24 research outputs found
New evidence on palaeoenvironmental conditions in SW Cameroon since the Late Pleistocene derived from alluvial sediments of the Ntem River
An interior delta in the lower course of the Ntem River near the sub-prefecture Maâan was identified after interpretation of satellite images, topographical maps of SW Cameroon and geological as well as hydrological references and a reconnaissance fieldtrip to the study area. Here neotectonic processes have initiated the establishment of a âsediment trapâ (step fault), which in combination with environmental changes strongly generated the fluvial morphology. It transitionally led to temporary lacustrine and palustrine conditions in parts of this river section. Inside the interior delta an anastomosing multi-branched river system has developed, which contains âstillwater locations', periodically inundated sections, islands and rapids. Following geomorphological, physiogeographical and sedimentological research approaches, the alluvial plain has been prospected and studied extensively. 91 hand-corings, including three NEâSW transects, were carried out on river benches, levees, cut-off and periodical branches, islands as well as terraces throughout the entire alluvial plain and have unveiled multi-layered, sandy to clayey alluvia reaching up to 440 cm depth. At many locations, fossil organic horizons and palaeosurfaces were discovered, containing valuable palaeoenvironmental proxy data. At these sites, through additional detailed stratigraphical analysis (close-meshed hand-coring and exposure digging) a comprehensive insight into the stratification (lamination) of the alluvia could be gained, clarifying processes and conditions that prevailed in the catchment area during the period of their deposition. 32 Radiocarbon data of macro-rests (leafs, wood), charcoal and organic sediment sampled from these horizons provided ages between 48.230 ± 6.411 and 217 ± 46 years BP (not calibrated). This constitutes the importance of the alluvia as an additional, innovative palaeoarchive for proxy data contributing to the reconstruction of palaeoenvironment and palaeoclimate in western Equatorial Africa. The further examination of the alluvia will not only provide additional information on the dynamics of vegetation, climate and hydrology (esp. fluvial morphology) in SW Cameroon since the âFirst Millennium BC Crisisâ (around 3.000 years BP), the main focus of the DFG-research project, but also on conditions prevailing since the Late Pleistocene, during the Last Glacial Maximum (~18.000 years BP), the Younger Dryas impact (~11.000 years BP) and the âHumid African Periodâ (~9.000â6.000 years BP). Delta13C-values (â31,4 to â26,4â°) evidence that at the particular drilling sites rain forest has prevailed during the corresponding time period (rain forest refuge theory). The sampled macrorests all indicate rain forest dominated ecosystems, which were able to persist in fluvial habitats, even during arid periods
Physiogeographical research on Pleistocene and Holocene palaeoenvironmental conditions in southern Cameroon derived from alluvia of the Ntem interior delta and alluvial sediments of the rivers Boumba, Ngoko, Nyong and Sanaga
Die Studie zur holozĂ€nen und pleistozĂ€nen Umweltgeschichte SĂŒd-Kameruns betrachtet den Aussagewert alluvialer Ablagerungen der FlĂŒsse Boumba, Dja, Nyong, Ntem und Sanaga fĂŒr die PalĂ€oumweltforschung. Die zugrundeliegende Forschungsarbeit fand im Rahmen des ReSaKo-Projektes, als Teil der interdisziplinĂ€ren DFG-Forschergruppe 510 (âĂkologischer Wandel und kulturelle UmbrĂŒche in West- und Zentralafrikaâ) statt, welches die zeitliche und rĂ€umliche Korrelation zwischen Klimawandel, Landnutzungsstrategien und kulturellen Innovationen wĂ€hrend der âFirst Millennium BC Crisisâ untersucht hat. HierfĂŒr wurde der ökologisch sensitive Bereich des tropischen bis Ă€quatorialen, immergrĂŒnen bis halb-immergrĂŒnen Guineisch-Kongolesischen Regenwaldes und dessen Ăbergangszone zur Savanne im SĂŒden Kameruns ausgewĂ€hlt. Als Hauptziele galten dabei zum einen der Nachweis und die Interpretation umweltgeschichtlich verwertbarer Alluvionen in einer diesbezĂŒglich bisher unerforschten Region und zum anderen die Korrelation der Befunde mit bereits vorliegenden terrestrischen und hemi-pelagischen PalĂ€oumweltarchiven zur weiteren Rekonstruktion der PalĂ€oumweltbedingungen im westlichen (monsunalen) Ăquatorialafrika. Nach der Identifizierung geeigneter Arbeitsgebiete entlang verzweigter, mĂ€andrierender und verflochtener bis anastomosierender Flussabschnitte mittels Fernerkundung von Satellitenbildszenen (LANDSAT ETM+ und ASTER), wurden unter Verwendung physiogeographischer und geomorphologischer Arbeitsmethoden ausgedehnte Feldarbeiten wĂ€hrend der Trockenzeiten der Jahre 2005-2008 durchgefĂŒhrt. Zahlreiche Bohrarbeiten (161 Handbohrungen bis 550 cm Tiefe) zur Sedimentprobennahme (1093 Proben) innerhalb der Alluvial- und Auenbereiche der fluvialen Systeme lieferten einen umfassenden Einblick in die Stratigraphie und fluvial-morphologische als auch palĂ€oökologische und âhydrologische Entwicklung der verschiedenen fluvialen Ăkosysteme. Die mehrschichtigen, sandigen bis tonigen Alluvionen enthalten PalĂ€ooberflĂ€chen (z. B. Gyttjen, reliktische SĂŒmpfe, fossile organische Lagen/Horizonte), die hervorragende zusĂ€tzliche Proxydaten-Archive fĂŒr die Rekonstruierung umweltgeschichtlicher Bedingungen darstellen. Bohrtransekte und die Interpretation von KorngröĂensequenzen (Verfeinerung, Vergröberung) und PalĂ€ooberflĂ€chen aus solchen alluvialen Sedimentarchiven stellen ein wichtiges, diagnostisches Instrument bei der Rekonstruktion palĂ€oökologischer und palĂ€ohydrologischer Bedingungen und VerĂ€nderungen dar und belegen zeitweise einsetzende Austrocknung und Bodenbildung in den Auen sowie die Entstehung von SĂŒmpfen, Mudden, Altarmen und Altwasserseen. Dies zeugt eindeutig von einer modifizierten Dynamik der fluvialen Systeme als Reaktion auf endogene Steuer-gröĂen und (fluss-)interner VariabilitĂ€t (equilibrium). Eine Vielzahl (76) von 14C (AMS)-Datierungen an organischem Sediment und Makroresten aus diesen Alluvionen lieferten spĂ€tpleistozĂ€ne bis rezente Alter (~48 â 0,2 ka BP). Die dazugehörigen δ13C-Werte (-35.5 bis -18.0 â°) belegen fĂŒr den GroĂteil der Untersuchungsstandorte (auĂer OberlĂ€ufe des Nyong und Sanaga) den Fortbestand von C3-Spezies dominierter Galleriewald-Ăkosysteme entlang der Flusssysteme (âfluviale Regenwaldrefugienâ) trotz einiger klimatischer VerĂ€nderungen/Aridisierungen (z. B. Letztes Glaziales Maximum um etwa 20.000 BP). Trotz der bestehenden Schwierigkeiten bei der Interpretation tropischer Sedimentarchive (z. B. Hiatusproblematik) und fluvialer Archive im Allgemeinen, unterstĂŒtzen weitere sedimentologische und pedologische Analysen (bodenchemische und -physikalische Laboranalysen: KorngröĂen, Kohlenstoff [Ctot], Stickstoff [N], Eisengehalt [Feo und Fed], pH, Munsell-Farben und C/N) und ausgewĂ€hlte 14C (AMS)-Datierungen und δ13C-Bestimmungen diesen Beitrag zur hypothetischen Rekonstruktion der umweltgeschichtlichen und palĂ€ohydrologischen Entwicklung des Untersuchungsraumes. Die Interpretation des Alluvialarchivs liefert zusĂ€tzlich fundierte Informationen hinsichtlich der komplexen ZusammenhĂ€nge zwischen Klima, Ozean, fluvialen und ökologischen Systemen und anthropogener Einflussnahme in einem regional weitestgehend unerforschten Gebiet mit hoch-sensitiven tropischen Ăkosystemen. Die Ergebnisse zeigen eine hohe Korrelation mit frĂŒheren PalĂ€oumweltstudien, die ĂŒber Untersuchungen an weiteren terrestrischen (lakustrin und palustrin) und hemi-pelagischen Archiven dieser Region gewonnen werden konnten. Sie bekrĂ€ftigen Milanković- bis sub-Milanković-skalige Fluktuationen (bes. PrĂ€zession-Zyklus) der IntensitĂ€t des westafrikanischen Monsuns und daraus resultierende klimatische, hydrologische und ökologische Modifikationen im Untersuchungsgebiet, was wiederum weitreichende Telekonnektionen und Reorganisationen impliziert. Insgesamt können im Liegenden grobkörnige, sandige sedimentĂ€re Einheiten, welche turbulente fluvial-morphologische Bedingungen und geöffnete Landschaftsstrukturen wĂ€hrend des SpĂ€tpleistozĂ€ns (48-30 ka BP) vermuten lassen, von fein-sandigen LGM-zeitlichen (22-16 ka BP) und mĂ€chtigen schluffigen bis tonigen, holozĂ€nen Sedimenteinheiten im Hangenden unterschieden werden, welche eher stabilisierte und saisonale UmweltverhĂ€ltnisse widerspiegeln. GröĂere Um- und Verlagerungen innerhalb der Alluvialbereiche (v. a. Gerinnebettverlagerungen, Versumpfung) konnten fĂŒr den Ăbergang vom PleistozĂ€n zum HolozĂ€n (14-10 ka BP) nachgewiesen werden. Weitere einschneidende VerĂ€nderungen traten im SpĂ€tholozĂ€n auf (um 4, 2 und 0,8 ka BP), wahrscheinlich begĂŒnstigt durch die einsetzende Sesshaftwerdung Bantu sprechender Volksgruppen im tropischen Regenwald Zentralafrikas und die EinfĂŒhrung der Metallurgie um 3 ka BP. Die Informationen ĂŒber regionale umweltgeschichtliche Oszillationen und Variationen im Prozess- und LandschaftsgefĂŒge sind in den alluvialen Sedimenten gut dokumentiert und erhalten geblieben und ergĂ€nzen somit frĂŒhere Ergebnisse (z. B. ECOFIT Programm) zur spĂ€tquartĂ€ren Umweltgeschichte des vom Monsun geprĂ€gten westlichen Ăquatorialafrikas. Die Ergebnisse bestĂ€tigen vor allem die Bedeutung und Anwendbarkeit tropischer (afrikanischer) alluvialer Sedimente fĂŒr die PalĂ€oumweltforschung und belegen zudem, dass neben (neo-)tektonischen Impulsen das Klima die tragende Rolle in der Gestaltung der Landschaft und der Dynamik, sowie der Entwicklung der Flusseinzugsgebiete gespielt hat.This study on the Holocene and Pleistocene palaeoenvironment in southern Cameroon elucidates the value and relevance of mayor fluvial systemsâ (Boumba, Dja, Nyong, Ntem and Sanaga) alluvial sediments for palaeoenvironmental research. It was realized within the framework of the âRegenwald-Savannen-Kontakt (ReSaKo)â-project, as part of the interdisciplinary DFG-research group 510 (âEcological and cultural changes in West and Central Africaâ). The latter focused on examining the temporal and spatial coherence of altering land-use strategies, cultural innovations and climate change during the so-called âFirst Millennium BC Crisisâ. For this approach, study areas in the ecologically sensitive ecosystem of the equatorial and tropical evergreen to semi-deciduous Guinean-Congolian rain forest and its adjacent savanna margin in southern Cameroon were chosen. Mayor objectives of this study were the detection of palaeoenvironmentally interpretable alluvial sediments in a hitherto unexplored region and their subsequent interpretation and correlation with already existing terrestrial and hemi-pelagical sediment archives to further reconstruct palaeoenvironmental conditions in western (monsoonal) equatorial Africa. After remote-sensing of satellite imageries (LANDSAT ETM+, ASTER) to detect suitable study sites across braiding, meandering and anabranching to anastomosing river sections, extended fieldworks including physiogeographic and geomorphological research methods were carried out during dry seasons of 2005-2008. Numerous hand-corings (161 cores, up to depths of 550 cm) for sediment sampling (1093 samples) on alluvial ridges and floodplains of mayor fluvial systems provided a comprehensive insight into the stratigraphic record and fluvial-morphological as well as palaeoecological and -hydrological evolution of the fluvial ecosystems. The multilayered, sandy to clayey alluvia contain sedimentary form-units and palaeosurfaces (e.g. gyttja, relict swamp, fossil organic layers) which provide excellent additional proxy data archives for the reconstruction of palaeoenvironmental conditions. Coring transects and sedimentary profiles showing grain-size shifts and alternating sedimentary units in the stratigraphic records evidence temporal phases of desiccation