Introduction: Colonoscopy insertion is technically challenging, time-consuming, and painful, especially for the sigmoid. Many factors have been found to affect the difficulty of colonoscope insertion, such as age, gender, body mass index, history of abdominal surgery and operator ect. It is reported that the difficult colonoscopy score (DCS) \>1 can predict the difficulty during colonoscopy. DCS=1\*A(1 if age≥65y, 0 if \<65y) + 2\*B (1 if BMI \<18.5, 0 if BMI≥18.5) + 1\*C (1 if colonoscopist is junior, 0 if senior)+ 1\*S(1 if sleep quality was fair or bad, 0 if excellent or good). Patients with DCS\>1 had longer insertion time, higher pain score and needed more abdominal compression and position changes. For these potentially difficult cases we can use special intubation techniques such as water-aided or cap-assisted method at the very start to avoid of excessive insertion time, increased discomfort and even unnecessary adverse events.

Water-aided method colonoscopy examination is an important and useful method because it reduces discomfort and increases cecal intubation rate compared with usual air insufflation method. This examination is usually performed using two different methods: water immersion and water exchange. In the water immersion method, the water is infused into the colon beginning with the scope inserted into the anus during examination until the scope reaches the cecum. The water is evacuated during colonoscope withdrawal. In the water exchange method, the water is evacuated during colonoscope advancement until the cecum is reached. The air pump of the endoscopy machine is turned off during examination in both procedures. The aim of this study was to investigate the application of water-aided method on cecal intubation time in potentially difficult colonoscopy. We chose water immersion method rather than water exchange for this evaluation because water immersion, characterized by suction removal of the infused water predominantly during withdrawal, is more appropriate for reducing the cecal intubation time. Further more ,as reported, left-colon water exchange(LWE) shorten the insertion time while preserving the benefits of whole colon water exchange(WWE). We modified whole colon water immersion(WWI) method to the sigmoid colon water immersion(SWI), where the most difficult and painful part of colonoscopy resides. If water immersion is limited to the sigmoid colon in such patients, would it be more efficient and less time consuming? Methods:This prospective, randomized controlled study allocated patients who's difficult colonoscopy score(DCS) \>1 (18-80 years) to sigmoid-colon water immersion(SWI), whole colon water immersion(WWI) or carbon dioxide (CO2) insufflation (CI) group (1:1:1). Patients were randomized to SWI, WWI or CI group according to a computer-generated randomization list in 1:1:1 ratio. Group assignments were revealed immediately before the insertion of colonoscopy by a researcher , who did not participate in data collection and data analysis. The monitor screen was placed over the head of patients to keep them from knowing the insertion method. Endoscopists and assisting nurses were not blinded. For the bowel preparation, all patients were instructed to take low-fiber diet for lunch and clear liquid diets for dinner the day before examination. They ingested 2L of PEG powder (WanHe Pharmaceutical Co, Shenzhen, China) diluted with water within 2 h, between 4:00 AM and 5:00 AM on the day of the examination. Those with chronic constipation received an additional 2L of PEG solution on the evening prior to the examination. Drinking more clear water and pacing back and forth after purgatives were encouraged to enhance laxative effect. The time interval between preparation and colonoscopy was limited to less than 5 h to ensure the quality of bowel preparation.

Endoscopic procedure Two endoscopists (WBH and YJ) with extensive experience in both air (\>5000) and water methods (\>500) performed the colonoscopies. The standard adult colonoscope (EC-600WM, Fujinon, Beijing) was used. Patients were placed in the left lateral position at the beginning of the procedure. Maneuvers such as abdominal compression and position change were implemented if needed (e.g. when looping, paradoxical movement or lack of advancement occurred). Successful cecal intubation was confirmed by the visualization of appendiceal orifice or ileocecal valve with the tip of the colonoscope touching the base of the cecum. For the AI method, air was insufflated through out the whole procedure for advancement and inspection when needed. In the WWI method,the air supply was turn off until the cecum was reached. For adequate lumen distention to advance the colonoscope tip, warm water which stored in 1L bottles and maintained 37°C with a water bath, was instilled intermittently into the colon through the auxiliary working channel of colonoscope using a footswitch-controlled flushing pump. For patients allocated to SWI group, air pump would be turned off and the procedure would be switched from water immersion method to air insufflation method after successful passage through the descending sigmoid junction.

The primary outcome was cecal intubation time. The secondary outcomes included the maximum pain score (0=none,10=most severe) during the insertion phase in left, transverse and right colon; cecal intubation rate; adenoma detection rate (ADR); bowel preparation quality; withdrawal time(from cecum to rectum excluding time for biopsy and polypectomy); willingness to undergo a repeat unsedated colonoscopy; number of abdominal compressions, position change during the insert.

Descriptive statistics were used to summarize demographic and baseline data. Quantitative variables are expressed as means and standard deviations and analyzed by ANOVA followed by Bonferroni test for multiple comparisons. Categorical variables in three groups were compared with chi-square test or Fisher exact test when appropriate. All p-Values were two-sided and those \< 0.05 were considered to be significant. Analyses were performed with SPSS software version 24.0 for Windows (SPSS Inc, IBM Company).