CT prognostic signs of postoperative complications in emergency surgery for acute obstructive colonic cancer.

PURPOSE: To identify CT prognostic signs of poor outcomes in acute obstructive colonic cancer (AOCC). METHODS: Demographic, clinical, laboratory, radiological and surgical data of 65 consecutive patients with AOCC who underwent emergency surgery were analyzed. CT exams were reviewed to assess diameters of cecum, ascending, transverse, descending, and sigmoid proximal to the tumor; colon segments' CD/L1-VD ratios, continence of the ileocecal valve, small bowel overdistension, presence of small bowel feces sign and cecal pneumatosis. Post Operative complications (PO), according to the Clavien-Dindo classification, were analyzed. RESULTS: Gender, age and location of the tumor were not predictive factors of complications. Among laboratory exams, CRP was the most important predictive value of PO (OR 8.23). A cecum distension ≥ 9 cm represented the critical diameter beyond which perforation and cecal necrosis were found at surgery. Cecal pneumatosis at CT was correlated with cecal necrosis at surgery in < 50% of patients. Pre-operative transverse colon CD/L1-VD ratio ≥ 1.43 and descending colon CD/L1-VD ratio ≥ 1.31 were associated with the development of PO (grade ≥ III-V). PO (grade ≥ III-V) occurred in 18/65 patients. CONCLUSION: Postoperative complications in emergency surgery of AOCC were not related to the age, sex and tumor's location. Preoperative PCR values (≥ 2.17) predict the development of postoperative complications. CT resulted a valid diagnostic tool to identify patients at higher risk of complications: a CD/L1-VD ratios with cut-off values of 1.43 (transverse) and 1.31 (descending) predicted major complications (grade ≥ III-V) and a cecum distension ≥ 9 cm represented the critical diameter beyond which perforation occurred in > 84% of patients.

[Prognostic factors: Degree of subserosal invasion, tumor-serosal distance and subserosal elastic boundary invasion in colonic adenocarcinoma]. / Facteurs pronostiques : degré d'invasion de la sous-séreuse, distance tumeur-séreuse et invasion de la limitante élastique de la sous-séreuse dans l'adénocarcinome colique.

The aim was to study the prognostic impact of tumor infiltration of the subserosa in colonic adenocarcinoma, by evaluating the degree of tumor infiltration in the subserosa (DISS), tumor-serosa distance (DTS), and invasion of the elastic boundary of the subserosa (ILE) after elastic fiber staining. MATERIAL AND METHODS: All patients operated on for colonic adenocarcinoma classified as pT3 without lymph node or visceral metastasis operated on at the CHU d'Amiens between 2004 and 2017 were included. All slides were reviewed by 2 pathologists. Bivariate and subgroup analyses were performed according to the presence of a DISS≤5mm or>5mm, a DTS≤1mm or>1mm and the presence or absence of an ILE. These statistical analyses were then correlated with the 5-year survival. RESULTS: One hundred and one patients were included in the study. We performed elastic fiber staining on an average of 2 tumor blocks per case and 39.6% of patients had invasion of the elastic boundary. However, bivariate and subgroup analyses showed no statistically significant association between DISS, DTS or ILE and 5-year survival. CONCLUSION: None of these three histopathological criteria proved to have prognostic value in our series, contrary to some results in the literature. However, as these data are subject to a number of confounding factors, we do not recommend that pathologists specify these different criteria in their reports.

Robot-assisted versus laparoscopic short- and long-term outcomes in complete mesocolic excision for right-sided colonic cancer: a systematic review and meta-analysis.

BACKGROUND: Complete mesocolic excision (CME) surgery is increasingly implemented for the resection of right-sided colonic cancer, possibly resulting in improved 5-year overall and disease-free survival compared to non-CME surgery. However, it is not clear what surgical platform should be used. The aim of this study was to compare the following outcomes between robot-assisted and laparoscopic CME-surgery for right-sided colonic cancer: (i) short-term clinical outcomes, (ii) pathological specimen quality, and (iii) long-term oncological outcomes. METHODS: Medline, Embase, and Cochrane Database of Systematic Reviews were searched from inception until August 2021. Pooled proportions were calculated by applying the inverse variance method. Heterogeneity was explored by I-square and supplemented by sensitivity- and meta-regression analyses. The risk of bias was evaluated by either MINORS or Cochrane's risk-of-bias tool (RoB 2). RESULTS: Fifty-five studies with 5.357 patients (740 robot-assisted and 4617 laparoscopic) were included in the meta-analysis. Overall postoperative morbidity was 17% [95% CI (14-20%)] in the robot-assisted group and 13% [95%CI (12-13%)] in the laparoscopic group. Robot-assisted CME was associated with a shorter hospital stay, lower intraoperative blood loss, a higher amount of harvested lymph nodes, and better 3-year oerall and disease-free survival. MINORS and RoB2 indicated a serious risk of bias across studies included. CONCLUSIONS: This review which includes predominantly non-randomized studies suggests a possible advantage of the robot-assisted CME compared with a laparoscopic technique for several short-term outcomes.

Re-interpreting mesenteric vascular anatomy on 3D virtual and/or physical models: positioning the middle colic artery bifurcation and its relevance to surgeons operating colon cancer.

BACKGROUND: The impact of the position of the middle colic artery (MCA) bifurcation and the trajectory of the accessory MCA (aMCA) on adequate lymphadenectomy when operating colon cancer have as of yet not been described and/or analysed in the literature. The aim of this study was to determine the MCA bifurcation position to anatomical landmarks and to assess the trajectory of aMCA. METHODS: The colonic vascular anatomy was manually reconstructed in 3D from high-resolution CT datasets using Osirix MD and 3-matic Medical and analysed. CT datasets were exported as STL files and supplemented with 3D printed models when required. RESULTS: Thirty-two datasets were analysed. The MCA bifurcation was left to the superior mesenteric vein (SMV) in 4 (12.1%), in front of SMV in 17 (53.1%) and right to SMV in 11 (34.4%) models. Median distances from the MCA origin to bifurcation were 3.21 (1.18-15.60) cm. A longer MCA bifurcated over or right to SMV, while a shorter bifurcated left to SMV (r = 0.457, p = 0.009). The main MCA direction was towards right in 19 (59.4%) models. When initial directions included left, the bifurcation occurred left to or anterior to SMV in all models. When the initial directions included right, the bifurcation occurred anterior or right to SMV in all models. The aMCA was found in 10 (31.3%) models, following the inferior mesenteric vein (IMV) in 5 near the lower pancreatic border. The IMV confluence was into SMV in 18 (56.3%), splenic vein in 11 (34.4%) and jejunal vein in 3 (9.4%) models. CONCLUSION: Awareness of the wide range of MCA bifurcation positions reported is crucial for the quality of lymphadenectomy performed. The aMCA occurs in 31.3% models and its trajectory is in proximity to the lower pancreatic border in one half of models, indicating that it needs to be considered when operating splenic flexure cancer.

Tunnel versus medial approach in laparoscopic radical right hemicolectomy for right colon cancer: a retrospective cohort study.

PURPOSE: This study aimed to explore the feasibility and safety of the tunnel approach in laparoscopic radical right hemicolectomy for colon cancer. METHODS: From July 2016 to October 2018, a total of 106 consecutive patients with colon cancer who underwent laparoscopic radical right hemicolectomy at the Affiliated Cancer Hospital of Zhengzhou University were enrolled. The patients were stratified into either a tunnel approach (TA) (n = 56) group or traditional medial approach (MA) (n = 50) group according to the surgical technique performed. The baseline demographics, perioperative outcomes and oncologic outcomes were compared between the two groups. RESULTS: The baseline characteristics did not differ between groups. The TA group had significantly less blood loss [20.0 (10.0-40.0) vs. 100 (100.0-150.0) ml, p < 0.001] and a shorter operation time [128.4 ± 16.7 vs. 145.6 ± 20.3 min, p < 0.001] than the MA group. The time to first flatus and postoperative hospital stay were similar [3.0 (2.0-4.0) vs. 3.0 (3-4.0) days, p = 0.329; 10.4 ± 2.6 vs. 10.7 ± 3.0 days, p = 0.506] between the two groups. The conversion to laparotomy and complication rates were similar between groups (0 vs. 6.0%, p = 0.203; 14.3% vs. 18.0%, p = 0.603, respectively). No treatment-related deaths occurred in either group. The TA group did not have significantly better survival outcomes than the MA group (p = 0.372). CONCLUSIONS: The TA seems to allow for more favourable results in terms of blood loss and operative time than the MA, with similar results regarding time to first flatus, hospital stay, postoperative complication rate, conversion rate and oncologic outcomes; moreover, the TA is easier for beginners to master.

