Early and Late Results Following Choledochoduodenostomy and Choledochojejunostomy

Objective —To evaluate the results and complications of choledochoduodenostomy and choledochojejunostomy for benign and malignant disease and to review them in the light of the survival of the underlying disorders

Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years

Background: The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation.Methods: An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention.Results: The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5.5years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0.61, 95 per cent c. i. 0.42 to 089; P = 0010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 040, 95 per cent c. i. 022 to 074). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 516, 149 to 1789; P = 0010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0022) in the period from 6 months to 4 years after randomization.Conclusion: The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM(Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anevrysme de l'aorte abdominale, Chirurgie versus Endoprothsse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.</p

The Effects of Long-Term Graft Preservation on Intraoperative Hemostatic Changes in Liver Transplantation:A Comparison Between Orthotopic and Heterotopic Transplantation in the Pig

We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. Material and Methods: 69 pigs underwent either OLT (N = 32) or HLT (N = 37) with a graft stored for 2 hr (N = 31), 24 hr (N = 16), 48 hr (N = 7), or 72 hr (N = 15). PGE1 was given intravenously to both donor and recipient animals and was added to the preservation and flushing solutions. Fibrinolysis (euglobulin clot lysis time, t-PA activity and α2-antiplasmin) and coagulation parameters (activated partial thromboplasmin time, prothrombin time, fibrinogen and platelet count) were measured at several intervals during transplantation. Statistics: Univariate non-parametric tests were used for analysis of coagulation and fibrinolysis parameters. For the three main variables- i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. Results: Fibrinolytic activity increased during the anhepatic period of OLT. Graft reperfusion was followed by a rise in t-PA in both OLT and HLT. In HLT, t-PA quickly returned to normal, whereas a continuous increase was found in OLT. The coagulation parameters, in turn, remained unchanged during the anhepatic period and deteriorated in OLT compared to HLT. The duration of graft storage was directly related to the severity of the hemostatic changes, although this effect was more apparent in OLT than in HLT. Conclusions: Changes in hemostasis are more pronounced in OLT than in HLT. This suggests that the host liver protects the recipient from the effects of graft storage damage, even after long preservation times. Early postreperfusion fibrinolytic activity was presumably due to t-PA release from the graft both in OLT and HLT. The further rise t-PA in OLT might be caused by the release of cytokines from the graft, that subsequently evoke endothelial t-PA release. In HLT, t-PA and cytokines may be cleared by the native liver. No positive or negative effect of PGE1 on coagulation or fibrinolysis parameters was noticed.\</p

The Effects of Long-Term Graft Preservation on Intraoperative Hemostatic Changes in Liver Transplantation:A Comparison Between Orthotopic and Heterotopic Transplantation in the Pig

We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. Material and Methods: 69 pigs underwent either OLT (N = 32) or HLT (N = 37) with a graft stored for 2 hr (N = 31), 24 hr (N = 16), 48 hr (N = 7), or 72 hr (N = 15). PGE1 was given intravenously to both donor and recipient animals and was added to the preservation and flushing solutions. Fibrinolysis (euglobulin clot lysis time, t-PA activity and α2-antiplasmin) and coagulation parameters (activated partial thromboplasmin time, prothrombin time, fibrinogen and platelet count) were measured at several intervals during transplantation. Statistics: Univariate non-parametric tests were used for analysis of coagulation and fibrinolysis parameters. For the three main variables- i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. Results: Fibrinolytic activity increased during the anhepatic period of OLT. Graft reperfusion was followed by a rise in t-PA in both OLT and HLT. In HLT, t-PA quickly returned to normal, whereas a continuous increase was found in OLT. The coagulation parameters, in turn, remained unchanged during the anhepatic period and deteriorated in OLT compared to HLT. The duration of graft storage was directly related to the severity of the hemostatic changes, although this effect was more apparent in OLT than in HLT. Conclusions: Changes in hemostasis are more pronounced in OLT than in HLT. This suggests that the host liver protects the recipient from the effects of graft storage damage, even after long preservation times. Early postreperfusion fibrinolytic activity was presumably due to t-PA release from the graft both in OLT and HLT. The further rise t-PA in OLT might be caused by the release of cytokines from the graft, that subsequently evoke endothelial t-PA release. In HLT, t-PA and cytokines may be cleared by the native liver. No positive or negative effect of PGE1 on coagulation or fibrinolysis parameters was noticed.\</p

The Effects of Long-Term Graft Preservation on Intraoperative Hemostatic Changes in Liver Transplantation

We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied

Results from a nationwide prospective registry on open surgical or endovascular repair of juxtarenal abdominal aortic aneurysms

Background: Juxtarenal abdominal aortic aneurysms (JRAAAs) can be treated either with open surgical repair (OSR) including suprarenal clamping or by complex endovascular aneurysm repair (cEVAR). In this study, we present the comparison between the short-term mortality and complications of the elective JRAAA treatment modalities from a national database reflecting daily practice in the Netherlands. Methods: All patients undergoing elective JRAAA open repair or cEVAR (fenestrated EVAR or chimney EVAR) between January 2016 and December 2018 registered in the Dutch Surgical Aneurysm Audit (DSAA) were eligible for inclusion. Descriptive perioperative variables and outcomes were compared between patients treated with open surgery or endovascularly. Adjusted odds ratios for short-term outcomes were calculated by logistic regression analysis. Results: In all, 455 primary treated patients with JRAAAs could be included (258 OSR, 197 cEVAR). Younger patients and female patients were treated more often with OSR vs cEVAR (72 ± 6.1 vs 76 ± 6.0; P < .001 and 22% vs 15%; P = .047, respectively). Patients treated with OSR had significantly more major and minor complications as well as a higher chance of early mortality (OSR vs cEVAR, 45% vs 21%; P < .001; 34% vs 23%; P = .011; and 6.6% vs 2.5%; P = .046, respectively). After logistic regression with adjustment for confounders, patients who were treated with OSR showed an odds ratio of 3.64 (95% confidence interval [CI], 2.25-5.89; P < .001) for major complications compared with patients treated with cEVAR, and for minor complications, the odds ratios were 2.17 (95% CI, 1.34-3.53; P = .002) higher. For early mortality, the odds ratios were 3.79 (95% CI, 1.26-11.34; P = .017) higher after OSR compared with cEVAR. Conclusions: In this study, after primary elective OSR for JRAAA, the odds for major complications, minor complications, and short-term mortality were significantly higher compared with cEVAR

Genomic DNA Pooling Strategy for Next-Generation Sequencing-Based Rare Variant Discovery in Abdominal Aortic Aneurysm Regions of Interest—Challenges and Limitations

The costs and efforts for sample preparation of hundreds of individuals, their genomic enrichment for regions of interest, and sufficient deep sequencing bring a significant burden to next-generation sequencing-based experiments. We investigated whether pooling of samples at the level of genomic DNA would be a more versatile strategy for lowering the costs and efforts for common disease-associated rare variant detection in candidate genes or associated loci in a substantial patient cohort. We performed a pilot experiment using five pools of 20 abdominal aortic aneurysm (AAA) patients that were enriched on separate microarrays for the reported 9p21.3 associated locus and 42 additional AAA candidate genes, and sequenced on the SOLiD platform. Here, we discuss challenges and limitations connected to this approach and show that the high number of novel variants detected per pool and allele frequency deviations to the usually highly false positive cut-off region for variant detection in non-pooled samples can be limiting factors for successful variant prioritization and confirmation. We conclude that barcode indexing of individual samples before pooling followed by a multiplexed enrichment strategy should be preferred for detection of rare genetic variants in larger sample sets rather than a genomic DNA pooling strategy

Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome

\ua9 The Author(s) 2024.Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5’ untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.</p