Risk of recurrence in high-risk T1 colon cancer following endoscopic and surgical resection: registry-based cohort study.

BACKGROUND: Endoscopic resection of T1 colon cancer (CC) is currently limited by guidelines related to risk of lymph node metastases. However, clinical outcome following endoscopic and surgical resection is poorly investigated. METHOD: A retrospective multicentre national cohort study was conducted on prospectively collected data from the Swedish colorectal cancer registry on all non-pedunculated T1 CC patients undergoing surgical and endoscopic resection between 2009 and 2021. Patients were categorized on the basis of deep submucosal invasion (Sm2-3), lymphovascular invasion (LVI), poor tumour differentiation, and R1/Rx into low- and high-risk cases. The primary outcomes of interest were recurrence rates and disease-free interval (DFI, defined as time from treatment to date of recurrence) according to resection methods and risk factors (sex, age at diagnosis, histologic grade, LVI, perineural invasion, mucinous subtype, submucosal invasion, tumour location, resection margin and nodal positivity in the surgical group). RESULTS: In total, 1805 patients undergoing endoscopic (488) and surgical (1317) resection with 60.0 months median follow-up were included. Recurrence occurred in 18 (3.7%) endoscopically and 48 (3.6%) surgically resected patients. Adjuvant treatment was administered in 7.4% and 0.2% of the cases respectively in the surgical and endoscopically treated patients. Five-year DFI was 95.6% after endoscopic and 96.2% after surgical resection, with no significant difference when adjusting for confounding factors (HR 1.03, 95% c.i. 0.56 to 1.91, P = 0.920). There were no statistically significant differences in recurrence comparing endoscopic (1.7%) versus surgical (3.6%) low-risk and endoscopic (5.4%) versus surgical (3.8%) high-risk cases. LVI was the only significant risk factor for recurrence in multivariate Cox regression (HR 3.73, 95% c.i. 1.76 to 7.92, P < 0.001). CONCLUSIONS: This study shows no difference in recurrence after endoscopic and surgical resection in high-risk T1 CC. Although it was not possible to match groups according to treatment, the multivariate analysis showed that lymphovascular invasion was the only independent risk factor for recurrence.

Curriculum for training in endoscopic mucosal resection in the colon: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

Endoscopic mucosal resection (EMR) is the standard of care for the complete removal of large (≥ 10 mm) nonpedunculated colorectal polyps (LNPCPs). Increased detection of LNPCPs owing to screening colonoscopy, plus high observed rates of incomplete resection and need for surgery call for a standardized approach to training in EMR. 1 : Trainees in EMR should have achieved basic competence in diagnostic colonoscopy, < 10-mm polypectomy, pedunculated polypectomy, and common methods of gastrointestinal endoscopic hemostasis. The role of formal training courses is emphasized. Training may then commence in vivo under the direct supervision of a trainer. 2 : Endoscopy units training endoscopists in EMR should have specific processes in place to support and facilitate training. 3: A trained EMR practitioner should have mastered theoretical knowledge including how to assess an LNPCP for risk of submucosal invasion, how to interpret the potential difficulty of a particular EMR procedure, how to decide whether to remove a particular LNPCP en bloc or piecemeal, whether the risks of electrosurgical energy can be avoided for a particular LNPCP, the different devices required for EMR, management of adverse events, and interpretation of reports provided by histopathologists. 4: Trained EMR practitioners should be familiar with the patient consent process for EMR. 5: The development of endoscopic non-technical skills (ENTS) and team interaction are important for trainees in EMR. 6: Differences in recommended technique exist between EMR performed with and without electrosurgical energy. Common to both is a standardized technique based upon dynamic injection, controlled and precise snare placement, safety checks prior to the application of tissue transection (cold snare) or electrosurgical energy (hot snare), and interpretation of the post-EMR resection defect. 7: A trained EMR practitioner must be able to manage adverse events associated with EMR including intraprocedural bleeding and perforation, and post-procedural bleeding. Delayed perforation should be avoided by correct interpretation of the post-EMR defect and treatment of deep mural injury. 8: A trained EMR practitioner must be able to communicate EMR procedural findings to patients and provide them with a plan in case of adverse events after discharge and a follow-up plan. 9: A trained EMR practitioner must be able to detect and interrogate a post-endoscopic resection scar for residual or recurrent adenoma and apply treatment if necessary. 10: Prior to independent practice, a minimum of 30 EMR procedures should be performed, culminating in a trainer-guided assessment of competency using a validated assessment tool, taking account of procedural difficulty (e. g. using the SMSA polyp score). 11: Trained practitioners should log their key performance indicators (KPIs) of polypectomy during independent practice. A guide for target KPIs is provided in this document.