LEF1 Enhances the Progression of Colonic Adenocarcinoma via Remodeling the Cell Motility Associated Structures.

Lymphoid enhancer-binding factor 1 (LEF1) is a key transcription factor mediating the Wnt signaling pathway. LEF1 is a regulator that is closely associated with tumor malignancy and is usually upregulated in cancers, including colonic adenocarcinoma. The underlying molecular mechanisms of LEF1 regulation for colonic adenocarcinoma progression remain unknown. To explore it, the LEF1 expression in caco2 cells was inhibited using an shRNA approach. The results showed that downregulation of LEF1 inhibited the malignancy and motility associated microstructures, such as polymerization of F-actin, ß-tubulin, and Lamin B1 in caco2 cells. LEF1 inhibition suppressed the expression of epithelial/endothelial-mesenchymal transition (EMT) relevant genes. Overall, the current results demonstrated that LEF1 plays a pivotal role in maintaining the malignancy of colonic adenocarcinoma by remodeling motility correlated microstructures and suppressing the expression of EMT-relevant genes. Our study provided evidence of the roles LEF1 played in colonic adenocarcinoma progression, and suggest LEF1 as a potential target for colonic adenocarcinoma therapy.

[Right ventricle metastasis from a colonic cancer: Diagnosis by using endomyocardial biopsy]. / Métastase ventriculaire droite d'un adénocarcinome colique : diagnostic par biopsie endomyocardique.

The diagnosis of cardiac tumors has been dramatically improved by modern cardiac imaging. In cases presenting with right intracavitary mass the diagnosis can rely on right endomyocardial biopsy. We report here a case of right ventricle tumor whose diagnosis was established as a colonic metastasis by using right endomyocardial biopsy.

A 10-year review of colonoscopy at aminu kano teaching hospital, Kano Nigeria.

BACKGROUND: Colonoscopy is an investigation modality used for colorectal examination; it is the most accurate technique for the diagnosis and surveillance of important colorectal diseases such as cancers (colorectal cancer) and polyps. Aims: Most studies on colonoscopy in Nigeria were conducted in southwest such as Ilorin, Ife, Ibadan, and Lagos. We therefore feel the need to get information from other regions such as northwest, the area of this study. The aim of this study was to identify the common indications as well as colonoscopic findings among patients who had colonoscopy in Aminu Kano Teaching Hospital, Kano. METHODOLOGY: It was a 10-year retrospective descriptive study of patients who had colonoscopy between January 2008 and December 2017 at the study center. Colonoscopy register was used to extract information concerning the patient's age, gender, symptoms that necessitated the request for the procedure, and the endoscopic findings. RESULTS: A total of 839 patient records were reviewed, males constituted 62.2% of the patients. The mean age ± standard deviation was 43.86 ± 18.36 years, with a range of 8-96 years. The 30-39 years constituted the modal age group, followed by 40-49 years and 50-59 years. The commonest indications for the procedure were rectal bleeding (52.4%), chronic abdominal pain (51.3%), and diarrhea (48.8%). The cecal intubation rate was 98.2% with hemorrhoids as the commonest finding (42.3%) followed by suspected inflammatory bowel disease lesions (18.1%) and suspected colorectal tumors (16.2%). CONCLUSION: The commonest reason for colonoscopy was rectal bleeding while the commonest colonoscopic finding was hemorrhoids.

Zinc finger protein 750(ZNF750), negatively regulated by miR-17-5p, inhibits proliferation, motility and invasion of colonic cancer cells.

BACKGROUND: The present study aimed to investigate the expression, function and clinical implication of zinc finger protein 750 (ZNF750) in colonic cancer and explore the mechanism of its dysregulation. METHODS: The expression of ZNF750 in 76 pairs of colonic cancer tissues was determined using immunohistochemistry. The expression of ZNF750 in colonic cancer cells was detected using western blotting. The correlation between the expression level of ZNF750 and clinicopathological parameters in patients with colonic cancer was analyzed using a chi-squared test. CCK-8 and colony formation assays were used to monitor cell proliferation. Additionally, flow cytometry was used to detect apoptosis of cells; scratch healing and Transwell assays were conducted to evaluate the migration and invasion of cells. Ultimately, the binding relationship between miR-17-5p and ZNF750 was validated using western blotting, a real-time polymerase chaub reaction and a dual-luciferase reporter gene assay. RESULTS: The expression level of ZNF750 in colonic cancer tissues, as well as colonic cancer cell lines, was significantly down-regulated. Low expression of ZNF750 was associated with larger tumor size and poor tumor differentiation. The over-expression of ZNF750 inhibited the proliferation, motility and invasion but promoted the apoptosis of colonic cancer cells. After the cells were transfected with miR-17-5p mimics, the expression of ZNF750 at both mRNA and protein levels was markedly decreased, whereas the expression of ZNF750 was markedly increased after transfection of miR-17-5p inhibitors. MiR-17-5p could suppresses the malignant biological behaviors via negatively regulating ZNF750. CONCLUSIONS: ZNF750 is negatively regulated by miR-17-5p and inhibits the progression of colonic cancer.

Colon sparing resection versus extended colectomy for left-sided obstructing colon cancer with caecal ischaemia or perforation: a nationwide study from the French Surgical Association.

AIM: It is not known whether patients with obstructive left colon cancer (OLCC) with caecal ischaemia or diastatic perforation (defined as a blowout of the caecal wall related to colonic overdistension) should undergo a (sub)total colectomy (STC) or an ileo-caecal resection with double-barrelled ileo-colostomy. We aimed to compare the results of these two strategies. METHOD: From 2000 to 2015, 1220 patients with OLCC underwent surgery by clinicians who were members of the French Surgical Association. Of these cases, 201 (16%) were found to have caecal ischaemia or diastatic perforation intra-operatively: 174 patients (87%) underwent a STC (extended colectomy group) and 27 (13%) an ileo-caecal resection with double-end stoma (colon-sparing group). Outcomes were compared retrospectively. RESULTS: In the extended colectomy group, 95 patients (55%) had primary anastomosis and 79 (45%) had a STC with an end ileostomy. In the colon-sparing group, 10 patients (37%) had simultaneous resection of their primary tumour with segmental colectomy and an anastomosis which was protected by a double-barrelled ileo-colostomy. The demographic data for the two groups were comparable. Median operative time was longer in the STC group (P = 0.0044). There was a decrease in postoperative mortality (7% vs 12%, P = 0.75) and overall morbidity (56% vs 67%, P = 0.37) including surgical (30% vs 40%, P = 0.29) and severe complications (17% vs 27%, P = 0.29) in the colon-sparing group, although these differences did not reach statistical significance. Cumulative morbidity included all surgical stages and the rate of permanent stoma was 66% and 37%, respectively, with no significant difference between the two groups. Overall survival and disease-free survival were similar between the two groups. CONCLUSION: The colon-sparing strategy may represent a valid and safe alternative to STC in OLCC patients with caecal ischaemia or diastatic perforation.

A meta-analysis comparing hand-assisted laparoscopic right hemicolectomy and open right hemicolectomy for right-sided colon cancer.

BACKGROUND: Mini-invasive colorectal cancer surgery was adopted widely in recent years. This meta-analysis aimed to compare hand-assisted laparoscopic surgery (HALS) with open right hemicolectomy (OS) for malignant disease. METHODS: PRISMA guidelines with random effects model were adopted using Review Manager Version 5.3 for pooled estimates. RESULTS: Seven studies that involved 506 patients were included. Compared to OS, HALS improved results in terms of blood loss (MD = 53.67, 95% CI 10.67 to 96.67, p = 0.01), time to first flatus (MD = 21.11, 95% CI 14.99 to 27.23, p < 0.00001), postoperative pain score, and overall hospital stay (MD = 3.47, 95% CI 2.12 to 4.82, p < 0.00001). There was no difference as concerns post-operative mortality, morbidity (OR = 1.55, 95% CI 0.89 to 2.7, p = 0.12), wound infection (OR = 1.69, 95% CI 0.60 to 4.76, p = 0.32), operative time (MD = - 16.10, 95% CI [- 36.57 to 4.36], p = 0.12), harvested lymph nodes (MD = 0.59, 95% CI - 0.18 to 1.36, p = 0.13), and recurrence (OR = 0.97, 95% CI 0.30 to 3.15, p = 0.96). CONCLUSIONS: HALS is an efficient alternative to OS in right colectomy which combines the advantages of OS with the mini-invasive surgery.

Correlation between a continent ileocecal valve and CT signs of severity in patients presenting with obstructive colonic cancer.

