Search

Purpose: Anastomotic leakage (AL) continues to be a challenge after restorative rectal resection (RRR). Various treatment options of AL are available; however, their long-term outcomes are uncertain. We explored the impact of AL on the risk of stoma presence 1 year after RRR for rectal cancer and described treatment of AL after RRR including impact on the probability of receiving adjuvant chemotherapy and stoma presence following different treatment options of AL. Methods: We included 859 patients undergoing RRR in Central Denmark Region between 2013 and 2019. Stoma presence was calculated as the proportion of patients with stoma 1 year after RRR. Multivariable logistic regression was conducted to estimate the impact of AL on stoma presence adjusting for potential predictors. Descriptive data of outcomes were stratified for various treatment options of AL. Results: The risk of stoma presence 1 year after surgery was 9.8% (95% CI 7.98–12.0). Predictors for having stoma 1 year after RRR were AL (OR 8.43 (95% CI 4.87–14.59)) and low tumour height (OR 3.85 (95% CI 1.22–13.21)). For patients eligible for adjuvant chemotherapy, the probability of receiving it was 42.9% (95% CI 21.8–66.0) if treated with endo-SPONGE and 71.4% (95% CI 47.8–88.7) if treated with other anastomosis preserving treatment options. The risk of having stoma 1 year after RRR was 33.9% (95% CI 21.8–47.8) for patients treated with endo-SPONGE and 13.5% (95% CI 5.6–25.8) for patients treated with other anastomosis preserving treatment options (p = 0.013). Conclusion: AL is a strong predictor for stoma presence 1 year after RRR. Patients treated with endo-SPONGE seem to have worse outcomes compared to other anastomosis preserving treatment options. [ABSTRACT FROM AUTHOR]

Purpose: Anastomotic leakage (AL) after colorectal resection is a serious postoperative complication with grave consequences for patients. Despite several efforts to reduce its incidence, AL is still seen among 2–20% of colorectal cancer patients receiving an anastomosis. The use of tissue adhesives and sealants as an extra layer of protection around the anastomosis has shown promising results. We conducted a scoping review to provide an overview of the current knowledge on the effect of tissue adhesives and sealants on colorectal anastomosis healing, as well as their effect on the postoperative outcome. Methods: The databases of PubMed, Embase, and Cochrane Library were systematically searched on 14/10/2022. Studies addressing the use of a tissue adhesive or tissue sealant applied around a colorectal anastomosis, with the goal to prevent AL or to decrease AL-related complications, were included. We presented an overview of the available studies and summarized their results narratively. Results: Seven studies were included out of the 846 screened. All authors reported the rate of AL in their interventions group. Five of the studies found a decreased rate of AL compared to the control group. One study had no incidences of AL, while the last study had a seemingly low rate of AL but no comparison group. Information on secondary outcomes was sparingly reported, but the results hinted at a positive effect. Conclusion: Tissue adhesives and sealants might have a beneficial effect on colorectal anastomosis healing. The literature is sparse, and this review has shown the need for further clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the anastomotic leakage (AL) rate and predictors for AL following minimally invasive restorative rectal resection (RRR) among rectal cancer patients managed according to up-to-date standardized treatment. Furthermore, we explored the impact of symptomatic AL on long-term survival.The study cohort was rectal cancer patients undergoing minimally invasive RRR in Central Denmark Region between 2013 and 2017. Data was retrieved from a prospective clinical quality database and supplemented with data from medical records. The AL rate was calculated as the proportion of patients who developed symptomatic AL within 30 days. Predictors for AL were identified through logistic regression. The impact of AL on long-term survival was analyzed using Kaplan–Meier methods and Cox regression.AL occurred in 15.1% of 604 