Optimal postoperative pain management after VATS lung resection by thoracic epidural analgesia, continuous paravertebral block or single-shot intercostal nerve block (OPtriAL): study protocol of a three-arm multicentre randomised controlled trial.

BACKGROUND: Adequate pain control after video-assisted thoracoscopic surgery (VATS) for lung resection is important to improve postoperative mobilisation, recovery, and to prevent pulmonary complications. So far, no consensus exists on optimal postoperative pain management after VATS anatomic lung resection. Thoracic epidural analgesia (TEA) is the reference standard for postoperative pain management following VATS. Although the analgesic effect of TEA is clear, it is associated with patient immobilisation, bladder dysfunction and hypotension which may result in delayed recovery and longer hospitalisation. These disadvantages of TEA initiated the development of unilateral regional techniques for pain management. The most frequently used techniques are continuous paravertebral block (PVB) and single-shot intercostal nerve block (ICNB). We hypothesize that using either PVB or ICNB is non-inferior to TEA regarding postoperative pain and superior regarding quality of recovery (QoR). Signifying faster postoperative mobilisation, reduced morbidity and shorter hospitalisation, these techniques may therefore reduce health care costs and improve patient satisfaction. METHODS: This multi-centre randomised study is a three-arm clinical trial comparing PVB, ICNB and TEA in a 1:1:1 ratio for pain (non-inferiority) and QoR (superiority) in 450 adult patients undergoing VATS anatomic lung resection. Patients will not be eligible for inclusion in case of contraindications for TEA, PVB or ICNB, chronic opioid use or if the lung surgeon estimates a high probability that the operation will be performed by thoracotomy. PRIMARY OUTCOMES: (1) the proportion of pain scores ≥ 4 as assessed by the numerical rating scale (NRS) measured during postoperative days (POD) 0-2; and (2) the QoR measured with the QoR-15 questionnaire on POD 1 and 2. Secondary outcome measures are cumulative use of opioids and analgesics, postoperative complications, hospitalisation, patient satisfaction and degree of mobility. DISCUSSION: The results of this trial will impact international guidelines with respect to perioperative care optimization after anatomic lung resection performed through VATS, and will determine the most cost-effective pain strategy and may reduce variability in postoperative pain management. Trial registration The trial is registered at the Netherlands Trial Register (NTR) on February 1st, 2021 (NL9243). The NTR is no longer available since June 24th, 2022 and therefore a revised protocol has been registered at ClinicalTrials.gov on August 5th, 2022 (NCT05491239). PROTOCOL VERSION: version 3 (date 06-05-2022), ethical approval through an amendment (see ethical proof in the Study protocol proof).

Feasibility and accuracy of confocal endomicroscopy in comparison with narrow-band imaging and chromoendoscopy for the differentiation of colorectal lesions.

OBJECTIVES: Several advanced imaging techniques have been developed to improve differentiation of colorectal lesions. These techniques need to be assessed for both feasibility and accuracy in order to prove their value in daily clinical practice. The current study assessed the feasibility of probe-based confocal laser endomicroscopy (pCLE) in acquiring videos of sufficient quality. Furthermore, the accuracy of pCLE for the differentiation of colorectal lesions was assessed and compared with narrow-band imaging (NBI) and chromoendoscopy (CE). METHODS: Consecutive patients scheduled for surveillance colonoscopy at our centre were included. All procedures were performed by two expert colonoscopists, who previously participated in studies evaluating pCLE, NBI, and CE. All detected lesions during colonoscopy were differentiated real-time with NBI and CE for Kudo pit pattern. Lesions were also assessed real-time for vascular pattern intensity (VPI) during NBI. Subsequently, pCLE videos of each lesion were acquired and biopsies were taken for histopathology. All pCLE videos were assessed post-hoc for the percentage of time demonstrating sufficient image quality (i.e., depicting at least one crypt or vessel). Finally, pCLE videos were assessed post-hoc for diagnostic accuracy by two experts. RESULTS: A total of 154 lesions detected in 64 patients were included. Accuracy of Kudo pit pattern with NBI for predicting neoplasia (88.7%) was significantly better than accuracy of VPI (77.5%, P = 0.05) but not significantly different from CE (89.3%, P = 0.125). During pCLE, no histology was shown at all on the video in 19 lesions (12%). The mean time to acquire a pCLE video of the remaining 135 lesions was 50 seconds (s.d. 47) per lesion. The median percentage demonstrating sufficient quality per video was 40.5% (interquartile range 21.2-67.0). Accuracy of pCLE for both observers (66.7 and 71.9%) was significantly lower than accuracy of CE (P < 0.001) and NBI (P < 0.001). CONCLUSIONS: Video acquisition with pCLE could not be achieved in a small number of lesions. The majority of pCLE videos demonstrated insufficient quality in more than half of the time recorded. Moreover, post-hoc accuracy of pCLE was significantly lower in comparison with real-time accuracy of CE and NBI. Future research should assess whether further increase in experience could improve pCLE video acquisition and determine the real-time accuracy of pCLE for differentiating colorectal lesions.

