P. Fockens

Endoscopic tri-modal imaging for surveillance in ulcerative colitis: randomised comparison of high-resolution endoscopy and autofluorescence imaging for neoplasia detection; and evaluation of narrow-band imaging for classification of lesions

Background: Endoscopic tri-modal imaging (ETMI) incorporates white light endoscopy (WLE), autofluorescence imaging (AFI) and narrow-band imaging (NBI). Aims: To assess the value of ETMI for the detection and classification of neoplasia in patients with longstanding ulcerative colitis. Design: Randomised comparative trial of tandem colonoscopies. Setting: Academic Medical Centre Amsterdam, Netherlands. Patients and methods: Fifty patients with ulcerative colitis underwent surveillance colonoscopy with ETMI. Each colonic segment was inspected twice, once with AFI and once with WLE, in random order. All detected lesions were inspected by NBI for Kudo pit pattern analysis and additional random biopsies were taken. Main outcome measures: Neoplasia miss-rates of AFI and WLE, and accuracy of the Kudo classification by NBI. Results: Among patients assigned to inspection with AFI first (nu200a=u200a25), 10 neoplastic lesions were primarily detected. Subsequent WLE detected no additional neoplasia. Among patients examined with WLE first (nu200a=u200a25), three neoplastic lesions were detected; subsequent inspection with AFI added three neoplastic lesions. Neoplasia miss-rates for AFI and WLE were 0% and 50% (pu200a=u200a0.036). The Kudo classification by NBI had a sensitivity and specificity of 75% and 81%; however, all neoplasia was coloured purple on AFI (sensitivity 100%). No additional patients with neoplasia were detected by random biopsies. Conclusion: Autofluorescence imaging improves the detection of neoplasia in patients with ulcerative colitis and decreases the yield of random biopsies. Pit pattern analysis by NBI has a moderate accuracy for the prediction of histology, whereas AFI colour appears valuable in excluding the presence of neoplasia. Trial registration number: ISRCTN05272746

Eradication of Barrett Esophagus with Early Neoplasia by Radiofrequency Ablation, with or without Endoscopic Resection

BackgroundRadiofrequency ablation is safe and effective for complete eradication of nondysplastic Barrett esophagus (BE). The aim was to report the combined results of two published and two ongoing studies on radiofrequency ablation of BE with early neoplasia, as presented at SSAT presidential plenary session DDW 2008.MethodsEnrolled patients had BE ≤12xa0cm with early neoplasia. Visible lesions were endoscopically resected. A balloon-based catheter was used for circumferential ablation and an endoscope-based catheter for focal ablation. Ablation was repeated every 2xa0months until the entire Barrett epithelium was endoscopically and histologically eradicated.ResultsForty-four patients were included (35 men, median age 68xa0years, median BE 7xa0cm). Thirty-one patients first underwent endoscopic resection [early cancer (nu2009=u200916), high-grade dysplasia (nu2009=u200912), low-grade dysplasia (nu2009=u20093)]. Worst histology remaining after resection was high-grade (nu2009=u200932), low-grade (nu2009=u200910), or no (nu2009=u20092) dysplasia. After ablation, complete histological eradication of all dysplasia and intestinal metaplasia was achieved in 43 patients (98%). Complications following ablation were mucosal laceration at resection site (nu2009=u20093) and transient dysphagia (nu2009=u20094). After 21xa0months of follow-up (interquartile range 10–27), no dysplasia had recurred.ConclusionsRadiofrequency ablation, with or without prior endoscopic resection for visible abnormalities, is effective and safe in eradicating BE and associated neoplasia.

Immunochemical Fecal Occult Blood Testing Is Equally Sensitive for Proximal and Distal Advanced Neoplasia

OBJECTIVE:Fecal immunochemical testing (FIT) is increasingly used for colorectal cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in invitational population screening measured against colonoscopy.METHODS:Participants (50–75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy. We estimated FIT sensitivity, specificity, and predictive values in detecting CRC and advanced neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75 (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with, respectively, 10, 15 and 20u2009μg Hb/g feces.RESULTS:A total of 1,256 participants underwent a FIT and screening colonoscopy. Advanced neoplasia was detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121 (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including 1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29–47) for advanced neoplasia and 88% (95% CI: 37–99) for CRC at a specificity of 93% (95% CI: 92–95) and 91% (95% CI: 89–92), respectively. The positive and negative predictive values for FIT50 were 6% (95% CI: 3–12) and almost 100% (95% CI: 99–100) for CRC, and 37% (95% CI: 29–46) and 93% (95% CI: 92–95) for advanced neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were 33% (95% CI: 25–42) and 96% (95% CI: 94–97). At FIT100, 71 screenees (6%) had a positive test result. The sensitivity and specificity of FIT100 were for advanced neoplasia 31% (95% CI: 23–40) and 97% (95% CI: 96–98), and for CRC 75% (95% CI: 36–96) and 95% (95% CI: 93–96). The area under curve for detecting advanced neoplasia was 0.70 (95% CI: 0.64–0.76). FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75 (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml.DISCUSSION:Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff. Sensitivity in detecting proximal and distal advanced neoplasia is comparable.

In vitro comparison and evaluation of seven gastric closure modalities for natural orifice transluminal endoscopic surgery (NOTES)

BACKGROUND AND STUDY AIMSnSecure transluminal closure is the most fundamental prerequisite for the safe introduction of natural orifice transluminal endoscopic surgery (NOTES). The aim was to compare acute strength of various gastrotomy closure techniques in an in vitro porcine stomach model by assessing leak pressures.nnnMETHODSnStandardized gastrotomies were closed manually, without the use of an endoscope, by one of seven NOTES closure devices: (i) T tags, (ii) purse string modified T tags, (iii) Eagle Claw VIII, (iv) Resolution clips, (v) flexible stapler; (vi) purse string suturing device, and (vii) flexible Endostitch. After closure, each specimen was fixed on the experimental apparatus and the pressure was gradually increased. By linking the pressure gauge and two cameras, the leak location and pressure could be determined in detail. We began by collecting gold standard reference values, by testing 15 gastrotomies closed with interrupted surgical sutures; these were associated with a mean leak pressure of 206 mmHg (SD 59). Using a noninferiority design, a sample size of 11 specimens for each NOTES closure technique was determined.nnnRESULTSnThe Resolution clips ( P = 0.0285), Eagle Claw VIII ( P = 0.0325), flexible stapler ( P < 0.001) and flexible Endostitch ( P = 0.002) produced noninferior closures in comparison with the predetermined gold standard; T tags ( P > 0.6775), purse string modified T tags ( P > 0.999), and the purse string suturing device ( P = 0.9875) resulted in inferior closures.nnnCONCLUSIONSnThe Eagle Claw VIII, Resolution clips, flexible stapler and flexible Endostitch produced noninferior closures in comparison with surgical closure in this model. These techniques seem to be the prime candidates for further testing in animal experiments before human trials can be initiated.

Systematic review of endoscopic mucosal resection versus transanal endoscopic microsurgery for large rectal adenomas.

BACKGROUND AND STUDY AIMSnLarge (u200a> 2 cm) rectal adenomas are currently treated by either transanal endoscopic microsurgery (TEM) or piecemeal endoscopic mucosal resection (EMR). The potential lower morbidity of EMR may become irrelevant if EMR is less effective. The aim of this study was to compare the safety and effectiveness of EMR and TEM for large rectal adenomas.nnnPATIENTS AND METHODSnA systematic review of the literature published between January 1980 and January 2009 was conducted. Pooled estimates of the proportion of patients with recurrence or complications in EMR and TEM studies were compared using random effects meta-regression analysis. Early (after single intervention) and late (excluding re-treatment of residual adenoma detected within 3 months) recurrence rates were calculated.nnnRESULTSnA total of 20 EMR studies and 48 TEM studies were included. No studies directly compared EMR with TEM. Mean polyp size was 31 mm (range 2 - 86 mm) for EMR vs. 37 mm (range 3 - 182 mm) for TEM (P = 0.02). Early recurrence rates were 11.2 % (95 % confidence interval [CI] 6.0 - 19.9) for EMR vs. 5.4 % (95 %CI 4.0 - 7.3) for TEM (P = 0.04). Late recurrence rates were 1.5 % (95 %CI 0.6 - 3.9) for EMR vs. 3.0 % (95 %CI 1.3 - 6.9) for TEM (P = 0.29). Postoperative complication rates were 3.8 % (95 %CI 2.8 - 5.3) for EMR vs. 13.0 % (95 %CI 9.8 - 17.0) for TEM (P < 0.001).nnnCONCLUSIONSnAfter single intervention, EMR for large rectal adenomas appears to be less effective but safer than TEM. When outcome data for re-treatment of residual adenoma within 3 u200amonths are included, EMR and TEM seem equally effective. Nevertheless, the added morbidity of additional EMRs could not be accounted for in this analysis. A prospective randomized trial seems imperative before making recommendations concerning the treatment of large rectal adenomas.

