Risk factors for metachronous colorectal cancer or advanced lesions after endoscopic resection of serrated polyps: a systematic review and meta-analysis

\ua9 2024 American Society for Gastrointestinal Endoscopy. Background and Aims: Serrated polyps (SPs) are precursors to 15% to 20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps. Methods: We systematically searched PubMed, Embase, and Cochrane for cohort studies, case-control studies, and clinical trials from inception to December 31, 2023, of CRC or advanced polyps (advanced adenoma [AA] or advanced SP) incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those ≥10 mm or with dysplasia. CRC and advanced polyp incidence per 1000 person-years were estimated. We performed a meta-analysis by calculating pooled relative risks (RRs) using a random-effects model. Results: A total of 5903 studies were reviewed, and 14 were included with 493,949 patients (mean age, 59.5 years; 55% men). The mean follow-up was 4.9 years. CRC incidence per 1000 person-years was 2.09 (95% confidence interval [CI], 1.29-2.90) for advanced SPs, 1.52 (95% CI, 0.78-2.25) for SPs of ≥10 mm, 5.86 (95% CI, 2.16-9.56) for SPs with dysplasia, 1.18 (95% CI, 0.77-1.60) for proximal SPs, 0.52 (95% CI, 0.08-1.12) for ≥3 SPs, 0.50 (95% CI, 0.35-0.66) for nonadvanced SPs, and 0.44 (95% CI, 0.41-0.46) for normal colonoscopy findings. Metachronous CRC risk was higher in advanced SPs versus nonadvanced SPs (RR, 1.84; 95% CI, 1.11-3.04) and versus normal colonoscopy findings (RR, 2.92; 95% CI, 2.26-3.77), in SPs of ≥10 mm versus <10 mm (RR, 2.61; 95% CI, 1.43-4.77) and versus normal colonoscopy findings (RR: 3.52; 95% CI, 2.17-5.69); and in SPs with dysplasia versus normal colonoscopy findings (RR: 2.71; 95% CI, 2.00-3.67). No increase in CRC or advanced polyp risk was found in patients with proximal versus distal SPs, nor in ≥3 SPs versus 1 or 2 SPs. Conclusions: CRC risk is significantly higher in patients with baseline advanced SPs after 4.9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SPs

Establishment of a human cell-based in vitro battery to assess developmental neurotoxicity hazard of chemicals

Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. However, DNT data from animal studies are available for only a small percentage of manufactured compounds. Test methods with a higher throughput than current regulatory guideline methods, and with improved human relevance are urgently needed. We therefore explored the feasibility of DNT hazard assessment based on new approach methods (NAMs). An in vitro battery (IVB) was assembled from ten individual NAMs that had been developed during the past years to probe effects of chemicals on various fundamental neurodevelopmental processes. All assays used human neural cells at different developmental stages. This allowed us to assess disturbances of: (i) proliferation of neural progenitor cells (NPC); (ii) migration of neural crest cells, radial glia cells, neurons and oligodendrocytes; (iii) differentiation of NPC into neurons and oligodendrocytes; and (iv) neurite outgrowth of peripheral and central neurons. In parallel, cytotoxicity measures were obtained. The feasibility of concentration-dependent screening and of a reliable biostatistical processing of the complex multi-dimensional data was explored with a set of 120 test compounds, containing subsets of pre-defined positive and negative DNT compounds. The battery provided alerts (hit or borderline) for 24 of 28 known toxicants (82% sensitivity), and for none of the 17 negative controls. Based on the results from this screen project, strategies were developed on how IVB data may be used in the context of risk assessment scenarios employing integrated approaches for testing and assessment (IATA).European Food Safety Authority (EFSA-Q-2018-00308), the Danish Environmental Protection Agency (EPA), Denmark, under the grant number MST-667-00205, the State Ministry of Baden-Wuerttemberg, Germany, for Economic Affairs, Labour and Tourism (NAM-Accept), the project CERST (Center for Alternatives to Animal Testing) of the Ministry for culture and science of the State of North-Rhine Westphalia, Germany (file number 233–1.08.03.03- 121972/131–1.08.03.03–121972), the European Chemical Industry Council Long-Range Research Initiative (Cefic LRI) under the project name AIMT11 and the BMBF (NeuroTool). It has also received funding from the European Union's Horizon 2020 research and innovation program under grant agreements No. 964537 (RISK-HUNT3R), No. 964518 (ToxFree), No. 101057014 (PARC) and No. 825759 (ENDpoiNTs)

Factors associated with lesion detection in colonoscopy among different indications

Background and objective: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. Methods: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. Results: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). Conclusions: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications

El foro romano de <i>Termes (Hispania Citerior)</i>. Síntesis histórica, arqueológica y topográfica. S. I a. C.- s. II d. C.

The urban development of the central public area of the Roman city of <i>Termes (Hispania Citerior)</i> between the 1^st century B.C and the 2^nd century A.D. is linked to the progressive institutional transformation of the community and to its social and economic development. After the <i>Bellum Sertorianum</i>, the urban space previously occupied by the Celtiberian oppidum was used as a shrine related to one of the founding rites of the city, and which would become the origin of the forum. This area was refurbished during the Augustan era (31 B.C. – 14 A.D.), when a temple was built that overlooked a communal area, although we are not aware of its general layout due to the progressive overlapping of structures in the zone. During the reign of Julius Claudius (14-37 A.D.), a new public area was created, next to the earlier one, which was made up by an arched complex with a temple. This complex was part of a main public area, which was either a Julius Claudius Forum or just an urban sanctuary. Finally, during the Flavian era, from 75 A.D, the site of the Augustan forum would be transformed with the construction of a large scenographic and monumental agora, the Flavian Forum, a complex that would be both a forum and an <i>Augusteum,</i> a place for performances and a shrine for dynastic worship.<br><br>La evolución urbanística del área pública central de la ciudad romana de <i>Termes (Hispania Citerior)</i> entre el s. I a. C. y el s. II d. C. está conectada a la progresiva transformación institucional de la comunidad y a su desarrollo social y económico. Tras el <i>Bellum Sertorianum</i> el espacio urbano ocupado anteriormente por el <i>oppidum</i> celtibérico vio la creación de un santuario relacionado con un rito fundacional de la ciudad, elemento que constituirá el germen del foro. Esta área fue reformada en época augustea (31 a. C.-14 d. C.), con la construcción de un templo que presidía un espacio foral, aunque desconocemos la configuración general de éste último, por la progresiva superposición de estructuras en la zona. Durante la etapa Julio Claudia (14-37 d. C.) se creó una nueva área pública, junto a la anterior, conformada por un recinto porticado con un templo. Este conjunto formaba parte de un espacio público principal, bien un Foro Julio Claudio, bien simplemente un santuario urbano. Finalmente, en época flavia, a partir de 75 d. C., el sitio del foro augusteo será transformado con la construcción de un gran cuadripórtico monumental y escenográfico, el Foro Flavio, complejo que se constituirá, al mismo tiempo, como un foro y un <i>Augusteum</i>, espacio de representación y santuario de culto dinástico

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

BACKGROUND: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. PATIENTS AND METHODS: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. RESULTS: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. CONCLUSIONS: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor

Mucopolysaccharidoses in northern Brazil: Targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy

Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients’ clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers