Background Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral gastric cancer microbiome and its relationship with clinicopathological variables have not yet been characterized in detail. We hypothesized that variation in gastric cancer microbial abundance, alpha diversity, and composition is related to clinicopathological characteristics. Methods Metagenomic analysis of 529 GC samples was performed, including whole exome sequencing data from The Cancer Genome Atlas (TCGA) and whole genome sequencing data from the 100,000 Genomes Project. Microbial abundance, alpha diversity, and composition were compared across patient age, sex, tumor location, geographic origin, pathological depth of invasion, pathological lymph node status, histological phenotype, microsatellite instability status, and TCGA molecular subtype. Results Gastric cancer microbiomes resembled previous results, with Prevotella , Selenomonas , Stomatobaculum , Streptococcus , Lactobacillus , and Lachnospiraceae commonly seen across both cohorts. Within the TCGA cohort, microbial abundance and alpha diversity were greater in gastric cancers with microsatellite instability, lower pathological depth of invasion, intestinal-type histology, and those originating from Asia. Microsatellite instability status was associated with microbiome composition in both cohorts. Sex and pathological depth of invasion were associated with microbiome composition in the TCGA cohort. Conclusion The intratumoral gastric cancer microbiome appears to differ according to clinicopathological factors. Certain clinicopathological factors associated with favourable outcomes in gastric cancer were observed to be associated with greater microbial abundance and diversity. This highlights the need for further work to understand the underlying biological mechanisms behind the observed microbiome differences and their potential clinical and therapeutic impact.

Oesophageal and gastric cancers respectively account for the loss of about 9.8 million and 19.1 million disability-adjusted life years globally [[1]Kamangar F. Nasrollahzadeh D. Safiri S. Sepanlou S.G. Fitzmaurice C. Ikuta K.S. et al.The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2020; 5: 582-597Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar,[2]Etemadi A. Safiri S. Sepanlou S.G. Ikuta K. Bisignano C. Shakeri R. et al.The global, regional, and national burden of stomach cancer in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017.Lancet Gastroenterol Hepatol. 2020; 5: 42-54Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar]. This includes an annual UK burden of around 16 000 cases, representing 4% of all cancer diagnoses but translating to a disproportionately greater 8% of all cancer-related deaths. This reflects the relatively poorer oesophagogastric cancer outcomes seen in the UK when compared with similarly developed countries [[3]Arnold M. Morgan E. Bardot A. Rutherford M.J. Ferlay J. Little A. et al.International variation in oesophageal and gastric cancer survival 2012–2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study).Gut. 2022; 71: 1532-1543PubMed Google Scholar]. Most oesophagogastric cancer patients present with locoregional or metastatic disease, with a growing range of multimodal treatment approaches commonly used across all stages. This, coupled with the comorbidity and frequent nutritional and swallowing difficulties with which oesophagogastric cancers are commonly associated, necessitates strong multidisciplinary input. However, despite the centralisation of some services, the relative infrequency of oesophagogastric cancers means that the experience of individual multidisciplinary teams (MDTs) is limited, particularly for rarer scenarios. Additionally, it is increasingly apparent that significant and unacceptable variation is present in both practice and outcomes across UK and Republic of Ireland (ROI) MDTs [[4]Singh P. Gossage J. Markar S. Pucher P.H. Wickham A. Weblin J. et al.Association of Upper Gastrointestinal Surgery of Great Britain and Ireland (AUGIS)/Perioperative Quality Initiative (POQI) consensus statement on intraoperative and postoperative interventions to reduce pulmonary complications after oesophagectomy.Br J Surg. 2022; 109: 1096-1106Crossref PubMed Scopus (1) Google Scholar,[5]Bull A. Pucher P.H. Maynard N. Underwood T.J. Lagergren J. Gossage J.A. Nasogastric tube drainage and pyloric intervention after oesophageal resection: UK practice variation and effect on outcomes.Eur J Surg Oncol. 2022; 48: 1033-1038Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. The UK & Ireland Oesophagogastric Group (UKIOG) was created in February 2021 and established as a registered charity in March 2022 in response to these challenges, with a remit to promote best practice, deliver high-quality education and training, promote access to research and support patient advocacy. One avenue through which it has sought to achieve these aims is an innovative national oesophagogastric MDT programme. We outline this here and provide an analysis of its introduction, reception and the resulting key learning points for the oesophagogastric and wider oncology communities. The first UKIOG MDT was held in May 2021. It has since proceeded monthly, with meetings held virtually using the Microsoft Teams platform. Each 90-min MDT is held within normal working hours and is hosted by a UK National Health Service (NHS) centre, with 12 MDTs delivered from inception to September 