Transanal formation of anastomosis using C-REX device is feasible and effective in high anterior resection.

PURPOSE: C-REX is a novel instrument for creating stapleless colorectal anastomosis by compression. The aim of this study was to evaluate the feasibility and effectiveness of C-REX in open and laparoscopic high anterior resections. METHODS: A prospective clinical safety study on 21 patients reconstructed with C-REX colorectal anastomosis following high anterior resection of the sigmoid colon using two different devices for intraabdominal (n = 6) or transanal (n = 15) placement of the anastomotic rings. Any signs of complications were prospectively monitored by a predefined protocol. Anastomotic contact pressure (ACP) was measured via a catheter-based system, and time for evacuation of the anastomotic rings by the natural route was noted. Blood samples were collected daily, and flexible endoscopy was performed postoperatively to examine macroscopic appearance of the anastomoses. RESULTS: One of six patients operated with the intraabdominal anastomosis technique with an ACP of 50 mBar had to be reoperated because of anastomotic leakage. None of the 15 patients operated with the transanal technique (5 open and 10 laparoscopic procedures) had anastomotic complications, and their ACP ranged between 145 and 300 mBar. C-REX rings were uneventfully expelled by the natural route in all patients after a median of 10 days. Flexible endoscopy showed well-healed anastomoses without stenosis in 17 patients and a moderate subclinical stricture in one patient. CONCLUSION: These results indicate that the novel transanal C-REX device is a feasible and effective method for colorectal anastomosis following high anterior resections, irrespective of open or laparoscopic approach. Moreover, C-REX allows measurement of intraoperative ACP and thereby a quantitative evaluation of the anastomotic integrity.

[A new study raises unexpected questions about colonoscopy as primary screening method]. / Är koloskopi rätt metod för att screena för kolorektalcancer?

Convincing data in the literature demonstrate that screening reduces mortality in colorectal cancer. A recent study (NordICC) randomising nearly 85 000 healthy men and women drawn from population registries in Norway, Poland and Sweden to either colonoscopy or no screening reported 18 % reduction in incidence of colorectal cancer but no effect on mortality at 10-year follow-up. This finding is in contrast to previous randomised studies on sigmoidoscopy and cohort studies on coloscopy showing clear-cut effects on both colorectal cancer incidence and mortality. There could be several explanations for these discrepancies. In the NordICC study, only 42 % of the invited individuals performed a colonoscopy compared to 60-90 % in the other studies. Moreover, the follow-up time was only 10 years, and longer follow-up times will clarify the results better especially considering the fact that the number of colorectal cancer cases increases in the colonoscopy arms during the first year due to detection of presymptomatic cancers. Finally, adenoma detection rate varied a lot and nearly 30 % of the colonoscopists in the NordICC study had an adenoma detection rate below the recommended level of 25 %. Nonetheless, this is an important study that raises critical questions about colonscopy as a primary screening method for colorectal cancer.

S100A9 induces reactive oxygen species-dependent formation of neutrophil extracellular traps in abdominal sepsis.

