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BACKGROUND: Familial adenomatous polyposis (FAP) predisposes individuals to duodenal adenomas. This study describes the histopathological features of endoscopic and surgical specimens from the duodenum, as well as genotype-phenotype associations. METHODS: All known FAP patients were included from the Danish Polyposis Register. FAP patients were defined as having more than 100 cumulative colorectal adenomas and/or having a known germline pathogenic variant in the APC gene. Endoscopic procedures, histopathology, and genetics were evaluated. RESULTS: Of 500 FAP patients, 70.6% underwent esophagogastroduodenoscopy (EGD) at least once. Of these, 59.2% presented with detectable duodenal adenomas. The most severe morphology was tubular in 62.7% patients, tubulovillous in 25.4%, and villous in 12.0%, while the most severe dysplasia was low-grade in 67.5% patients, high-grade in 25.4%, and 6.7% had adenocarcinoma. In 6.2% of FAP patients, duodenal resection was recommended, including 29% with duodenal adenocarcinoma. The risk of duodenal surgery was 1.31 per 1,000 person-years (median age: 53 years). The predominant reason for surgery was extensive polyposis (67.7%). Of the patients who underwent duodenal resection, a median of six (IQR: 4-8) EGDs were performed within five years prior to surgery, but 67.6% and 83.9% never underwent a duodenal polypectomy or endoscopic mucosa resection, respectively. Of note, seventeen of 500 patients (3.4%) developed duodenal adenocarcinoma, of which 47% were advanced at diagnosis. Genetic evaluations revealed various pathogenic variants in the APC gene, with no strong genotype-phenotype association. CONCLUSIONS: The prevalence of duodenal adenomas and cancer in FAP warrants vigilant endoscopic surveillance. Nevertheless, the need for duodenal surgery persists and should together with endoscopic practice be monitored in national registers.

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BACKGROUND AND AIM: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal dominant syndrome characterized by fundic gland polyps (FGP) as well as an increased risk of gastric cancer. The syndrome has been recognized as a clinical entity for less than a decade. A clinical suspicion may be complex and can vary from incidental findings of FGPs at gastroscopy to obstructive symptoms with dyspepsia and vomiting. The diagnosis is established by genetic detection of a pathogenic variant in the promotor 1B region of the APC gene. As of yet there are no established clinical criteria for the diagnosis. To increase knowledge of the condition and to discuss possible genetic testing and surveillance strategies, we performed a systematic review of all reported patients with GAPPS. METHODS: This review was organized according to PRISMA guidelines. The search, which was conducted on September 7th, 2023, was applied to MEDLINE and restricted to only humans and papers in the English language. Only the studies on patients/families with GAPPS verified by identification of a pathogenic variant in the APC promoter 1B were included. RESULTS: Twelve publications with a total of 113 patients were identified. In all instances the diagnosis was genetically verified with reports of four different variants within the APC promotor 1B region. Eighty-eight patients (90.1%) had gastric polyps, of these seven patients had low-grade dysplasia and five patients had both low- and high-grade dysplasia. Thirty-seven patients (45.7%) underwent gastrectomy. There were no reports of duodenal polyps (0%). Gastric cancer was found in 31 patients (30.1%) with a median age of 48 years (range 19-75). Twenty-six patients died (23.2%) of which 19 had developed gastric cancer (73.1%). One patient was diagnosed with metastatic colorectal cancer (2.2%) and died at 73 years of age. Nineteen patients had colorectal manifestations with < 20 polyps (41.3%). CONCLUSION: Patients with a pathogenic variant in the APC promoter 1B region have an increased risk of gastric polyposis and early-onset gastric cancer. However, there is considerable variation in clinical expression and penetrance, which makes decisions on surveillance and the timing of prophylactic gastrectomy challenging.

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Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.

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BACKGROUND: EUS-guided gastroenterostomy (EUS-GE) with lumen-apposing metallic stents (LAMS) in patients with gastric outlet obstruction (GOO) has proven to be an alternative to luminal stenting in the duodenum and surgical gastroenterostomy. In severely ill patients, the method can provide improved quality of life (QoL) and symptom relief by restoration of the luminal passage of fluid and nutrients to the small intestine. AIM: To assess the technical and clinical success and safety of EUS-GE. MATERIAL AND METHODS: A dual center retrospective case series of 33 consecutive patients with GOO due to malignant (n = 28) or non-malignant conditions (n = 5). The patients were treated with EUS-GE using cautery enhanced LAMS. Procedures were performed guided by EUS and fluoroscopy in general anesthesia or conscious sedation. RESULTS: Technical success was achieved in all patients. The median procedure time was 71 min and the median hospital stay was three days. Thirty (91%) patients were able to resume oral nutrition after the procedure. Ten patients (30%) experienced adverse events (AEs), including migration of the stent, bleeding, and infection. Four patients had fatal AEs (12%). All stent-related AEs were handled endoscopically. Five patients (15%) needed re-intervention. The median survival time for patients with malignant obstruction was 8.5 weeks (0.5-76), and 13 patients with obstructing malignancies lived 12 weeks or longer. CONCLUSION: EUS-GE is a minimally invasive and efficient method for restoration of the gastrointestinal passage and may improve palliative care for patients with GOO. The method has potential hazards and should only be offered in expert centers that regularly perform the procedure.