OBJECTIVE: To study the association of a continent ileocecal valve and the degree of severity of the CT signs in patients presenting with large bowel obstruction due to colonic cancer. PATIENTS AND METHODS: Sixty-six patients undergoing emergency surgery for confirmed obstructive colonic cancer were included. The CT examinations were analyzed without consultation of the surgical results. For each patient, the diameter of the cecum at its widest point and that of the last ileal loop were measured. The ileocecal valve was considered incontinent when there was a distension of the last ileal loop greater than or equal to 25 mm. Below 25 mm, the ileocecal valve was considered continent. The presence of CT signs of severity of the LBO was noted, i.e., intestinal pneumatosis, absence of contrast enhancement of the large bowel wall, defect in the large bowel wall, and presence of extra-digestive air and ascites. RESULTS: Among the 66 patients included, 42 had an incontinent ileocecal valve and 24 had a continental ileocecal valve. There was a statistically significant difference between the two groups in the diametrical measurements of the cecum's widest point (mean diameter measured at 10.3 cm in patients with continent ileocecal valve vs 8.4 cm in patients with incontinent ileocecal valve, P = 0.0023). Patients with a continent valve had statistically higher rates of CT severity (79% vs 40%, P < 0.005). Perforation of the cecum remained rare (8%) and was only observed in patients with continent ileocecal valve in our series. CONCLUSION: Continence of the ileocecal valve appears to be statistically correlated both with cecum distension and the presence of CT signs of severity in patients with obstructive colonic cancer. As such, its presence must be retained as a risk factor for a pejorative evolution of this type of LBO and must be specified in the CT report of these patients.

Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi-centre, prospective audit.

INTRODUCTION: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). METHODS: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. RESULTS: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30-0.92, P = 0.02) but MBP was not (OR 0.92, 0.63-1.36, P = 0.69) compared to NBP. CONCLUSION: This non-randomised study adds 'real-world', contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice.

Endoscopic ultrasonography and computed tomography scanning for preoperative staging of colonic cancer.

PURPOSE: With an increasing demand for more accurate preoperative staging methods for colon cancer, we aimed to compare preoperative tumour (T)- and nodal (N)-stage in patients with left-sided colon cancer by endoscopic ultrasonography (EUS) and computed tomography (CT) with post-operative histology as gold standard. METHODS: A total of 44 patients were prospectively recruited at Herlev and Roskilde University Hospitals during November 2014-January 2016. Thirty-five patients were included in the final analysis and underwent EUS, CT and surgery within 2 weeks. Diagnostic values were evaluated for "low risk" (T1+T2+T3 with ≤5 mm extramural invasion) and "high risk" (T3 with >5 mm of extramural spread + T4) colonic cancer. RESULTS: Sensitivity and specificity in "low risk" colonic cancer evaluated with EUS was 0.90 [0.74;0.98] and 0.75 [0.19;0.99] and with CT 0.96 [0.80;0.99] and 0.25 [<0.01;0.81]. EUS and CT were poor in predicting N0 or N+ disease. CONCLUSIONS: The sensitivity of EUS and CT were good and comparable regarding T-stage evaluation, while EUS had a significantly higher specificity in the evaluation of "low risk" tumours. The results obtained for "high risk" colonic cancer were difficult to evaluate due to small patient numbers. EUS could be considered as a supplement to CT scans in selecting patients for neoadjuvant therapies, or local transmural treatment, in the future. TRIAL REGISTRATION: NCT02324023.

Type of incision does not predict abdominal wall outcome after emergency surgery for colonic anastomotic leakage.

PURPOSE: Most literature on abdominal incision is based on patients undergoing elective surgery. In a cohort of patients with anastomotic leakage after colonic cancer resection, we analyzed the association between type of incision, fascial dehiscence, and incisional hernia. METHODS: Data were extracted from the Danish Colorectal Cancer Group database and merged with information from the Danish National Patient Register. All patients with anastomotic leakage after colonic resection in Denmark from 2001 until 2008 were included and surgical records on re-operations were retrieved. The primary outcome of the study was incisional hernia formation, and the secondary outcome was fascial dehiscence. Multivariable logistic, Cox, and competing risks regression analysis, as well as propensity score matching were used for confounder control. RESULTS: A total of 363 patients undergoing reoperation for anastomotic leakage were included with a median follow-up of 5.4 years. Incisional hernia occurred in 41 of 227 (15.3%) patients undergoing midline incision compared with 14 of 81 (14.7%) following transverse incision, P = 1.00. After adjusting for confounders, there was no association between the type of incision and incisional hernia (transverse incision hazard ratio 1.36, 0.68-2.72, P = 0.390) or fascial dehiscence (transverse incision odds ratio 1.66, 0.57-4.49, P = 0.331). This conclusion was confirmed after propensity score matching, P = 0.507. CONCLUSIONS: In the current study, type of incision did not predict abdominal wall outcome after emergency surgery for colonic anastomotic leakage.

Long non-coding ribonucleic acid zinc finger antisense 1 promotes the progression of colonic cancer by modulating ZEB1 expression.

BACKGROUND AND AIM: Long non-coding RNA zinc finger antisense 1 (ZFAS1) is frequently amplified in hepatocellular carcinoma and promotes metastasis by increasing zinc finger E-box binding homeobox 1 (ZEB1), which can potentiate the progression of epithelial-to-mesenchymal transition (EMT). However, the expression pattern and role of ZFAS1 in colonic cancer remains unknown. The present study aimed to investigate the role of ZFAS1 and its clinical significance in colonic cancer. METHODS: Paired clinical colonic cancer tissue samples and clinicopathologic characteristics of 73 patients were analyzed. Quantitative real-time polymerase chain reaction analysis was used to evaluate expression levels of ZFAS1 in colonic cancer tissues, cell lines, and plasma. ZEB1 and EMT-related markers expression levels also were explored. Cell biology assays were used to explore the biologic consequences of ZFAS1 in regulating cell proliferation and invasion, as well as the roles in regulating EMT. RESULTS: Zinc finger antisense 1 was up-regulated in colonic cancer tissues compared with adjacent mucosa (P < 0.01), and its expression level was significantly correlated with TNM stage, vascular invasion, and lymph node metastasis (P < 0.05). ZFAS1 and ZEB1 were also increased in patients' plasma. Moreover, ZFAS1 promoted proliferation, invasion, and impeded apoptosis. Knockdown of ZFAS1 decreased expression of ZEB1 and increased the epithelial markers E-cadherin, ZO-1 while decreasing mesenchymal markers vimentin and N-cadherin. CONCLUSIONS: Long non-coding RNA ZFAS1 may function as an oncogene by modulating ZEB1 to induce EMT. Manipulation of ZFAS1 level may be a novel approach to suppress colonic cancer progression. In addition, ZFAS1 in plasma has the potential to be a diagnostic biomarker of colonic cancer.

"Ultra" E.R.A.S. in laparoscopic colectomy for cancer: discharge after the first flatus? A prospective, randomized trial.

BACKGROUND: Enhanced Recovery After Surgery (E.R.A.S.) programs are now widely accepted in colonic laparoscopic resections because of faster recovery and less perioperative complications. The aim of this study was to assess safety and feasibility of discharging patients operated on by laparoscopic colectomy on postoperative day 2, so long as the first flatus has passed and in the absence of complication-related symptoms. METHODS: This study was a non-inferiority, open-label, single-center, prospective, randomized study comparing "Ultra" to Classic E.R.A.S. with discharge on POD 2 and 4, respectively. Seven hundred and sixty-five patients with resectable non-metastatic colonic cancer were analyzed: 384 patients were assigned to "Ultra" E.R.A.S. and 381 to Classic E.R.A.S. Primary end-point was mortality; secondary end-points were morbidity, readmission and reoperation rate. Limitations are: it is a single-center experience; it is not double-blind, with the intrinsic risk of intentional or unconscious bias; exclusion criteria because of "non-compliance" may be considered arbitrary. RESULTS: Mortality was 0.89 % in "Ultra" E.R.A.S. group and 0.59 % in Classic E.R.A.S. (p = 0.571). Morbidity was 34.1 % for "Ultra" E.R.A.S. arm and 35.4 % for Classic E.R.A.S. (p = 0.753). Readmissions were 5.6 % for "Ultra" E.R.A.S. and 5.9 % for Classic E.R.A.S. (p = 0.359). Reoperation rate was 3.8 % for "Ultra" ERAS and 4.7 % for Classic E.R.A.S. (p = 0.713). Multivariate regression analyses using Cox's proportional hazard model showed that mortality (primary end-point), morbidity, reoperation and readmission (secondary end-points) were not significantly influenced by the two different perioperative regimens; conversely, the global cost of "Ultra" E.R.A.S. regimen was more economically effective. CONCLUSION: "Ultra" E.R.A.S. showed to be safe, actual and effective; discharge on postoperative day 2 after the first flatus passage, in the absence of complication-related symptoms, should be actively considered in a modern, multidisciplinary, multimodal laparoscopic management of colonic cancer.

