Risk factors of short-term survival in the aged in elective colon cancer surgery : a population-based study

Purpose Patients aged > 80 years represent an increasing proportion of colon cancer diagnoses. Selecting patients for elective surgery is challenging because of possibly compromised health status and functional decline. The aim of this retrospective, population-based study was to identify risk factors and health measures that predict short-term mortality after elective colon cancer surgery in the aged. Methods All patients > 80 years operated electively for stages I-III colon cancer from 2005 to 2016 in four Finnish hospitals were included. The prospectively collected data included comorbidities, functional status, postoperative surgical and medical outcomes as well as mortality data. Results A total of 386 patients (mean 84.0 years, range 80-96, 56% female) were included. Male gender (46% vs 35%, p = 0.03), higher BMI (51% vs 37%, p = 0.02), diabetes mellitus (51% vs 37%, p = 0.02), coronary artery disease (52% vs 36%, p = 0.003) and rheumatic diseases (67% vs 39%, p = 0.03) were related to higher risk of complications. The severe complications were more common in patients with increased preoperative hospitalizations (31% vs 15%, p = 0.05) and who lived in nursing homes (30% vs 17%, p = 0.05). The 30-day and 1-year mortality rates were 6.0% and 15% for all the patients compared with 30% and 45% in patients with severe postoperative complications (p <0.001). Severe postoperative complications were the only significant patient-related variable affecting 1-year mortality (OR 9.60, 95% CI 2.33-39.55, p = 0.002). Conclusions The ability to identify preoperatively patients at high risk of decreased survival and thus prevent severe postoperative complications could improve overall outcome of aged colon cancer patients.Peer reviewe

Surgical and functional outcomes and survival following Colon Cancer surgery in the aged : a study protocol for a prospective, observational multicentre study

BackgroundThe number of colorectal cancer patients increases with age. The decision to go through major surgery can be challenging for the aged patient and the surgeon because of the heterogeneity within the older population. Differences in preoperative physical and cognitive status can affect postoperative outcomes and functional recovery, and impact on patients' quality of life.Methods / designA prospective, observational, multicentre study including nine hospitals to analyse the impact of colon cancer surgery on functional ability, short-term outcomes (complications and mortality), and their predictors in patients aged >= 80years. The catchment area of the study hospitals is 3.88 million people, representing 70% of the population of Finland. The data will be gathered from patient baseline characteristics, surgical interventional data, and pre- and postoperative patient-questionnaires, to an electronic database (REDCap) especially dedicated to the study.DiscussionThis multicentre study provides information about colon cancer surgery's operative and functional outcomes on older patients. A further aim is to find prognostic factors which could help to predict adverse outcomes of surgery.Trial registrationClinicalTrials.gov (NCT03904121). Registered on 1 April 2019.Peer reviewe

Mechanical and oral antibiotic bowel preparation versus no bowel preparation for elective colectomy (MOBILE) : a multicentre, randomised, parallel, single-blinded trial

Background Decreased surgical site infections (SSIs) and morbidity have been reported with mechanical and oral antibiotic bowel preparation (MOABP) compared with no bowel preparation (NBP) in colonic surgery. Several societies have recommended routine use of MOABP in patients undergoing colon resection on the basis of these data. Our aim was to investigate this recommendation in a prospective randomised context. Methods In this multicentre, parallel, single-blinded trial, patients undergoing colon resection were randomly assigned (1: 1) to either MOABP or NBP in four hospitals in Finland, using a web-based randomisation technique. Randomly varying block sizes (four, six, and eight) were used for randomisation, and stratification was done according to centre. The recruiters, treating physicians, operating surgeons, data collectors, and analysts were masked to the allocated treatment. Key exclusion criteria were need for emergency surgery; bowel obstruction; colonoscopy planned during surgery; allergy to polyethylene glycol, neomycin, or metronidazole; and age younger than 18 years or older than 95 years. Study nurses opened numbered opaque envelopes containing the patient allocated group, and instructed the patients according to the allocation group to either prepare the bowel, or not prepare the bowel. Patients allocated to MOABP prepared their bowel by drinking 2 L of polyethylene glycol and 1 L of clear fluid before 6 pm on the day before surgery and took 2 g of neomycin orally at 7 pm and 2 g of metronidazole orally at 11 pm the day before surgery. The primary outcome was SSI within 30 days after surgery, analysed in the modified intention-to-treat population (all patients who were randomly allocated to and underwent elective colon resection with an anastomosis) along with safety analyses. The trial is registered with ClinicalTrials. gov, NCT02652637, and EudraCT, 2015-004559-38, and is closed to new participants. Findings Between March 17, 2016, and Aug 20, 2018, 738 patients were assessed for eligibility. Of the 417 patients who were randomised (209 to MOABP and 208 to NBP), 13 in the MOABP group and eight in the NBP were excluded before undergoing colonic resection; therefore, the modified intention-to-treat analysis included 396 patients (196 for MOABP and 200 for NBP). SSI was detected in 13 (7%) of 196 patients randomised to MOABP, and in 21 (11%) of 200 patients randomised to NBP (odds ratio 1 . 65, 95% CI 0 . 80-3 . 40; p= 0 . 17). Anastomotic dehiscence was reported in 7 (4%) of 196 patients in the MOABP group and in 8 (4%) of 200 in the NBP group, and reoperations were necessary in 16 (8%) of 196 compared with 13 (7%) of 200 patients. Two patients died in the NBP group and none in the MOABP group within 30 days. Interpretation MOABP does not reduce SSIs or the overall morbidity of colon surgery compared with NBP. We therefore propose that the current recommendations of using MOABP for colectomies to reduce SSIs or morbidity should be reconsidered. Copyright (c) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Purely ropivacaine-based TEA vs single TAP block in pain management after elective laparoscopic colon surgery within an upgraded institutional ERAS program

