Water Exchange Produces Significantly Higher Adenoma Detection Rate Than Water Immersion: Pooled Data From 2 Multisite Randomized Controlled Trials.

GOALS: To test the hypothesis that water exchange (WE) significantly increases adenoma detection rates (ADR) compared with water immersion (WI). BACKGROUND: Low ADR was linked to increased risk for interval colorectal cancers and related deaths. Two recent randomized controlled trials of head-to-head comparison of WE, WI, and traditional air insufflation (AI) each showed that WE achieved significantly higher ADR than AI, but not WI. The data were pooled from these 2 studies to test the above hypothesis. STUDY: Two trials (5 sites, 14 colonoscopists) that randomized 1875 patients 1:1:1 to AI, WI, or WE were pooled and analyzed with ADR as the primary outcome. RESULTS: The ADR of AI (39.5%) and WI (42.4%) were comparable, significantly lower than that of WE (49.6%) (vs. AI P=0.001; vs. WI P=0.033). WE insertion time was 3 minutes longer than that of AI (P<0.001). WE showed significantly higher detection rate (vs. AI) of the >10 mm advanced adenomas. Right colon combined advanced and sessile serrated ADR of AI (3.4%) and WI (5%) were comparable and were significantly lower than that of WE (8.5%) (vs. AI P<0.001; vs. WI P=0.039). CONCLUSIONS: Compared with AI and WI, the superior ADR of WE offsets the drawback of a significantly longer insertion time. For quality improvement focused on increasing adenoma detection, WE is preferred over WI. The hypothesis that WE could lower the risk of interval colorectal cancers and related deaths should be tested.

Water exchange for screening colonoscopy increases adenoma detection rate: a multicenter, double-blinded, randomized controlled trial.

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).

Impact of carbon dioxide insufflation and water exchange on postcolonoscopy outcomes in patients receiving on-demand sedation: a randomized controlled trial.

BACKGROUND AND AIMS: Water exchange (WE) is the least painful insertion method during colonoscopy. Its impact on postcolonoscopy discomfort has not been well-described. Carbon dioxide (CO2) insufflation consistently reduced postcolonoscopy discomfort. We compared postcolonoscopy outcomes of various combinations of insertion and withdrawal techniques (insertion-withdrawal modality): WE-CO2, WE-air insufflation (WE-AI), and CO2-CO2. METHODS: A total of 240 patients undergoing on-demand sedation diagnostic colonoscopy were randomized to WE-CO2 (n = 79), WE-AI (n = 80), CO2-CO2 (n = 81), with postprocedural data collected up to 24 hours. The primary outcome was postcolonoscopy bloating. Other postcolonoscopy outcomes included pain scores, flatus and incontinence episodes, toilet use, interference with normal activities, patient satisfaction, and patient willingness to repeat the procedure. RESULTS: Demographic and procedural data were comparable. Compared with WE-AI, WE-CO2 and CO2-CO2 resulted in significantly less bloating (all P < .0005) and lower pain scores (P values ranged from .008 to < .0005) up to 3 hours and fewer flatus episodes up to 6 hours (P values ranged from .003 to < .0005). WE-CO2 resulted in less interference with same-day activities compared with WE-AI (P = .043). The differences in postprocedural outcomes were significant, but the magnitude was small. Patient satisfaction and willingness to repeat the procedure were high and comparable among groups. WE was the least painful insertion technique (P < .0005). CONCLUSIONS: The combination WE-CO2 appears to be the optimal choice to decrease pain during the examination and to reduce bloating and other undesired procedural outcomes afterward. If a CO2 insufflator is already available, it seems advisable to adopt the combination WE-CO2. In the absence of a CO2 insufflator, the cost effectiveness of the addition of withdrawal CO2 to WE in diagnostic and nondiagnostic settings needs to be critically assessed. (Clinical trial registration number: NCT02409979.).

Carbon dioxide insufflation during colonoscopy in inflammatory bowel disease patients: a double-blind, randomized, single-center trial.

OBJECTIVE: Bowel distension by insufflated air causes abdominal discomfort after colonoscopy. Carbon dioxide (CO2) instead of air insufflation during colonoscopy can reduce postprocedural discomfort in diagnostic and screening cases. Discomfort after colonoscopy and CO2 insufflation have never been studied in inflammatory bowel disease (IBD) patients, characterized by younger age, structural changes of the colon, and need for repeated and frequently uncomfortable colonoscopies. Our trial was designed to evaluate postprocedural discomfort associated with CO2 compared with air insufflation in unsedated or minimally sedated patients with known IBD. METHODS: In a double-blind, randomized, single-center study, 64 patients were randomized to either CO2 insufflation (CO2) or air insufflation colonoscopy (Air). Abdominal pain, bloating, and flatulence scores during 24 h after colonoscopy were recorded using a continuous scale of 0-10 (0=none, 10=maximum discomfort). The primary endpoint used for power calculation was bloating score at 1 h after colonoscopy. RESULTS: Pain, bloating, and flatulence scores at end, 1, and 3 h after colonoscopy were significantly lower in CO2 than in Air arm (P<0.001). Scores at 6, 12, and 24 h were comparable. Procedural parameters such as cecal and terminal ileum intubation rate, intubation and total time, pain during insertion, need for repositioning, and abdominal compression were not different between arms. No complications were recorded in the study. CONCLUSION: Compared with air, CO2 insufflation significantly reduces abdominal pain, bloating, and flatulence scores during at least 3 h after colonoscopy in IBD patients, achieving comparable intraprocedural outcomes.

Insertion water exchange increases right colon adenoma and hyperplastic polyp detection rates during withdrawal.

BACKGROUND: Single site studies in male Veterans in the U.S. reported increased detection of presumptive cancer precursors (adenomas, hyperplastic polyps) in the proximal colon (cecum-splenic flexure) by water exchange. AIMS: Assess the reproducibility of the observation. METHODS: Analysis of secondary outcomes collected prospectively in 3 similarly designed randomized controlled trials using water exchange, water immersion and insufflation (air or carbon dioxide). MAIN OUTCOME: detection rates of adenomas and hyperplastic polyps in proximal, transverse and right colon (cecum-ascending). RESULTS: 704 males (173 screening) were evaluated. In the proximal colon, WE showed increased detection of small adenomas (p=0.009) and adenomas plus hyperplastic polyps (p=0.015) (vs insufflation); increased detection of adenomas plus hyperplastic polyps of any size (p=0.045) and of small size (p=0.04) (vs water immersion). In the right colon water exchange increased detection of small adenomas (19% vs 12.1%, p=0.04) (vs insufflation); small adenomas (19% vs 12%, p=0.038), adenomas plus hyperplastic polyps of any size (25% vs 16.7%, p=0.028) and of small size (23.7% vs 14.6%, p=0.012) (vs water immersion). Water exchange significantly improved bowel cleanliness. Sedation had no impact on lesion detection. CONCLUSIONS: Water exchange is a superior insertion technique for detection of adenomas and hyperplastic polyps primarily in the right colon, especially those of small size.

Impact of Colonoscopy Insertion Techniques on Adenoma Detection.

BACKGROUND: Low adenoma detection rate (ADR) predicts development of interval cancers, found mainly in the right (cecum-ascending) colon, where poor bowel preparation is an associated factor. Single-site studies reported increased detection of adenomas in the proximal colon segments by water exchange (WE). Data about colon cleansing revealed that WE had the greatest impact in the right colon. AIMS: To test the hypothesis that WE had the greatest impact on ADR in colon segments with the most favorable bowel cleanliness scores, namely the right colon. METHODS: We pooled right colon and overall ADR data of three similarly designed colonoscopy trials that compared WE, water immersion (WI) and insufflation of air or carbon dioxide (AICD) in a mixed gender European population. RESULTS: In this study, 1200 (704 males) subjects and were included. 288 were screening cases. Demographic and procedural data were comparable. Water exchange achieved significantly higher right colon <10 mm ADR (11.9 %, vs WI 6.9 %, p = 0.016; vs AICD 7.2 %, p = 0.025). Water exchange achieved the lowest proportions of poor bowel preparation and the highest right colon and overall Boston bowel preparation scale scores (p range 0.003, <0.0005). In patients with right colon excellent bowel cleanliness, water exchange was the only method significantly associated with right colon adenoma detection. One of the limitations is unblinded colonoscopists. CONCLUSIONS: In a mixed gender European population, water exchange is confirmed to be a superior insertion technique showing a significant increase in <10 mm right colon adenoma detection, achieving the cleanest colon and lowest proportions of poor bowel preparation requiring repeat procedures. CLINICALTRIALS. GOV NO: NCT01781650, 01954862, 01780818.

Evidence to suggest adoption of water exchange deserves broader consideration: Its pain alleviating impact occurs in 90% of investigators.

