Head-to-head comparison between F-18-DOPA PET/CT and Ga-68-DOTA-peptide PET/CT in detecting intestinal neuroendocrine tumours:A systematic review and meta-analysis

Objective: The imaging of intestinal neuroendocrine tumours (NETs) relies on functional PET tracers; these tumours can be studied by means of both Ga-68-DOTA-peptides and F-18-DOPA PET/CT. As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data. Design: PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of Ga-68-DOTA-peptides and F-18-DOPA PET/CT; papers up to February 2021 were considered. Patients and Measurements: In each study, we considered sensitivity in terms of patient-based (PBA), region-based (RBA) and lesion-based analysis (LBA) and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth. Results: Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NET patients were included. The pooled sensitivity of F-18-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. Ga-68-DOTA peptide PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of F-18-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of F-18-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found, while no publication bias was observed. Conclusion: Both F-18-DOPA PET/CT and Ga-68-DOTA-peptide PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of F-18-DOPA PET/CT was observed. Thus, the use of F-18-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs

Pathology Reporting in Neuroendocrine Neoplasms of the Digestive System: Everything You Always Wanted to Know but Were Too Afraid to Ask

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals

The use of nematodes in assessing ecological conditions in shallow waters surrounding a Mediterranean harbour facility

The spatial distribution and structure of nematode assemblages in the area surrounding the harbour of Vado Ligure (Savona, NW Mediterranean) were studied in relation to the influence of natural and anthropogenic environmental factors. Stations were selected following an “anthropogenic gradient” from sites located near the city centre and its harbour to more pristine and distant sites. Sediment quality was determined by considering both sediment granulometric and chemical parameters (hydrocarbons, heavy metals, total organic matter, proteins, carbohydrates) as well as nematode abundance, diversity, life strategies, trophic structure and assemblage composition. A high correlation between environmental characteristics and the nematode response was found. On the basis of the comparison of these results, which identified three distinct sub-areas associated with different levels of environmental quality, a set of nematode indicator genera was selected for the future evaluation of quality status

Emerging therapies in pheochromocytoma and paraganglioma: Immune checkpoint inhibitors in the starting blocks

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respec-tively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progres-sive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology

ZMIZ1 Preferably Enhances the Transcriptional Activity of Androgen Receptor with Short Polyglutamine Tract

The androgen receptor (AR) is a ligand-induced transcription factor and contains the polyglutamine (polyQ) tracts within its N-terminal transactivation domain. The length of polyQ tracts has been suggested to alter AR transcriptional activity in prostate cancer along with other endocrine and neurologic disorders. Here, we assessed the role of ZMIZ1, an AR co-activator, in regulating the activity of the AR with different lengths of polyQ tracts as ARQ9, ARQ24, and ARQ35 in prostate cancer cells. ZMIZ1, but not ZMIZ2 or ARA70, preferably augments ARQ9 induced androgen-dependent transcription on three different androgen-inducible promoter/reporter vectors. A strong protein-protein interaction between ZMIZ1 and ARQ9 proteins was shown by immunoprecipitation assays. In the presence of ZMIZ1, the N and C-terminal interaction of the ARQ9 was more pronounced than ARQ24 and ARQ35. Both Brg1 and BAF57, the components of SWI/SNF complexes, were shown to be involved in the enhancement of ZMIZ1 on AR activity. Using the chromatin immunoprecipitation assays (ChIP), we further demonstrated a strong recruitment of ZMIZ1 by ARQ9 on the promoter of the prostate specific antigen (PSA) gene. These results demonstrate a novel regulatory role of ZMIZ1 in modulating the polyQ tract length of AR in prostate cancer cells

Eclipse in the Dark Years: Pick-up Flights, Routes of Resistance and the Free French

This article charts the importance of clandestine flights from Britain into occupied France during the Second World War as a route of resistance. These pick-up flights were coordinated from London and were an example of the inter-allied cooperation and Franco-British negotiation that took place between the BCRA, SIS, and SOE. The flights allowed General Charles de Gaulle to hold court with the leaders of resistance networks, smoothing problems on the route to a unified resistance council. Likewise, they allowed him to build bridges between vying factions in France and in London, drawing together the movements under his command and personalising the narrative of resistance. From busy London restaurants and family homes via secret flights to darkened fields in Occupied France, the route of these transfers shaped the character of resistance. This article draws out the personal interactions and connections that underpinned these networks and describes the enduring connections of this route of resistance, starting with the commemoration of Jean Moulin's crash landing at RAF Tangmere, the forward station for many of these flights