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Changes in the Atlantic Meridional Overturning Circulation, which have the potential to drive societally-important climate impacts, have traditionally been linked to the strength of deep water formation in the subpolar North Atlantic. Yet there is neither clear observational evidence nor agreement among models about how changes in deep water formation influence overturning. Here, we use data from a trans-basin mooring array (OSNAP-Overturning in the Subpolar North Atlantic Program) to show that winter convection during 2014-2018 in the interior basin had minimal impact on density changes in the deep western boundary currents in the subpolar basins. Contrary to previous modeling studies, we find no discernable relationship between western boundary changes and subpolar overturning variability over the observational time scales. Our results require a reconsideration of the notion of deep western boundary changes representing overturning characteristics, with implications for constraining the source of overturning variability within and downstream of the subpolar region.

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To provide an observational basis for the Intergovernmental Panel on Climate Change projections of a slowing Atlantic meridional overturning circulation (MOC) in the 21st century, the Overturning in the Subpolar North Atlantic Program (OSNAP) observing system was launched in the summer of 2014. The first 21-month record reveals a highly variable overturning circulation responsible for the majority of the heat and freshwater transport across the OSNAP line. In a departure from the prevailing view that changes in deep water formation in the Labrador Sea dominate MOC variability, these results suggest that the conversion of warm, salty, shallow Atlantic waters into colder, fresher, deep waters that move southward in the Irminger and Iceland basins is largely responsible for overturning and its variability in the subpolar basin.

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The Atlantic Meridional Overturning Circulation (AMOC) is a key component of the global climate system through its transport of heat and freshwater. The subpolar North Atlantic (SPNA) is a region where the AMOC is actively developed and shaped though mixing and water mass transformation and where large amounts of heat are released to the atmosphere. Two hydrographic transbasin sections in the summers of 2014 and 2016 provide highly spatially resolved views of the SPNA velocity and property fields on a line from Canada to Greenland to Scotland. Estimates of the AMOC, isopycnal (gyre-scale) transport, and heat and freshwater transport are derived from the observations. The overturning circulation, the maximum in northward transport integrated from the surface to seafloor and computed in density space, has a high range, with 20.6 ± 4.7 Sv in June-July 2014 and 10.6 ± 4.3 Sv in May-August 2016. In contrast, the isopycnal (gyre-scale) circulation was lowest in summer 2014: 41.3 ± 8.2 Sv compared to 58.6 ± 7.4 Sv in 2016. The heat transport (0.39 ± 0.08 PW in summer 2014, positive is northward) was highest for the section with the highest AMOC, and the freshwater transport was largest in summer 2016 when the isopycnal circulation was high (-0.25 ± 0.08 Sv). Up to 65% of the heat and freshwater transport was carried by the isopycnal circulation, with isopycnal property transport highest in the western Labrador Sea and the eastern basins (Iceland Basin to Scotland).

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Nitrous oxide (N2O) is a climate relevant trace gas, and its production in the ocean generally increases under suboxic conditions. The Atlantic Ocean is well ventilated, and unlike the major oxygen minimum zones (OMZ) of the Pacific and Indian Oceans, dissolved oxygen and N2O concentrations in the Atlantic OMZ are relatively high and low, respectively. This study, however, demonstrates that recently discovered low oxygen eddies in the eastern tropical North Atlantic (ETNA) can produce N2O concentrations much higher (up to 115 nmol L-1) than those previously reported for the Atlantic Ocean, and which are within the range of the highest concentrations found in the open-ocean OMZs of the Pacific and Indian Oceans. N2O isotope and isotopomer signatures, as well as molecular genetic results, also point towards a major shift in the N2O cycling pathway in the core of the low oxygen eddy discussed here, and we report the first evidence for potential N2O cycling via the denitrification pathway in the open Atlantic Ocean. Finally, we consider the implications of low oxygen eddies for bulk, upper water column N2O at the regional scale, and point out the possible need for a reevaluation of how we view N2O cycling in the ETNA.

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INTRODUCTION: Endoscopic ultrasound (EUS) is an established tool in diagnosing pancreatic masses and enables guided fine-needle aspiration (FNA). Confocal laser endomicroscopy (CLE) has allowed in vivo microscopic analysis during on-going endoscopy. Recently, CLE has gone beyond luminal indications with the development of a new microprobe (nCLE). The aim of this case series was to study the feasibility of EUS-guided nCLE and to correlate the findings with microscopy. METHODS: A total of 25 patients with pancreatic masses were included. During the procedure, an nCLE fiber preloaded into a 19 gauge FNA needle was advanced into the lesion under EUS guidance. Fluorescein was administered intravenously and imaging performed. Afterwards EUS-FNA was performed in the same location. Safety and feasibility were evaluated and CLE structures were registered and correlated to the standard hematoxylin and eosin cytopathology specimens. Moreover, additional topical acriflavine-enhanced ex vivo examinations on fresh pancreatic specimens were conducted. RESULTS: EUS-guided nCLE procedures were accomplished in all patients. No adverse advents were registered. Furthermore, it was feasible to do nCLE inside pathological lesions and relatively easy to visualize organ specific tissue. Despite selecting predefined structures the diagnostic value was limited mainly due to the missing ability to elucidate the cell nuclei, In the ex vivo examinations, where acriflavine was administered topically on excised pancreatic tissue, the nuclei were clearly visualized, thus increasing the diagnostic value. CONCLUSION: EUS-guided nCLE procedures on focal pancreatic masses are feasible and safe, but the diagnostic value seems limited. Thus, further studies using different contrast agents are required to optimize the diagnostic accuracy.