and pedogenesis as well as formation of swamps, muds, oxbows and oxbow lakes (palaeochannels and palaeomeanders). This unequivocally indicates modified dynamics of the fluvial systems in response to external forcing and (river-)internal variability (equilibrium). Multiple (76) 14C-(AMS)-dated samples from organic sediment and macro-rests embedded in these sedimentary units indicate Late Pleistocene to recent ages (14C-ages: 48-0.2 ka BP). Corresponding δ13C-values (-35.5 to -18.0 â°) for most study areas (except Nyong and Sanaga upper catchments) indicate the persistence of C3-dominated gallery forest ecosystems across the rivers (âfluvial rain forest refugesâ) despite several climatic deteriorations/aridifications (e.g. Last Glacial Maximum [LGM], around approx. 20 ka BP). Regarding general problems and uncertainties of interpreting alluvial sediments (i.e. hiatus), additional sedimentological and pedological analysis (chemical and physical sediment analysis: texture, carbon [Ctot], nitrogen [N], organic material [OM], iron [Feo and Fed], pH and Munsell colour determination as well as C/N evaluation) and 14C (AMS) as well as δ13C data of selected samples substantiate this approach to hypothetically reconstruct the palaeoenvironmental and palaeohydrological conditions in the research area. The interpretation of the alluvial record offers excellent additional information on the complex feedbacks between climate, ocean, fluvial as well as ecological systems and human activity in a marginal studied region with high sensitive tropical ecosystems. The findings highly correlate with former palaeoenvironmental and palaeoclimatic reconstructions from additional terrestrial (lacustrine and palustrine) and hemi-pelagical archives from the region. They substantiate Milankovitch- to sub-Milankovitch-scale fluctuations (esp. precession cycle) of the western African monsoon intensity and inherited climatic, hydrological as well as ecological modifications in the study area, inducing large-scale teleconnections and reorganizations. Generally, several basal coarse-grained sandy units, representing turbulent fluvial-morphological conditions and instable landscape settings during the Late Pleistocene (48-30 ka BP), can be distinguished from more fine-grained sandy LGM-age (22-16 ka BP) and thick upper loamy to clayey Holocene units, indicating rather stable and seasonal environmental settings. Mayor reorganizations of the alluvial ridges (i.e. channel migration and wandering, swamp formation) have been allocated to the Pleistocene-Holocene transition around 14-10 ka BP. Further striking changes have been found for the Late Holocene (i.e. around 4, 2 and 0.8 ka BP), probably significantly enhanced by emerging sedentariness of Bantu speaking people in the tropical Central African rain forest and the inventory of metallurgy around 3 ka BP. However, the information on inherited regional oscillations, process and landscape variations have well been preserved in the alluvial sediment archives and thereby complement the earlier results (e.g. ECOFIT programme) on the Late Quaternary history of monsoonal western equatorial Africa. The results most of all corroborate the significance and applicability of tropical (African) alluvial sediment archives for palaeoenvironmental research and evidence that next to (neo-)tectonic impulses, climate may have played the mayor determining role in landscape and catchment dynamics and evolution
Spatio-temporal evolution of the West African monsoon during the last deglaciation