Cytotoxic effect of different treatment parameters in pressurized intraperitoneal aerosol chemotherapy (PIPAC) on the in vitro proliferation of human colonic cancer cells.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been recently reported as a new approach for intraperitoneal chemotherapy (IPC). By means of a patented micropump, the liquid chemotherapy is delivered into the peritoneal cavity as an aerosol which is supposed to achieve "gas-like" distribution. However, recent data report that the fraction of the submicron aerosol (gas-like) is less than 3 vol% of the total amount of aerosolized chemotherapy. Until today, possible modifications of treatment parameters during PIPAC with the aim of improving therapeutic outcomes have not been studied yet. This study aims to establish an in vitro PIPAC model to explore the cytotoxic effect of the submicron aerosol fraction and to investigate the impact of different application parameters on the cytotoxic effect of PIPAC on human colonic cancer cells. METHODS: An in vitro model using HCT8 colon adenocarcinoma wild-type cells (HCT8WT) and multi-chemotherapy refractory subline (HCT8RT) was established. Different experimental parameters such as pressure, drug dosage, time exposure, and system temperature were monitored in order to search for the conditions with a higher impact on cell toxicity. Cell proliferation was determined by means of colorimetric MTT assay 48 h following PIPAC exposures. RESULTS: Standard operational parameters applied for PIPAC therapy depicted a cytotoxic effect of the submicron aerosol fraction generated by the PIPAC micropump. We also observed that increasing pressure significantly enhanced tumor cell toxicity in both wild-type and chemotherapy-resistant cells. A maximum of cytotoxicity was observed at 15 mmHg. Pressure >15 mmHg did not show additional cytotoxic effect on cells. Increased oxaliplatin dosage resulted in progressively higher cell toxicity as expected. However, in resistant cells, a significant effect was only found at higher drug concentrations. Neither an extension of exposure time nor an increase in temperature of the aerosolized chemotherapy solution added an improvement in cytotoxicity. CONCLUSIONS: In this in vitro PIPAC model, the gas-like PIPAC aerosol fraction showed a cytotoxic effect which was enhanced by higher intra-abdominal pressure with a maximum at 15 mmHg. Similar findings were observed for drug dose escalation. A phase I dose escalation study is currently performed at our institution. However, increasing the intra-abdominal pressure might be a first and simple way to enhance the cytotoxic effect of PIPAC therapy which needs further clinical investigations.

Preparation and Bioactivity Assessment of Chitosan-1-Acetic Acid-5-Flurouracil Conjugates as Cancer Prodrugs.

5-fluorouracil (5-FU) is a specific anti-cancer agent that is generally used to treat gastrointestinal, colorectal, and breast cancer. In this work, chitosan (CS) was extracted from local fish scales using an established method. 5-FU was then converted to 1-acetic acid-5-fluorouracil (FUAC) and reacted with this CS to prepare chitosan-1-acetic acid-5-fluorouracil (CS-FUAC) conjugates as a colon-specific prodrug. All compounds were characterized by Proton nuclear magnetic resonance (¹H-NMR), Fourier-transform infrared (FTIR), and UV-visible spectroscopy. The synthesized compound was subjected to a chemical stability study in phosphate buffer (0.2 M, pH 7.4) and in KCl/HCl buffer (0.2 M, pH 1.2) at different time intervals (0-240 min) and incubation at 37 °C. This revealed a significantly greater stability and a longer half-life for the CS-FUAC than for FUAC. Hemolytic activity results indicated a much lower toxicity for CS-FUAC than for 5-FU and supported consideration of CS-FUAC for further biological screening and application trials. The percentage of FUAC in the conjugates was determined by subjecting the prodrug to treatment in basic media to hydrolyze the amide bond, followed by absorbency measurements at 273 nm. The cytotoxicity studies of the conjugates were also evaluated on human colorectal cancer cell line (HT-29), which showed that the conjugates are more cytotoxic than the free drug. Therefore, CS-FUAC conjugates can be considered to represent potential colon-specific drug delivery agents, with minimal undesirable side effects, for colon cancer therapy.

The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention.