Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study.

Early-stage colorectal carcinoma (CRC)-pT1-is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5-2%. Among these cases, approximately 6-16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/µL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.

Dilemmas in the Clinical Management of pT1 Colorectal Cancer.

Implementation of population-based colorectal cancer screening programs has led to increases in the incidence of pT1 colorectal cancer. These incipient invasive cancers have a very good prognosis and can be treated locally, but more than half of these cases are treated with surgery due to the presence of histological high-risk criteria. These high-risk criteria are suboptimal, with no consensus among clinical guidelines, heterogeneity in definitions and assessment, and poor concordance in evaluation, and recent evidence suggests that some of these criteria considered high risk might not necessarily affect individual prognosis. Current criteria classify most patients as high risk with an indication for additional surgery, but only 2-10.5% have lymph node metastasis, and the residual tumor is present in less than 20%, leading to overtreatment. Patients with pT1 colorectal cancer have excellent disease-free survival, and recent evidence indicates that the type of treatment, whether endoscopic or surgical, does not significantly impact prognosis. As a result, the protective role of surgery is questionable. Moreover, surgery is a more aggressive treatment option, with the potential for higher morbidity and mortality rates. This article presents a comprehensive review of recent evidence on the clinical management of pT1 colorectal cancer. The review analyzes the limitations of histological evaluation, the prognostic implications of histological risk status and the treatment performed, the adverse effects associated with both endoscopic and surgical treatments, and new advances in endoscopic treatment.

Prevalence of adenomatous polyposis in a fecal immunochemical test-based colorectal cancer screening program and risk of advanced neoplasia during follow-up.

BACKGROUND : Current guidelines recommend genetic counseling and intensive colonoscopy surveillance for patients with ≥ 10 colorectal adenomas based on scarce data. We investigated the prevalence of this condition in a fecal immunochemical test (FIT)-based colorectal (CRC) screening program, and the incidence of metachronous lesions during follow-up. METHODS: We retrospectively included all FIT-positive participants with ≥ 10 adenomas at index colonoscopy between 2010 and 2018. Surveillance colonoscopies were collected until 2019. Patients with inherited syndromes, serrated polyposis syndrome, total colectomy, or lacking surveillance data were excluded. The cumulative incidence of CRC and advanced neoplasia were analyzed by Kaplan-Meier analysis. Risk factors for metachronous advanced neoplasia were investigated by multivariable logistic regression analysis. RESULTS: 215 of 9582 participants (2.2 %) had ≥ 10 adenomas. Germline genetic testing was performed in 92 % of patients with ≥ 20 adenomas, identifying two inherited syndromes (3.3 %). The 3-year cumulative incidence of CRC and advanced neoplasia were 1 % and 16 %, respectively. In 39 patients (24.2 %), no polyps were found on first surveillance colonoscopy. The presence of an advanced adenoma was independently associated with a higher risk of advanced neoplasia at first surveillance colonoscopy (odds ratio 3.91, 95 %CI 1.12-13.62; P = 0.03). Beyond the first surveillance colonoscopy, the risk of metachronous advanced neoplasia was lower. CONCLUSIONS: The prevalence of ≥ 10 adenomas in a FIT-based CRC screening program was 2.2 %; a small proportion of inherited syndromes were detected, even amongst those with ≥ 20 adenomas. A low rate of post-colonoscopy CRC was observed and the risk of advanced neoplasia beyond the first surveillance colonoscopy tended to progressively decrease throughout successive follow-ups.

Randomized Clinical Trial: A Normocaloric Low-Fiber Diet the Day Before Colonoscopy Is the Most Effective Approach to Bowel Preparation in Colorectal Cancer Screening Colonoscopy.

BACKGROUND: Clinical guidelines recommend either a clear-liquid diet or a low-fiber diet for colonoscopy preparation. Participants in a screening program are usually motivated healthy individuals in which a good tolerability is important to improve adherence to potential surveillance colonoscopies. OBJECTIVE: Our aim was to assess whether or not a normocaloric low-fiber diet followed the day before a screening colonoscopy compromises the efficacy of bowel cleansing and may improve the tolerability of bowel preparation. DESIGN: This is a randomized, endoscopist-blinded, noninferiority clinical trial. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: A total of 276 consecutive participants of the Barcelona colorectal cancer screening program were included. INTERVENTION: Participants were randomly assigned to a clear-liquid diet or a normocaloric low-fiber diet the day before the colonoscopy. Both groups received 4 L of polyethylene glycol in a split-dose regimen. MAIN OUTCOME MEASURES: Primary outcome was the adequate bowel preparation rate measured with the Boston bowel preparation scale. Secondary outcomes included tolerability, fluid-intake perception, hunger, side effects, and acceptability. RESULTS: Participants in both groups were similar in baseline characteristics. Adequate bowel preparation was achieved in 89.1% vs 95.7% in clear-liquid diet and low-fiber diet groups, showing not only noninferiority, but also superiority (p = 0.04). Low-fiber diet participants reported less fluid-intake perception (p = 0.04) and less hunger (p = 0.006), with no differences in bloating or nausea. LIMITATIONS: The single-center design of the study could limit the external validity of the results. The present findings may not be comparable to other clinical settings. CONCLUSION: A normocaloric low-fiber diet the day before a screening colonoscopy achieved better results than a clear-liquid diet in terms of adequate colon preparation. Moreover, it also improved the perception of hunger and excessive fluid intake. Registered at clinicaltrials.gov: NCT02401802. See Video Abstract at http://links.lww.com/DCR/A829.

Changes in FIT values below the threshold of positivity and short-term risk of advanced colorectal neoplasia: Results from a population-based cancer screening program.

INTRODUCTION: Increased values in the fecal immunochemical test (FIT) are correlated with increasingly severe colorectal neoplasia, but little attention has been given to FIT values below the cut-off point (negative FIT, nFIT). We analysed the relationship between the concentrations of two consecutive nFIT and the risk of following screen-detected advanced neoplasia and interval cancer (IC) in a population-based colorectal cancer screening program. METHODS: FIT results were categorised into non-detectable nFIT (0-3.8 µg haemoglobin/g feces), low nFIT (3.9-9.9) and high nFIT (10.0-19.9). Multivariable adjusted logistic regression was used to estimate the odds ratios (OR) of advanced neoplasia and IC with the nFIT results in the first two screens. RESULTS: More than 90% of the 42,524 persons had non-detectable nFIT in the first and second screen; 4.5% and 5.8% had a low nFIT, respectively, and 2.2% and 2.9% had a high nFIT. The probability of testing positive and being diagnosed of advanced neoplasia or IC rose with increasing values of nFIT. Compared with those with two non-detectable nFIT results, the highest OR were found among those who had two high nFIT results (OR 21.75; 95% confidence interval: 12.44, 38.04) and those with one low nFIT and one high nFIT (ORs around 20). CONCLUSIONS: Participants with nFIT results above the detection limit of the test had an increased risk of advanced neoplasia and IC in subsequent participations. This information could be used in the design of personalised screening strategies.

Routine lower gastrointestinal endoscopy for radiographically confirmed acute diverticulitis. In whom and when is it indicated? / Endoscopia digestiva baja de rutina en la diverticulitis aguda confirmada radiológicamente. ¿En quién y cuándo está indicada?

Introduction: international guidelines recommend a routine colonoscopy to rule out advanced neoplasm after an acute diverticulitis event. However, in recent years, this recommendation has been called into question following the advent of computerized tomography (CT), particularly with regard to uncomplicated diverticulitis. Furthermore, colonoscopy is associated with a risk and additional costs. Objective: to understand the diagnostic yield, quality and safety of colonoscopy in the setting of acute diverticulitis. Methods: this was a retrospective study of all patients diagnosed with acute diverticulitis via CT between 2005 and 2013, who subsequently underwent a colonoscopy. Results: two hundred and sixteen patients diagnosed with acute diverticulitis via CT were enrolled. These included 58 cases with complicated diverticulitis (27%) and 158 with uncomplicated diverticulitis (73%). An advanced neoplasm was found in 12 patients (5.6%); 11.7% were complicated and 3.2% were uncomplicated (p = 0.02). No major complications were identified. The quality was low but improved over time; the complete procedure rate was 88%, an effective preparation was achieved in 75% and excision of polyps < 2 cm was performed in 78% of cases. The optimum colonoscopy quality cu-off was 9.5 weeks. Conclusion: routine colonoscopy is advisable after a complicated diverticulitis event but its recommendation is unclear with regard to uncomplicated episodes. Colonoscopy is safe even when performed early. The overall quality is low but may be optimized via a subsequent endoscopy, two months after a diverticulitis diagnosis