patients. The AL rate for males was 20.1% (95% CI 16.3–24.3) and 5.0% (95% CI 2.4–9.0) for females. Odds ratio (OR) of AL in females vs. males was 0.25 (95% CI 0.12–0.51). The use of at least three firings when transecting the rectum was associated with OR of 2.71 (95% CI 1.17–6.26) for AL. The 5-year survival for patients with vs. those without AL was 76.1% (95%CI 65.1–84.0) and 83.6% (95%CI 79.8–86.7), corresponding to adjusted hazard ratio of 1.43 (95%CI 0.84–2.41).Symptomatic AL is still a challenge in a standardized setting using minimally invasive surgery in rectal cancer patients undergoing RRR, especially in men. Multiple firings should be avoided in transection of the rectum with an endoscopic stapler. AL had a statistical non-significant negative impact on survival.Methods: The aim of this study was to evaluate the anastomotic leakage (AL) rate and predictors for AL following minimally invasive restorative rectal resection (RRR) among rectal cancer patients managed according to up-to-date standardized treatment. Furthermore, we explored the impact of symptomatic AL on long-term survival.The study cohort was rectal cancer patients undergoing minimally invasive RRR in Central Denmark Region between 2013 and 2017. Data was retrieved from a prospective clinical quality database and supplemented with data from medical records. The AL rate was calculated as the proportion of patients who developed symptomatic AL within 30 days. Predictors for AL were identified through logistic regression. The impact of AL on long-term survival was analyzed using Kaplan–Meier methods and Cox regression.AL occurred in 15.1% of 604 patients. The AL rate for males was 20.1% (95% CI 16.3–24.3) and 5.0% (95% CI 2.4–9.0) for females. Odds ratio (OR) of AL in females vs. males was 0.25 (95% CI 0.12–0.51). The use of at least three firings when transecting the rectum was associated with OR of 2.71 (95% CI 1.17–6.26) for AL. The 5-year survival for patients with vs. those without AL was 76.1% (95%CI 65.1–84.0) and 83.6% (95%CI 79.8–86.7), corresponding to adjusted hazard ratio of 1.43 (95%CI 0.84–2.41).Symptomatic AL is still a challenge in a standardized setting using minimally invasive surgery in rectal cancer patients undergoing RRR, especially in men. Multiple firings should be avoided in transection of the rectum with an endoscopic stapler. AL had a statistical non-significant negative impact on survival.Results: The aim of this study was to evaluate the anastomotic leakage (AL) rate and predictors for AL following minimally invasive restorative rectal resection (RRR) among rectal cancer patients managed according to up-to-date standardized treatment. Furthermore, we explored the impact of symptomatic AL on long-term survival.The study cohort was rectal cancer patients undergoing minimally invasive RRR in Central Denmark Region between 2013 and 2017. Data was retrieved from a prospective clinical quality database and supplemented with data from medical records. The AL rate was calculated as the proportion of patients who developed symptomatic AL within 30 days. Predictors for AL were identified through logistic regression. The impact of AL on long-term survival was analyzed using Kaplan–Meier methods and Cox regression.AL occurred in 15.1% of 604 patients. The AL rate for males was 20.1% (95% CI 16.3–24.3) and 5.0% (95% CI 2.4–9.0) for females. Odds ratio (OR) of AL in females vs. males was 0.25 (95% CI 0.12–0.51). The use of at least three firings when transecting the rectum was associated with OR of 2.71 (95% CI 1.17–6.26) for AL. The 5-year survival for patients with vs. those without AL was 76.1% (95%CI 65.1–84.0) and 83.6% (95%CI 79.8–86.7), corresponding to adjusted hazard ratio of 1.43 (95%CI 0.84–2.41).Symptomatic AL is still a challenge in a standardized setting using minimally invasive surgery in rectal cancer patients undergoing RRR, especially in men. Multiple firings should be avoided in transection of the rectum with an endoscopic stapler. AL had a statistical non-significant negative impact on survival.Conclusion: The aim of this study was to evaluate the anastomotic leakage (AL) rate and predictors for AL following minimally invasive restorative rectal resection (RRR) among rectal cancer patients managed according to up-to-date standardized treatment. Furthermore, we explored the impact of symptomatic AL on long-term survival.The study cohort was rectal cancer patients undergoing minimally invasive RRR in Central Denmark Region between 2013 and 2017. Data was retrieved from a prospective clinical quality database and supplemented with data from medical records. The AL rate was calculated as the proportion of patients who developed symptomatic AL within 30 days. Predictors for AL were identified through logistic regression. The impact of AL on long-term survival was analyzed using Kaplan–Meier methods and Cox regression.AL occurred in 15.1% of 604 patients. The AL rate for males was 20.1% (95% CI 16.3–24.3) and 5.0% (95% CI 2.4–9.0) for females. Odds ratio (OR) of AL in females vs. males was 0.25 (95% CI 0.12–0.51). The use of at least three firings when transecting the rectum was associated with OR of 2.71 (95% CI 1.17–6.26) for AL. The 5-year survival for patients with vs. those without AL was 76.1% (95%CI 65.1–84.0) and 83.6% (95%CI 79.8–86.7), corresponding to adjusted hazard ratio of 1.43 (95%CI 0.84–2.41).Symptomatic AL is still a challenge in a standardized setting using minimally invasive surgery in rectal cancer patients undergoing RRR, especially in men. Multiple firings should be avoided in transection of the rectum with an endoscopic stapler. AL had a statistical non-significant negative impact on survival. [ABSTRACT FROM AUTHOR]

The burst firing of midbrain dopamine neurons releases a phasic dopamine signal that mediates reinforcement learning. At many synapses, however, high firing rates deplete synaptic vesicles (SVs), resulting in synaptic depression that limits release. What accounts for the increased release of dopamine by stimulation at high frequency? We find that adaptor protein-3 (AP-3) and its coat protein VPS41 promote axonal dopamine release by targeting vesicular monoamine transporter VMAT2 to the axon rather than dendrites. AP-3 and VPS41 also produce SVs that respond preferentially to high-frequency stimulation, independent of their role in axonal polarity. In addition, conditional inactivation of VPS41 in dopamine neurons impairs reinforcement learning, and this involves a defect in the frequency dependence of release rather than the amount of dopamine released. Thus, AP-3 and VPS41 promote the axonal polarity of dopamine release but enable learning by producing a distinct population of SVs tuned specifically to high firing frequency that confers the phasic release of dopamine. [ABSTRACT FROM AUTHOR]

The solute carrier 17 family transports diverse organic anions using two distinct modes of coupling to a source of energy. Transporters that package glutamate and nucleotide into secretory vesicles for regulated release by exocytosis are driven by membrane potential but subject to allosteric regulation by H+ and Cl-. Other solute carrier 17 members including the lysosomal sialic acid exporter couple the flux of organic anion to cotransport of H+. To begin to understand how similar proteins can perform such different functions, we have studied Escherichia coli DgoT, a H+/galactonate cotransporter. A recent structure of DgoT showed many residues contacting D-galactonate, and we now find that they do not tolerate even conservative substitutions. In contrast, the closely related lysosomal H+/sialic acid cotransporter Sialin tolerates similar mutations, consistent with its recognition of diverse substrates with relatively low affinity. We also find that despite coupling to H+, DgoT transports more rapidly but with lower apparent affinity at high pH. Indeed, membrane potential can drive uptake, indicating electrogenic transport and suggesting a H+:galactonate stoichiometry >1. Located in a polar pocket of the N-terminal helical bundle, Asp46 and Glu133 are each required for net flux by DgoT, but the E133Q mutant exhibits robust exchange activity and rescues exchange by D46N, suggesting that these two residues operate in series to translocate protons. E133Q also shifts the pH sensitivity of exchange by DgoT, supporting a central role for the highly conserved TM4 glutamate in H+ coupling by DgoT. [ABSTRACT FROM AUTHOR]