The prevalence of dysplasia in the ileoanal pouch following restorative proctocolectomy for ulcerative colitis with associated dysplasia.

AIM: A recent systematic review indicated that dysplasia present before restorative proctocolectomy is a predictor of subsequent dysplasia in the pouch. This prospective study was carried out to assess the prevalence of dysplasia in the ileal pouch in patients having RPC for ulcerative colitis with co-existing dysplasia in the operation specimen. METHOD: Eligible patients were invited for a surveillance endoscopy. The afferent and blind efferent ileal loop, ileoanal pouch and rectal cuff were examined by standard endoscopy using a dye-spray technique with methylene blue. Mucosal abnormalities were biopsied and random biopsies were taken from the afferent and blind ileal loop, pouch and rectal cuff. RESULTS: Fourty-four patients (25 male, mean 49 years) underwent pouch endoscopy at a mean interval from RPC of 8.6 years. Dysplasia was detected in two (4.5%) patients. In one, low-grade dysplasia was found in the rectal cuff and in the other low-grade dysplasia was detected in random biopsies from the pouch and the efferent ileal loop. CONCLUSION: This prospective pouch-endoscopy study detected dysplasia in < 5% of patients over nearly 10 years. The benefit of routine surveillance for dysplasia in the pouch is uncertain, as the significance of low-grade dysplasia in the pouch is not clear.

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

AIM: Large (> 2 cm) 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. METHOD: Data from patients undergoing TEM or EMR for a rectal adenoma > 2 cm in eight hospitals were retrospectively collected. Patient- and procedure-related characteristics, complications and recurrences were recorded. As EMR may require several attempts to achieve complete resection, early (after a single intervention) and late (permitting re-treatment for residual adenoma within 6 months) recurrence rates were determined. RESULTS: Two hundred and ninety-two (292) patients (49% male; mean age 67 years) were included; 219 were treated by TEM and 73 by EMR. Adenomas treated by EMR were smaller (median 30 vs 40 mm; P = 0.007). Perioperative complication rates were 2% for TEM and 6% for EMR (P = 0.171). Postoperative complications occurred in 24% of TEM patients and in 13% of EMR patients (P = 0.038). Median hospitalization after TEM was 3 days vs 0 days after EMR (P < 0.001). Median follow-up was 12.6 months (0-47 months); Early recurrence rates were 10.2% in TEM patients and 31.0% in EMR patients (P < 0.001); late recurrence rates were 9.6% and 13.8%, respectively (P = 0.386). CONCLUSION: After a single intervention, EMR of large rectal adenomas seems less effective, but safer than TEM. When allowing re-treatment of residual adenoma within 6 months, EMR and TEM seem equally effective. A prospective randomized comparison seems to be necessary.

New classification for probe-based confocal laser endomicroscopy in the colon.

