Ismail Gögenur

Impact of sleep and circadian disturbances in urinary 6-sulphatoxymelatonin levels, on cognitive function after major surgery

Abstract:u2002 Sleep and circadian disturbances may underlie cognitive dysfunction after major surgery. The aim of this study was to examine the association between sleep and circadian disturbances (as assessed by changes in the melatonin rhythm) and postoperative cognitive dysfunction (POCD). We measured subjective and objective sleep quality, excretion of the major metabolite of melatonin, 6‐sulphatoxymelatonin (aMT6s) in urine and cognitive function before and 4u2003days after major abdominal surgery in 36 patients. Subjective sleep quality was measured by visual analogue scale, objective sleep quality was measured by actigraphy, and cognitive function was assessed by neuropsychological testing. Eighteen patients (50%) had POCD on day 4 after surgery. At that time, the excretion of aMT6s was disturbed with significantly higher daytime excretion and a reduced night/day ratio compared with the preoperative measure (Pu2003=u20030.05). Patients with POCD had significantly worse sleep quality and more night awakenings (Pu2003<u20030.05) but we found no significant differences in day time (06:00–22:00u2003hr), night‐time (22:00–06:00u2003hr) or total aMT6s excretion (μg/24u2003hr). A significant correlation was found between the total excretion of aMT6s and actigraphically measured sleep efficiency (rsu2003=u20030.45, Pu2003=u20030.03) and wakefulness after sleep onset (rsu2003=u2003−0.44, Pu2003=u20030.04). In conclusion, POCD was associated with worse subjective sleep quality and more awakenings. Circadian rhythmicity as assessed by aMT6s excretion was disturbed after surgery but we were unable to show an association with POCD. Strategies to improve postoperative sleep quality should be investigated in the future.

Melatonin for pre- and postoperative anxiety in adults

BACKGROUNDnAnxiety in relation to surgery is a well-known problem. Melatonin offers an atoxic alternative to benzodiazepines in ameliorating this condition in the pre- and postoperative period.nnnOBJECTIVESnTo assess the effect of melatonin on pre- and postoperative anxiety in adults when comparing melatonin with placebo or when comparing melatonin with benzodiazepines.nnnSEARCH METHODSnThe following databases were searched on 19 April 2013: CENTRAL, MEDLINE, EMBASE, CINAHL and Web of Science. For ongoing trials and protocols we searched clinicaltrials.gov, Current Controlled Trials and the World Health Organization (WHO) International Clinical Trials Registry Platform. We reran the search in October 2014. We will deal with any studies of interest when we update the review.nnnSELECTION CRITERIAnRandomized, placebo-controlled or standard treatment-controlled, or both, studies that evaluated the effect of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both genders (15 to 90 years of age) undergoing any kind of surgical procedure in which it was necessary to use general, regional or topical anaesthesia.nnnDATA COLLECTION AND ANALYSISnData were extracted independently by two review authors. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimen, preoperative anxiety outcome measures and postoperative anxiety outcome measures.nnnMAIN RESULTSnThis systematic review identified 12 randomized controlled trials (RCTs) including 774 patients that assessed melatonin for treating preoperative anxiety, postoperative anxiety or both. Four of the 12 studies compared melatonin, placebo and midazolam, whereas the remaining eight studies compared melatonin and placebo only.The quality of the evidence for our primary outcome (melatonin versus placebo for preoperative anxiety) was high. More than half of the included studies had a low risk of selection bias and at least 75% of the included studies had a low risk of attrition, performance and detection bias. Most of the included studies had an unclear risk of reporting bias.Eight out the 10 studies that assessed the effect of melatonin on preoperative anxiety using a visual analogue scale (VAS) (ranging from 0 to 100 mm, higher scores indicate greater anxiety) showed a reduction compared to placebo. The reported estimate of effect (relative effect -13.36, 95% confidence interval (CI) -16.13 to -10.58; high quality evidence) was based on a meta-analysis of seven studies. Two studies did not show any difference between melatonin and placebo. Two studies comparing melatonin with midazolam using a VAS found no evidence of a difference in preoperative anxiety between the two groups (relative effect -1.18, 95% CI -2.59 to 0.23; low quality evidence).Eight studies assessed the effect of melatonin on postoperative anxiety. Four of these studies measuring postoperative anxiety 90 minutes postoperatively using a VAS did not find any evidence of a difference between melatonin and placebo (relative effect -3.71, 95% CI -9.26 to 1.84). Conversely, two studies showed a reduction of postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) when comparing melatonin with placebo (relative effect -5.31, 95% CI -8.78 to -1.84; moderate quality evidence). Two studies comparing melatonin with midazolam using a VAS did not find any evidence of a difference between the two groups in postoperative anxiety (relative effect -2.02, 95% CI -5.82 to 1.78).nnnAUTHORS CONCLUSIONSnWhen compared to placebo, melatonin given as premedication (tablets or sublingually) can reduce preoperative anxiety in adults (measured 50 to 100 minutes after administration). Melatonin may be equally as effective as standard treatment with midazolam in reducing preoperative anxiety in adults (measured 50 to 100 minutes after administration). The effect of melatonin on postoperative anxiety (measured 90 minutes and 6 hours after surgery) in adults is mixed but suggests an overall attenuation of the effect compared to preoperatively.

