Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Several factors within the perioperative period may influence postoperative metastatic spread. Dexmedetomidine and midazolam are widely used general anesthetics during surgery. The authors assessed their effects on human lung carcinoma (A549) and neuroglioma (H4) cell lines in vitro and in vivo. Methods Cell proliferation and migration were measured after dexmedetomidine (0.001 to 10 nM) or midazolam (0.01 to 400 μM) treatment. Expression of cell cycle and apoptosis markers were assessed by immunofluorescence. Mitochondrial membrane potential and reactive oxygen species were measured by JC-1 staining and flow cytometry. Antagonists atipamezole and flumazenil were used to study anesthetic mechanisms of action. Tumor burden after anesthetic treatment was investigated with a mouse xenograft model of lung carcinoma. Results Dexmedetomidine (1 nM) promoted cell proliferation (2.9-fold in A549 and 2-fold in H4 cells vs. vehicle, P < 0.0001; n = 6), migration (2.2-fold in A549 and 1.9-fold in H4 cells vs. vehicle, P < 0.0001; n = 6), and upregulated antiapoptotic proteins in vitro. In contrast, midazolam (400 μM) suppressed cancer cell migration (2.6-fold in A549 cells, P < 0.0001; n = 4), induced apoptosis via the intrinsic mitochondrial pathway, decreased mitochondrial membrane potential, and increased reactive oxygen species expression in vitro—effects partly attributable to peripheral benzodiazepine receptor activation. Furthermore, midazolam significantly reduced tumor burden in mice (1.7-fold vs. control; P < 0.05; n = 6 per group). Conclusions Midazolam possesses antitumorigenic properties partly mediated by the peripheral benzodiazepine receptor, whereas dexmedetomidine promotes cancer cell survival through signaling via the α2-adrenoceptor in lung carcinoma and neuroglioma cells.

Intertrochanteric fractures, accountable for 50% of hip fractures, can be fixed with cephalomedullary devices such as Proximal Femoral Nail Antirotation (PFNA™), Gamma3 nailing system and TRIGEN™ InterTAN™ nail (IT). IT uniquely uses two cephalocervical screws that allow for linear compression and provide additional resistance to femoral head rotation. A literature review assessing clinical outcomes of these devices was conducted, with 14 studies enrolling 3104 patients meeting the inclusion criteria. PFNA and Gamma3 had better intraoperative outcomes compared with IT; however, IT had superior implant-related outcomes of cut-out and screw migration. No difference was found between IT and PFNA or Gamma3 in Harris Hip Scores, time to union, malunion and nonunion. Further long-term studies are needed to evaluate clinical outcomes and cost–effectiveness of cephalomedullary devices.

The anesthetic state and natural sleep share many neurobiological features and yet are two distinct states. The hallmarks of general anesthesia include hypnosis, analgesia, akinesia and anxiolysis. These are the principal parameters by which the anesthetic state differs from natural sleep. These properties are mediated by systemic administration of a combination of agents producing balanced anesthesia. The exact nature of anesthetic narcosis is dose dependent and agent specific. It exhibits a relative lack of nociceptive response and active suppression of motor and autonomic reflexes. Surgical anesthesia displays a signature electroencephalogram pattern of burst suppression that differs from rapid eye movement sleep, representing more widespread disruption of thalamocortical connectivity, impairing information integration and processing. These differences underpin successful anesthetic action. This review explores the differences between natural sleep and anesthetic-induced unconsciousness as induced by balanced anesthesia.

Adhesive capsulitis of the shoulder (ACS) is a condition with significant clinical and economic implications. The etiology of adhesive capsulitis is not clearly understood and there remains lack of consensus in clinical management for this condition. It can occur as a primary idiopathic condition or secondary to medical conditions or trauma. The hallmarks of ACS are pain and stiffness, caused by formation of adhesive or scar tissue in the glenohumeral joint. Management strategies vary depending on stage of presentation, patient factors and clinician preferences, and can range from conservative options to surgical intervention. The aim of this review is to summarize the pathophysiology and clinical presentation of ACS and to discuss the evidence base for various management strategies employed today.

Background: Elective surgery is the treatment of choice for symptomatic giant hiatus hernia (GHH), and quality of life (QoL) has become an important outcome measure following surgery. The aim of this study is to review the literature assessing QoL following repair of GHH. Methodology: A systematic literature search was performed by two reviewers independently to identify original studies evaluating QoL outcomes after GHH surgery. MeSH terms such as paraoesophageal; hiatus hernia; giant hiatus hernia and quality of life were used in the initial search. Original studies in English language using validated questionnaires on humans were included. Review articles, conference abstracts and case reports and studies with duplicate data were excluded. Results: Two hundred and eight articles were identified on initial search, of which 38 studies (4404 patients) were included. Studies showed a significant heterogeneity in QoL assessment tools, surgical techniques and follow-up methods. All studies assessing both pre-operative and post-operative QoL ( n = 31) reported improved QoL on follow-up after surgical repair of GHH. Improvement in QoL following GHH repair was not affected by patient age, surgical technique or the use of mesh. Recurrence of GHH after surgery may, however, adversely impact QoL. Conclusion: Surgical repair of GHH improved QoL scores in all the 38 studies. The impact of recurrence on QoL needs further assessment. The authors also recommend uniform reporting of surgical outcomes in future studies.

We read with interest an article written by David W da Costa et al. entitled "Predicting a 'difficult cholecystectomy' after mild gallstone pancreatitis". 1 We congratulate the authors for publishing the first large prospective study predicting difficulties specific to only one indication of cholecystectomy.In acute gallstone pancreatitis (AGP), the primary pathology is in pancreas and not in gallbladder. For this reason, cholecystectomy should not be difficult in pancreatitis patients. This logic was confirmed in our recently published study. 2 The combined data from this and our previous study had total of 454 patients who underwent cholecystectomy; 50 of these were for AGP. 2,3 Two patients required conversion; one for abnormal anatomy and the other for gallbladder perforation.We feel that the Nassar classification of degree of difficulty (DoD) used in our recent study is more reliable and specific to cholecystectomy. 4 The markers of DoD in this study are either subjective (Visual Analogue Score) or surrogate (i.e. operating time, conversion) and carry the risk of including general factors like obesity or previous surgery. In the context of this paper, DoD should be specifically secondary to pancreatitis.The authors report preoperative endoscopic sphincterotomy in 31% patients (n = 81). This appears to be a very high number compared to standard UK practice where very few patients would undergo the procedure preoperatively (none in our series).In summary, pancreatitis per se does not increase operative difficulty but associated gallbladder pathology as described in literature 5 , as well as in our study, would increase DoD.

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