Interdisciplinary Spanish consensus on a watch-and-wait approach for rectal cancer / Consenso español interdisciplinar sobre un enfoque de vigilancia y espera en el cáncer de recto

Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.(AU)

Interdisciplinary Spanish consensus on a watch-and-wait approach for rectal cancer.

Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.

The "diagnose and leave in" strategy for diminutive rectosigmoid polyps in Lynch syndrome: a post hoc analysis from a randomized controlled trial.

BACKGROUND: The "diagnose-and-leave-in" policy has been established to reduce the risks and costs related to unnecessary polypectomies in the average-risk population. In individuals with Lynch syndrome, owing to accelerated carcinogenesis, the general recommendation is to remove all polyps, irrespective of size, location, and appearance. We evaluated the feasibility and safety of the diagnose-and-leave-in strategy in individuals with Lynch syndrome. METHODS : We performed a post hoc analysis based on per-polyp data from a randomized, clinical trial conducted by 24 dedicated colonoscopists at 14 academic centers, in which 256 patients with confirmed Lynch syndrome underwent surveillance colonoscopy from July 2016 to January 2018. In vivo optical diagnosis with confidence level for all detected lesions was obtained before polypectomy using virtual chromoendoscopy alone or with dye-based chromoendoscopy. Primary outcome was the negative predictive value (NPV) for neoplasia of high-confidence optical diagnosis among diminutive (≤ 5 mm) rectosigmoid lesions. Histology was the reference standard. RESULTS: Of 147 rectosigmoid lesions, 128 were diminutive. In 103 of the 128 lesions (81 %), the optical diagnostic confidence was high and showed an NPV of 96.0 % (95 % confidence interval [CI] 88.9 %-98.6 %) and accuracy of 89.3 % (95 %CI 81.9 %-93.9 %). By following the diagnose-and-leave-in policy, we would have avoided 59 % (75/128) of polypectomies at the expense of two diminutive low grade dysplastic adenomas and one diminutive sessile serrated lesion that would have been left in situ. CONCLUSION: In patients with Lynch syndrome, the diagnose-and-leave-in strategy for diminutive rectosigmoid polyps would be feasible and safe.

Compound Endoscopic Morphological Features for Identifying Non-Pedunculated Lesions ≥20 mm with Intramucosal Neoplasia.

BACKGROUND: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion. OBJECTIVE: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that present intramucosal neoplasia (includes low-grade neoplasia and high-grade neoplasia) and are suitable for piecemeal EMR. DESIGN: A post-hoc analysis from an observational prospective multicentre study conducted by 58 endoscopists at 17 academic and community hospitals was performed. Unbiased conditional inference trees (CTREE) were fitted to analyse the association between intramucosal neoplasia and the lesions' endoscopic characteristics. RESULT: 542 lesions from 517 patients were included in the analysis. Intramucosal neoplasia was present in 484 of 542 (89.3%) lesions. A conditional inference tree including all lesions' characteristics assessed with white light imaging and narrow-band imaging (NBI) found that ulceration, pseudodepressed type and sessile morphology changed the accuracy for predicting intramucosal neoplasia. In ulcerated lesions, the probability of intramucosal neoplasia was 25% (95%CI: 8.3-52.6%; p < 0.001). In non-ulcerated lesions, its probability in lateral spreading lesions (LST) non-granular (NG) pseudodepressed-type lesions rose to 64.0% (95%CI: 42.6-81.3%; p < 0.001). Sessile morphology also raised the probability of intramucosal neoplasia to 86.3% (95%CI: 80.2-90.7%; p < 0.001). In the remaining 319 (58.9%) non-ulcerated lesions that were of the LST-granular (G) homogeneous type, LST-G nodular-mixed type, and LST-NG flat elevated morphology, the probability of intramucosal neoplasia was 96.2% (95%CI: 93.5-97.8%; p < 0.001). CONCLUSION: Non-ulcerated LST-G type and LST-NG flat elevated lesions are the most common non-pedunculated lesions ≥20 mm and are associated with a high probability of intramucosal neoplasia. This means that they are good candidates for piecemeal EMR. In the remaining lesions, further diagnostic techniques like magnification or diagnostic +/- therapeutic endoscopic submucosal dissection should be considered.

Long-Term Incidence of Advanced Colorectal Neoplasia in Patients with Serrated Polyposis Syndrome: Experience in a Single Academic Centre.

