Preoperative intravenous iron treatment reduces postoperative complications and postoperative anemia in preoperatively anemic patients with colon carcinoma.

PURPOSE: Anemia is common among patients with colorectal cancer and is associated with an increased risk of complications and poorer survival rate. The main objective of our study was to determine the effect of preoperative intravenous iron supplementation therapy on the need for red blood cell transfusions, other postoperative complications, and length of hospital stay in colon cancer patients undergoing colon resection. METHODS: In this retrospective cohort study, data were collected from medical records of all 549 colon carcinoma patients who underwent a colon resection in Helsinki University Hospital during the years 2017 and 2018. The patients were divided into two cohorts: one with anemic patients treated with preoperative intravenous iron supplementation therapy (180 patients) and one with anemic patients without preoperative intravenous iron supplementation therapy (138 patients). Non-anemic patients and patients requiring emergency surgery were excluded (231 patients). RESULTS: Patients treated with intravenous iron had less postoperative complications (33.9% vs. 45.9%, p = 0.045) and a lower prevalence of anemia at 1 month after surgery (38.7% vs. 65.3%, p < 0.01) when compared with patients without preoperative iv iron treatment. No difference was found in the amount of red blood cell transfusions, length of stay, or mortality between the groups. CONCLUSION: This is the first study demonstrating a significant decrease in postoperative complications in anemic colon cancer patients receiving preoperative intravenous iron supplementation therapy. This treatment also diminishes the rate of postoperative anemia, which is often associated with a facilitated recovery.

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

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.

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. FUNDING: Vatsatautien Tutkimussäätiö Foundation, Mary and Georg Ehrnrooth's Foundation, and Helsinki University Hospital research funds.

Predictive factors for postoperative ileus after elective right hemicolectomy performed on over 80% Enhanced Recovery After Surgery-adherent patients: a retrospective cohort study.

Purpose: Laparoscopic right hemicolectomy is the standard surgical approach for treatment of right-sided colonic neoplasms. Although performed within a strict Enhanced Recovery After Surgery (ERAS) program, patients still develop postoperative ileus. The aim of this study was to describe the factors responsible for postoperative ileus after right hemicolectomy in a patient population with over 80% ERAS adherence. Methods: In this retrospective study, we analyzed 499 consecutive patients undergoing elective right-sided colectomy for neoplastic disease in a single high-volume center. All patients followed an updated ERAS program. Results: The overall median ERAS adherence was 80%. Patients with ≥ 80% adherence (n = 271) were included in further analysis. Their median ERAS adherence was 88.9% (interquartile range, 80-90; range, 80-100). Twenty-four of 271 patients (8.9%) developed postoperative ileus. A univariate regression analysis revealed carcinoma situated in the transverse colon, duration of operation over 200 minutes, and opiate consumption over 10 mg on the second postoperative day (POD) to be associated with a significantly higher risk of postoperative ileus. Multivariate regression analysis revealed that duration of surgery over 200 minutes (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.0-5.8; P = 0.045) and opiate consumption over 10 mg on POD 2 (OR, 4.8; 95% CI, 1.6-14.3; P = 0.005) independently predict a higher risk for postoperative ileus. The median length of hospital stay was significantly longer in patients with postoperative ileus (8 days vs. 3 days, P < 0.001). None of the 271 patients died during a 30-day follow-up. Conclusion: Long duration of surgery, even minor postoperative opiate use, predict a higher risk for postoperative ileus in strictly ERAS-adherent patients undergoing laparoscopic right hemicolectomy.

Superior primary fascial closure rate and lower mortality after open abdomen using negative pressure wound therapy with continuous fascial traction.

