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Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data.
Jongeneel, G, Klausch, T, van Erning, FN, Vink, GR, Koopman, M, Punt, CJA, Greuter, MJE, Coupé, VMH
International journal of cancer. 2020;(11):2968-2978
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Abstract
There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease-free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real-world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient-level data from reported DFS data and (iii) estimating treatment effect in the patient-level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient-level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups.
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Comparing the safety, efficacy, and oncological outcomes of laparoscopic and open colectomy in transverse colon cancer: a meta-analysis.
Baloyiannis, I, Perivoliotis, K, Ntellas, P, Dadouli, K, Tzovaras, G
International journal of colorectal disease. 2020;(3):373-386
Abstract
INTRODUCTION In order to compare the safety, efficacy, and oncological outcomes of laparoscopic (LC) and open colectomy (OC) for transverse colon cancer (TCC) patients, the present systematic review of the literature and meta-analysis was designed. METHODS This study was conducted following the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. A systematic screening of the electronic databases was performed (Medline, Web of Science and Scopus). The validity of the pooled results was verified through the performance of trial sequential analysis (TSA). The level of evidence was estimated using the GRADE approach. RESULTS Overall, 21 studies and 2498 patients were included in our study. Pooled comparisons and TSA analyses reported a superiority of LC over OC in terms of postoperative complications (OR 0.64, p = 0.0003), blood loss (WMD - 86.84, p < 0.00001), time to first flatus (WMD - 0.94, p < 0.00001) and oral diet (WMD - 1.25, p < 0.00001), and LOS (WMD - 2.39, p < 0.00001). Moreover, OC displayed a lower operation duration (p < 0.00001). A higher rate of complete mesocolic excision (p = 0.001) was related to OC. Although inconclusive in TSA, the recurrence rate in LC group was lower. LC and OC were equivalent in terms of postoperative survival outcomes. CONCLUSIONS Considering several limitations of the eligible studies and the subsequent low level of evidence, further RCTs of a higher quality and methodological level are required to verify the findings of our meta-analysis.
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A systematic review of the use of the alkaline comet assay for genotoxicity studies in human colon-derived cells.
Bankoglu, EE, Kodandaraman, G, Stopper, H
Mutation research. Genetic toxicology and environmental mutagenesis. 2019;:402976
Abstract
This review describes the use of the comet assay for assessment of DNA damage in human colon cells. We screened 98 papers, which employed human colon -derived cells to analyse DNA damage induced by different insults with the comet assay. In most cases tumour cell lines were used, and only a few studies were performed with primary colon cells. The comet assay was mostly applied to test chemotherapeutics and natural products. We could not find a clear difference between the susceptibility of cell lines to genotoxic insults and they were all suitable for comet assay experiments. Further comparisons between cell lines, and with primary cells and stem cells would be desirable to understand the relevance of the established cell lines as model for the human target tissue better.
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Laparoscopic versus open transverse-incision right hemicolectomy: a retrospective comparison study.
Feo, CF, Feo, CV, Fancellu, A, Ginesu, GC, Cherchi, G, Zese, M, Targa, S, Porcu, A
ANZ journal of surgery. 2019;(7-8):E292-E296
Abstract
BACKGROUND The optimal surgical approach to right colon cancer is still under debate. The aim of the present study was to compare the short- and long-term outcomes of laparoscopic and transverse-incision open approaches to right hemicolectomy for colon cancer. METHODS Data on 99 adult patients with right-side colon cancer undergoing either laparoscopic or open transverse-incision right hemicolectomy at two different university hospitals, between January 2013 and December 2016, were retrospectively reviewed. Data concerning patients' characteristics, operative details and post-operative recovery were retrieved from prospective databases and analysed. RESULTS Forty-nine subjects were operated on laparoscopically, while 50 through an open transverse incision. Operating time was significantly longer in the laparoscopic group compared with the open group (182 versus 105 min; P < 0.01). Patients treated laparoscopically had a shorter time to first bowel movement, while time to resume a normal diet and post-operative length of hospital stay were comparable in between groups. The median number of lymph nodes harvested was higher in the laparoscopic group (25.6 versus 18.6; P < 0.01), but no significant difference in overall survival between groups was detected. At long-term follow-up, the incidence of incisional hernia was higher in the laparoscopic group as compared to the open group (24.5% versus 0%; P = 0.0002). CONCLUSION Our results show that laparoscopic right hemicolectomy when compared to the transverse-incision open procedure may guarantee the same oncological radicality, but short-term functional benefits are still unclear. Randomized control studies are warranted to better clarify the comparison of these two approaches for right-sided colon cancers.