2022 (Figure 1). Host centres select a panel of discussants and between two and four cases for them to review. Participants are invited via a mailing list curated and maintained by the UKIOG according to GDPR regulations. Presented case vignettes are generally supported by a wider presentation outlining the evidence base relevant to the case and audience participation is sought, including through the use of the online audience interaction platform, slido (sli.do, Slovakia). Recordings are made available online for those unable to make the live meeting and feedback is collated using an online survey instrument hosted by SurveyMonkey (Momentive Inc, USA). Attendees are eligible for five continuing professional development credits in accordance with the Royal College of Radiologists' continuing professional development scheme. A mean of 79 participants (range 66–116) attended each session, with attendance remaining stable across the first 12 MDT meetings. For the seven MDTs for which full attendance data are available, participants were drawn from England (62%), Wales (19%), Northern Ireland (8%), Scotland (6%) and the ROI (5%). Feedback data are available for seven of 12 meetings held between May 2021 and September 2022. Across these, 94–100% and 89–100% of attendees, respectively, reported that the quality of the cases and associated talks met their expectations, while 94–100% of attendees considered presentational quality to be of a sufficiently high standard. When asked to rate how likely they were to attend further meetings and recommend MDT sessions to professional colleagues on a scale of 0 (least likely) to 100 (most likely), respective median responses ranged from 90 to 97 and 91 to 98. In total, 33 topics were presented over 12 meetings chaired by 10 centres across the UK and ROI. These were presented by 61 clinicians or non-clinical researchers who work within the oesophagogastric field, including 23 (38%) surgeons, 11 (18%) medical oncologists, 11 (20%) clinical oncologists, four (7%) gastroenterologists, five (8%) radiologists and three (5%) allied health professionals. Three (5%) cases were presented by specialists outside the conventional MDT. Case domains comprised of investigation and staging (4/33, 12%), treatment (20/33, 61%), research and service development (7/33, 21%) and surveillance and survivorship (2/33, 6%). Of the 20 cases relating to treatment, four (20%) were predominantly related to surgery, four (20%) to systemic therapy, three to radiotherapy (15%) and three (15%) to endoscopic intervention. The remaining six (30%) cases focussed on multimodal management. Topics broadly fell under three themes. The first was diagnostic and treatment uncertainty, such as relating to the neoadjuvant treatment approach and the use of endoscopic ultrasound for disease staging. The second was less commonly encountered clinical scenarios, such a management of oligometastatic disease and oesophageal re-irradiation. The third centred on research and development, including clinical trial data across the domains of oncogeriatrics, prognostication and disease surveillance, as well as sharing experiences of local practice, including multidisciplinary clinics and cardiac rehabilitation services. Discussions within these areas revealed considerable variation in practice across centres. For example, the use of cardiopulmonary exercise testing ranged from none to three times per treatment pathway and there were often contrasting views on whether the treatment intent for a specific case should be curative or palliative. Views concerning optimal treatment pathways also differed when considering specific case vignettes, including for instance the use of neoadjuvant chemoradiation or perioperative chemotherapy for oesophageal adenocarcinoma, and the use of definitive versus neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. It is important to highlight that attendees had for the most part not met the patients discussed, nor had access to full medical records, and borderline cases were often chosen to stimulate discussion. Nevertheless, the MDT programme provided an avenue through which contemporary evidence and the contextual interpretation of this could be highlighted. The UKIOG was established in the wake of the coronavirus disease 2019 (COVID-19) pandemic. One positive consequence of the need to discuss rapidly changing treatment paradigms during the first and subsequent waves of COVID-19 was the connection of a large community of oesophagogastric clinicians via the messaging service, WhatsApp. Alongside, much of the NHS had pivoted to and gained experience of virtual meetings. It was recognised that these developments together offered an opportunity to share best practice for oesophagogastric care. This gave rise to the national MDT programme outlined here, as well as the broader UKIOG initiative that oversees it. This programme is, to our knowledge, the first of its kind for the UK and ROI cancer community. Its success is reflected in the positive feedback and attendance figures presented here and in the wide geographical distribution of participating centres. The sessions have afforded a forum for sharing ideas and experiences, the opportunity for junior healthcare professionals to gain experience from presenting and an environment in which new research can be presented. These meetings have also served to highlight areas where care is not currently harmonised across the UK and ROI, and areas where there is a need to collect better data or undertake prospective research. These advantages would probably translate to other tumour sites if the model outlined here were replicated across other oncological MDTs. Nevertheless, there are a number of areas for further development of our programme. First, nursing and allied health professionals are underrepresented in those presenting MDTs thus far, despite their considerable importance to all phases of oesophagogastric cancer management. Second, patients have not been represented among speakers and are not routinely invited to meetings, in line with current NHS practice. It is unclear how their participation could be effectively facilitated, although ensuring that the patient voice is included in case discussions is critical and an area of ongoing development. Third, case selection is presently guided by individual MDTs, which while affording a diversity of cases has led to a bias towards the curative medical management of patients with oesophagogastric cancer. Finally, these meetings require considerable organisation and administrative support, which may be challenging to replicate across other tumour sites without specific funding in place to facilitate this. There are a number of plans to build on the success of this MDT programme. A registry of interested professionals compliant with appropriate information governance guidance will be developed to facilitate the communication of UKIOG information, alongside the development of a UKIOG website. Annual UKIOG meetings are planned and an inaugural hybrid face-to-face and virtual event was held on 30 January 2023 at the Royal Society of Medicine. Material support will be sought from industry and third sector partners to further the development of MDTs, such as through enabling dissemination of MDT discussions via short publications, podcasts and online blogs. The UKIOG oversight committee is keen to further develop links with patient and public groups, as well as engaging with existing professional bodies. In the longer term, there are plans for the UKIOG to become considered as a multiprofessional engagement group for treatment and service guidelines. Overall, the national UKIOG MDT – catalysed by changes in working and a strong oesophagogastric community that have together developed in response to the pandemic – provides a replicable model for pooling experience, addressing complex cases and identifying areas in which cancer-specific practice varies across the UK and ROI. If you wish to participate in the UKIOG MDT or work with the UKIOG, please get in touch ([email protected]). M.E. Booth reports a relationship with Wellcome Trust 4Ward North that includes: funding grants. C.M. Jones reports a relationship with Cancer Research UK RadNet Cambridge that includes: funding grants. R.D. Petty reports a relationship with Amgen Inc. that includes: consulting or advisory and funding grants. R.D. Petty reports a relationship with AstraZeneca that includes: consulting or advisory and funding grants. R.D. Petty reports a relationship with Bristol Myers Squibb Co. that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. R.D. Petty reports a relationship with Servier that includes: consulting or advisory, funding grants, and speaking and lecture fees. R.D. Petty reports a relationship with Merck Sharp & Dohme UK Ltd that includes: travel reimbursement. R.D. Petty reports a relationship with Basilea Pharmaceutica Ltd that includes: funding grants. R.D. Petty reports a relationship with Five Prime Therapeutics Inc. that includes: funding grants. R.D. Petty reports a relationship with Platinum Therapeutics that includes: funding grants. R.D. Petty reports a relationship with Roche that includes: funding grants. T.J. Underwood reports a relationship with Royal College of Surgeons of England that includes: funding grants. T.J. Underwood reports a relationship with Cancer Research UK that includes: funding grants. T.J. Underwood reports a relationship with Heartburn Cancer UK (Charity) that includes: non-financial support. T.J. Underwood reports a relationship with Education in Action that includes: speaking and lecture fees. E.C. Smyth reports a relationship with Amal Therapeautics that includes: consulting or advisory. E.C. Smyth reports a relationship with Aptitude Health that includes: consulting or advisory. E.C. Smyth reports a relationship with Amgen Inc. that includes: funding grants, speaking and lecture fees, and travel reimbursement. E.C. Smyth reports a relationship with Astellas Pharma that includes: consulting or advisory and funding grants. E.C. Smyth reports a relationship with AstraZeneca that includes: consulting or advisory and funding grants. E.C. Smyth reports a relationship with BeiGene that includes: consulting or advisory. E.C. Smyth reports a relationship with Bristol Myers Squibb Co. that includes: consulting or advisory, funding grants, and speaking and lecture fees. E.C. Smyth reports a relationship with Celgene that includes: consulting or advisory. E.C. Smyth reports a relationship with Daiichi Sankyo Inc. that includes: consulting or advisory and funding grants. E.C. Smyth reports a relationship with Elsevier that includes: consulting or advisory. E.C. Smyth reports a relationship with Everest Clinical Research that includes: consulting or advisory. E.C. Smyth reports a relationship with First World Group that includes: consulting or advisory. E.C. Smyth reports a relationship with Five