lozano-Kuehne J, Badman PD, Clarke A, Chetal S, Fyvie G, Stevenson A, Krell Jet al., 2023, Immune modulation and the oral live biotherapeutic product, MRx0518, in treatment-naive patients with cancer: Updated safety data, Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X

Conference paper

Papadakos SP, Ferraro D, Carbone G, Frampton AE, Vennarecci G, Kykalos S, Schizas D, Theocharis S, Machairas Net al., 2023, The Emerging Role of Metformin in the Treatment of Hepatocellular Carcinoma: Is There Any Value in Repurposing Metformin for HCC Immunotherapy?, CANCERS, Vol: 15

Journal article

Phillips ME, Hart KH, Frampton AE, Robertson MDet al., 2023, Do Patients Benefit from Micronutrient Supplementation following Pancreatico-Duodenectomy?, NUTRIENTS, Vol: 15

Journal article

Spiers HVM, Lancellotti F, Carino NDL, Pandanaboyana S, Frampton AE, Jegatheeswaran S, Nadarajah V, Siriwardena AKet al., 2023, Irreversible Electroporation for Liver Metastases from Colorectal Cancer: A Systematic Review, CANCERS, Vol: 15

Journal article

Jainarayanan A, Mouroug-Anand N, Arbe-Barnes EH, Bush AJ, Bashford-Rogers R, Frampton A, Heij L, Middleton M, Dustin ML, Abu-Shah E, Sivakumar Set al., 2023, Pseudotime dynamics of T cells in pancreatic ductal adenocarcinoma inform distinct functional states within the regulatory and cytotoxic T cells, iScience, Vol: 26

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer and has a 5-year survival of less than 8% owing to its complex biology. As PDAC is refractory to immunotherapy, we need to understand the functional dynamics of T cells in the PDAC microenvironment to develop alternative therapeutic strategies. In this study, we performed RNA velocity-based pseudotime analysis on a scRNA-seq dataset from surgically resected human PDAC specimens to gain insight into temporal gene expression patterns that best characterize the cell fates. The tumor microenvironment was seen to encompass a range of terminal states for the T cell trajectories with suppressive and non-tumor-responsive T cells dominating them. However, the results also reveal the existence of a functional branch of the T cell population that was not transitioning to exhausted and senescent states. These findings reveal various microenvironmental signals driving T cell patterns which can be useful in identifying new therapeutic avenues.

Journal article

Merali N, Frampton A, 2023, Liver Resection, Nutritional Management of the Surgical Patient, Pages: 153-161, ISBN: 9781119809098

Patients undergoing liver resection may present with malnutrition and/or sarcopenia, especially if they have already undergone neo-adjuvant chemotherapy. Modification of fatty liver is an important part of pre-operative management. Liver surgery is typically carried out laparoscopically or robotically and patients typically make a good recovery. However, post-operative bile leaks predispose patients to ileus, malabsorption, and electrolyte depletion. Nutritional management plays a key role in the management of post-operative liver failure/small-for-size syndrome, but more evidence is required to confirm clinical experience-based treatment.

Book chapter

Lythgoe MP, Mullish BH, Frampton A, Krell Jet al., 2022, Polymorphic microbes: a new emerging hallmark of cancer, Trends in Microbiology, Vol: 30, Pages: 1131-1134, ISSN: 0966-842X

Recognition of the microbiome (and ‘polymorphic microbes’ within them) as a new emerging hallmark of cancer reflects a wide body of rapidly evolving research. Microbes may be directly carcinogenic, impact host immune responses to promote malignancy, and key effectors in determining anti-cancer therapy efficacy. Manipulation of the microbiome is showing promise as an opportunity to influence cancer outcomes.

Journal article

Lythgoe M, Mullish B, Frampton A, Dama P, Pickford E, Tookman L, Cunnea P, Fotopoulou C, Jeffery I, Fyvie G, Stevenson A, Krell Jet al., 2022, ORAL ADMINISTRATION OF MRX0518 IN TREATMENTNAIVE CANCER PATIENTS IS ASSOCIATED WITH COMPOSITIONAL TAXONOMIC AND METABOLOMIC CHANGES INDICATIVE OF ANTI-TUMORIGENIC EFFICACY, Publisher: BMJ PUBLISHING GROUP, Pages: A659-A659

Conference paper

Liu DSK, Frampton AE, 2022, Plasma extracellular vesicles contain unannotated small RNA clusters suitable as biomarkers for detecting early hepatocellular carcinoma, GUT, Vol: 71, Pages: 1935-1936, ISSN: 0017-5749

Journal article

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