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Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus Bisacodyl (The PICO-MOVI Study).
Mathus-Vliegen, EMH, van der Vliet, K, Wignand-van der Storm, IJ, Stadwijk, JS
Diseases of the colon and rectum. 2018;(2):239-249
Abstract
BACKGROUND Because of its volume, adequate bowel preparation remains problematic in physically unfit patients. OBJECTIVE This study aimed to compare a small-volume sodium picosulfate/magnesium citrate preparation with a 2-L ascorbic acid-enriched polyethylene glycol solution plus bisacodyl. DESIGN This study has a noninferiority design, assuming that ascorbic acid-enriched polyethylene glycol solution plus bisacodyl is 70% efficacious in achieving an Ottawa score ≤7 and accepting a difference in success rate of <15% with a target enrollment of 146 patients per group. SETTING This study was conducted in an outpatient department. PATIENTS Patients referred for diagnostic colonoscopy were randomly assigned. Key exclusion criteria were severe kidney disease, ASA class ≥III, and hospital admission. INTERVENTION Patients were randomly assigned to receive sodium picosulfate/magnesium citrate or ascorbic acid-enriched polyethylene glycol solution plus bisacodyl according to a split-dose regimen. Patients in the sodium picosulfate/magnesium citrate group received advice on the recommended 4-L fluid intake. Patients in the ascorbic acid-enriched polyethylene glycol solution plus bisacodyl group received 2 bisacodyl tablets 2 days before and advice on the additionally recommended 2-L fluid intake. MAIN OUTCOME MEASURES To assess bowel-cleansing adequacy, the Ottawa, Aronchick, and Boston scores were used. Colonoscopy quality measures were obtained. Safety was assessed for a 30-day follow-up period. RESULTS Overall, 341 patients (169 men, mean age 57.0 years; BMI 26.2 kg/m) were included. Comorbidities were present in 76.2% of patients, and 75.4% of patients used medication. An adequate Ottawa score was obtained in 81.4% and 75.8% of patients receiving ascorbic acid-enriched polyethylene glycol solution plus bisacodyl and sodium picosulfate/magnesium citrate (difference of 5.6% (95% CI, -3.5 to -14.6; p = 0.023)), showing noninferiority of the sodium picosulfate/magnesium citrate therapy. Ottawa segmental scores were lower for sodium picosulfate/magnesium citrate in the right and transverse colon. In both groups, successful ileocecal intubation was achieved in 95%. No medication-related adverse events were reported. LIMITATIONS These results in a physically disabled ambulant population cannot be extrapolated to immobile, hospitalized patients. CONCLUSIONS Sodium picosulfate/magnesium citrate proved to be noninferior to ascorbic acid-enriched polyethylene glycol solution plus bisacodyl in efficacy and safety. Timing of the colonoscopy and addition of bisacodyl to sodium picosulfate/magnesium citrate warrants further consideration. See Video Abstract at http://links.lww.com/DCR/A461.
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Water exchange for screening colonoscopy increases adenoma detection rate: a multicenter, double-blinded, randomized controlled trial.
Cadoni, S, Falt, P, Rondonotti, E, Radaelli, F, Fojtik, P, Gallittu, P, Liggi, M, Amato, A, Paggi, S, Smajstrla, V, et al
Endoscopy. 2017;(5):456-467
Abstract
Background and study aims Single-center studies, which were retrospective and/or involved unblinded colonoscopists, have suggested that water exchange, but not water immersion, compared with air insufflation significantly increases the adenoma detection rate (ADR), particularly in the proximal and right colon. Head-to-head comparison of the three techniques with ADR as primary outcome and blinded colonoscopists has not been reported to date. In a randomized controlled trial with blinded colonoscopists, we aimed to evaluate the impact of the three insertion techniques on ADR. Patients and methods A total of 1224 patients aged 50 - 70 years (672 males) and undergoing screening colonoscopy were randomized 1:1:1 to water exchange, water immersion, or air insufflation. Split-dose bowel preparation was adopted to optimize colon cleansing. After the cecum had been reached, a second colonoscopist who was blinded to the insertion technique performed the withdrawal. The primary outcome was overall ADR according to the three insertion techniques (water exchange, water immersion, and air insufflation). Secondary outcomes were other pertinent overall and right colon procedure-related measures. Results Baseline characteristics of the three groups were comparable. Compared with air insufflation, water exchange achieved a significantly higher overall ADR (49.3 %, 95 % confidence interval [CI] 44.3 % - 54.2 % vs. 40.4 % 95 %CI 35.6 % - 45.3 %; P = 0.03); water exchange showed comparable overall ADR vs. water immersion (43.4 %, 95 %CI 38.5 % - 48.3 %; P = 0.28). In the right colon, water exchange achieved a higher ADR than air insufflation (24.0 %, 95 %CI 20.0 % - 28.5 % vs. 16.9 %, 95 %CI 13.4 % - 20.9 %; P = 0.04) and a higher advanced ADR (6.1 %, 95 %CI 4.0 % - 9.0 % vs. 2.5 %, 95 %CI 1.2 % - 4.6 %; P = 0.03). Compared with air insufflation, the mean number of adenomas per procedure was significantly higher with water exchange (P = 0.04). Water exchange achieved the highest cleanliness scores (overall and in the right colon). These variables were comparable between water immersion and air insufflation. Conclusions The design with blinded observers strengthens the validity of the observation that water exchange, but not water immersion, can achieve significantly higher adenoma detection than air insufflation. Based on this evidence, the use of water exchange should be encouraged.Trial registered at ClinicalTrials.gov (NCT02041507).