BACKGROUND: Open abdomen (OA) is a useful option for treatment strategy in many acute abdominal catastrophes. A number of temporary abdominal closure (TAC) methods are used with limited number of comparative studies. The present study was done to examine risk factors for failed delayed primary fascial closure (DPFC) and risk factors for mortality in patients treated with OA. METHODS: This study was a multicenter retrospective analysis of the hospital records of all consecutive patients treated with OA during the years 2009 to 2016 at five tertiary referral hospitals and three secondary referral centers in Finland. RESULTS: Six hundred seventy-six patients treated with OA were included in the study. Vacuum-assisted closure with continuous mesh-mediated fascial traction (VACM) was the most popular TAC method used (N = 398, 59%) followed by VAC (N = 128, 19%), Bogota bag (N = 128, 19%), and self-designed methods (N = 22, 3%). In multivariate analysis, enteroatmospheric fistula and the number of needed TAC changes increased the risk for failed DPFC (odds ratio [OR], 8.9; 95% confidence interval [CI], 6.2-12.8; p < 0.001 and OR, 1.1; 95% CI, 1.0-1.3; p < 0.001, respectively). Instead, VACM and ruptured abdominal aortic aneurysm as cause for OA both decreased the risk for failed DPFC (OR, 0.1; 95% CI, 0.0-0.3; p < 0.001 and OR, 0.2; 95% CI, 0.1-0.7; p = 0.012). The overall mortality rate was 30%. In multivariate analysis for mortality, multiorgan dysfunction (OR, 2.4; 95% CI, 1.6-3.6; p < 0.001), and increasing age (OR, 4.5; 95% CI, 2.0-9.7; p < 0.001) predicted increased mortality. Institutional large annual patient volume (OR, 0.4; 95% CI, 0.3-0.6; p < 0.001) and ileus and postoperative peritonitis in comparison to severe acute pancreatitis associated with decreased mortality (OR, 0.2; 95% CI, 0.1-0.4; p < 0.001; OR, 0.5; 95% CI, 0.3-0.8; p = 0.009). Kaplan-Meier analysis showed increased survival in patients treated with VACM in comparison with other TAC methods (LogRank p = 0.019). CONCLUSION: We report superior role for VACM methodology in terms of successful primary fascial closure and increased survival in patients with OA. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Open abdomen with vacuum-assisted wound closure and mesh-mediated fascial traction in patients with complicated diffuse secondary peritonitis: A single-center 8-year experience.

BACKGROUND: Open abdomen (OA) treatment in patients with peritonitis is increasing worldwide. Various temporary abdominal closure devices are being used. This study included patients with complicated diffuse secondary peritonitis, OA, and vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM). The aim of this study was to describe mortality and major morbidity in terms of delayed primary fascial closure and enteroatmospheric fistula rates. METHODS: This was a single-academic-center retrospective study of consecutive patients with diffuse peritonitis, OA, and VAWCM between years 2008 and 2016. Descriptive and univariate analyses were performed. RESULTS: Forty-one patients were identified and analyzed. Median age was 59 years, preoperative septic shock was diagnosed in 54% (n = 22), and 59% (n = 24) had a postoperative peritonitis. Mortality was 29% (n = 12), and 76% (n = 31) of patients were admitted in the intensive care unit. The median duration of OA was 7 days with a median of two dressing changes. Delayed primary fascial closure rate among survivors was 92% (n = 33), and enteroatmospheric fistulas developed in 7% (n = 3). In a subgroup analysis, patients with OA in the primary laparotomy for peritonitis (n = 27) were compared with patients with OA in the subsequent laparotomies (n = 14). There were no significant differences between groups. CONCLUSIONS: The VAWCM technique in patients with complicated secondary diffuse peritonitis and OA yields excellent results in terms of delayed primary fascial closure rate and a low number of enteroatmospheric fistulas. It seems to be safe to close the abdomen at the index laparotomy, if possible, even if there is a risk of a need of OA later. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV.

Microbial colonization of open abdomen in critically ill surgical patients.

INTRODUCTION: This study was designed to describe the time-course and microbiology of colonization of open abdomen in critically ill surgical patients and to study its association with morbidity, mortality and specific complications of open abdomen. A retrospective cohort analysis was done. METHODS: One hundred eleven consecutive patients undergoing vacuum-assisted closure with mesh as temporary abdominal closure method for open abdomen were analyzed. Microbiological samples from the open abdomen were collected. Statistical analyses were performed using Fisher's exact test for categorical variables. Mann-Whitney U test was used when comparing number of temporary abdominal closure changes between colonized and sterile patients. Kaplan-Meier analysis was done to calculate cumulative estimates for colonization. Cox regression analyses were performed to analyze risk factors for colonization. RESULTS: Microbiological samples were obtained from 97 patients. Of these 76 (78 %) were positive. Sixty-one (80 %) patients were colonized with multiple micro-organisms and 27 (36 %) were cultured positive for candida species. The duration of open abdomen treatment adversely affected the colonization rate. Thirty-three (34 %) patients were colonized at the time of laparostomy. After one week of open abdomen treatment 69, and after two weeks 76 patients were colonized with cumulative colonization estimates of 74 % and 89 %, respectively. Primary fascial closure rate was 80 % (61/76) and 86 % (18/21) for the colonized and sterile patients, respectively. The rate of wound complications did not significantly differ between these groups. CONCLUSIONS: Microbial colonization of open abdomen is associated with the duration of open abdomen treatment. Wound complications are common after open abdomen, but colonization does not seem to have significant effect on these. The high colonization rate described herein should be taken into account when primarily sterile conditions like acute pancreatitis and aortic aneurysmal rupture are treated with open abdomen.

Dose-dependent cysteine-mediated protection of insulin-producing cells from damage by hydrogen peroxide.