BACKGROUND AND AIMS: Probe-based confocal laser endomicroscopy (pCLE; Cellvizio, Mauna Kea Technologies, Paris, France) enables in vivo histology during colonoscopy and may allow endoscopists to make real-time diagnoses. A collaboration of five experts proposed a new pCLE classification for colonic use. The aim of this study was to assess interobserver agreement and accuracy of the new pCLE classification in the colon. PATIENTS AND METHODS: Eligible patients were prospectively investigated by pCLE. A subset of 13 pCLE video sequences was reviewed post hoc for the establishment of a new classification, which comprised three vessel categories and seven crypt categories. All five blinded observers then scored another set of 102 video sequences, using the new classification. Histopathology was used as a reference standard. RESULTS: The interobserver agreements on vessel and crypt architecture were 'fair' with kappa values of 0.29 and 0.27, respectively. When the classification was reduced to neoplasia vs. non-neoplasia (i.e. vessel or crypt type 3), overall agreement became 'moderate' (κ = 0.56). Overall sensitivity and specificity for predicting neoplasia was 66 % and 83 %, respectively. When all observers agreed (69 % of videos), the corresponding figures became 80 % and 95 %. CONCLUSION: A new classification for pCLE in the colon had a 'moderate' interobserver agreement for differentiating neoplasia from non-neoplastic tissue in the colon. The overall accuracy (81 %) for predicting neoplasia was acceptable and became excellent (94 %) when all five observers agreed. Future research should focus on refinement and validation of the classification.

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

BACKGROUND AND STUDY AIMS: Large ( > 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. PATIENTS AND METHODS: A 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. RESULTS: A 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). CONCLUSIONS: After 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  months 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.

Increased polyp detection using narrow band imaging compared with high resolution endoscopy in patients with hyperplastic polyposis syndrome.

BACKGROUND AND STUDY AIMS: Hyperplastic polyposis syndrome (HPS) is associated with colorectal cancer and is characterized by multiple hyperplastic polyps, sessile serrated adenomas (SSAs) and adenomas. Narrow band imaging (NBI) may improve the detection of polyps in HPS. We aimed to compare polyp miss rates with NBI with those of high resolution endoscopy (HRE). PATIENTS AND METHODS: In a single center, randomized crossover study consecutive HPS patients underwent tandem colonoscopy with HRE and NBI, in randomized order with removal of all detected polyps. RESULTS: In 22 patients with HPS, 209 polyps were detected, including 27 with normal histology, 116 hyperplastic polyps, 42 SSAs, and 24 adenomas. Among patients assigned to HRE first (n = 11) a total of 78 polyps was detected; subsequent NBI added 44 polyps. In patients examined with NBI first, 78 polyps were detected and subsequent HRE added 9. Polyp miss rates of HRE and NBI were 36% and 10% (OR 0.21; 0.09-0.45). Flat polyp shape was independently associated with increased miss rate. CONCLUSION: NBI significantly reduces polyp miss rates in HPS patients. We recommend using either NBI or chromoendoscopy for colonoscopic surveillance of HPS patients with removal of all detected polyps.

Pilot study of probe-based confocal laser endomicroscopy during colonoscopic surveillance of patients with longstanding ulcerative colitis.

BACKGROUND AND AIMS: Surveillance of patients with ulcerative colitis consists of taking targeted and random biopsies, which is time-consuming and of doubtful efficiency. The use of probe-based confocal laser endomicroscopy (pCLE) may increase efficiency. This prospective pilot study aimed to evaluate the feasibility and diagnostic accuracy of pCLE in ulcerative colitis surveillance. METHODS: In 22 patients with ulcerative colitis, 48 visible lesions and 87 random areas were initially evaluated by real-time narrow-band imaging (NBI) and high-definition endoscopy (HDE). Before taking biopsies, fluorescein-enhanced pCLE was performed. All pCLE videos were scored afterwards by two endoscopists who were blinded to histology and endoscopy. Outcome measures were: (1) the feasibility of pCLE, expressed as pCLE imaging time required, percentage of imaging time with clear pCLE histology, and pCLE video quality as rated by two endoscopists; and (2) the diagnostic accuracy of pCLE. RESULTS: The median pCLE imaging time required was 98 seconds for lesions vs. 66 seconds for random areas ( P = 0.002). The median percentages of imaging time with clear pCLE histology were 61 % vs. 81 % respectively ( P < 0.001). The pCLE video quality was rated as good/excellent in 69 %. Feasibility was significantly poorer for sessile and pedunculated mobile lesions. The sensitivity, specificity, and accuracy of blinded pCLE were 65 %, 82 %, and 81 %, whereas these figures were 100 %, 89 %, and 92 % for real-time endoscopic diagnosis with NBI and HDE. CONCLUSION: This study demonstrates that pCLE for ulcerative colitis surveillance is feasible with reasonable diagnostic accuracy. Future research should show whether increased experience with pCLE improves its ease of use and whether real-time pCLE diagnosis is associated with greater diagnostic accuracy.