Serrated polyposis syndrome (SPS) implies a slightly elevated risk of colorectal cancer (CRC) during endoscopic follow-up, but its natural course is still not well known. The main objective of this study was to describe the long-term risk of developing advanced neoplasia (AN) in these patients. Until October 2020, individuals who fulfilled 2010 WHO criteria I and/or III for SPS were retrospectively recruited. We selected those under endoscopic surveillance after resection of all lesions >3 mm in a high-quality colonoscopy. We excluded patients with total colectomy at diagnosis and those with any interval between colonoscopies >3.5 years. We defined AN as advanced serrated polyp (≥10 mm and/or with dysplasia), advanced adenoma, or CRC. In 109 patients, 342 colonoscopies were performed (median = 3, median interval = 1.8 years) during a median follow-up after colonic clearance of 5.0 years. Five-year cumulative incidences of AN were 21.6% globally, and 5.6%, 10.8%, and 50.8% in patients who fulfilled criterion I, III, and both, respectively (p < 0.001). No CRC was diagnosed and only 1 (0.9%) patient underwent surgery. In conclusion, cumulative incidences of AN could be lower than previously described, at least in patients who fulfil the 2010 WHO criterion III alone. Therefore, low-risk individuals might benefit from less stringent surveillance.

White-Light Endoscopy Is Adequate for Lynch Syndrome Surveillance in a Randomized and Noninferiority Study.

BACKGROUND & AIMS: Dye-based pancolonic chromoendoscopy is recommended for colorectal cancer surveillance in patients with Lynch syndrome. However, there is scarce evidence to support its superiority to high-definition white-light endoscopy. We performed a prospective study assess whether in the hands of high detecting colonoscopists, high-definition, white-light endoscopy is noninferior to pancolonic chromoendoscopy for detection of adenomas in patients with Lynch syndrome. METHODS: We conducted a parallel controlled study, from July 2016 through January 2018 at 14 centers in Spain of adults with pathogenic germline variants in mismatch repair genes (60% women; mean age, 47 ± 14 years) under surveillance. Patients were randomly assigned to groups that underwent high-definition white-light endoscopy (n = 128) or pancolonic chromoendoscopy (n = 128) evaluations by 24 colonoscopists who specialized in detection of colorectal lesions in high-risk patients for colorectal cancer. Adenoma detection rates (defined as the proportion of patients with at least 1 adenoma) were compared between groups, with a noninferiority margin (relative difference) of 15%. RESULTS: We found an important overlap of confidence intervals (CIs) and no significant difference in adenoma detection rates by pancolonic chromoendoscopy (34.4%; 95% CI 26.4%-43.3%) vs white-light endoscopy (28.1%; 95% CI 21.1%-36.4%; P = .28). However, pancolonic chromoendoscopy detected serrated lesions in a significantly higher proportion of patients (37.5%; 95% CI 29.5-46.1) than white-light endoscopy (23.4%; 95% CI 16.9-31.4; P = .01). However, there were no significant differences between groups in proportions of patients found to have serrated lesions of 5 mm or larger (9.4% vs 7.0%; P = .49), of proximal location (11.7% vs 10.2%; P = .68), or sessile serrated lesions (3.9% vs 5.5%; P = .55), respectively. Total procedure and withdrawal times with pancolonic chromoendoscopy (30.7 ± 12.8 minutes and 18.3 ± 7.6 minutes, respectively) were significantly longer than with white-light endoscopy (22.4 ± 8.7 minutes and 13.5 ± 5.6 minutes; P < .001). CONCLUSIONS: In a randomized parallel trial, we found that for Lynch syndrome surveillance, high-definition white-light endoscopy is not inferior to pancolonic chromoendoscopy if performed by experienced and dedicated endoscopists. ClinicalTrials.gov no: NCT02951390.

Endocuff-assisted colonoscopy for surveillance of serrated polyposis syndrome: a multicenter randomized controlled trial.