AIMS/HYPOTHESIS: Oxidative damage is believed to play a key role in the process of pancreatic beta cell destruction leading to type 1 diabetes. The beta cells are sensitive to oxidative stress because their intracellular anti-oxidative defence mechanisms are weak. The defence mechanisms depend heavily on glutathione, the synthesis of which is dependent on the availability of cysteine. We investigated whether an increased amount of cysteine available could protect beta cells from oxidative damage. METHODS: Rat insulinoma cells (RINm5F) were exposed to 50 or 100 microM hydrogen peroxide in the presence of three different cysteine concentrations (0.1, 1 and 5mM). Cell viability was analyzed by vital staining and the cellular metabolic status by C,N-diphenyl-N'-4,5-dimethyl thiazol-2-yl tetrazolium bromide (MTT) analysis. Intracellular insulin, DNA and glutathione contents were measured. The mechanism of death was further clarified by gel electrophoretic DNA fragmentation analysis. RESULTS: Hydrogen peroxide decreased cell viability and induced functional impairment. Vital staining indicated that 1mM cysteine effectively protected the cells. The protective effect was confirmed by the MTT assay showing preserved metabolic integrity, and by measurements of intact intracellular insulin and DNA content. Cysteine increased intracellular glutathione. Gel electrophoretic analysis of DNA revealed hydrogen peroxide-induced apoptotic fragmentation. This was also abolished by 1mM cysteine. The therapeutic window of cysteine was narrow: 0.1mM cysteine provided inadequate protection, and 5mM cysteine was already toxic in this setting. CONCLUSION: A proper dose of cysteine could provide a safe and effective means to protect beta cells from oxidative damage.

Mechanisms of beta cell death during restricted and unrestricted enterovirus infection.

Coxsackie B virus (CVB-5) infections potentially trigger and accelerate pancreatic beta cell damage leading to type 1 diabetes. In vivo, all viruses face natural resistance mediated by various host factors which restrict the progression of infection. Thus, the aims of this study were to generate a tissue culture model of restricted coxsackie B virus infection in primary islet cells by preventing the production of viral progeny with a selective inhibitor of viral RNA replication and to investigate the mechanisms of virus-induced islet cell death during productive and restricted infective conditions. Cultured foetal porcine islet cells were infected effectively with the prototype strain of coxsackievirus B5 (CVB-5). Nuclear viability stainings and electron microscopy showed productive infection to result in dominantly necrotic cell death with additional slight induction of apoptosis during the 7 days of follow-up. The restricted conditions were created by addition of guanidine-hydrochloride (G-HCl) into culture medium. At 1 mM concentration, it significantly protected the infected cells from necrosis and thus maintained high viability. This was associated with increased significantly apoptosis. In perifusion analysis, the cellular ability to release insulin was reduced, although the metabolic integrity was preserved as shown by MTT-analysis and cellular ATP levels. These data show that restriction of CVB-5 replication with G-HCl protects islet cells against virus-induced necrosis. However, restriction of viral replication shifts the mechanism of cell death from necrosis toward apoptosis. A slowly progressing subclinical infection of islets could thus lead to increased beta-cell apoptosis.

Mechanisms of coxsackievirus B5 mediated beta-cell death depend on the multiplicity of infection.

Coxsackievirus infections may trigger and accelerate pancreatic beta-cell death, leading to type I diabetes. Unrestricted coxsackievirus B5 replication in cultured beta-cells inoculated with high multiplicity leads to rapid lytic cell death. Evidence from other virus-host cell systems indicates that host cell responses to infection may depend on the multiplicity of infection (MOI). Thus, the aim of this study was to compare the mechanisms of beta-cell death during high versus low multiplicity of coxsackievirus B5 infection. Cultures of highly differentiated mouse insulinoma cells and primary adult human islets were infected with coxsackievirus B5 at multiplicities of >1,000 or <0.5 TCID50 per cell. The results of nuclear morphology and viability stainings, TUNEL staining and electrophoretic DNA fragmentation analysis showed high multiplicity infection to predominantly induce necrosis and transient apoptosis. In low multiplicity culture, however, necrosis was only moderately induced and apoptosis increased steadily with time. This was best demonstrated by a tenfold higher apoptosis/necrosis ratio than after high multiplicity inoculation. Expression of gamma-glutamyl cysteine synthetase increased in both infective cultures but the level of intracellular glutathione permanently depleted only at high multiplicity and recovered fully at low multiplicity. Thus, apoptosis represents an important mechanism of beta-cell death after low multiplicity of coxsackievirus B5 infection. This process is associated with maintenance of a physiological intracellular glutathione profile differing dramatically from the high multiplicity infection during which necrosis dominates and intracellular thiol balance deteriorates. These data suggest that the pattern and mechanisms of coxsackievirus B5 infection induced beta-cell death depend on the MOI.