Narrow-band imaging versus high-definition endoscopy for the diagnosis of neoplasia in ulcerative colitis.

BACKGROUND AND STUDY AIMS: Controversy exists about which colonoscopic technique is most sensitive for the diagnosis of neoplasia in patients with ulcerative colitis. We compared new-generation narrow-band imaging (NBI) to high-definition endoscopy (HDE) for the detection of neoplasia and evaluated NBI for the differentiation of neoplastic from non-neoplastic mucosa. PATIENTS AND METHODS: Randomized crossover trial in which patients with ulcerative colitis underwent both NBI and HDE colonoscopy in random order with at least 3 weeks between the two procedures, which were performed by different endoscopists. Lesions detected during the first examination were left in situ in order to enable detection during the second examination as well. Main outcome measures were (1) neoplasia detection, and (2) diagnostic accuracy of NBI for differentiating neoplastic from non-neoplastic mucosa by using the Kudo classification and vascular pattern intensity (VPI). RESULTS: Twenty-five patients were randomized to undergo HDE first and 23 to undergo NBI first. Of 16 neoplastic lesions, 11 (69 %) were detected by HDE and 13 (81 %) by NBI ( P = 0.727). Of 11 patients with neoplasia, 9 (82 %) were diagnosed by HDE and 8 (73 %) by NBI ( P = 1.0). The sensitivity, specificity, and accuracy of the Kudo classification were 76 %, 66 % and 67 %. Corresponding figures for VPI were 80 %, 72 %, and 73 %. CONCLUSION: NBI does not improve the detection of neoplasia in patients with ulcerative colitis compared to HDE. In addition, NBI proves unsatisfactory for differentiating neoplastic from non-neoplastic mucosa.

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 (n = 25), 10 neoplastic lesions were primarily detected. Subsequent WLE detected no additional neoplasia. Among patients examined with WLE first (n = 25), three neoplastic lesions were detected; subsequent inspection with AFI added three neoplastic lesions. Neoplasia miss-rates for AFI and WLE were 0% and 50% (p = 0.036). 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.

Review article: New developments in colonic imaging.

BACKGROUND: Colonoscopic detection and removal of neoplasia from the colorectum prevent the development of colorectal cancer. Sporadic adenomas and neoplasia associated with ulcerative colitis are frequently missed during colonoscopy, as a result of which, interval cancers might develop. AIM: To review new developments in colonoscopic imaging concerning the detection of neoplasia. METHODS: Medical databases were searched for relevant publications, dealing with advanced endoscopic imaging techniques during colonoscopy. RESULTS: Pancolonic chromoendoscopy has shown to increase the detection of sporadic adenomas and ulcerative colitis associated neoplasia, at the expense of longer examination times. As chromoendoscopy is labour intensive and time-consuming, its widespread use has been hampered. Narrow band imaging is a novel endoscopic imaging technique, which enhances mucosal and vascular details. Recent studies indicate that narrow band imaging has a high yield for neoplasia; however, no improvement compared to standard colonoscopy has been demonstrated. Autofluorescence imaging is another new technique for which blue endoscopic light is used to induce mucosal autofluorescence. So far, preliminary results have shown promising results of autofluorescence imaging for neoplasia detection. CONCLUSION: Whether chromoendoscopy or novel advanced imaging techniques will change current colonoscopic practice depends on results of future studies comparing these different colonoscopic techniques.