No differences in short-term morbidity and mortality after robot-assisted laparoscopic versus laparoscopic resection for colonic cancer: a case–control study of 263 patients

BackgroundRobot-assisted laparoscopy has been reported to be a safe and feasible alternative to traditional laparoscopy. The aim of this study was to compare short-term results in patients with colonic cancer who underwent robot-assisted laparoscopic colonic resection (RC) or laparoscopic colonic resection (LC).MethodsThe study was a retrospective case control study of all patients with colonic cancer who underwent RC from March 2010 to March 2012 or LC from January 2009 to December 2011 at a tertiary-care university hospital. Data were retrieved from the national chart database and patient journals. Biochemical markers [C-reactive protein (CRP), hemoglobin, white blood cell count, and thrombocyte count] were recorded before surgery and for the first 3xa0days after surgery.ResultsA total of 101 patients underwent RC and 162 patients underwent LC. There were no significant differences in the rate of conversion to open surgery, number of permanent enterostomies, number of intraoperative complications, level of postoperative cellular stress response, number of postoperative complications, length of postoperative hospital stay, or 30-day mortality between the two groups. There was a significantly longer setup time for RC (77.1 vs. 69.7xa0min, Pxa0=xa00.000), but surgical time was significantly shorter for RC (165.8 vs. 183.4xa0min, Pxa0=xa00.006) and there was no difference in the overall procedure time (254.0 vs. 243.6xa0min, Pxa0=xa00.086).ConclusionWe found RC to be a safe and feasible alternative to LC for colonic cancer. We found that for RC surgical time was shorter and overall procedure time was comparable to that for LC; however, these results should be confirmed in future randomized clinical trials.

Reply to: Re: No differences in short-term morbidity and mortality after robot-assisted laparoscopic versus laparoscopic resection for colonic cancer: A case-control study of 263 patients (Surg Endosc 2013)

We thank Dr. Colantonio for his comments. We agree that there is an overlap in the literature where ‘‘case-control’’ is inappropriately used in studies where the more correct term would be ‘‘retrospective cohort’’ study. We thank Dr. Colantonio for bringing this to attention. We also agree with Dr. Colantonio that an obvious limitation of retrospective study designs such as ours is the difference in risk factors between the observed groups. However, when looking at relatively new techniques (such as robot-assisted colectomy for colon cancer), the small number of surgical cases can become an obstacle for the use of analytic methods, such as stratification and matching. We agree that restriction with regard to surgeon experience would have been preferable, but because our hospital is a teaching hospital, a large part of the laparoscopic colectomies are performed by junior surgeons under supervision. Restriction would have entailed a significant risk of selection bias in favor of the robotic colectomies, because one can assume that the patients selected for laparoscopic operation by a senior surgeon would have more advanced cancers, older age, and poorer health status with regard to comorbidity. In contrast, all patients were eligible for robotic surgery and were selected for robotic surgery on the basis of robot and surgeon availability. We addressed these limitations in our discussion, and we emphasized that our outcomes, including the shorter surgical time in the robot-assisted laparoscopic colectomy group, could indeed be affected by them. Our study concluded that ‘‘robot-assisted laparoscopic colonic resection is a safe and feasible alternative to traditional laparoscopic resection for colonic cancer.’’ We do not dissuade surgeons from using robot-assisted laparoscopy for colonic resection because we believe that randomized clinical trials of robotassisted laparoscopic colectomy versus laparoscopic colectomy, larger than those currently available, could yet prove that the superior technical possibilities of robotassisted surgery will translate into improved functional and oncological outcomes in patients with colon cancer.