Prime Therapeutics Inc. that includes: consulting or advisory. E.C. Smyth reports a relationship with Gritstone Oncology Inc. that includes: consulting or advisory. E.C. Smyth reports a relationship with Imedex that includes: consulting or advisory. E.C. Smyth reports a relationship with Merck that includes: consulting or advisory. E.C. Smyth reports a relationship with My Personal Therapeutics that includes: consulting or advisory. E.C. Smyth reports a relationship with Novartis that includes: consulting or advisory, funding grants, and speaking and lecture fees. E.C. Smyth reports a relationship with Pfizer that includes: consulting or advisory. E.C. Smyth reports a relationship with Roche that includes: consulting or advisory and funding grants. E.C. Smyth reports a relationship with Sai-Med that includes: consulting or advisory. E.C. Smyth reports a relationship with Servier that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. E.C. Smyth reports a relationship with Touch Oncology that includes: consulting or advisory. E.C. Smyth reports a relationship with Turning Point Therapeutics Inc. that includes: consulting or advisory. E.C. Smyth reports a relationship with Zymeworks Inc. that includes: consulting or advisory. E.C. Smyth reports a relationship with Basilea that includes: funding grants. E.C. Smyth reports a relationship with Merck Sharp & Dohme UK Ltd that includes: funding grants. E.C. Smyth reports a relationship with MacroGenics Inc. that includes: funding grants. E.C. Smyth reports a relationship with Merus that includes: funding grants. E.C. Smyth reports a relationship with Seagen that includes: funding grants. E.C. Smyth reports a relationship with EORTC GI Clinical Trials Group Gastric Task Force Co-lead that includes: board membership. T. Crosby reports a relationship with Bristol Myers Squibb Co. that includes: consulting or advisory and travel reimbursement. T. Crosby reports a relationship with Servier that includes: consulting or advisory and travel reimbursement. T. Crosby reports a relationship with Merck Sharp & Dohme UK Ltd that includes: consulting or advisory and travel reimbursement. T. Crosby reports a relationship with Roche that includes: consulting or advisory and travel reimbursement. T. Crosby reports a relationship with Cancer Research UK that includes: funding grants. E.C. Smyth reports a relationship with ESMO GI Faculty that includes: board membership. The authors are involved in establishing UKIOG and the related MDT programme. The authors are grateful to all contributors to, and attendees at, the OG National MDT programme. The authors are also grateful to Carly Biscoe for her support in running the MDT programme and for compiling the feedback data presented here. MEB is supported by a Wellcome Trust 4Ward North Clinical Research Training Fellowship. CMJ is supported by a Clinical Lectureship part-funded by Cancer Research UK RadNet Cambridge.

Initial studies of immune checkpoint inhibitors in biomarker unselected gastro-oesophageal cancer yielded limited improvement in survival. However, emerging data from recent clinical trials suggest immunotherapies may offer a meaningful clinical benefit within selected populations. Gastro-oesophageal cancer is a heterogeneous disease with respect to histopathological and molecular features; hypermutation and the biology of immune checkpoint pathways are key to appropriate selection of populations most likely to benefit from immune checkpoint inhibitors. Programmed death-ligand 1 expression, typically measured using the combined positive score, is an important biomarker in determining which patients may benefit from immunotherapy agents. However, combined positive score thresholds are not standardised across trials and the benefit in programmed death-ligand 1-negative cohorts is uncertain. Data suggest that patients with tumours with microsatellite instability, high tumour mutational burden and Epstein–Barr Virus positivity are more likely to benefit from immunotherapy, which may be of importance within programmed death-ligand 1-negative populations. Here, we describe the current evidence base for the use of checkpoint inhibitors in the treatment of advanced gastro-oesophageal cancer and adjuvant treatment of high-risk oesophageal cancer, as well as the ongoing studies of immunotherapy in the treatment of patients with gastro-oesophageal cancers across an increasing range of clinical settings.

Gold nanorods (AuNRs) have attracted a great deal of attention due to their potential for use in a wide range of biomedical applications. However, their production typically requires the use of the relatively toxic cationic surfactant cetyltrimethylammonium bromide (CTAB) leading to continued demand for protocols to detoxify them for in vivo applications. In this study, a robust and facile protocol for the displacement of CTAB from the surface of AuNRs using phospholipids is presented. After the displacement, CTAB is not detectable by NMR spectroscopy, surface-enhanced Raman spectroscopy, or using pH-dependent ζ-potential measurements. The phospholipid functionalized AuNRs demonstrated superior stability and biocompatibility (IC50  > 200 µg mL-1 ) compared to both CTAB and polyelectrolyte functionalized AuNRs and are well tolerated in vivo. Furthermore, they have high near-infrared (NIR) absorbance and produce large amounts of heat under NIR illumination, hence such particles are well suited for plasmonic medical applications.