Novel over-the-scope-clip system for gastrotomy closure in natural orifice transluminal endoscopic surgery (NOTES): an ex vivo comparison study

BACKGROUND AND STUDY AIMSnSecure transluminal closure remains a fundamental barrier to clinical introduction of natural orifice transluminal endoscopic surgery (NOTES). Current NOTES closure modalities either do not provide secure closure or are too challenging to apply in vivo. The aims of this study were to evaluate gastric closure using the over-the-scope clip (OTSC) system in a previously described experimental setup, comparing the acute strength with a gold standard (hand surgical suturing).nnnMETHODSnComparison was done using an ex vivo porcine stomach experimental setup. The gastric opening was created by a needle knife puncture followed by dilation with 18-mm balloon. Control gastrotomies (n = 15; surgical suturing) showed a mean leak pressure of 206 mmHg (SD 59). A noninferiority design required a sample size of 11 specimens for the OTSC group. Closure comprised: (i) approximation of muscular layers using a flexible twin grasper; (ii) pulling the tissue into the OTSC cap at the tip of the scope; (iii) releasing the clip. Main outcome measures were leak pressure of closed gastrotomies, leak location, and time needed for adequate closure.nnnRESULTSnClosure was successful in all specimens in a median of 3 minutes. Closed gastrotomies showed air leakage at mean pressure of 233 mmHg (SD 47), which was non-inferior compared with the predetermined gold standard (P = 0.003).nnnCONCLUSIONSnClosure of gastric incisions to meet a predetermined leak pressure criterion was attainable and easy with the OTSC system. In vivo survival animal experiments are needed to further evaluate this promising closure modality.

Colorectal surgeons' learning curve of transanal endoscopic microsurgery.

BackgroundTransanal endoscopic microsurgery (TEM) is a technically demanding key technique in minimally invasive rectal surgery. We investigated the learning curve of colorectal surgeons commencing with TEM.MethodsAll TEM procedures of four colorectal surgeons were analyzed. Procedures were ranked chronologically per surgeon. Outcomes included conversion, postoperative complications, procedure time, and recurrence. Backward multivariable regression analysis identified learning curve effects and other predictors.ResultsFour surgeons resected 693 rectal lesions [69.9xa0% adenoma/25.5xa0% carcinoma; median size 20xa0cm2; interquartile range (IQR) 11–35; 7xa0±xa04xa0cm ab ano]. A total of 555 resections (80.1xa0%) were histopathologically radical (R0). Conversion (4.3xa0%) was influenced by a learning curve [odds ratio (OR) 0.991 per additional procedure; 95xa0% confidence interval (CI) 0.984–0.998] and by lesion size. Postoperative complications depended only on the individual surgeon and lesion size in benign lesions (10.4xa0% complications). A learning curve (OR 0.99; 95xa0% CI 0.988–0.998) and peritoneal entrance affected complications in malignant lesions (13.3xa0%). Procedure time [median 55xa0min (IQR 30–90)] was influenced by a learning curve [B −0.11 (95xa0% CI −0.14 to −0.09)], individual surgeon, single-piece resection, peritoneal entrance, lesion size, and rectal quadrant. Recurrence of benign lesions (4.5xa0%) depended on lesion size, R0 resection, and prior resection attempts. Recurrence of malignant lesions (8.9xa0%) depended on 3D stereoscopic view, lesion size, full-thickness resection, and length of follow-up. Recurrence-free survival of patients operated during the 36th through 80th procedure per surgeon was significantly shorter than in patients operated during procedures 1–35 and 81 onwards.ConclusionsA surgical learning curve affected conversion rate, procedure time, and complication rate. It did not influence recurrence rates, possibly due to evolving patient populations. This first insight into the learning curve of TEM stresses the importance of quality monitoring and centralisation of care.

Combining risk factors with faecal immunochemical test outcome for selecting CRC screenees for colonoscopy

Objective Faecal immunochemical testing (FIT) is increasingly used in colorectal cancer (CRC) screening but has a less than perfect sensitivity. Combining risk stratification, based on established risk factors for advanced neoplasia, with the FIT result for allocating screenees to colonoscopy could increase the sensitivity and diagnostic yield of FIT-based screening. We explored the use of a risk prediction model in CRC screening. Design We collected data in the colonoscopy arm of the Colonoscopy or Colonography for Screening study, a multicentre screening trial. For this study 6600 randomly selected, asymptomatic men and women between 50 years and 75u2005years of age were invited to undergo colonoscopy. Screening participants were asked for one sample FIT (OC-sensor) and to complete a risk questionnaire prior to colonoscopy. Based on the questionnaire data and the FIT results, we developed a multivariable risk model with the following factors: total calcium intake, family history, age and FIT result. We evaluated goodness-of-fit, calibration and discrimination, and compared it with a model based on primary screening with FIT only. Results Of the 1426 screening participants, 1112 (78%) completed the questionnaire and FIT. Of these, 101 (9.1%) had advanced neoplasia. The risk based model significantly increased the goodness-of-fit compared with a model based on FIT only (p<0.001). Discrimination improved significantly with the risk-based model (area under the receiver operating characteristic (ROC) curve: from 0.69 to 0.76, (p=0.02)). Calibration was good (Hosmer-Lemeshow test; p=0.94). By offering colonoscopy to the 102 patients at highest risk, rather than to the 102 cases with a FIT result >50u2005ng/mL, 5 more cases of advanced neoplasia would be detected (net reclassification improvement 0.054, p=0.073). Conclusions Adding risk based stratification increases the accuracy FIT-based CRC screening and could be used in preselection for colonoscopy in CRC screening programmes.

Using CT colonography as a triage technique after a positive faecal occult blood test in colorectal cancer screening

Objective: The purpose of this study was to evaluate the effectiveness of CT colonography (CTC) as a triage technique in faecal occult blood test (FOBT)-positive screening participants. Methods: Consecutive guaiac (G-FOBT) and immunochemical (I-FOBT) FOBT-positive patients scheduled for colonoscopy underwent CTC with iodine tagging bowel preparation. Each CTC was read independently by two experienced observers. Per patient sensitivity, specificity and positive and negative predictive values (PPV and NPV) were calculated based on double reading with different CTC cut-off lesion sizes using segmental unblinded colonoscopy as the reference standard. The acceptability of the technique to patients was evaluated with questionnaires. Results: 302 FOBT-positive patients were included (54 G-FOBT and 248 I-FOBT). 22 FOBT-positive patients (7%) had a colorectal carcinoma and 211 (70%) had a lesion ⩾6 mm. Participants considered colonoscopy more burdensome than CTC (p<0.05). Using a 6 mm CTC size cut-off, per patient sensitivity for CTC was 91% (95% CI 85% to 91%) and specificity was 69% (95% CI 60% to 89%) for the detection of colonoscopy lesions ⩾6 mm. The PPV of CTC was 87% (95% CI 80% to 93%) and NPV 77% (95% CI 69% to 85%). Using CTC as a triage technique in 100 FOBT-positive patients would mean that colonoscopy could be prevented in 28 patients while missing ⩾10 mm lesions in 2 patients. Conclusion: CTC with limited bowel preparation has reasonable predictive values in an FOBT-positive population and a higher acceptability to patients than colonoscopy. However, due to the high prevalence of clinically relevant lesions in FOBT-positive patients, CTC is unlikely to be an efficient triage technique in a first round FOBT population screening programme.

Endoscopic mucosal resection vs transanal endoscopic microsurgery for the treatment of large rectal adenomas

Aimu2002 Large (>u20032u2003cm) rectal adenomas are currently treated by transanal endoscopic microsurgery (TEM) or piecemeal endoscopic mucosal resection (EMR). The potential lower morbidity of EMR becomes irrelevant if it is less effective. We aimed to compare the safety and effectiveness of EMR and TEM for large rectal adenomas.