Assessment of perioperative stress in colorectal cancer by use of <i>in vitro</i> cell models:a systematic review

Background The perioperative period is important for patient outcome. Colorectal cancer surgery can lead to metastatic disease due to release of disseminated tumor cells and the induction of surgical stress response. To explore the overall effects on surgically-induced changes in serum composition, in vitro model systems are useful. Methods A systematic search in PubMed and EMBASE was performed to identify studies describing in vitro models used to investigate cancer cell growth/proliferation, cell migration, cell invasion and cell death of serum taken pre- and postoperatively from patients undergoing colorectal tumor resection. Results Two authors (MG and TK) independently reviewed 984 studies and identified five studies, which fulfilled the inclusion criteria. Disagreements were solved by discussion. All studies investigated cell proliferation and cell invasion, whereas three studies investigated cell migration, and only one study investigated cell death/apoptosis. One study investigated postoperative peritoneal infection due to anastomotic leak, one study investigated mode of anesthesia (general anesthesia with volatile or intravenous anesthetics), and one study investigated preoperative intervention with granulocyte macrophage colony stimulating factor (GMCSF). In all studies an increased proliferation, cell migration and invasion was demonstrated after surgery. Anesthetics with propofol and intervention with GMCSF significantly reduced postoperative cell proliferation, whereas peritoneal infection enhanced the invasive capability of tumor cells. Conclusion This study suggests that in vitro cell models are useful and reliable tools to explore the effect of surgery on colorectal cancer cell proliferation and metastatic ability. The models should therefore be considered as additional tests to investigate the effects of perioperative interventions

Epidural analgesia and postoperative complications in colorectal cancer surgery:An observational registry-based study

Background: In colorectal cancer, surgical resection is fundamental for curative treatment. Epidural analgesia mitigates the perioperative physiologic stress response caused by surgery, and reduction in perioperative stress may reduce postoperative complications. Nevertheless, epidural analgesia also causes hypotension and lower limb motor weakness that can impair postoperative recovery. Here, we aimed to assess the association between epidural analgesia and postoperative complications after colorectal cancer surgery. Methods: We identified patients undergoing colorectal cancer surgery 2008–2018 in Denmark in the Danish Colorectal Cancer Group Database and obtained anaesthesia data from the Danish Anaesthesia Database. The Danish National Prescription Registry was used to obtain data on prescriptions filled preoperatively reflecting current comorbidities. Databases were linked using the Danish Central Person Registry number and the operation day. Patients were classified according to preoperative insertion of an epidural catheter for analgesia. Confounders were adjusted by propensity score matching. Logistic regression was used to compute effect estimates of epidural analgesia on postoperative complications. Results: We identified 19 932 individuals undergoing colorectal cancer surgery with available anaesthesia data. Propensity score matching yielded 5691 individuals in each group with balanced preoperative covariates. In the epidural analgesia group 1400 (24.6%) experienced complications compared with 1453 (25.5%) without epidural analgesia. We found no statistically significant association between epidural use and postoperative complications (OR 0.95, 95% CI 0.87–1.04). Conclusion: In total, in this observational study based on Danish registries, we found no association between epidural analgesia and postoperative complications after colorectal cancer surgery.</p

Use of proton pump inhibitors after laparoscopic gastric bypass and sleeve gastrectomy:a nationwide register-based cohort study