Introducción: las guías internacionales recomiendan la colonoscopia de rutina tras un episodio de diverticulitis aguda para descartar la presencia de neoplasia avanzada. Sin embargo, tras la incorporación en los últimos años de la tomografía axial computarizada dicha recomendación ha quedado en entredicho, sobre todo en lo que se refiere a la diverticulitis no complicada. Por otro lado, la colonoscopia es una técnica que comporta riesgos y costes adicionales. Objetivo: conocer la rentabilidad diagnóstica, calidad y seguridad de la colonoscopia en la diverticulitis aguda. Métodos: estudio retrospectivo de todos los pacientes diagnosticados de diverticulitis aguda por tomografía computarizada (TC) entre los años 2005 y 2013, a los que posteriormente se les realizó una colonoscopia. Resultados: doscientos dieciséis pacientes diagnosticados de diverticulitis aguda por TC (58 diverticulitis complicada [27%] y 158 diverticulitis no complicada [73%]) fueron incluidos. Se detectó neoplasia avanzada en 12 pacientes (5,6% [complicada/no complicada 11,7/3,2%, p = 0,02]). No se observaron complicaciones mayores. La calidad fue baja (completa: 88%; preparación eficaz: 75%; resección de pólipos < 2 cm: 78%), si bien mejoró con el paso del tiempo, siendo las 9,5 semanas el punto de corte óptimo de calidad para realizar la colonoscopia. Conclusión: es aconsejable la realización de una colonoscopia de rutina tras un episodio de diverticulitis complicada, pero la recomendación no es clara en la no complicada. La colonoscopia es segura incluso realizada de forma precoz. La calidad es globalmente baja pero podría optimizarse realizando la endoscopia posteriormente a los dos meses del diagnóstico de la diverticulitis

Routine lower gastrointestinal endoscopy for radiographically confirmed acute diverticulitis. In whom and when is it indicated?

INTRODUCTION: international guidelines recommend a routine colonoscopy to rule out advanced neoplasm after an acute diverticulitis event. However, in recent years, this recommendation has been called into question following the advent of computerized tomography (CT), particularly with regard to uncomplicated diverticulitis. Furthermore, colonoscopy is associated with a risk and additional costs. OBJECTIVE: to understand the diagnostic yield, quality and safety of colonoscopy in the setting of acute diverticulitis. METHODS: this was a retrospective study of all patients diagnosed with acute diverticulitis via CT between 2005 and 2013, who subsequently underwent a colonoscopy. RESULTS: two hundred and sixteen patients diagnosed with acute diverticulitis via CT were enrolled. These included 58 cases with complicated diverticulitis (27%) and 158 with uncomplicated diverticulitis (73%). An advanced neoplasm was found in 12 patients (5.6%); 11.7% were complicated and 3.2% were uncomplicated (p = 0.02). No major complications were identified. The quality was low but improved over time; the complete procedure rate was 88%, an effective preparation was achieved in 75% and excision of polyps < 2 cm was performed in 78% of cases. The optimum colonoscopy quality cu-off was 9.5 weeks. CONCLUSION: routine colonoscopy is advisable after a complicated diverticulitis event but its recommendation is unclear with regard to uncomplicated episodes. Colonoscopy is safe even when performed early. The overall quality is low but may be optimized via a subsequent endoscopy, two months after a diverticulitis diagnosis.