Recent evidence suggests that targeting S100A9 reduces pathological inflammation in abdominal sepsis. Herein, we investigated the role of S100A9 in neutrophil extracellular trap (NET) formation in septic lung damage. NETs were detected by electron microscopy in the lung and by confocal microscopy in vitro. Stimulation of isolated mouse bone marrow-derived neutrophils with S100A9 triggered formation of NETs. Blocking TLR4 and RAGE reduced S100A9-induced generation of NETs and DNA-histone complexes. Moreover, S100A9 challenge increased generation of reactive oxygen species (ROS) in bone marrow neutrophils. Co-incubation with the NADPH oxidase inhibitor not only decreased ROS formation but also attenuated induction of DNA-histone complexes in S100A9-stimulated neutrophils. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Administration of the S100A9 inhibitor ABR-238901 decreased CLP-induced formation of NETs in lungs and DNA-histone complexes in plasma. In addition, transmission electron microscopy revealed that S100A9 was abundantly expressed on NETs in the lungs in CLP mice. By use of intravital microscopy, we found that local injection of NETs increased leukocyte adhesion and migration in the mouse cremaster muscle microvasculature. Notably, treatment with ABR-238901 attenuated NET-induced leukocyte adhesion and extravasation in the cremaster muscle, suggesting that NET-associated S100A9 promotes leukocyte recruitment in vivo. Taken together, these novel findings suggest that S100A9 triggers ROS-dependent formation of NETs via TLR4 and RAGE signaling in neutrophils. Moreover, S100A9 regulates both formation of NETs and NET-induced leukocyte recruitment in vivo. Thus, targeting S100A9 might be useful to ameliorate lung damage in abdominal sepsis.

[Updated Swedish guidelines for endoscopic surveillance after colorectal polypectomy]. / Nya riktlinjer: endoskopisk kontroll efter kolorektal polypektomi.

These new guidelines are based on the recommendations published by European Society of Gastrointestinal Endoscopy (ESGE) in 2020. Low risk patients, i.e. after removal of 1-4 <10 mm adenomas with low grade dysplasia (irrespective of villous components), or any serrated lesion (hyperplastic polyp, sessile serrated lesion, or traditional serrated adenoma) <10 mm without dysplasia, are not recommended a surveillance colonoscopy. High-risk patients, i.e. after removal of at least one adenoma ≥10 mm or with high grade dysplasia or any serrated lesion ≥10 mm or with dysplasia, should undergo a surveillance colonoscopy after 3 years. If high-risk lesions are detected at surveillance colonoscopy, a 3-year repetition of the next endoscopic examination is recommended. If a high-risk patient has no high-risk lesions at surveillance colonoscopy, a 5-year period is recommended until the next surveillance colonoscopy. In general, follow-up should be terminated at 80 years of age.

Risk of recurrence after endoscopic resection of nonpedunculated T1 colorectal cancer.

BACKGROUND: The long-term outcome after local excision of T1 colorectal cancer (CRC) remains unknown. The aim of this study was to examine clinical and histopathological risk factors for recurrence in patients with T1 CRC undergoing endoscopic resection. METHODS: This was a retrospective registry-based population study on prospectively collected data of all patients with nonpedunculated T1 CRC undergoing only local excision (no salvage surgery) in Sweden between 2009 and 2018. Potential risk factors for recurrence, including age, sex, tumor location, resection margins, lymphovascular, perineural, and submucosal invasion, grade of differentiation, and mucinous subtype, were analyzed using univariate and multivariate cox regression. RESULTS: Median follow-up time was 60 months, and 28 /602 patients (4.7 %) had a recurrence (13 local and 18 distant). Recurrence rate stratified by submucosal invasion was: Sm1 3.5 % (14 /397), Sm2 6.0 % (8 /133), and Sm3 8.3 % (6 /72), with no significant differences. Resection margins, lymphovascular and perineural invasion, grade of differentiation, mucinous subtype, and age were not significant risk factors for recurrence. In contrast, rectal location was found to be a significant risk factor for tumor recurrence in multivariate analysis (hazard ratio 3.08, P = 0.006). The 3- and 5-year disease-free survival was 96.2 % and 91.1 %, respectively, in T1 CRC patients undergoing endoscopic resection. CONCLUSION: Tumor recurrence was rare (4.7 %) in this large population-based study on recurrence after local excision of nonpedunculated T1 CRC. Rectal location was an independent risk factor for recurrence, suggesting the need for strict surveillance after endoscopic resection of early rectal cancer.