Widespread screening mammography programmes mean that ductal carcinoma in situ (DCIS), a pre-invasive breast lesion, is now more frequently diagnosed. However, not all diagnosed DCIS lesions progress to invasive breast cancer, which presents a dilemma for clinicians. As such, there is much interest in studying DCIS in the laboratory, in order to help understand more about its biology and determine the characteristics of those that progress to invasion. Greater knowledge would lead to targeted and better DCIS treatment. Here, we outline some of the models available to study DCIS, with a particular focus on animal-free systems.

Despite surgical removal of ductal carcinoma in situ (DCIS), recurrences still occur. This retrospective cohort study evaluated the risk of invasive recurrence following surgery and investigated factors which may be predictive of recurrence. We specifically investigated invasive recurrence with respect to mode of detection of DCIS. Patients whose DCIS was detected outside of the NHS Breast Screening Programme have a higher risk of subsequent ipsilateral invasive breast cancer than those whose DCIS is detected through screening. There is no significant difference in risk of subsequent contralateral invasive recurrence according to mode of detection.

Introduction: DCIS is treated surgically either by mastectomy or wide local excision (WLE) with or without breast radiotherapy to prevent recurrence or progression into invasive breast carcinoma. The aim of this study was to evaluate the risk of invasive recurrence following surgical treatment of DCIS and to study factors, which may predict recurrence. We specifically evaluated the risk of ipsilateral and contralateral invasive recurrence with respect to the mode of detection - screen-detected (SD) and non screen-detected (NSD).

AimsThis study aimed to assess the feasibility of using virtual slides to create 3D histopathological reconstructions to aid in the study of the biology of DCIS.MethodsFour μm thick serial sections of formalin fixed paraffin embedded tissue from three cases were cut and mounted onto glass slides, stained with haematoxylin and eosin, then scanned. The three image stacks comprised 30, 115 and 100 scanned sections creating a similar number of virtual slides. The virtual slides were registered using custom 3D software to create 3D tissue volumes. The volumes were annotated to highlight distinct features and 3D visualisations (segmentations) were created to study these features in 3D.ResultsThe most time‐intensive step was the manual annotation of virtual slides 3D histopathological reconstructions were created of (i) DCIS surrounded by adjacent invasion; (ii) pure DCIS and (iii) a ‘normal’ lobule.Conclusion3D in silico reconstructions of DCIS were created and more extensive studies can now be done within a realistic timescale. We have identified structural similarities between a benign lobule and DCIS which support the view that much DCIS, apparently in a ‘duct’ is contained within and expanded lobule. This method has the potential to provide insights into the biology of DCIS.

AIM:The recent Breast Cancer Screening Review has estimated that for one life saved three patients are overtreated. The dramatic increase in the diagnosis of Ductal carcinoma in-situ (DCIS) has not lead to the expected decrease in the incidence of invasive cancer. It is not clear if all DCIS progress to invasive cancer if untreated. The Low Risk DCIS Trial (LORIS) intends to compare the current treatment of low risk DCIS i.e. surgery, with active monitoring. For effective implementation, concordance between diagnostic biopsy using large volume vacuum assisted biopsy (VAB) and excision histology is vital. A two-centre UK audit was done to assess concordance in patients diagnosed with low grade DCIS diagnosed using VAB. METHODS:Data of DCIS diagnosed with VAB from year 2001-2010 in University Hospital Birmingham and Leeds Teaching Hospitals was retrospectively collected and concordance between diagnostic and excision histology was assessed. Low Grade DCIS diagnoses were further evaluated retrospectively with regard to their eligibility for LORIS. RESULTS:Of 225 DCIS diagnoses 128 (57%) were high grade, 66 (29%) intermediate grade and 31 (14%) low grade. Overall 18% were upgraded to invasive cancer. The upgrade rate to invasive cancer for high grade was 23% and for low grade DCIS was 10%. In the low grade group eligible for LORIS, there were no upgrades to invasive cancer. CONCLUSION:The upgrade rates to invasive cancer are comparable to series published in literature. The concordance for the low risk DCIS with zero upgrade to invasive cancer supports the stringent LORIS eligibility criteria for trial selection.