BACKGROUND AND STUDY AIMS: Serrated polyposis syndrome (SPS) is a condition with high risk for colorectal cancer. The Endocuff device has been shown to increase adenoma detection in the general and screening population. We aimed to ascertain whether Endocuff-assisted colonoscopy increases detection of serrated lesions in comparison with standard colonoscopy during the surveillance of patients with SPS.  METHODS: In a multicenter randomized controlled study, patients who met SPS criteria I and/or III under surveillance (previous resection of all serrated lesions ≥ 4 mm) were consecutively randomly allocated 1:1 to Endocuff-assisted colonoscopy or standard colonoscopy, performed by expert endoscopists. The main outcome was the mean number of serrated lesions detected per patient. RESULTS: 122 patients (standard colonoscopy n = 60; Endocuff-assisted colonoscopy n = 62; 59 % men; mean age 60.6 (standard deviation [SD] 7.5) were included at 4 centers. Baseline variables (demographic data, SPS phenotype, colorectal cancer [CRC] history, cumulative polyps, and follow-up), cecal intubation rate, and withdrawal time were similar between groups. There was no statistically significant difference between Endocuff-assisted colonoscopy and standard colonoscopy for the mean number of serrated lesions detected per patient: 5.8 (95 % confidence interval [95 %CI] 4.4 - 7.2) and 5.0 (3.9 - 6.1), respectively (P = 0.36). There were also no differences between Endocuff-assisted and standard colonoscopy for detection of sessile serrated lesions (mean number per patient 2.5 [1.3 - 3.6] vs. 2.0 [1.1 - 3.0], P = 0.54) and adenomas (0.9 [0.5 - 1.3] vs. 0.5 [0.3 - 0.7], P = 0.12). CONCLUSION: Use of Endocuff-assisted colonoscopy did not significantly increase the number of serrated lesion detected per patient during surveillance of SPS.

High incidence of advanced colorectal neoplasia during endoscopic surveillance in serrated polyposis syndrome.

BACKGROUND: Serrated polyposis syndrome (SPS) has been associated with an increased risk of colorectal cancer (CRC). Accordingly, intensive surveillance with annual colonoscopy is advised. The aim of this multicenter study was to describe the risk of advanced lesions in SPS patients undergoing surveillance, and to identify risk factors that could guide the prevention strategy. METHODS: From March 2013 to April 2015, 296 patients who fulfilled criteria I and/or III for SPS were retrospectively recruited at 18 centers. We selected patients in whom successful clearing colonoscopy had been performed and who underwent subsequent endoscopic surveillance. Advanced neoplasia was defined as CRC, advanced adenoma, or advanced serrated lesion that were ≥ 10 mm and/or with dysplasia. Cumulative incidence of advanced neoplasia was calculated and independent predictors of advanced neoplasia development were identified. RESULTS: In 152 SPS patients a total of 315 surveillance colonoscopies were performed (median 2, range 1 - 7). The 3-year cumulative incidence of CRC and advanced neoplasia were 3.1 % (95 % confidence interval [CI] 0 - 6.9) and 42.0 % (95 %CI 32.4 - 51.7), respectively. Fulfilling both I + III criteria and the presence of advanced serrated lesions at baseline colonoscopy were independent predictors of advanced neoplasia development (odds ratio [OR] 1.85, 95 %CI 1.03 - 3.33, P  = 0.04 and OR 2.62, 95 %CI 1.18 - 5.81, P  = 0.02, respectively). During follow-up, nine patients (5.9 %) were referred for surgery for invasive CRC (n = 4, 2.6 %) or because of polyp burden (n = 5, 3.3 %). After total colectomy, 17.9 % patients developed advanced neoplasia in the retained rectum. CONCLUSIONS: Patients with SPS have a substantial risk of developing advanced neoplasia under endoscopic surveillance, whereas CRC incidence is low. Personalized endoscopic surveillance based on polyp burden and advanced serrated histology could help to optimize prevention in patients with SPS.

Accuracy of the Narrow-Band Imaging International Colorectal Endoscopic Classification System in Identification of Deep Invasion in Colorectal Polyps.

BACKGROUND & AIMS: T1 colorectal polyps with at least 1 risk factor for metastasis to lymph node should be treated surgically and are considered endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification system, is used to identify neoplasias with invasion of the submucosa that require endoscopic treatment. We assessed the accuracy of the NICE classification, along with other morphologic characteristics, in identifying invasive polyps that are endoscopically unresectable (have at least 1 risk factor for metastasis to lymph node). METHODS: We performed a multicenter, prospective study of data collected by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17 university and community hospitals in Spain from July 2014 through June 2016. All consecutive lesions >10 mm assessed with narrow-band imaging were included. The primary end point was the accuracy of the NICE classification for identifying lesions with deep invasion, using findings from histology analysis as the reference standard. Conditional inference trees were fitted for the analysis of diagnostic accuracy. RESULTS: Of the 2123 lesions analyzed, 89 (4.2%) had features of deep invasion and 91 (4.3%) were endoscopically unresectable. The NICE classification system identified lesions with deep invasion with 58.4% sensitivity (95% CI, 47.5-68.8), 96.4% specificity (95% CI, 95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference tree that included all variables found the NICE classification to most accurately identify lesions with deep invasion (P < .001). However, pedunculated morphology (P < .007), ulceration (P = .026), depressed areas (P < .001), or nodular mixed type (P < .001) affected accuracy of identification. Results were comparable for identifying lesions that were endoscopically unresectable. CONCLUSIONS: In an analysis of 2123 colon lesions >10 mm, we found the NICE classification and morphologic features identify those with deep lesions with >96% specificity-even in non-expert hands and without magnification. ClinicalTrials.gov number NCT02328066.