Actin-related protein 2/3 complex regulates neutrophil extracellular trap expulsion and lung damage in abdominal sepsis.

Neutrophil extracellular trap (NET) formation is a key feature in sepsis. The aim of the present study was to examine the role of the actin cytoskeleton in regulating the expulsion of NETs. Actin-related protein 2/3 (Arp 2/3) complex is an important regulator of F-actin polymerization. Coincubation with CK666, a specific Arp 2/3 inhibitor, decreased 12-phorbol 13-myristate acetate-induced NET formation in vitro. CK666 not only abolished F-actin polymerization but also caused intracellular retention of NETs. Inhibition of Arp 2/3 reduced NET formation on circulating neutrophils and in the bronchoalveolar space in mice undergoing cecal ligation and puncture (CLP). Notably, treatment with CK666 attenuated CLP-induced neutrophil recruitment, edema formation, and tissue damage in the lungs. Moreover, Arp 2/3 inhibition decreased levels of C-X-C motif chemokine ligand 1 (CXCL-1) and interleukin-6 in the lung and plasma of septic animals. Taken together, this study shows that expulsion of NETs is regulated by the actin cytoskeleton and that inhibition of Arp 2/3-dependent F-actin polymerization not only decreases NET formation but also protects against pathological inflammation and tissue damage in septic lung injury. Thus, we suggest that targeting NET release is a novel and useful way to ameliorate lung damage in abdominal sepsis.

Lymphovascular Infiltration, Not Depth of Invasion, is the Critical Risk Factor of Metastases in Early Colorectal Cancer: Retrospective Population-based Cohort Study on Prospectively Collected Data, Including Validation.

OBJECTIVE: To identify clinical and histopathological risk factors of LNM in T1 CRC. SUMMARY OF BACKGROUND DATA: The requisite of additional surgery after locally resected T1 CRC is dependent on the risk of LNM. Depth of submucosal invasion is used as a key predictor of lymphatic metastases although data are conflicting on its actual impact. METHODS: Retrospective population-based cohort study on prospectively collected data on all patients with T1 CRC undergoing surgical resection in Sweden, 2009-2017 and Denmark 2016-2018. The Danish cohort was used for validation. Potential risk factors of LNM investigated were; age, sex, tumor location, submucosal invasion, grade of differentiation, mucinous subtype, lymphovascular, and perineural invasion. RESULTS: One hundred fifty out of the 1439 included patients (10%) had LNM. LVI (P < 0.001), perineural invasion (P < 0.001), mucinous subtype (P = 0.006), and age <60 years (P < 0.001) were identified as independent risk factors whereas deep submucosal invasion was only a dependent (P = 0.025) risk factor and not significant in multivariate analysis (P = 0.075). The incidence of LNM was 51/882 (6%) in absence of the independent risk factors. The Danish validation cohort, confirmed our findings regarding the role of submucosal invasion, LVI, and age. CONCLUSIONS: This is a large study on LNM in T1 CRC, including validation, showing that LVI and perineural invasion, mucinous subtype, and low age constitute independent risk factors, whereas depth of submucosal invasion is not an independent risk factor of LNM. Thus, our findings provide a useful basis for management of patients after local excision of early CRC.

MiR-155 regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis.