Publisher Copyright: © 2021, The Author(s).Background: The aim of this study was to compare thoracic epidural analgesia (TEA) with transversus abdominis plane (TAP) block in post-operative pain management after laparoscopic colon surgery. Methods: One hundred thirty-six patients undergoing laparoscopic colon resection randomly received either TEA or TAP with ropivacaine only. The primary endpoint was opioid requirement up to 48 h postoperatively. Intensity of pain, time to onset of bowel function, time to mobilization, postoperative complications, length of hospital stay, and patients’ satisfaction with pain management were also assessed. Results: We observed a significant decrease in opioid consumption on the day of surgery with TEA compared with TAP block (30 mg vs 14 mg, p < 0.001). On the first two postoperative days (POD), the balance shifted to opioid consumption being smaller in the TAP group: on POD 1 (15.2 mg vs 10.6 mg; p = 0.086) and on POD 2 (9.2 mg vs 4.6 mg; p = 0.021). There were no differences in postoperative nausea/vomiting or time to first postoperative bowel movement between the groups. No direct blockade-related complications were observed and the length of stay was similar between TEA and TAP groups. Conclusion: TEA is more efficient for acute postoperative pain than TAP block on day of surgery, but not on the first two PODs. No differences in pain management-related complications were detected.Peer reviewe

Laparoscopic Colectomy vs Laparoscopic CME : a Retrospective Study of Two Hospitals with Comparable Laparoscopic Experience

Purpose To compare laparoscopic non-CME colectomy with laparoscopic CME colectomy in two hospitals with similar experience in laparoscopic colorectal surgery. Methods Data was collected retrospectively from Paijat-Hame Central Hospital (PHCH, NCME group) and Central Finland Central Hospital (CFCH, CME group) records. Elective laparoscopic resections performed during 2007-2016 for UICC stage I-III adenocarcinoma were included to assess differences in short-term outcome and survival. Results There were 340 patients in the NCME group and 325 patients in the CME group. CME delivered longer specimens (p <0.001), wider resection margins (p <0.001), and more lymph nodes (p <0.001) but did not result in better 5-year overall or cancer-specific survival (NCME 77.9% vs CME 72.9%, p = 0.528, NCME 93.2% vs CME 88.9%, p = 0.132, respectively). Thirty-day morbidity, mortality, and length of hospital stay were similar between the groups. Conversion to open surgery was associated with decreased survival. Discussion Complete mesocolic excision (CME) is reported to improve survival. Most previous studies have compared open CME with open non-CME (NCME) or open CME with laparoscopic CME. NCME populations have been historical or heterogeneous, potentially causing bias in the interpretation of results. Studies comparing laparoscopic CME with laparoscopic NCME are few and involve only small numbers of patients. In this study, diligently performed laparoscopic non-CME D2 resection delivered disease-free survival results comparable with laparoscopic CME but was not safer.Peer reviewe

One-year functional outcomes of patients aged 80 years or more undergoing colonic cancer surgery : prospective, multicentre observational study

Background Older patients are at high risk of experiencing delayed functional recovery after surgical treatment. This study aimed to identify factors that predict changes in the level of support for activities of daily living and mobility 1 year after colonic cancer surgery. Methods This was a multicentre, observational study conforming to STROBE guidelines. The prospective data included pre-and postoperative mobility and need for support in daily activities, co-morbidities, onco-geriatric screening tool (G8), clinical frailty scale (CFS), operative data, and postoperative surgical outcomes. Results A total of 167 patients aged 80 years or more with colonic cancer were recruited. After surgery, 30 per cent and 22 per cent of all patients had increased need for support and decreased motility. Multivariableanalysis with all patients demonstrated that preoperative support in daily activities outside the home (OR 3.23, 95 per cent c.i. 1.06 to 9.80, P = 0.039) was associated with an increased support at follow-up. A history of cognitive impairment (3.15, 1.06 to 9.34, P = 0.038) haemoglobin less than 120 g/l (7.48, 1.97 to 28.4, P = 0.003) and discharge to other medical facilities (4.72, 1.39 to 16.0, P = 0.013) were independently associated with declined mobility. With functionally independent patients, haemoglobin less than 120 g/l (8.31, 1.76 to 39.2, P = 0.008) and discharge to other medical facilities (4.38, 1.20 to 16.0, P = 0.026) were associated with declined mobility. Conclusion Increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicts an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should focus on anaemia correction, nutritional status, and mobility with detailed rehabilitation plan. Greater increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicted an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should especially focus on anaemia correction, nutritional status, and mobility with a detailed rehabilitation plan.Peer reviewe

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

Common Genetic Variation And Age at Onset Of Anorexia Nervosa

Background Genetics and biology may influence the age at onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to AN age at onset and to investigate the genetic associations between age at onset of AN and age at menarche. Methods A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed which included 9,335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age at onset, early-onset AN (< 13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (SNP-h2) were 0.01-0.04 for age at onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age at onset and early-onset AN estimated from independent GWASs significantly predicted age at onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions Our results provide evidence consistent with a common variant genetic basis for age at onset and implicate biological pathways regulating menarche and reproduction.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202