Additional value of EUS in oesophageal cancer patients staged N0 on PET/CT: validation of a prognostic model

Background Lymph node metastases are a major prognostic indicator in oesophageal cancer. Radiological staging largely influences treatment decisions and is becoming more reliant on PET and CT. However, the sensitivity of these modalities is suboptimal and is known to under-stage disease. The primary aim of this study was to validate a published prognostic model in oesophageal cancer patients staged N0 with PET/CT, which showed that EUS nodal status was an independent predictor of survival. The secondary aim was to assess the prognostic significance of pathological lymph node metastases in this cohort. Methods An independent validation cohort included 139 consecutive patients from a regional upper gastrointestinal cancer network staged N0 with PET/CT between 1st January 2013 and 31st June 2015. Replicating the original study, two Cox regression models were produced: one included EUS T-stage and EUS N-stage, and one included EUS T-stage and EUS N0 versus N+. The primary outcome of the prognostic model was overall survival (OS). Kaplan–Meier analysis assessed differences in OS between pathological node-negative (pN0) and node-positive (pN+) groups. A p value of < 0.05 was considered statistically significant. Results The mean OS of the validation cohort was 29.8 months (95% CI 27.1–35.2). EUS T-stage was significantly and independently associated with OS in both models (p = 0.011 and p = 0.012, respectively). EUS N-stage and EUS N0 versus N+ were not significantly associated with OS (p = 0.553 and p = 0.359, respectively). There was a significant difference in OS between pN0 and pN+ groups (χ2 13.315, df 1, p < 0.001). Conclusion Lymph node metastases have a significant detrimental effect on OS. This validation study did not replicate the results of the developed prognostic model but the continued benefit of EUS in patients staged N0 with PET/CT was demonstrated. EUS remains a valuable component of a multi-modality approach to oesophageal cancer staging

State-of-the-art imaging in oesophago-gastric cancer

Radiological investigations are essential in the management of oesophageal and gastro-oesophageal junction cancers. The current multimodal combination of CT, 18F-fluorodeoxyglucose positron emission tomography combined with CT (PET/CT) and endoscopic ultrasound (EUS) has limitations, which hinders the prognostic and predictive information that can be used to guide optimum treatment decisions. Therefore, the development of improved imaging techniques is vital to improve patient management. This review describes the current evidence for state-of-the-art imaging techniques in oesophago-gastric cancer including high resolution MRI, diffusion-weighted MRI, dynamic contrast-enhanced MRI, whole-body MRI, perfusion CT, novel PET tracers, and integrated PET/MRI. These novel imaging techniques may help clinicians improve the diagnosis, staging, treatment planning, and response assessment of oesophago-gastric cancer

The Impact of baseline 18F-FDG PET-CT on the management and outcome of patients with gastric cancer: a systematic review

Objective: CT and staging laparoscopy are routinely used to stage patients with gastric cancer, however the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with CT (PET-CT) is uncertain. This systematic review synthesised the evidence regarding the impact of baseline PET-CT staging on treatment decisions and patient outcomes. Methods: Systematic database searches were performed without date restriction. Studies reporting data in patients with gastric adenocarcinoma who underwent radiological staging were included. One reviewer screened titles and abstracts for suitability and two reviewers extracted data from included articles. Primary outcome was the reported change in management after PET-CT. Secondary outcomes were the rates of recurrence and overall survival between patients staged with and without PET-CT. Risk of bias was assessed using the ROBINS-I tool. PROSPERO registration (CRD42022304314). Results: Data from 11 studies recruiting 2101 patients between 2012 and 2021 were included. PET-CT was performed in 1422 patients. Change of management varied between 3% and 29% of cases. No studies compared recurrence or survival rates between patients staged with or without PET-CT. Adenocarcinoma of intestinal subtype tended to be more FDG-avid compared to diffuse or signet-ring subtypes. No randomised data existed, and studies were considered low quality with high risk of bias. Conclusion: Evidence for the additional value of PET-CT in the gastric cancer staging pathway is limited. All studies reported a positive impact by preventing those with undetected metastatic disease on CT undergoing futile surgery. Future national guidelines should consider routine staging PET-CT in gastric cancer

