Reduction of peritoneal trauma by using nonsurgical gauze leads to less implantation metastasis of spilled tumor cells

OBJECTIVES: To evaluate whether infliction of peritoneal trauma would promote tumor cell adherence to damaged peritoneal surfaces; to investigate whether peritoneal damage could promote tumor growth of extraperitoneal tumors; and to evaluate whether the amount of trauma correlated with the degree of tumor cell adherence and local and distant tumor growth. BACKGROUND DATA: After potentially curative resection of colorectal carcinoma, the most common site for recurrence is locoregional. We previously demonstrated that surgical trauma induces a cascade of events leading to adhesion formation. The same mechanisms may be responsible for improved tumor cell adherence and growth facilitation in early local recurrence. METHODS: A reproducible rat model was used in which peritoneal damage was inflicted by standardized rubbing of the peritoneum with surgical gauzes of different texture. In the first experiment, tumor cell adherence and growth at traumatized and nontraumatized peritoneal sites were assessed semiquantitatively 3 weeks after perioperative intra-abdominal injection of CC-531 tumor cells. In the second experiment, the effect of peritoneal trauma on ectopic tumor growth was investigated (CC-531 implanted under the renal capsule). In the final experiment, we evaluated how soon after peritoneal traumatization tumor cell adhesion and growth-promoting factors were active and whether they could be passively transferred to naive nontraumatized abdominal cavities. RESULTS: A significant correlation between the amount of peritoneal trauma and the degree of tumor take at damaged peritoneal surfaces was found (p < or = 0.018). Tumor take at remote peritoneal sites not directly traumatized was also significantly higher after severe trauma than after moderate trauma of the peritoneum (p < or = 0.005). In addition, a significant correlation between the degree of peritoneal trauma and the growth of ectopic tumors under the renal capsule was observed (p < or = 0.009). The final experiment demonstrated that within a few hours after infliction of peritoneal trauma, tumor growth-promoting effects could be passively transferred to naive recipients. CONCLUSIONS: Surgical trauma is an important factor in the promotion of local recurrence. The enhancing effect of trauma is not restricted to the inflicted site but rather has a generalized character. Avoidance of unnecessary surgical trauma by using gentle techniques and materials is therefore indicated

Pectoral fascia preservation in oncological mastectomy to reduce complications and improve reconstructions: a systematic review

Excision of the pectoral fascia (PF) is routinely performed in oncological mastectomies. Preservation of the PF may, however, decrease postoperative complication rates for bleeding, infections, and seroma. It may also improve reconstructive outcomes by better prosthesis coverage, thereby reducing implant extrusion rates and improving cosmetic outcomes.Methods: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis principles was performed. Studies describing PF preservation were searched in 3 databases. All studies including more than 10 patients were included. The main outcomes were oncological safety (local recurrence, regional and distant metastases, and mortality rates), complication rates (bleeding, infections, seroma), loss of the prosthesis after reconstructive surgery, and cosmetic outcomes following reconstruction.Results: Five studies were included. Three reported on 2 different randomized controlled trials (n = 73, and n = 244), and 2 studies were retrospective case series (n = 203 and n = 256). PF preservation did not affect oncological outcomes in terms of local recurrences, regional and distant metastases, or mortality rates. One study described a significantly lower incidence of seroma in the PF preservation group. No differences were found for bleeding complications and infections. No objective data were provided for reconstructive complications or cosmetic outcomes.Conclusions: The literature on PF preservation is scarce. Based on the current evidence, PF preservation seems oncologically safe while potentially reducing postoperative complication rates. It is expected that reconstructive outcomes will benefit from PF preservation, but these studies lack evidence on this topic. Future studies should provide insight into all aspects of PF preservation.</p

Hospital variation in combined liver resection and thermal ablation for colorectal liver metastases and impact on short-term postoperative outcomes: a nationwide population-based study

Background: Combining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation.Methods: In this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery.Results: Of 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy.Conclusion: Significant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017