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A patient-blinded randomized, controlled trial comparing air insufflation, water immersion, and water exchange during minimally sedated colonoscopy.
Hsieh, YH, Koo, M, Leung, FW
The American journal of gastroenterology. 2014;(9):1390-400
Abstract
OBJECTIVES Minimal sedation obviates patient recovery burdens, but intolerable pain limits success of cecal intubation. Painless or minimally uncomfortable insertion ensures success of cecal intubation, current patient satisfaction, and willingness to repeat future colonoscopy with minimal sedation. Water immersion (WI) and water exchange (WE), when separately compared with air insufflation (AI), significantly reduced insertion pain. To assess comparative effectiveness, we conducted a randomized controlled trial with head-to-head comparison of these three methods. We hypothesized that WE could produce the highest proportion of patients reporting painless insertion. METHODS This prospective patient-blinded trial (NCT01535326) enrolled minimally sedated (25 mg intramuscular meperidine) patients randomized to AI, WI, or WE (90 patients/group) to aid insertion. The previously validated primary outcome was the proportion of patients reporting painless insertion. RESULTS Painless insertion was reported by 30.0% (AI), 43.3% (WI), and 61.1% (WE) of patients (P<0.001). Multivariate logistic regression analysis revealed that, after adjusting for gender, body mass index, abdominal compression, position change, insertion time to cecum, and length of scope at cecum, only WE was significantly associated with painless insertion compared with AI (odds ratio (OR)=0.08, 95% confidence interval (CI)=0.03-0.24, P<0.001) or WI (OR=0.14, 95% CI=0.05-0.40, P<0.001). Adenoma detection rate (ADR) in the right (cecum and ascending) colon was 11.1% (AI), 14.4% (WI), and 26.7% (WE) (P=0.015). The limitations included single site study with unblinded colonoscopist and assistant. CONCLUSIONS This head-to-head comparison of AI vs. WI vs. WE confirmed that WE was superior to WI and AI, with a significantly greater proportion of patients reporting painless insertion. The significantly higher ADR in the right colon in the WE group warrants further investigations.
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Randomized controlled trial comparing subcuticular absorbable suture with conventional interrupted suture for wound closure at elective operation of colon cancer.
Tanaka, A, Sadahiro, S, Suzuki, T, Okada, K, Saito, G
Surgery. 2014;(3):486-92
Abstract
BACKGROUND Subcuticular closure provides a superior cosmetic result in clean wounds. The aim of this work was to investigate the safety in terms of postoperative infection and cosmetic effectiveness of subcuticular wound closure after elective colon cancer surgery in clean-contaminated wounds. METHODS Patients who underwent elective resection of colon cancer were randomized to interrupted subcuticular and interrupted transdermal suture groups. The large bowel was prepared by mechanical washout with polyethylene glycol. All patients received metronidazole and kanamycin orally and flomoxef sodium once parenterally for antimicrobial prophylaxis. The primary end point was the incidence of incisional surgical-site infections within 30 days after operation. We assessed noninferiority of subcuticular suture within a margin of 10%. Analysis was by intent-to-treat. Secondary objectives include comparison of wound closure time, comfort, and cosmesis of the scar and satisfaction of patients. This study was registered with UMIN-CTR, UMIN000003005. RESULTS A total of 293 patients were randomized to the two groups. Incisional surgical-site infection rates were 11.0% (90% confidence interval 7.0-16.3%) for both groups. The relative risk of subcuticular suture was 1.00 (0.58-1.73, one-tail P = .57). Interrupted subcuticular suture was noninferior to interrupted transdermal suture (P = .0088). Throughout 6 months after operation, patients expressed a significant preference for the subcuticular suture technique, noting rapid relief from pain, decreased vascularity, and smaller width, although the procedure took twice as long. CONCLUSION Subcuticular suture did not increase the incidence of wound complications in elective colon cancer operation. Patients preferred a technique of interrupted subcuticular closure, citing better cosmetic results, and less pain.