Chronic Pain, Quality of Life, and Functional Impairment After Surgery Due to Small Bowel Obstruction

BackgroundEmergency laparotomy is a high-risk procedure regarding short-term outcomes; however, long-term outcomes are not well described. The aim of this study was to determine the frequency of chronic postoperative pain, pain-related functional impairment, and incisional hernias and to evaluate the gastrointestinal quality of life after emergency laparotomy due to small bowel obstruction.MethodsThis study was a questionnaire study, conducted at a major gastrointestinal-surgery department in a single tertiary university hospital in Denmark. Patients who had been through emergency laparotomy due to small bowel obstruction were included in the study. The extent of acute and chronic postoperative pain and the prevalence of incisional hernias were examined with specially designed questionnaires, while the pain quality was assed by the self-report version of the S-LANSS-questionnaire. Pain-related functional impairment and quality of life were measured using the AAS and the GIQLI questionnaire, respectively.ResultsA total of 90 patients returned the questionnaire (response rate 82xa0%). Nineteen patients (21xa0%) suffered from chronic postoperative pain. Seventeen patients (19xa0%) had pain-related functional impairment as a result of the surgery, and 17 patients (19xa0%) had an incisional hernia at follow-up. Patients with chronic postoperative pain had significantly lower gastrointestinal quality of life score compared with the remaining study population (109 (IQR 39) vs. 127 (IQR 19), Pxa0<xa00.001).ConclusionsChronic postoperative pain is a common long-term complication after emergency laparotomy, and it is related to decreased quality of life. These results should be confirmed in prospective studies.

Techniques to reduce shoulder pain after laparoscopic surgery for benign gynaecological disease: a systematic review

Due to the well-known advantages of minimal invasive surgery, the majority of procedures for benign gynaecological diseases are performed by laparoscopy. Although laparoscopic surgery results in improved patient satisfaction, a considerable portion of patients have complaints of post-operative shoulder pain. This review presents an overview of the currently evaluated techniques to reduce shoulder pain after laparoscopic surgery for benign gynaecological disease. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted using Medline, Embase and Cochrane databases. Randomised clinical trials reporting techniques to reduce shoulder pain after laparoscopic gynaecologic procedures for benign diseases were included. Eighty-eight articles were screened for inclusion. A total of 15 articles were included in the final review. The following studies described the techniques used to reduce shoulder pain: six studies evaluated the effect of local anaesthetics, three studies evaluated the effect of pulmonary recruitment manoeuvre and three studies evaluated the effect of intraperitoneal drainage. The remaining three studies evaluated the effect of saline installation, minilaparoscopy and gasless laparoscopy by using the Laprolift®. Overall, the pulmonary recruitment manoeuvre and intraperitoneal drainage were found to reduce the incidence and severity of shoulder pain (SP). Based on the current evidence, safety and possibility to implement the technique in daily practice, pulmonary recruitment manoeuvre can be recommended to reduce both the incidence and severity of SP.

Exploring Postoperative Cognitive Dysfunction and Delirium in Noncardiac Surgery Using MRI: A Systematic Review

Surgical patients are at high risk of developing postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). POCD and POD are associated with increased morbidity and mortality and worsening functional outcomes leading to severe socioeconomic consequences for the patient and the society in general. Magnetic resonance imaging (MRI) offers a unique opportunity to study the anatomy and function of the brain. MRI thus plays an important role in elucidating the neuronal component of POCD and POD. Our aim has been to systematically gather MRI findings that are related to POCD and POD. Systematic searches were conducted in PubMed, EMBASE, and PsycINFO: MRI studies investigating patients with POCD as identified by perioperative cognitive testing or patients with delirium identified postoperatively by the Confusion Assessment Method. A total of ten eligible papers were included with a total of 269 surgical patients, 36 patient controls, and 55 healthy controls who all underwent MRI examination. These studies suggested that reduction of thalamic and hippocampal volumes and reduction of cerebral blood flow may be associated with POCD, while presurgery/preexisting and postoperative white matter pathology may be associated with POD. However, the evidence from these studies is rather weak. Future MRI studies are warranted to verify the current findings.

AnAnkle Trial study protocol: a randomised trial comparing pain profiles after peripheral nerve block or spinal anaesthesia for ankle fracture surgery

Introduction Ankle fracture surgery is a common procedure, but the influence of anaesthesia choice on postoperative pain and quality of recovery is poorly understood. Some authors suggest a benefit of peripheral nerve block (PNB) in elective procedures, but the different pain profile following acute fracture surgery and the rebound pain on cessation of the PNB both remain unexplored. We present an ongoing randomised study aiming to compare primary PNB anaesthesia with spinal anaesthesia for ankle fracture surgery regarding postoperative pain profiles and quality of recovery. Methods and analysis AnAnkle Trial is a randomised, dual-centre, open-label, blinded analysis trial of 150 adult patients undergoing primary internal fixation of an ankle fracture. Main exclusion criteria are habitual opioid use, impaired pain sensation, other painful injuries or cognitive impairment. The intervention is ultrasound-guided popliteal sciatic (20u2009mL) and saphenal nerve (8u2009mL) PNB with ropivacaine 7.5u2009mg/mL, and controls receive spinal anaesthesia (2u2009mL) with hyperbaric bupivacaine 5u2009mg/mL. Postoperatively all receive paracetamol, ibuprofen and patient-controlled intravenous morphine on demand. Morphine consumption and pain scores are registered in the first 27u2009hours and reported as an integrated pain score as the primary endpoint. Pain score intervals are 3u2009hours and we will use the area under curve to get a longitudinal measure of pain. Secondary outcomes include rebound pain on cessation of anaesthesia, opioid side effects (Opioid-Related Symptom Distress Scale), quality of recovery (Danish Quality of Recovery-15 score) and pain scores and medication days 1–7 (diary). Ethics and dissemination The study has been approved by the Regional Ethics Committees in the Capital Region of Denmark, the Danish Data Protection Agency and the Danish Health and Medical Authority. We will publish the results in international peer-reviewed medical journals. Trial registration number AnAnkle Trial is registered in the European Clinical Trials Database (EudraCT 2015-001108-76).

Abstract LB-381: Childhood body size and the risk of colon or rectal cancer in adulthood

Background: Adult obesity and height are well-established risk factors for colorectal cancer, however, few studies have examined the possible association with childhood body size. It is therefore unknown if the association is due to the body size in adult life or may be influenced by body size already from childhood. In the present study, we examined if childhood body mass index (BMI: kg/m 2 ) and height from ages 7 to 13 years are associated with the risk of colon and rectal cancer in adulthood. Methods: We used the Copenhagen School Health Records Register to identify children who were born from 1930-1972 and had information on height and weight from their school health examinations. BMI and height were transformed into z-scores. Cases were identified by linkage to the Danish Cancer Registry using ICD-10 codes (colon: C18.0-18.9, rectal: C19.9, 20.9). Analyses were conducted using Cox proportional hazard regressions stratified by birth cohort and sex since no significant sex interactions were observed. Results: Among 257,623 individuals (49.7% women), 2,676 were diagnosed with colon cancer (47.5% women) and 1,681 with rectal cancer (38.9% women). Per z-score increase in BMI at age 13 years the hazard ratio (HR) for colon cancer in adulthood was 1.09 (95% confidence interval [CI]: 1.04 to 1.14) in sex-stratified analyses. Per z-score increase in height at age 13 years the HR for colon cancer in adulthood was 1.14 (95% CI: 1.09 to 1.19). In a model including BMI and height (thus comparing two children of the same height with different weights and vice versa), the effect of BMI was attenuated (HR per z-score of BMI: 1.05, 95% CI: 1.00 to 1.10) but the HR for height changed little (HR per z-score of height: 1.13, 95% CI: 1.08 to 1.17). Essentially similar results were observed at all other ages (7 to 12 years). Examining the associations by colon sub-sites showed that the results observed mainly were driven by the associations with sigmoid colon cancer (C18.7, 1100 cases). Per z-score unit increase in BMI at age 13 years the HR was 1.11 (95% CI: 1.04 to 1.19) for a cancer in sigmoid colon as adult, while the HR for height was 1.21 (95% CI: 1.14 to 1.29). Associations between BMI and rectal cancer were generally not significant, at age 13 years the HR was 0.97 (95% CI: 0.92 to 1.03). Overall similar results were observed at ages 7-10 years and at age 12 years. Only at age 11 years was a borderline significant association observed, with a HR of 0.95 (95% CI: 0.89 to 1.00) per unit of BMI z-score. For height no significant associations were observed with the later risk of rectal cancer, at age 13 years the HR was 1.03 (95% CI: 0.98 to 1.08) and essentially similar results were observed at ages 7 to 12 years. Conclusion: Body size in childhood was positively associated with the later risk of colon cancer, whereas no associations were observed for rectal cancer. However, the results indicate that among children the associations observed between body size and colon cancer were mainly but not exclusively explained by height. Citation Format: Britt W. Jensen, Michael Gamborg, Ismail Gogenur, Thorkild I.A. Sorensen, Jennifer L. Baker. Childhood body size and the risk of colon or rectal cancer in adulthood. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-381.