Gallbladder polyps and adenomyomatosis

Incidental findings are commonly detected during examination of the gallbladder. Differentiating benign from malignant lesions is critical because of the poor prognosis associated with gallbladder malignancy. Therefore, it is important that radiologists and sonographers are aware of common incidental gallbladder findings, which undoubtedly will continue to increase with growing medical imaging use. Ultrasound is the primary imaging modality used to examine the gallbladder and biliary tree, but contrast-enhanced ultrasound and MRI are increasingly used. This review article focuses on two common incidental findings in the gallbladder; adenomyomatosis and gallbladder polyps. The imaging features of these conditions will be reviewed and compared between radiological modalities, and the pathology, epidemiology, natural history, and management will be discussed

Risk of developing gallbladder cancer in patients with gallbladder polyps detected on transabdominal ultrasound: a systematic review and meta-analysis

Objective: To estimate the risk of malignancy in gallbladder polyps of incremental sizes detected during transabdominal ultrasound (TAUS). Methods: We searched databases including MEDLINE, Embase, and Cochrane Library for eligible studies recording the polyp size from which gallbladder malignancy developed, confirmed following cholecystectomy, or by subsequent follow-up. Primary outcome was the risk of gallbladder cancer in patients with polyps. Secondary outcome was the effect of polyp size as a prognostic factor for cancer. Risk of bias was assessed using the Quality in Prognostic Factor Studies (QUIPS) tool. Bayesian meta-analysis estimated the median cancer risk according to polyp size. This study is registered with PROSPERO (CRD42020223629). Results: 82 studies published since 1990 reported primary data for 67,837 patients. 67,774 gallbladder polyps and 889 cancers were reported. The cumulative median cancer risk of a polyp measuring 10 mm or less was 0.60% (99% credible range 0.30–1.16%). Substantial heterogeneity existed between studies (I2 = 99.95%, 95% credible interval 99.86–99.98%). Risk of bias was generally high and overall confidence in evidence was low. 13 studies (15.6%) were graded with very low certainty, 56 studies (68.3%) with low certainty, and 13 studies (15.6%) with moderate certainty. In studies considered moderate quality, TAUS monitoring detected 4.6 cancers per 10,000 patients with polyps less than 10 mm. Conclusion: Malignant risk in gallbladder polyps is low, particularly in polyps less than 10 mm, however the data are heterogenous and generally low quality. International guidelines, which have not previously modelled size data, should be informed by these findings

Erratum to: ‘Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis’

ErratumErratum to: ‘Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis’ -http://hdl.handle.net/11019/90

Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows

peer-reviewedBackground: All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP) which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR). Results: mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P < 0.1) included the T cell receptor signalling pathway, graft-versus-host disease and cytokine-cytokine receptor interaction pathways. However 30 DPP, where the majority of genes were differentially expressed, the enrichment (adjusted P < 0.1) of tissue repair and proliferative activity pathways was observed. Nineteen candidate genes selected from mRNA-Seq results, were independently assessed by qRT-PCR in additional postpartum cows (5 animals) at both time points. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum. Conclusions: The results of this study reveal an early activation of the immune response which undergoes a temporal functional change toward tissue proliferation and regeneration during endometrial involution in healthy postpartum cows. These molecular changes mirror the activation and resolution of endometrial inflammation during involution previously classified by the degree of neutrophil infiltration. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes may become potential markers for resolution of endometrial inflammation in the postpartum cow

Propensity score analysis of 18-FDG PET/CT-enhanced staging in patients undergoing surgery for esophageal cancer

Purpose PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy. Methods A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy [median age 63 years (31–80), 395 males, 425 adenocarcinomas, 71 squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary outcome measure was overall survival (OS) based on intention to treat. Results Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi2 6.571, df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28–1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04–1.19], p = 0.001) and PET/CT staging (HR 0.688 [95% CI 0.53–0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006). Conclusions Enhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer