The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Pharmacological GSK-3beta inhibition improves osteoblast differentiation on titanium surfaces.

Rough titanium surfaces enhance the activation of Wnt canonical signaling, a pathway required for osteoblast differentiation. The present study investigated the effects of GSK3b-inhibitor (2’Z,3’E)- hydrophilic SLA titanium discs (modSLA) and stimulated with increasing doses of BIO. Activation of same cell system by Real Time PCR. Osteoblastic MC3T3 cells were then plated on discs with or without activated Wnt canonical signaling in C2C12 cells on all surfaces, and the highest effect was on rough rough surfaces at the concentration of 100 nM, and on all surfaces at the concentration of 1 mM. BIO be a viable approach to improve cell response to implant surfaces

Spontaneous in-the-bag intraocular lens luxation into the vitreous cavity: last-stage complication of pseudoexfoliative syndrome after phacoemulsification. Ophthalmologica

PURPOSE: We describe 8 cases of late spontaneous in-the-bag intraocular lens (IOL) luxation into the vitreous cavity, which occurred at the Department of Ophthalmology and Neurosurgery of the University of Siena between January and December 2006. METHODS: In this interventional case series, the medical records of all patients with posterior luxation of in-the-bag IOLs - who had undergone a pars plana vitrectomy with IOL removal and scleral fixation IOL implantation between January and December 2007 at the Department of Ophthalmology and Neurosurgery of Siena, Italy - were retrospectively reviewed. RESULTS: The final post- operative visual acuity was 20/30 or better in 6 patients, while myopic macular degeneration and total retinal detachment limited visual acuity in the remaining 2 patients. CONCLUSION: The high prevalence of pseudoexfoliation (PEX) in the patients who had been operated for cataract phacoemulsification in our department could explain the occurrence of 8 posterior luxations of in-the-bag IOLs in only 1 year. Our study suggests that for the next years we will expect an increase in occurrence of spontaneous in-the- bag IOL luxations in the vitreous cavity. This condition could represent the last stage of PEX syndrome

RhoA Controls Wnt Upregulation on Microstructured Titanium Surfaces.

Rough topography enhances the activation of Wnt canonical signaling in vitro, and this mediates its effects on cell differentiation. However, the molecular mechanisms underlying topography-dependent control of Wnt signaling are still poorly understood. As the small GTPase RhoA controls cytoskeletal reorganization and actomyosin-induced tensional forces, we hypothesized that RhoA could affect the activation of Wnt signaling in cells on micropatterned titanium surfaces. G-LISA assay revealed that RhoA activation was higher in C2C12 cells on rough (SLA) surfaces under basal conditions than on smooth (Polished) titanium. Transfection with dominant negative RhoA decreased Wnt activation by normalized TCF-Luc activity on SLA, whilst transfection with constitutively active RhoA increased TCF-Luc activation on Polished titanium. One mM Myosin II inhibitor Blebbistatin increased RhoA activation but decreased Wnt activation on SLA surfaces, indicating that tension-generating structures are required for canonical Wnt modulation on titanium surfaces. Actin inhibitor Cytochalasin markedly enhanced RhoA and TCF-Luc activation on both surfaces and increased the expression of differentiation markers in murine osteoblastic MC3T3 cells. Taken together, these data show that RhoA is upregulated in cells on rough surfaces and it affects the activation of Wnt canonical signaling through Myosin II modulation