AIM: To determine whether observations were reproducible among investigators. METHODS: From March 2013 through June 2014, 18-85-year-old diagnostic and 50-70-year-old screening patients were enrolled at each center to on-demand sedation colonoscopy with water exchange (WE), water immersion (WI) and insufflation with air or CO2 for insertion and withdrawal [air or carbon dioxide (AICD)]. Data were aggregated for analysis. PRIMARY OUTCOME: Variations in real-time maximum insertion pain (0 = none, 1-2 = discomfort, 10 = worst). RESULTS: One thousand and ninety-one cases analyzed: WE (n = 371); WI (n = 338); AICD (n = 382). Demographics and indications were comparable. The WE group had the lowest real-time maximum insertion pain score, mean (95%CI): WE 2.8 (2.6-3.0), WI 3.8 (3.5-4.1) and AICD 4.4 (4.1-4.7), P < 0.0005. Ninety percent of the colonoscopists were able to use water exchange to significantly decrease maximum insertion pain scores. One investigator had high insertion pain in all groups, nonetheless WE achieved the lowest real-time maximum insertion pain score. WE had the highest proportions of patients with painless unsedated colonoscopy (vs WI, P = 0.013; vs AICD, P < 0.0005); unsedated colonoscopy with only minor discomfort (vs AICD, P < 0.0005), and completion without sedation (vs AICD, P < 0.0005). CONCLUSION: Aggregate data confirm superiority of WE in lowering colonoscopy real-time maximum insertion pain and need for sedation. Ninety percent of investigators were able to use water exchange to significantly decrease maximum insertion pain scores. Our results suggest that the technique deserves consideration in a broader scale.

Bone mineral density and body composition after laparoscopic sleeve gastrectomy in men: A short-term longitudinal study.

INTRODUCTION: Longitudinal changes in bone and body composition occurring in obese men after laparoscopic sleeve gastrectomy (LSG) has been evaluated. METHODS: In short-term longitudinal study, 25 obese men in mean baseline age 44.8 ± 10.9 years and mean body mass index (BMI) 43.3 ± 4.4 kg/m(2)were assessed after undergoing LSG for obesity. Bone mineral density (BMD) (spine, femoral neck [FN], total hip [TH], and total body [TB]) and body composition (TB bone mineral content [BMC], fat, % of fat, lean, lean BMC, total mass) were assessed at baseline, and after three and six months. RESULTS: Mean body measurements, including weight, BMI, waist and hips, decreased significantly over the study period (p < 0.0001). FN BMD (p < 0.01) and TH BMD (p < 0.001) decreased, and spine BMD increased significantly (p < 0.001). TB BMD did not change. Weight decreased by 21.3 ± 7.3%, BMI by 21.2 ± 7.3%, FN BMD by 3.32 ± 6.35%, TH BMD by 3.51 ± 3.95% whereas spine BMD increased by 2.89 ± 5.1%. TB BMC increased by 2.4 ± 4.62%; all other variables relating to body composition decreased: fat by 33.0 ± 9.6%, lean mass by 12.8 ± 6.1%, lean BMC by 12.3 ± 5.9%, total mass by 20.1 ± 6.4%, and % fat by 15.8 ± 7.2%. CONCLUSIONS: After LSG, body size and variables related to body composition (except for TB BMC) decreased with an accompanying decrease in FN BMD in the men in this study. Spine BMD increased, and TB BMD did not change.

Water-Aided Colonoscopy in Inflammatory Bowel Disease Patients-A Randomised, Single-Centre Trial.

BACKGROUND: Water-aided colonoscope insertion reduces patients' discomfort and need for sedation in unsedated and minimally sedated patients. However, water-aided technique has never been studied in inflammatory bowel disease patients, characterised by younger age, structural changes of the colon and need for repeated colonoscopies. Our trial was designed to evaluate discomfort associated with water-aided colonoscopy compared with air insufflation in on-demand sedated patients with known inflammatory bowel disease. METHODS: In a randomised, single-centre study, 92 patients were randomised to either water-aided insertion and air insufflation during withdrawal [Water] or air insufflation during both insertion and withdrawal [Air]. The main outcome measured was success rate of unsedated colonoscopy, defined as reaching the caecum without requiring sedation and with discomfort during insertion of less than or equal to 5 using 0-10 continuous scale [0 = none, 10 = maximum pain]. RESULTS: Success rate of caecal intubation without sedation or invoking a discomfort score greater than 5 was significantly higher in the Water arm compared with the Air arm [73.9 vs 45.7%, p = 0.01]. Discomfort score during insertion [mean ± SD] was significantly lower in the Water than in the Air arm [3.8±2.4 vs 5.4±1.9, p < 0.001]. Other outcomes including procedural times, success rate of terminal ileum intubation, need for abdominal compression, and repositioning were comparable. There were no complications recorded in the study. CONCLUSIONS: Compared with air insufflation, water-aided colonoscopy significantly reduces discomfort in on-demand sedated patients with inflammatory bowel disease, achieving comparable procedural outcomes.

Water Exchange Is the Least Painful Colonoscope Insertion Technique and Increases Completion of Unsedated Colonoscopy.

BACKGROUND & AIMS: Unsedated colonoscopy is acceptable for diagnostic, surveillance, and screening indications worldwide. However, insertion of the colonoscope can be painful; it is not clear which technique is least painful and thereby increases the likelihood of colonoscopy completion. We performed a head-to-head comparison of air insufflation (AI), carbon dioxide (CO2) insufflation, water immersion (WI), and water exchange (WE) to determine which combination of insertion techniques produces the least amount of pain. METHODS: In a patient-blinded prospective trial, 624 subjects were assigned randomly to groups that underwent colonoscopy with AI-AI, CO2-CO2, WI-AI, WE-AI, WI-CO2, or WE-CO2 insertion and withdrawal techniques, including on-demand sedation, at the St. Barbara Hospital (Iglesias, Italy) or the Vìtkovice Hospital (Ostrava, Czech Republic), from October 2013 through June 2014. The primary outcome was real-time maximum insertion pain (0 = none, 10 = worst), recorded by an unblinded nurse assistant. At discharge, a blinded observer recorded the recalled maximum insertion pain and patients' and investigators' guesses about method or gas used. RESULTS: Patients and investigators correctly guessed the method used for fewer than 44% of procedures, confirming adequate blinding. The correlation between real-time and recalled maximum insertion pain (r = 0.9; P < .0005) confirmed internal validation of the primary outcome. The WE group had the lowest scores: mean pain values were 5.2 for AI-AI (95% confidence interval [CI], 4.6-5.8), 4.9 for CO2-CO2 (95% CI, 4.3-5.4), 4.3 for WI-CO2 (95% CI, 3.8-4.9), 4.0 for WI-AI (95% CI, 3.5-4.5), 3.1 for WE-CO2 (95% CI, 2.7-3.4), and 3.1 for WE-AI (95% CI, 2.7-3.6) (P < .0005). The highest proportions of patients completing unsedated colonoscopy were in the WE groups. WE groups also had significantly better colon cleanliness, particularly in the transverse and right colon (P < .0005). One limitation of the study was that colonoscopists and assistants were not blinded to water-aided insertion methods. CONCLUSIONS: In a prospective study of colonoscopy insertion methods, CO2 insufflation did not reduce real-time maximum insertion pain. Compared with AI or CO2, WI and WE reduced insertion pain. The least painful technique was WE, which significantly increased completion of unsedated colonoscopy and bowel cleanliness without prolonging insertion time. ClinicalTrials.gov number: NCT01954862.

ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones.

AIM: To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency. METHODS: Mutational analysis of ABCB4, screening for copy number variations by multiplex ligation-dependent probe amplification, genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome (LPAC, OMIM #600803) and in 5 young females with suspected LPAC and their families (5 probands, 15 additional family members). The probands came to medical attention for contraceptive-associated intrahepatic cholestasis. RESULTS: A possibly pathogenic variant of ABCB4 was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4. Among these 16, however, none developed gallstones in childhood. In 5 index patients, all young females carrying at least one pathogenic mutation in one allele of ABCB4, manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives. Variants ABCB11 c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC. CONCLUSION: Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied to pediatric patients with idiopathic gallstones. Sexual immaturity even prevents manifestation of LPAC.

Cap-assisted water immersion for minimal sedation colonoscopy: prospective, randomized, single-center trial.

BACKGROUND AND AIM: Water immersion insertion is able to reduce discomfort and need for sedation during colonoscopy. A cap attached to the colonoscope tip may improve insertion during air insufflation colonoscopy. According to several reports, both techniques alone may result in higher detection of neoplastic lesions. Our study was designed to evaluate the efficacy of cap-assisted water immersion compared to water immersion colonoscopy in minimally sedated patients. METHODS: A total of 208 consecutive outpatients were randomized to either cap-assisted water immersion (Cap Water) or water immersion colonoscopy (Water). The primary endpoint was cecal intubation time. RESULTS: Cecal intubation time was 6.9 ± 2.9 min in Cap Water and 7.4 ± 4.2 min in the Water arm (P = 0.73). Success rate of minimal sedation colonoscopy was equal in both groups (92.9%, P = 1.00). From the endoscopist's point of view, there were non-significant trends towards lower discomfort (P = 0.06), less need for abdominal compression (P = 0.06) and lower difficulty score (P = 0.05) during Cap Water colonoscopy. Adenoma detection rate was similar in both arms (44% in Cap Water vs 45% in the Water group, P = 0.88). There were no complications recorded in the present study. CONCLUSIONS: In comparison with water immersion without cap, cap-assisted water immersion colonoscopy was not able to shorten the cecal intubation time. However, it has the possibility of reducing patient discomfort and difficulty of colonoscope insertion. Potential impact on improved detection of neoplastic lesions has to be evaluated by further studies.

Combination of water immersion and carbon dioxide insufflation for minimal sedation colonoscopy: a prospective, randomized, single-center trial.

OBJECTIVE: Water immersion insertion and carbon dioxide (CO2) insufflation, as alternative colonoscopic techniques, are able to reduce patient discomfort during and after the procedure. We assessed whether the combination of water immersion and CO2 insufflation is superior in efficacy and patient comfort to other colonoscopic techniques. METHODS: In a prospective, randomized study, a total of 420 patients were randomized to either water immersion insertion and CO2 insufflation during withdrawal (water/CO2), water insertion and air insufflation during withdrawal (water/air), CO2 insufflation during both insertion and withdrawal (CO2/CO2), or air insufflation during both insertion and withdrawal (air/air). The main outcome was the success of minimal sedation colonoscopy, which was defined as reaching the cecum without switching to another insertion method and without additional sedation beyond the initial 2 mg of midazolam. Patient comfort during and after the procedure was assessed. RESULTS: A total of 404 patients were analyzed. The success rate of minimal sedation colonoscopy in the water insertion arm (water/CO2 and water/air) was 97% compared with 83.3% in the gas insertion arm (CO2/CO2 and air/air; P<0.0001). Intraprocedural pain and bloating were significantly lower in the water/CO2 group than in all other groups. Patient discomfort in the water/CO2 group during 24 h after the procedure was comparable with that in the CO2/CO2 group and significantly lower than that in the air groups (water/air and air/air). No complications were recorded during the study. CONCLUSION: The combination of water immersion and CO2 insufflation appears to be an effective and safe method for minimal sedation colonoscopy. Overall patient discomfort was significantly reduced compared with that in other techniques.

Bone mineral changes in spine and proximal femur in individual obese women after laparoscopic sleeve gastrectomy: a short-term study.

BACKGROUND: The aim of the study was to establish longitudinal bone changes in obese women after laparoscopic sleeve gastrectomy (LSG). METHODS: Twenty-nine women at baseline mean age of 40.41 ± 9.26 years and with mean body mass index (BMI) of 43.07 ± 4.99 kg/m(2) were included in a 6-month study. Skeletal status at hip [femoral neck (FN) and total hip (TH)] and spine was assessed at baseline, as well as in 3 and 6 months after surgery. Body size was measured at baseline and follow-up (weight, height, BMI, and waist). RESULTS: Baseline body weight was 117.5 ± 18.4 kg. The mean body weight and BMI decreased by 17.9 % during the first 3 months after surgery to obtain 28.4 % after 6 months. At 6 months, BMD decreased significantly for spine by 1.24 %, FN 6.99 %, and TH 5.18 %. The changes after 3 months in individual subjects showed that, in the majority of subjects, FN and TH BMD decreased significantly (in 52 % and 69 % of subjects, respectively), and in 24 % loss of BMD was found at the spine. After 6 months, the corresponding, significant decreases in individual subjects were found in 72 %, 86 %, and 38 % of woman, respectively. Those with a significant loss of FN BMD tended to lose more weight (30 ± 9.47 versus 23.25 ± 6.08 kg, p = 0.061) than others; women with a significant decrease of FN BMD lost more weight than those with no such decrease (30.43 ± 8.07 versus 15 ± 1.91 kg). CONCLUSION: LSG proved efficient for body weight reduction, however, with a parallel decline in bone mineral density.