Neutrophil extracellular traps (NETs)-mediated tissue damage is a hallmark in abdominal sepsis. Under certain conditions, microRNAs (miRs) can regulate protein expression and cellular functions. The aim of this study was to investigate the role of miR-155 in sepsis-induced NET formation, lung inflammation, and tissue damage. Abdominal sepsis was induced in wild-type (WT) C57BL/6 and miR-155 gene-deficient mice by cecal ligation and puncture (CLP). The amount of DNA-histone complex formation as well as myeloperoxidase (MPO) and citrullinated histone 3 in neutrophils isolated from bone marrow were examined by ELISA and flow cytometry. NETs were detected by electron microscopy in the septic lung. Levels of PAD4 and citrullinated histone 3 were determined by Western blot in the blood neutrophils. Lung levels of MPO, CXC chemokines, and plasma levels of DNA-histone complexes and CXC chemokines were quantified. In vitro studies revealed that neutrophils from miR-155 gene-deficient mice had less NETs forming ability than WT neutrophils. In the miR-155 gene-deficient mice, CLP yielded much less NETs in the lung tissue compared with WT control. CLP-induced PAD4 levels, histone 3 citrullination, edema, MPO activity, and neutrophil recruitment in the lung were markedly reduced in the mice lacking miR-155. Furthermore, tissue and plasma levels of CXCL1 and CXCL2 were significantly lower in the miR-155 gene-deficient mice compared with WT after induction of abdominal sepsis. Taken together, our findings suggest that miR-155 regulates pulmonary formation of NETs in abdominal sepsis via PAD4 up-regulation and histone 3 citrullination. Thus, targeting miR-155 could be a useful target to reduce pulmonary damage in abdominal sepsis.

c-Abl kinase regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis.

Sepsis is associated with exaggerated neutrophil responses although mechanisms remain elusive. The aim of this study was to investigate the role of c-Abelson (c-Abl) kinase in neutrophil extracellular trap (NET) formation and inflammation in septic lung injury. Abdominal sepsis was induced by cecal ligation and puncture (CLP). NETs were detected by electron microscopy in the lung and by confocal microscopy in vitro. Plasma levels of DNA-histone complexes, interleukin-6 (IL-6) and CXC chemokines were quantified. CLP-induced enhanced phosphorylation of c-Abl kinase in circulating neutrophils. Administration of the c-Abl kinase inhibitor GZD824 not only abolished activation of c-Abl kinase in neutrophils but also reduced NET formation in the lung and plasma levels of DNA-histone complexes in CLP mice. Moreover, inhibition of c-Abl kinase decreased CLP-induced lung edema and injury. Administration of GDZ824 reduced CLP-induced increases in the number of alveolar neutrophils. Inhibition of c-Abl kinase also markedly attenuated levels of CXC chemokines in the lung and plasma as well as IL-6 levels in the plasma of septic animals. Taken together, this study demonstrates that c-Abl kinase is a potent regulator of NET formation and we conclude that c-Abl kinase might be a useful target to ameliorate lung damage in abdominal sepsis.

E3 Ubiquitin Ligase Midline 1 Regulates Endothelial Cell ICAM-1 Expression and Neutrophil Adhesion in Abdominal Sepsis.

Septic lung damage is associated with endothelial cell and neutrophil activation. This study examines the role of the E3 ubiquitin ligase midline 1 (Mid1) in abdominal sepsis. Mid1 expression was increased in endothelial cells derived from post-capillary venules in septic mice and TNF-α challenge increased Mid1 levels in endothelial cells in vitro. The siRNA-mediated knockdown of Mid1 decreased TNF-α-induced upregulation of ICAM-1 and neutrophil adhesion to endothelial cells. Moreover, Mid1 silencing reduced leukocyte adhesion in post-capillary venules in septic lungs in vivo. The silencing of Mid1 not only decreased Mid1 expression but also attenuated expression of ICAM-1 in lungs from septic mice. Lastly, TNF-α stimulation decreased PP2Ac levels in endothelial cells in vitro, which was reversed in endothelial cells pretreated with siRNA directed against Mid1. Thus, our novel data show that Mid1 is an important regulator of ICAM-1 expression and neutrophil adhesion in vitro and septic lung injury in vivo. A possible target of Mid1 is PP2Ac in endothelial cells. Targeting the Mid1-PP2Ac axis may be a useful way to reduce pathological lung inflammation in abdominal sepsis.

