The surgical treatment of cerebrospinal fistula: Qualitative and quantitative analysis of indications and results

Cerebrospinal fistula might occur in different ways. CSF closure techniques have undergone significant evolution that has led to the consolidation of the transnasal endoscopic approach. Despite the existence of multiple publications, meaningful information is still lacking in clinical practice and the literature about the ideal method, material, and timing for repair of CSF. The purpose of this review was to summarize the success rate of endoscopic CSF leak repair as well as whether specific techniques or materials influence the primary success rate through a review of the latest advancements in endoscopic CSF management published in the past 10 years. The principles of multilayer reconstructions and the routine use of vascularized flaps in expanded endonasal surgery have reduced postoperative CSF leaks' failure rates between 5% and 10% (4% in this meta‐analysis). Effective endoscopic anterior skull base (ASB) closure may be achieved by multiple reconstructive techniques, which should be tailored case by case according to the patient and defect conditions.     

Connexin 43 Is Necessary for Murine Tendon Enthesis Formation and Response to Loading

The enthesis is a mineralized fibrocartilage transition that attaches tendon to bone and is vital for musculoskeletal function. Despite recent studies demonstrating the necessity of muscle loading for enthesis formation, the mechanisms that regulate enthesis formation and mechanoresponsiveness remain unclear. Therefore, the current study investigated the role of the gap junction protein connexin 43 in these processes by deleting Gja1 (the Cx43 gene) in the tendon and enthesis. Compared with their wild-type (WT) counterparts, mice lacking Cx43 showed disrupted entheseal cell alignment, reduced mineralized fibrocartilage, and impaired biomechanical properties of the supraspinatus tendon entheses during postnatal development. Cx43-deficient mice also exhibited reduced ability to complete a treadmill running protocol but no apparent deficits in daily activity, metabolic indexes, shoulder muscle size, grip strength, and major trabecular bone properties of the adjacent humeral head. To examine enthesis mechanoresponsiveness, young adult mice were subjected to modest treadmill exercise. Gja1 deficiency in the tendon and enthesis reduced entheseal anabolic responses to treadmill exercise: WT mice had increased expression of Sox9, Ihh, and Gli1 and increased Brdu incorporation, whereas Cx43-deficient mice showed no changes or decreased levels with exercise. Collectively, the results demonstrated an essential role for Cx43 in postnatal tendon enthesis formation, function, and response to loading; results further provided evidence implicating a link between Cx43 function and the hedgehog signaling pathway. © 2020 American Society for Bone and Mineral Research.     

Anethole and eugenol reduce in vitro and in vivo leukocyte migration induced by fMLP,LTB4, and carrageenan

The aim of this study was to investigate the effect of anethole (AN) and eugenol (EUG) on leukocyte migration using in vitro chemotaxis and in situ microcirculation assays. BALB/c mice were used for the in vitro chemotaxis assay, and Wistar rats for the in situ microcirculation assay. We evaluated (a) the in vitro leukocyte migration in response to chemotactic factors (formyl-methionyl-leucyl-phenylalanine [fMLP] and leukotriene B₄ [LTB₄]) and (b) the rolling, adhesion, and migration of leukocytes induced by an injection of carrageenan (100 µg/cavity) into the scrotum of the animal. In the in vitro chemotaxis assay, AN and EUG at doses of 1, 3, 9, and 27 µg/ml significantly inhibited leukocyte migration when stimulated by the chemotactic agents fMLP and LTB4. In the in situ microcirculation assay, AN at doses of 125 and 250 mg/kg and EUG at a dose of 250 mg/kg significantly decreased the number of leukocytes that rolled, adhered, and migrated to perivascular tissue. The results indicate that AN and EUG exert inhibitory effects on leukocyte migration, highlighting their possible use to diminish excessive leukocyte migration in the inflammatory process.     

Influence of Surgical Margins on the Outcome of Breast Cancer Patients: A Retrospective Analysis

Objective

Breast-conserving surgery has become the preferred treatment for early breast cancer. Yet the question of what constitutes a ‘safe margin’, in terms of impact on patient outcome, remains unanswered. Our aim was to address this knowledge gap by determining the prevalence of positive and narrow margins after breast-conserving surgery, and evaluating how margin status impacted local recurrence and overall survival.

Materials and Methods

We collected data about all women who underwent breast-conserving cancer surgery in our department between 2002 and 2011, focusing on patient and tumor characteristics, the distance from the tumor to the surgical margin, therapies administered, and outcome (measured in terms of local recurrence and overall survival). Data were analyzed by R (version 3.0.1), considering p < 0.05 as significant. Multivariate analyses were also performed.

Results

Of 1,192 women who received breast-conserving surgery, 264 were considered for widening; 111 of these patients had positive margins and 153 narrow (where narrow was defined as less than 5 mm). Widening was performed for 38 % of these patients (99/264) and mastectomy for 27 % (70/264), while 36 % (95/264) had no further surgery and were simply followed-up. Our multivariate analysis confirmed that local tumor recurrence and overall survival were not significantly influenced by margin status, either at initial surgery, or (for those patients with initially positive margins) at secondary margin-widening surgery. However, the following were found to be significantly correlated with local recurrence: tumor multifocality, high expression of Ki-67/Mib-1, comedo-like necrosis, and non-axillary lymph node positivity (p < 0.05).

Conclusions

We found the status of resection margins and the management of infiltrated or narrow margins to have no significant influence on local tumor recurrence rates or on overall patient survival. Instead, biological factors connected with tumor aggressiveness seem to play the most important role in breast cancer prognosis, independent of surgical radicality.