Background Anastomotic leak (AL) is a major source of morbidity in colorectal surgery and has become an area of interest in performance metrics. It is unclear whether AL is associated primarily with surgeons’ technical performance or explained better by patient characteristics and institutional factors. We sought to establish if AL could serve as a valid quality metric in colorectal surgery by evaluating provider variation after adjusting for patient factors. Methods We performed a retrospective cohort study of colorectal resection patients in the Michigan Surgical Quality Collaborative. Clinically relevant patient and operative factors were tested for association with AL. Hierarchical logistic regression was used to derive risk-adjusted rates of AL. Results Of 9,192 colorectal resections, 244 (2.7%) had a documented AL. The incidence of AL was 3.0% for patients with pelvic anastomoses and 2.5% for those with intra-abdominal anastomoses. Multivariable analysis showed that a greater operative duration, male sex, body mass index > 30 kg/m2, tobacco use, chronic immunosuppressive medications, thrombocytosis (platelet count > 400×109/L), and urgent/emergent surgery were independently associated with AL (C-statistic = 0.75). After accounting for patient and procedural risk factors, there were five hospitals with a significantly greater incidence of postoperative AL. Conclusions This population-based study shows that risk factors for AL include male sex, obesity, tobacco use, immunosuppression, thrombocytosis, greater operative duration, and urgent/emergent surgery; models including these factors predict most of the variation in AL rates. This study suggests that AL can serve as a valid metric that can identify opportunities for quality improvement.

Surgeons valued palliative and end-of-life care but reported multilevel barriers to its provision. These data will inform strategies to reduce these perceived barriers.

Introduction Despite significant advances in vascular biology, bioengineering and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and/or molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. In this article we provide a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis following vascular intervention. Methods A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials and funded NIH awards. Results The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents (DES). Until recently, however, DES were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies with a recent surge in trials involving drug-eluting balloons. Early data appears encouraging, particularly for treatment of lesions in the superficial femoral artery, with several devices having recently received the CE mark in Europe. Investigators have also explored periadventitial application of biomaterials containing anti-restenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past systemic drug delivery has been unsuccessful, however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting strategies including more than 65 new patents issued over the past two years for approaches to local drug delivery focused on preventing restenosis. Conclusion Restenosis following intraluminal or open vascular reconstruction remains an important clinical problem. Success in the coronary circulation has not translated into solutions for the peripheral arteries. However, our review of the literature reveals a number of promising approaches including drug-eluting balloons, periadventitial drug delivery as well as targeted systemic therapies. These innovations as well as others suggest that the future is bright and a solution for preventing restenosis in peripheral vessels will soon be at hand.

Although phlegmasia cerulea dolens, May-Thurner syndrome, and nutcracker syndrome are rare entities, knowledge of these syndromes associated with the deep veins is essential. This study presents current management of these disorders, including diagnostic and interventional strategies. Endovascular techniques have evolved and now play a significant role in the treatment of both phlegmasia cerulea dolens and May-Thurner syndrome. However, endovascular therapy for nutcracker syndrome remains untested.

Despite novel surgical therapies for the treatment of atherosclerosis, restenosis continues to be a significant impediment to the long-term success of vascular interventions. Transforming growth factor-beta (TGF-β), a family of cytokines found to be up-regulated at sites of arterial injury, has long been implicated in restenosis; a role that has largely been attributed to TGF-β-mediated vascular fibrosis. However, emerging data indicate that the role of TGF-β in intimal thickening and arterial remodeling, the critical components of restenosis, is complex and multidirectional. Recent advancements have clarified the basic signaling pathway of TGF-β, making evident the need to redefine the precise role of this family of cytokines and its primary signaling pathway, Smad, in restenosis. Unraveling TGF-β signaling in intimal thickening and arterial remodeling will pave the way for a clearer understanding of restenosis and the development of innovative pharmacological therapies.

Introduction We have previously demonstrated that TGF-β in the presence of elevated levels of its primary signaling protein, Smad3, stimulates rat vascular smooth muscle cell (VSMC) proliferation and intimal hyperplasia. Moreover, we have shown that the mechanism in part, is through the nuclear exportation of phosphorylated cyclin-dependent kinase inhibitor p27. The objective of this study is to clarify the downstream pathways through which Smad3 produces its proliferative effect. Specifically, we evaluate the role of the ERK mitogen-activated protein kinase (ERK MAPK) in TGF-β-induced VSMC proliferation. Methods Cultured rat aortic VSMCs were incubated with TGF-β at varying concentrations and times, and phosphorylated ERK was measured by Western blotting. Smad3 was enhanced in VSMCs using an adenovirus expressing Smad3 or inhibited with ansiRNA. For in vivo experiments, Male Sprague-Dawley rats underwent carotid balloon injury followed by intraluminal infection with an adenovirus expressing Smad3. Arteries were harvested at 3 days and subjected to immunohistochemistry for Smad3, phospho-ERK MAPK and Proliferating Cell Nuclear Antigen (PCNA). Results In cultured VSMCs, TGF-β induced activation and phosphorylation of ERK MAPK in a time and concentration-dependent manner. Overexpression of the signaling protein, Smad3 enhanced TGF-β-induced activation of ERK MAPK whereas inhibition of Smad3 with ansiRNA blocked ERK MAPK phosphorylation in response to TGF-β. These data suggest that Smad3 acts as a signaling intermediate between TGF-β and ERK MAPK. Inhibition of ERK MAPK activation with PD98059 completely blocked the ability of TGF-β/Smad3 to stimulate VSMC proliferation, demonstrating the importance of ERK MAPK in this pathway. Immunoprecipitation of phospho-ERK MAPK and blotting with Smad3 revealed a physical association, suggesting that activation of ERK MAPK by Smad3 requires a direct interaction. In an in vivo rat carotid injury model, overexpression of Smad3 resulted in an increase in phosphorylated ERK MAPK as well as increased VSMC proliferation as measured by PCNA. Conclusion Our findings demonstrate a mechanism through which TGF-β stimulates VSMC proliferation. Although TGF-β has been traditionally identified as an inhibitor of proliferation, our data suggest that through a Smad3/ERK MAPK signaling pathway, TGF-β enhances VSMC proliferation. These findings explain at least in part, the mechanism by which TGF-β enhances intimal hyperplasia. Knowledge of this pathway provides potential novel targets that may be used to prevent restenosis.

Surgeon-level variation in complications was nearly twice as great for MIC than for OC among surgeons enrolled in a statewide quality collaborative. Moreover, surgeon rankings for OC outcomes differed substantially from outcomes for those same surgeons performing MIC. This finding implies a need for improved training in adoption of MIC techniques among some surgeons.

Transforming growth factor-β (TGF-β) is upregulated at the time of arterial injury; however, the mechanism through which TGF-β enhances the development of intimal hyperplasia is not clear. Recent studies from our laboratory suggest that in the presence of elevated levels of Smad3, TGF-β stimulates smooth muscle cell (SMC) proliferation. This is a novel phenomenon in that TGF-β has traditionally been known as a potent inhibitor of cellular proliferation. In these studies we explore the signaling pathways through which TGF-β mediates its proliferative effect in vascular SMCs. We found that TGF-β phosphorylates and activates Akt in a time-dependent manner, and this effect is significantly enhanced by overexpression of Smad3. Furthermore, both chemical and molecular inhibition of Smad3 can reverse the effect of TGF-β on Akt. Although we found numerous signaling pathways that might function as intermediates between Smad3 and Akt, p38 appeared the most promising. Overexpression of Smad3 enhanced p38 phosphorylation and inhibition of p38 with a chemical inhibitor or a small interfering RNA blocked TGF-β-induced Akt phosphorylation. Moreover, TGF-β/Smad3 enhancement of SMC proliferation was blocked by inhibition of p38. Phosphorylation of Akt by TGF-β/Smad3 was not dependent on gene expression or protein synthesis, and immunoprecipitation studies revealed a physical association among p38, Akt, and Smad3 suggesting that activation requires a direct protein-protein interaction. Our findings were confirmed in vivo where overexpression of Smad3 in a rat carotid injury model led to enhancement of p-p38, p-Akt, as well as SMC proliferation. Furthermore, inhibition of p38 in vivo led to decreased Akt phosphorylation and SMC proliferation. In summary, our studies reveal a novel pathway whereby TGF-β/Smad3 stimulates SMC proliferation through p38 and Akt. These findings provide a potential mechanism for the substantial effect of TGF-β on intimal hyperplasia and suggest new targets for chemical or molecular prevention of vascular restenosis.