Time interval between self-expandable metal stent placement or creation of a decompressing stoma and elective resection of left-sided obstructive colon cancer

Background The optimal timing of resection after decompression of left-sided obstructive colon cancer is unknown. Revised expert-based guideline recommendations have shifted from an interval of 5-10 days to approximately 2 weeks following self-expandable metal stent (SEMS) placement, and recommendations after decompressing stoma are lacking. We aimed to evaluate the recommended bridging intervals after SEMS and explore the timing of resection after decompressing stoma.Methods This nationwide study included patients registered between 2009 and 2016 in the prospective, mandatory Dutch ColoRectal Audit. Additional data were collected through patient records in 75 hospitals. Only patients who underwent either SEMS placement or decompressing stoma as a bridge to surgery were selected. Technical SEMS failure and unsuccessful decompression within 48 hours were exclusion criteria.Results 510 patients were included (182 SEMS, 328 decompressing stoma). Median bridging interval was 23 days (interquartile range [IQR] 13-31) for SEMS and 36 days (IQR 22-65) for decompressing stoma. Following SEMS placement, no significant differences in post-resection complications, hospital stay, or laparoscopic resections were observed with resection after 11-17 days compared with 5-10 days. Of SEMS-related complications, 48% occurred in patients operated on beyond 17 days. Compared with resection within 14 days, an interval of 14-28 days following decompressing stoma resulted in significantly more laparoscopic resections, more primary anastomoses, and shorter hospital stays. No impact of bridging interval on mortality, disease-free survival, or overall survival was demonstrated.Conclusions Based on an overview of the data with balancing of surgical outcomes and timing of adverse events, a bridging interval of approximately 2 weeks seems appropriate after SEMS placement, while waiting 2-4 weeks after decompressing stoma further optimizes surgical conditions for laparoscopic resection with restoration of bowel continuity.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Engrailed 1 shapes the dopaminergic and serotonergic landscape through proper isthmic organizer maintenance and function

The isthmic organizer (IsO) is a signaling center that specifies the correct and distinct embryonic development of the dopaminergic midbrain and serotonergic hindbrain. The IsO is a linear boundary between the two brain regions, emerging at around embryonic day 7-8 of murine embryonic development, that shapes its surroundings through the expression of instructive signals such as Wnt and growth factors. Homeobox transcription factor engrailed 1 (En1) is present in midbrain and rostral hindbrain (i.e. rhombomere 1, R1). Its expression spans the IsO, and it is known to be an important survival factor for both dopaminergic and serotonergic neurons. Erroneous composition of dopaminergic neurons in the midbrain or serotonergic neurons in the hindbrain is associated with severe pathologies such as Parkinson's disease, depression or autism. Here we investigated the role of En1 in early mid-hindbrain development, using multiple En1-ablated mouse models as well as lineage-tracing techniques, and observed the appearance of ectopic dopaminergic neurons, indistinguishable from midbrain dopaminergic neurons based on molecular profile and intrinsic electrophysiological properties. We propose that this change is the direct result of a caudal relocation of the IsO as represented by ectopic presence of Fgf8, Otx2, Wnt1 and canonical Wnt-signalling. Our work suggests a newly-discovered role for En1: the repression of Otx2, Wnt1 and canonical Wnt-signaling in R1. Overall, our results suggest that En1 is essential for proper IsO maintenance and function

Tectonism and Its Relation to Magmatism Around Santorini Volcano From Upper Crustal P Wave Velocity

At extensional volcanic arcs, faulting often acts to localize magmatism. Santorini is located on the extended continental crust of the Aegean microplate and is one of the most active volcanoes of the Hellenic arc, but the relationship between tectonism and magmatism remains poorly constrained. As part of the Plumbing Reservoirs Of The Earth Under Santorini experiment, seismic data were acquired across the Santorini caldera and the surrounding region using a dense amphibious array of >14,300 marine sound sources and 156 short-period seismometers, covering an area 120 km by 45 km. Here a P wave velocity model of the shallow, upper-crustal structure (<3-km depth), obtained using travel time tomography, is used to delineate fault zones, sedimentary basins, and tectono-magmatic lineaments. Our interpretation of tectonic boundaries and regional faults are consistent with prior geophysical studies, including the location of basin margins and E-W oriented basement faults within the Christiana Basin west of Santorini. Reduced seismic velocities within the basement east of Santorini, near the Anydros and Anafi Basins, are coincident with a region of extensive NE-SW faulting and active seismicity. The structural differences between the eastern and western sides of Santorini are in agreement with previously proposed models of regional tectonic evolution. Additionally, we find that regional magmatism has been localized in NE-SW trending basin-like structures that connect the Christiana, Santorini, and Kolumbo volcanic centers. At Santorini itself, we find that magmatism has been localized along NE-SW trending lineaments that are subparallel to dikes, active faults, and regional volcanic chains. These results show strong interaction between magmatism and active deformation. ©2019. American Geophysical Union. All Rights Reserved

Corrigendum to “Seismic imaging of Santorini: Subsurface constraints on caldera collapse and present-day magma recharge” [Earth Planet. Sci. Lett. 514 (2019) 48–61](S0012821X19301360)(10.1016/j.epsl.2019.02.033)

The authors regret errors in the last two paragraphs of Section 6.3 (p. 57), these should read as follows: 6.3 Multistage, nested caldera collapse: In this scenario, the seismic and geological results from Santorini provide observational evidence for models of multistage, nested caldera formation during progressive caldera subsidence (Acocella, 2006). During stage A, the inner collapse column would be formed along outward-dipping reverse faults with breakup of the roof rock (Fig. 6f). During stage B, a new outer ring of collapse would cause subsidence of the entire topographic caldera and the opening of new vents during phase 4 (Fig. 6c). Accordingly, the geologically distinctive LBA eruptive phases form as a direct result of geological processes occurring during each stage of caldera formation (Fig. 6). It is quite possible that all three of the above scenarios (Fig. 6d-f) play a role in generating the inner cylinder of high porosities at Santorini. Thus, rock breakup by reverse faulting during inner caldera collapse may be accompanied by, or even promoted by, fracturing and reaming of the volcanic vent during violent magma-water interactions. In addition, the upper portions of the high-porosity cylinder are probably formed by the deposition of eruptive volcanic products including tuffs, pyroclasts, and ignimbrites. © 2019 Elsevier B.V

Magma accumulation beneath Santorini volcano, Greece, from P-wave tomography

Despite multidisciplinary evidence for crustal magma accumulation below Santorini volcano, Greece, the structure and melt content of the shallow magmatic system remain poorly constrained. We use three-dimensional (3-D) velocity models from tomographic inversions of active-source seismic P-wave travel times to identify a pronounced low-velocity anomaly (-21%) from 2.8 km to 5 km depth localized below the northern caldera basin. This anomaly is consistent with depth estimates of pre-eruptive storage and a recent inflation episode, supporting the interpretation of a shallow magma body that causes seismic attenuation and ray bending. A suite of synthetic tests shows that the geometry is well recovered while a range of melt contents (4%-13% to fully molten) are allowable. A thin mush region (2%-7% to 3%-10% melt) extends from the main magma body toward the northeast, observed as low velocities confined by tectono-magmatic lineaments. This anomaly terminates northwest of Kolumbo; little to no melt underlies the seamount from 3 to 5 km depth. These structural constraints suggest that crustal extension and edifice loads control the geometry of magma accumulation and emphasize that the shallow crust remains conducive to melt storage shortly after a caldera-forming eruption. © 2019 Geological Society of America. For permission to copy

Comparison of Decompressing Stoma vs Stent as a Bridge to Surgery for Left-Sided Obstructive Colon Cancer

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Risk factors for a permanent stoma after resection of left-sided obstructive colon cancer - A prediction model.

INTRODUCTION: In patients with left-sided obstructive colon cancer (LSOCC), a stoma is often constructed as part of primary treatment, but with a considerable risk of becoming a permanent stoma (PS). The aim of this retrospective multicentre cohort is to identify risk factors for a PS in LSOCC and to develop a pre- and postoperative prediction model for PS. MATERIALS AND METHODS: Data was retrospectively obtained from 75 hospitals in the Netherlands. Patients who had curative resection of LSOCC between January 1, 2009 to December 31, 2016 were included with a minimum follow-up of 6 months after resection. The interventions analysed were emergency resection, decompressing stoma or stent as bridge-to-elective resection. Main outcome measure was presence of PS at the end of follow-up. Multivariable logistic regression analysis was performed to identify risk factors for PS at primary presentation (T(0)) and after resection, in patients having a stoma in situ (T(1)). These risk factors were used to construct a web-based prediction tool. RESULTS: Of 2099 patients included in the study (T(0)), 779 had a PS (37%). A total of 1275 patients had a stoma in situ directly after resection (T(1)), of whom 674 had a PS (53%). Median follow-up was 34 months. Multivariable analysis showed that older patients, female sex, high ASA-score and open approach were independent predictors for PS in both the T(0) and T(1) population. Other predictors at T(0) were sigmoid location, low Hb, high CRP, cM1 stage, and emergency resection. At T(1), subtotal colectomy, no primary anastomosis, not receiving adjuvant chemotherapy and high pTNM stage were additional predictors. Two predictive models were built, with an AUC of 0.74 for T(0) and an AUC of 0.81 for T(1). CONCLUSIONS: PS is seen in 37% of the patients who have resection of LSOCC. In patients with a stoma in situ directly after resection, 53% PS are seen due to non-reversal. Not only baseline characteristics, but also treatment strategies determine the risk of a PS in patients with LSOCC. The developed predictive models will give physicians insight in the role of the individual variables on the risk of a PS and help in informing the patient about the probability of a PS