Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Underwater versus conventional EMR of large nonpedunculated colorectal lesions: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Underwater EMR (UEMR) is an alternative procedure to conventional EMR (CEMR) to treat large, nonpedunculated colorectal lesions (LNPCLs). In this multicenter, randomized controlled clinical trial, we aimed to compare the efficacy and safety of UEMR versus CEMR on LNPCLs. METHODS: We conducted a multicenter, randomized controlled clinical trial from February 2018 to February 2020 in 11 hospitals in Spain. A total of 298 patients (311 lesions) were randomized to the UEMR (n = 149) and CEMR (n = 162) groups. The main outcome was the lesion recurrence rate in at least 1 follow-up colonoscopy. Secondary outcomes included technical aspects, en bloc resection rate, R0 resection rates, and adverse events, among others. RESULTS: There were no differences in the overall recurrence rate (9.5% UEMR vs 11.7% CEMR; absolute risk difference, -2.2%; 95% CI, -9.4 to 4.9). However, considering polyp sizes between 20 and 30 mm, the recurrence rate was lower for UEMR (3.4% UEMR vs 13.1% CEMR; absolute risk difference, -9.7%; 95% CI, -19.4 to 0). The R0 resection showed the same tendency, with significant differences favoring UEMR only for polyps between 20 and 30 mm. Overall, UEMR was faster and easier to perform than CEMR. Importantly, the techniques were equally safe. CONCLUSIONS: UEMR is a valid alternative to CEMR for treating LNPCLs and could be considered the first option of treatment for lesions between 20 and 30 mm due to its higher en bloc and R0 resection rates. (Clinical trial registration number: NCT03567746.).

Panchromoendoscopy Increases Detection of Polyps in Patients With Serrated Polyposis Syndrome.

BACKGROUND & AIMS: Serrated polyposis syndrome (SPS), characterized by multiple and/or large proximal serrated lesions, increases the risk of colorectal cancer. Serrated lesions often are missed during colonoscopy but panchromoendoscopy can increase their detection in an average-risk population. We performed a randomized controlled study to determine the efficacy of panchromoendoscopy in detection of polyps in patients with SPS. METHODS: Patients with SPS (n = 86 patients) underwent tandem high-definition (HD) colonoscopies from February 2015 through July 2016 at 7 centers in Spain. Patients were assigned randomly to groups that received 2 HD white-light endoscopy examinations (HD-WLE group; n = 43) or HD-WLE followed by 0.4% indigo carmine panchromoendoscopy (HD-CE group; n = 43). For each procedure, polyps detected were described, removed, and analyzed by histology. The primary outcome was additional polyp detection rate, defined as the number of polyps detected during the second inspection divided by the total number of polyps detected during the first and the second examination. RESULTS: A total of 774 polyps were detected (362 in the HD-WLE group and 412 in the HD-CE group); 54.2% were hyperplastic, 13.8% were adenomas, and 10.9% were sessile serrated polyps. There was a significantly higher additional polyp detection rate in the HD-CE group (0.39; 95% CI, 0.35-0.44) than in the HD-WLE group (0.22; 95% CI, 0.18-0.27) (P < .001). A higher additional rate of serrated lesions proximal to the sigmoid colon were detected in the second inspection with HD-CE (0.40; 95% CI, 0.33-0.47) than with HD-WLE (0.24; 95% CI, 0.19-0.31) (P = .001). Detection of adenomas and serrated lesions greater than 10 mm did not differ significantly between groups. In a multivariate logistic regression analysis, only use of HD-CE was associated independently with increased polyp detection throughout the colon. CONCLUSIONS: In a randomized controlled trial, we found that panchromoendoscopy increases detection of polyps (mostly of small serrated lesions) and should be considered the standard of care in patients with SPS. Studies are needed to determine the effects of this strategy on the incidence of advanced neoplasia during long-term follow-up evaluation. ClinicalTrials.gov no: NCT03476434.

Use of electrosurgical units in the endoscopic resection of gastrointestinal tumors.

Electrosurgical units (ESUs) are indispensable devices in our endoscopy units. However, many endoscopists are not well-trained on their use and their physical bases are usually not properly studied or understood. In addition, comparative data concerning the settings that may be applied in different circumstances are scarce in the medical literature. Given that it is important to be aware of their strengths and risks, we conducted a review of the available information and research on this topic.

Comment to the letter "Acute appendicitis after a colonic endoscopic submucosal resection".

We read with interest the letter to the editor "Acute appendicitis after a colonic endoscopic submucosal resection" by Serrano González J et al., which was published in the Revista Española de Enfermedades Digestivas (The Spanish Journal of Gastroenterology) issue 3, 2018. We would like to clarify the following aspects mentioned in this letter.