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Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs 2 liter polyethylene glycol with ascorbic acid for afternoon colonoscopy.
Rivas, JM, Perez, A, Hernandez, M, Schneider, A, Castro, FJ
World journal of gastroenterology. 2014;(30):10620-7
Abstract
AIM: To compare the bowel cleansing efficacy of same day ingestion of 4-L sulfa-free polyethylene glycol (4-L SF-PEG) vs 2-L polyethylene glycol solution with ascorbic acid (2-L PEG + Asc) in patients undergoing afternoon colonoscopy. METHODS 206 patients (mean age 56.7 years, 61% male) undergoing outpatient screening or surveillance colonoscopies were prospectively randomized to receive either 4-L SF-PEG (n = 104) or 2-L PEG + Asc solution (n = 102). Colonoscopies were performed by two blinded endoscopists. Bowel preparation was graded using the Ottawa scale. Each participant completed a satisfaction and side effect survey. RESULTS There was no difference in patient demographics amongst groups. 4-L SF-PEG resulted in better Ottawa scores compared to 2-L PEG + Asc, 4.2 vs 4.9 (P = 0.0186); left colon: 1.33 vs 1.57 respectively (P = 0.0224), right colon: 1.38 vs 1.63 respectively (P = 0.0097). No difference in Ottawa scores was found for the mid colon or amount of fluid. Patient satisfaction was similar for both arms but those assigned to 4-L SF-PEG reported less bloating: 23.1% vs 11.5% (P = 0.0235). Overall polyp detection, adenomatous polyp and advanced adenoma detection rates were similar between the two groups. CONCLUSION Morning only 4-L SF-PEG provided superior cleansing with less bloating as compared to 2-L PEG + Asc bowel preparation for afternoon colonoscopy. Thus, future studies evaluating efficacy of morning only preparation for afternoon colonoscopy should use 4-L SF-PEG as the standard comparator.
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Intravenous alanyl-L-glutamine balances glucose-insulin homeostasis and facilitates recovery in patients undergoing colonic resection: a randomised controlled trial.
Cui, Y, Hu, L, Liu, YJ, Wu, YM, Jing, L
European journal of anaesthesiology. 2014;(4):212-8
Abstract
BACKGROUND Glucose and insulin homeostasis are altered in patients undergoing gastro-intestinal tumour resection and affect the postsurgical outcomes. OBJECTIVES To evaluate the impact of dipeptide alanyl-L-glutamine supplementation on glucose-insulin homeostasis, inflammatory mediators and surgical recovery in patients undergoing colonic cancer resection. DESIGN A randomised controlled trial. SETTING Southeast University Affiliated Zhongda Hospital, China, from January 2011 to May 2011. PARTICIPANTS Patients aged 35 to 75 years, ASA physical status I-II, scheduled for elective colon cancer resection. INTERVENTIONS Sixty patients were randomised into one of the three groups and received 22.4 ml kg of physiological saline, a 8.5% 18AA-II solution (a compound amino acid) or glutamine 0.5 g kg, given 24 h before and 1 h after the start of the surgical procedure. PRIMARY OUTCOMES MEASURE Insulin resistance index and insulin sensitivity check index. Secondary outcomes included blood glucose, insulin, tumour necrosis factor-alpha (TNF-α) and free fatty acid measured at 24 h before surgery (T1), 30 min before anaesthesia (T2), 2.5 h after the beginning of surgery (T3), and 1 h (T4) and 24 h (T5) after the end of surgery. The time of first passage of wind and the length of hospital stay were recorded. RESULTS Intraoperative and postoperative insulin resistance or calculated insulin sensitivity were worse in the physiological saline and 18AA-II treated patients compared with those treated with glutamine (P < 0.05). Blood glucose increased intraoperatively and postoperatively in all three groups compared with baselines (P < 0.05), but glutamine attentuated the peak level of blood glucose (P < 0.05). Glutamine reduced the intraoperative and postoperative concentrations of TNF-α and free fatty acid, (P < 0.05), and shortened the time to the first passage of wind after surgery and the length of hospital stay (P < 0.05). CONCLUSION Intravenous supplementation with glutamine balances glucose-insulin homeostasis and facilitates recovery in patients undergoing colon cancer resection.