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.

Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study.

OBJECTIVE: Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. DESIGN: From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. RESULTS: In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). CONCLUSIONS: Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.

Proctitis as the clinical presentation of lymphogranuloma venereum, a re-emerging disease in developed countries.

Lymphogranuloma venereum (LGV) is a sexually transmitted infectious disease caused by serovars L1, L2 and L3 of Chlamydia trachomatis. The initial presentation is usually a painless ulcerated papule on the genitalia or distal proctitis. The progression of the infection can lead to major complications: rectal strictures, intestinal obstruction or perforation. We present five cases of LGV proctitis as the initial presentation of the disease. All patients were male, mean age 44.6 years, with positive serology to human immunodeficiency virus (HIV) and promiscuous men who have sex with men (MSM).The initial diagnosis was made by rectosigmoidoscopy indicated for pain and anal discharge. All cases were confirmed by polymerase chain reaction technique in rectal tissue. Endoscopic images obtained showed a great variety of rectal lesions, from mild erythema of the mucosa and ulcers to deep ulcers with elevated borders and purulent exudate. All cases were resolved after treatment with doxycycline for 3 weeks. It emphasizes the importance of suspecting this re-emerging disease in patients with risk factors (HIV and MSM), with the aim of early treatment and to avoid major complications.

Proctitis como forma de presentación del linfogranuloma venéreo, una entidad emergente en los países desarrollados / Proctitis as the clinical presentation of lymphogranuloma venereum, a re-emerging disease in developed countries

El linfogranuloma venéreo (LGV) es una enfermedad infecciosa de transmisión sexual causada por los serotipos L1, L2 y L3 de Chlamydia trachomatis. Se manifiesta inicialmente como una pápula ulcerada e indolora en los genitales o como una proctitis distal. La progresión de la infección puede dar lugar a complicaciones mayores: estenosis rectal, obstrucción o perforación intestinal. Se presentan cinco casos de LGV con proctitis como signo inicial de la enfermedad. Todos los pacientes eran varones, de edad media 44,6 años, con serología positiva al virus de inmunodeficiencia humana (VIH) y homosexuales promiscuos. El diagnóstico se realizó mediante rectoscopia indicada por dolor y supuración anal. Todos los casos fueron confirmados mediante técnica de reacción en cadena de la polimerasa en tejido rectal. Las imágenes endoscópicas obtenidas muestran la gran diversidad de lesiones rectales posibles, desde leve eritema de la mucosa con aftas hasta úlceras profundas con bordes sobreelevados y abundante fibrina. Tras tratamiento con doxiciclina, durante 3 semanas, todos los casos se resolvieron de forma satisfactoria. Se enfatiza la importancia de sospechar esta patología emergente en pacientes con factores de riesgo (VIH y homosexuales), con el fin de instaurar un tratamiento precoz y evitar las complicaciones mayores (AU)

Lymphogranuloma venereum (LGV) is a sexually transmitted infectious disease caused by serovars L1, L2 and L3 of Chlamydia trachomatis. The initial presentation is usually a painless ulcerated papule on the genitalia or distal proctitis. The progression of the infection can lead to major complications: rectal strictures, intestinal obstruction or perforation. We present five cases of LGV proctitis as the initial presentation of the disease. All patients were male, mean age 44.6 years, with positive serology to human immunodeficiency virus (HIV) and promiscuous men who have sex with men (MSM). The initial diagnosis was made by rectosigmoidoscopy indicated for pain and anal discharge. All cases were confirmed by polymerase chain reaction technique in rectal tissue. Endoscopic images obtained showed a great variety of rectal lesions, from mild erythema of the mucosa and ulcers to deep ulcers with elevated borders and purulent exudate. All cases were resolved after treatment with doxycycline for 3 weeks. It emphasizes the importance of suspecting this re-emerging disease in patients with risk factors (HIV and MSM), with the aim of early treatment and to avoid major complications (AU)

Colestasis aguda en un varón con trasplante renal y hepatitis C crónica / No disponible

No disponible

Toxicidad hepática y síndrome de respuesta inflamatoria sistémica por clopidogrel / Hepatic toxicity and clopidogrel-induced systemic inflammatory response syndrome

No disponible