[Co-expression of estrogen receptors and Her2/neu in breast cancer. Neoadjuvant chemotherapy sentinel lymph node and hormonotherapy]. / Cancer de mama con Her-2-neu y receptores hormonales positivos. Quimioterapia neoadyuvante, biopsia de ganglio centinela y tratamiento hormonal.

Neoadjuvant chemotherapy is an interesting option in the therapy of some breast cancer cases. Cases in which the timing for sentinel lymph node biopsy is controversial. Co-expression of estrogen receptors and Her2/neu (c-erbB-2) in breast cancer may imply hormone resistance, especially to tamoxifen. We present a clinic case with co-expression of estrogen receptors and Her2/neu that was treated with neoadjuvant chemotherapy and previous sentinel lymph node biopsy followed by breasttumorectomy with axillar lymphadenectomy, radiotherapy and hormonotherapy with letrozol, geserelina and trastuzumab. A good treatment response was found.

Endoscopic management of Barrett's dysplasia and early neoplasia: efficacy, safety and long-term outcomes in a UK tertiary centre.

BACKGROUND AND OBJECTIVES: Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) are effective treatments for dysplastic Barrett's esophagus (BE). This study evaluates efficacy, durability and safety in a single high-volume UK tertiary centre with 15-years' experience. METHODS: Prospective data were collected from Nottingham University Hospitals 2004-2019 for endotherapy of dysplastic BE or intramucosal adenocarcinoma. Procedural outcome measures include complete resection, complications and surgery rates. Efficacy outcomes include complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM), recurrence, treatment failure rates, durability of RFA, median follow up and tumor-associated mortality. RESULTS: A total of 319 lesions were resected; 671 RFAs were performed on 239 patients. Median age was 67 (±9.5) years, male:female ratio was 5:1 and median BE length was C3 [interquartile range (IQR): 6] M6 (IQR: 5). The most common lesion was Paris IIa (64%) with a median size of 10 mm (3-70). Final histology was adenocarcinoma in 50%. Complete resection rates were 96%. The multiband mucosectomy technique (91%) was most commonly used. The median number of RFA sessions was 3 (IQR: 2). The rates of CR-D and CR-IM were 90.4%% and 89.8% achieved after a median of 20.1 (IQR: 14) months. The most common complications: EMR was bleeding 2.2% and RFA was stricture (5.4%) requiring a median of 2 (range 1-7) dilatations. Median follow up post CR-IM/CR-D was 38 months (14-60). Metachronous lesions developed in 4.7% after CR-D and tumor-related mortality was 0.8%. Dysplasia and intestinal metaplasia-free survival at 5 years was 95 and 90%, respectively. CONCLUSION: BE endotherapy is minimally invasive, effective, safe and deliverable in a day-case setting.

Aneuploidy in targeted endoscopic biopsies outperforms other tissue biomarkers in the prediction of histologic progression of Barrett's oesophagus: A multi-centre prospective cohort study.

BACKGROUND: The cancer risk in Barrett's oesophagus (BO) is difficult to estimate. Histologic dysplasia has strong predictive power, but can be missed by random biopsies. Other clinical parameters have limited utility for risk stratification. We aimed to assess whether a molecular biomarker panel on targeted biopsies can predict neoplastic progression of BO. METHODS: 203 patients with BO were tested at index endoscopy for 9 biomarkers (p53 and cyclin A expression; aneuploidy and tetraploidy; CDKN2A (p16), RUNX3 and HPP1 hypermethylation; 9p and 17p loss of heterozygosity) on autofluorescence-targeted biopsies and followed-up prospectively. Data comparing progressors to non-progressors were evaluated by univariate and multivariate analyses using survival curves, Cox-proportional hazards and logistic regression models. FINDINGS: 127 patients without high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) at index endoscopy were included, of which 42 had evidence of any histologic progression over time. Aneuploidy was the only predictor of progression from non-dysplastic BO (NDBO) to any grade of neoplasia (p = 0.013) and HGD/OAC (p = 0.002). Aberrant p53 expression correlated with risk of short-term progression within 12 months, with an odds ratio of 6.0 (95% CI: 3.1-11.2). A panel comprising aneuploidy and p53 had an area under the receiving operator characteristics curve of 0.68 (95% CI: 0.59-0.77) for prediction of any progression. INTERPRETATION: Aneuploidy is the only biomarker that predicts neoplastic progression of NDBO. Aberrant p53 expression suggests prevalent dysplasia, which might have been missed by random biopsies, and warrants early follow up.