Background/Objectives: L-RYGB and L-SG are the dominant bariatric procedures worldwide. While L-RYGB is an effective treatment of coexisting gastroesophageal reflux disease (GERD), L-SG is associated with an increased risk of de-novo or worsening of GERD. The study aimed to evaluate the long-term use of proton pump inhibitors (PPI) following laparoscopic Roux-en-Y gastric bypass (L-RYGB) and sleeve gastrectomy (L-SG). Subjects/Methods: This nationwide register-based study included all patients undergoing L-RYGB or L-SG in Denmark between 2008 and 2018. In total, 17,740 patients were included in the study, with 16,096 and 1671 undergoing L-RYGB and L-SG, respectively. The median follow up was 11 years after L-RYGB and 4 years after L-SG. Data were collected through Danish nationwide health registries. The development in PPI use was assessed through postoperative redeemed prescriptions. GERD development was defined by a relevant diagnosis code associated with gastroscopy, 24 h pH measurement, revisional surgery or anti-reflux surgery. The risk of initiation of PPI treatment or GERD diagnosis was evaluated using Kaplan–Meier plots and COX regression models. The risk of continuous PPI treatment was examined using logistic regression modeling. Results: The risk of initiating PPI treatment was significantly higher after L-SG compared with L-RYGB (HR 7.06, 95% CI 6.42–7.77, p &lt; 0.0001). The risk of continuous PPI treatment was likewise significantly higher after L-SG (OR 1.45, 95% CI 1.36–1.54, p &lt; 0.0001). The utilization of PPI consistently increased after both procedures. The risk of GERD diagnosis was also significantly higher after L-SG compared with L-RYGB (HR 1.93, 95% CI 1.27–2.93, p &lt; 0.0001). Conclusions: The risk of initiating and continuing PPI treatment was significantly higher after L-SG compared with L-RYGB, and a continuous increase in the utilization of PPI was observed after both procedures.</p

Postoperative mortality after a hip fracture over a 15-year period in Denmark:a national register study

Background and purpose — In Denmark, 44 per 10,000 persons over the age of 50 years suffered a hip fracture (HF) in 2011. We characterized the patients and identified risk factors associated with 30-day, 90-day, and 1-year postoperative mortality in Denmark from 2000 to 2014. Patients and methods — The study builds upon data from the Danish National Patients Register and the National Causes of Death Register including all acute hospitalized HF patients aged 18 years and above. Outcomes were 30-day, 90-day, and 1-year postoperative mortality. Mortality risk was analyzed with a univariable and multivariable Cox regression including predefined variables. Results — 113,721 acute hospitalized HF patients were admitted to Danish hospitals between 2000 and 2014. The 30-day mortality risk was 9.6%, 16% at 90 days, and 27% at 1 year after HF surgery. Mortality risk was similar from 2000 to 2014 while the median lengths of stay declined from 14 (IQR 8–25) to 8 (IQR 5–11) days. Male sex, increasing age, higher Charlson Comorbidity Index, per- and subtrochanteric fracture, and operation type other than total hip arthroplasty were independently associated with postoperative mortality. Interpretation — Short- and long-term mortality was high after hip fracture surgery and did not decline in Denmark from 2000 to 2014.</p

Chronic inflammation following hernia repair and cancer risk:A nationwide study

PurposeImplantation of mesh in patients undergoing hernia surgery or prolonged inflammation due to postoperative complication may be associated with increased risk of cancer. We aim to test whether implementation of mesh or complicated postoperative course with readmittance was associated with increased risk of cancer. MethodsThis register-based nationwide observational cohort study included 48,392 and 127,756 patients undergoing ventral and inguinal hernia surgery, respectively, during 1996–2004, with follow-up until Dec. 2014. In total, 16,909 patients undergoing ventral hernia repair with mesh, and 31,483 undergoing sutured repair, as well as 106,342 patients undergoing inguinal hernia repair with mesh and 21,414 undergoing sutured repair were included. Patients were matched with a reference cohort from the general Danish population and were followed in the Danish Cancer Registry. ResultsFor ventral hernia surgery, there was a significant association between mesh repair and risk of cancers, [(vs general population), HR 1.09 (95%CI, 1.00–1.18)]. Thirty-day readmission after mesh and sutured repair was associated with developing cancer [HR 1.15 (0.99–1.34) and 1.14 (1.00–1.31), respectively]. However, the association for suture repair (HR 1.14) did not reach statistical significance (p = 0.055). For inguinal hernia surgery, mesh repair was not associated with increased risk of cancer [(vs. general population), HR 1.00 (95%CI, 0.97–1.02)]. For both mesh and sutured repair, there was an increased risk for developing cancer after 30-day readmission, [HR 1.21 (1.12–1.31) and 1.24 (1.07–1.43), respectively]. ConclusionPatients undergoing ventral hernia repair with mesh and patients readmitted after inguinal or ventral hernia repair may have higher risk of developing cancer than the general population. These exploratory findings do not establish causality, but the association warrants further investigations in other populations.</p