The Effectiveness of a Very Low-Volume Compared to High-Volume Laxative in Colon Capsule Endoscopy.

Colon capsule endoscopy (CCE) is a promising modality for colonic investigations, but completion rates (CR) and adequate cleansing rates (ACR) must be improved to meet established standards for optical colonoscopy. Improvements should be made with patient acceptability in mind. We aimed to compare a very low-volume polyethylene glycol (PEG) laxative to a conventional high-volume laxative. We carried out a single-center retrospective comparative cohort study including patients referred for CCE. One hundred and sixty-six patients were included in the final analysis, with eighty-three patients in each group. We found a CR and ACR of 77% and 67% in the high-volume group and 72% and 75% in the very low-volume group, respectively. In the high-volume group, 54% had complete transit and adequate cleansing, whereas this was the case for 63% in the very low-volume group. No statistically significant difference in CR, ACR, or a combination of the two was found. A very low-volume bowel preparation regimen was non-inferior to a high-volume regimen before CCE in terms of CR and ACR.

Targeting S100A9 Reduces Neutrophil Recruitment, Inflammation and Lung Damage in Abdominal Sepsis.

S100A9, a pro-inflammatory alarmin, is up-regulated in inflamed tissues. However, the role of S100A9 in regulating neutrophil activation, inflammation and lung damage in sepsis is not known. Herein, we hypothesized that blocking S100A9 function may attenuate neutrophil recruitment in septic lung injury. Male C57BL/6 mice were pretreated with the S100A9 inhibitor ABR-238901 (10 mg/kg), prior to cercal ligation and puncture (CLP). Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested for analysis of neutrophil infiltration as well as edema and CXC chemokine production. Blood was collected for analysis of membrane-activated complex-1 (Mac-1) expression on neutrophils as well as CXC chemokines and IL-6 in plasma. Induction of CLP markedly increased plasma levels of S100A9. ABR-238901 decreased CLP-induced neutrophil infiltration and edema formation in the lung. In addition, inhibition of S100A9 decreased the CLP-induced up-regulation of Mac-1 on neutrophils. Administration of ABR-238901 also inhibited the CLP-induced increase of CXCL-1, CXCL-2 and IL-6 in plasma and lungs. Our results suggest that S100A9 promotes neutrophil activation and pulmonary accumulation in sepsis. Targeting S100A9 function decreased formation of CXC chemokines in circulation and lungs and attenuated sepsis-induced lung damage. These novel findings suggest that S100A9 plays an important pro-inflammatory role in sepsis and could be a useful target to protect against the excessive inflammation and lung damage associated with the disease.

Transcriptomic Analysis Reveals Differential Expression of Genes between Lung Capillary and Post Capillary Venules in Abdominal Sepsis.

Lung endothelial cell dysfunction plays a central role in septic-induced lung injury. We hypothesized that endothelial cell subsets, capillary endothelial cells (capEC) and post capillary venules (PCV), might play different roles in regulating important pathophysiology in sepsis. In order to reveal global transcriptomic changes in endothelial cell subsets during sepsis, we induced sepsis in C57BL/6 mice by cecal ligation and puncture (CLP). We confirmed that CLP induced systemic and lung inflammation in our model. Endothelial cells (ECs) from lung capillary and PCV were isolated by cell sorting and transcriptomic changes were analyzed by bioinformatic tools. Our analysis revealed that lung capEC are transcriptionally different than PCV. Comparison of top differentially expressed genes (DEGs) of capEC and PCV revealed that capEC responses are different than PCV during sepsis. It was found that capEC are more enriched with genes related to regulation of coagulation, vascular permeability, wound healing and lipid metabolic processes after sepsis. In contrast, PCV are more enriched with genes related to chemotaxis, cell-cell adhesion by integrins, chemokine biosynthesis, regulation of actin filament process and neutrophil homeostasis after sepsis. In addition, we predicted some transcription factor targets that regulate a significant number of DEGs in sepsis. We proposed that targeting certain DEGs or transcriptional factors would be useful in protecting against sepsis-induced lung damage.