On the basis of a multi-proxy data set from the Gulf of Guinea (eastern equatorial Atlantic) we reconstruct the spatio-temporal evolution of the West African monsoon (WAM) and present evidence for a decoupling between latitudinal shifts of the rain belt and WAM intensification. The onset of deglacial monsoon invigoration at âŒ16,600 years before present lagged northward migration of a weak rainfall zone by âŒ2800 years. Conversely, during the Younger Dryas (YD) time interval, WAM precipitation was severely reduced but we find no evidence for a large-scale retreat of the rainfall front. This observation is not in agreement with the hypothesis of a large-scale shift of the intertropical convergence zone south of the tropical WAM region during the YD. Our results can be better reconciled with the newly emerging concept of a strong influence of Tropical Easterly and African Easterly Jets on modern WAM
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Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification.
Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics. Here, we describe the application of a structure-guided fragment-based drug discovery approach to the design of a new class of inhibitors against TrmD in Mycobacterium abscessus. Fragment library screening, followed by structure-guided chemical elaboration of hits, led to the rapid development of drug-like molecules with potent in vitro TrmD inhibitory activity. Several of these compounds exhibit activity against planktonic M. abscessus and M. tuberculosis as well as against intracellular M. abscessus and M. leprae, indicating their potential as the basis for a novel class of broad-spectrum mycobacterial drugs
Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2-Positive Esophageal Adenocarcinoma:TRAP Study
PURPOSE: Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC. PATIENTS AND METHODS: Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as â„ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses. RESULTS: Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively. CONCLUSION: Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively
Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer:The Randomized Controlled CROSS Trial
PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years
The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine
AbstractThe Caenorhabditis elegans elt-2 gene encodes a single-finger GATA factor, previously cloned by virtue of its binding to a tandem pair of GATA sites that control the gut-specific ges-1 esterase gene. In the present paper, we show that elt-2 expression is completely gut specific, beginning when the embryonic gut has only two cells (one cell cycle prior to ges-1 expression) and continuing in every cell of the gut throughout the life of the worm. When elt-2 is expressed ectopically using a transgenic heat-shock construct, the endogenous ges-1 gene is now expressed in most if not all cells of the embryo; several other gut markers (including a transgenic elt-2-promoter: lacZ reporter construct designed to test for elt-2 autoregulation) are also expressed ectopically in the same experiment. These effects are specific in that two other C. elegans GATA factors (elt-1 and elt-3) do not cause ectopic gut gene expression. An imprecise transposon excision was identified that removes the entire elt-2 coding region. Homozygous elt-2 null mutants die at the L1 larval stage with an apparent malformation or degeneration of gut cells. Although the loss of elt-2 function has major consequences for later gut morphogenesis and function, mutant embryos still express ges-1. We suggest that elt-2 is part of a redundant network of genes that controls embryonic gut development; other factors may be able to compensate for elt-2 loss in the earlier stages of gut development but not in later stages. We discuss whether elements of this regulatory network may be conserved in all metazoa
European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)
Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with †3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI †2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.</p
European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)
Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with †3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI †2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.</p