Cost comparisons of endoscopic and surgical resection of stage T1 rectal cancer.

Background and study aims Management of T1 rectal cancer is complex and includes several resection methods, making cost comparisons challenging. The aim of this study was to compare costs of endoscopic and surgical resection and to investigate hypothetical cost scenarios for the treatment of T1 rectal cancer. Patients and methods Retrospective population-based cost minimization study on prospectively collected data on T1 rectal cancer patients treated using endoscopic submucosal dissection (ESD), transanal endoscopic microsurgery (TEM), open, laparoscopic, or robotic resection, in Skåne County, Sweden (2011-2017). The hypothetical cost scenarios were based on the distribution of high-risk features of lymph node metastases in a national cohort (2009-2017). Results Eighty-five patients with T1 RC undergoing ESD (n = 16), TEM (n = 17), open (n = 35), laparoscopic (n = 9), and robotic (n = 8) resection were included. ESD had a total 1-year cost of 5165 €â€Šand was significantly ( P  < 0.05) less expensive compared to TEM (14871€), open (21 453 €), laparoscopic (22 488 €) and robotic resection (26 562 €). Risk factors for lymph node metastases were seen in 68 % of 779 cases of T1 rectal cancers included in the national cohort. The hypothetical scenario of performing ESD on all T1 RC had the lowest total 1-year per patient cost compared to all other alternatives. Conclusions This is the first study analyzing total 1-year costs of endoscopic and surgical methods to resect T1 rectal cancer, which showed that the cost of ESD was significantly lower compared to TEM and surgical resection. In fact, based on hypothetical cost scenarios, ESD is still justifiable from a cost perspective even when all high-risk cases are followed by surgery in accordance to guidelines.

Heparin-binding protein is significantly increased in acute pancreatitis.

BACKGROUND: Most patients with acute pancreatitis (AP) experience mild, self-limiting disease with little or no need for hospital care. However, 20-25% of patients develop a more severe and potentially life-threatening condition with progressive systemic inflammatory response syndrome (SIRS) and multiorgan failure, resulting in high morbidity and mortality rates. Predicting disease severity at an early stage is important, as immediate supportive care has been demonstrated to reduce the incidence of SIRS and organ failure, improving patient outcome. Several studies have demonstrated elevated levels of heparin-binding protein (HBP) in patients with sepsis and septic shock, and HBP is believed to play a part in endothelial dysfunction leading to vascular leakage. As HBP levels increase prior to other known biomarkers, HBP has emerged as a promising early predictor of severe sepsis with organ dysfunction. METHODS: Patients admitted to Skåne University Hospital in Malmö between 2010 and 2013 fulfilling the criteria for AP were identified in the emergency department and prospectively enrolled in this study. The primary outcome was measured levels of HBP upon hospital admission in patients with confirmed AP. Correlations among HBP concentrations, disease severity and fluid balance were considered secondary endpoints. The correlation between HBP levels and fluid balance were analysed using Pearson correlation, and the ability of HBP to predict moderately severe/severe AP was assessed using a receiver operating characteristic (ROC) curve. RESULTS: The overall median HBP level in this study was 529 (307-898) ng/ml. There were no significant group differences in HBP levels based on AP severity. Fluid balance differed significantly between patients with mild versus moderately severe and severe pancreatitis, but we found no correlation between HBP concentration and fluid balance. CONCLUSIONS: HBP levels are dramatically increased in patients with AP, and these levels far exceed those previously reported in other conditions. In this study, we did not observe any significant correlation between HBP levels and disease severity or the need for intravenous fluid. Additional studies on HBP are needed to further explore the role of HBP in the pathogenesis of AP and its possible clinical implications.

Neutrophil Extracellular Traps in Colorectal Cancer Progression and Metastasis.

Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.