Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer.

Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC.

Familial component of early-onset colorectal cancer: opportunity for prevention.

BACKGROUND: Individuals with a non-syndromic family history of colorectal cancer are known to have an increased risk. There is an opportunity to prevent early-onset colorectal cancer (age less than 50 years) (EOCRC) in this population. The aim was to explore the proportion of EOCRC that is preventable due to family history of colorectal cancer. METHODS: This was a retrospective multicentre European study of patients with non-hereditary EOCRC. The impact of the European Society of Gastrointestinal Endoscopy (ESGE), U.S. Multi-Society Task Force (USMSTF), and National Comprehensive Cancer Network (NCCN) guidelines on prevention and early diagnosis was compared. Colorectal cancer was defined as potentially preventable if surveillance colonoscopy would have been performed at least 5 years before the age of diagnosis of colorectal cancer, and diagnosed early if colonoscopy was undertaken between 1 and 4 years before the diagnosis. RESULTS: Some 903 patients with EOCRC were included. Criteria for familial colorectal cancer risk in ESGE, USMSTF, and NCCN guidelines were met in 6.3, 9.4, and 30.4 per cent of patients respectively. Based on ESGE, USMSTF, and NCCN guidelines, colorectal cancer could potentially have been prevented in 41, 55, and 30.3 per cent of patients, and diagnosed earlier in 11, 14, and 21.1 per cent respectively. In ESGE guidelines, if surveillance had started 10 years before the youngest relative, there would be a significant increase in prevention (41 versus 55 per cent; P = 0.010). CONCLUSION: ESGE, USMSTF, and NCCN criteria for familial colorectal cancer were met in 6.3, 9.4, and 30.4 per cent of patients with EOCRC respectively. In these patients, early detection and/or prevention could be achieved in 52, 70, and 51.4 per cent respectively. Early and accurate identification of familial colorectal cancer risk and increase in the uptake of early colonoscopy are key to decreasing familial EOCRC.

Successful treatment of multidrug-resistant Pseudomonas aeruginosa breakthrough bacteremia with ceftolozane/tazobactam.

INTRODUCTION: Ceftolozane/tazobactam is a novel antibiotic approved for the treatment of complicated intra-abdominal and complicated urinary tract infections. CASE DESCRIPTION: We describe the use of off-label ceftolozane/tazobactam in the management of a multidrug-resistant Pseudomonas aeruginosa bacteremia that was already being treated with colistin and amikacin, the only active antibiotics according to the antibiogram.

Minimally Invasive Elective Surgery as a Treatment of Bowel Invagination in a Peutz-Jeghers Syndrome Case.

We present a case of a 24-year-old woman with Peutz-Jeghers syndrome, recurrent colic abdominal pain, and lower gastrointestinal bleed for the last 5 years. Colonoscopy showed hamartomas without any dysplasia. In the enteral magnetic resonance imaging, a distal jejunum and ileum invagination, secondary to hamartomas was detected. The patient was referred to the Surgery Department and despite few symptoms, elective surgery was proposed. By laparoscopic surgery approach, the entire bowel was carefully revised, 3 intussusceptions and bowel volvulus were found, 2 in jejunum and 1 in ileum, causing incomplete obstruction and intestinal dilatation, with a diameter of 6 cm. These intussusception areas were marked with a silk filament, after achieving devolvulation and disinvagination. A 5-cm laparotomy was done, to externalize the entire bowel, to explore it manually, to verify the absence of other lesions, and locate silk points. By longitudinal enterotomies on the antimesenteric intestinal border where silk filaments were located, the polyps were removed through their stalk, and the enterotomies were transversely closed. Postoperative evolution was favorable, starting oral tolerance on the fourth day and being discharged from the hospital on the seventh day. Eight months later, the patient was asymptomatic with a better quality of life.

A clinico-pathological and molecular analysis reveals differences between solitary (early and late-onset) and synchronous rectal cancer.

Rectal cancer (RC) appears to behave differently compared with colon cancer. We aimed to analyze existence of different subtypes of RC depending on distinct features (age of onset and the presence of synchronous primary malignant neoplasms). We compared the clinicopathological, familial and molecular features of three different populations diagnosed with RC (early-onset RC [EORC], late-onset RC, and synchronous RC [SRC]). Eighty-five RCs were identified and were evaluated according to their microsatellite instability, CpG Island Methylator Phenotype (CIMP) and chromosomal instability, as assessed by Next Generation Sequencing and microarray-based comparative genomic hybridization approaches. The results were subjected to cluster analysis. SRCs displayed the most specific characteristics including a trend for the development of multiple malignant neoplasms, a greater proportion of CIMP-High tumors (75%) and more frequent genomic alterations. These findings were confirmed by a clustering analysis that stratified RCs according to their genomic alterations. We also found that EORCs exhibited their own features including an important familial cancer component and a remarkable rate of mutations in TP53 (53%). Together, heterogeneity in RC characteristics by age of disease-onset and SRC warrants further study to optimize tailored prevention, detection and intervention strategies-particularly among young adults.

Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers.

Colorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a "unique" CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients.

Intermediate-onset colorectal cancer: A clinical and familial boundary between both early and late-onset colorectal cancer.

Comparative studies of colorectal cancer (CRC) according to the age of onset have found differences between early-onset CRC (EOCRC) and late-onset CRC (LOCRC). Using this as a starting point, we wished to determine whether intermediate-onset CRC (IOCRC) might also be considered as an independent group within CRC. We performed a retrospective comparative study of the clinicopathological and familial features, as well as of the symptoms and their duration, of a total of 272 subjects diagnosed with CRC classified into three groups according to the age-of-onset (98 EOCRC, 83 IOCRC and 91 LOCRC). The results show that from a clinicopathological point of view, IOCRC shared certain features with EOCRC (gender, prognosis), and with LOCRC (multiple primary CRCs), whereas it also had characteristics that were specific for IOCRC (mean number of associated polyps). A gradual progression was observed from EOCRC to LOCRC from a greater family aggregation to sporadic cases, in parallel with a change of Lynch Syndrome cases to the sporadic microsatellite instability pathway, with the IOCRC being a boundary group that is more related to EOCRC. With respect to symptoms, duration and correlation with stages, IOCRC appeared more similar to EOCRC. Clinically, IOCRC behaves as a transitional group between EOCRC and LOCRC, with features in common with both groups, but also with IOCRC-specific features. Excluding cases with familial cancer history, the awareness for EOCRC diagnosis should be extended to IOCRC.

Association of Polyps with Early-Onset Colorectal Cancer and Throughout Surveillance: Novel Clinical and Molecular Implications.

Early-onset colorectal cancer (EOCRC) is an increasing and worrisome entity. The aim of this study was to analyze its association with polyps concerning prognosis and surveillance. EOCRC cases were compared regarding the presence or absence of associated polyps (clinical and molecular features), during a minimum of 7 years of follow-up. Of 119 cases, 56 (47%) did not develop polyps (NP group), while 63 (53%) did (P group). The NP group showed a predominant location of the CRC in the rectum (50%), of sporadic cases (54%), and diagnosis at advanced stages: Only P53 and SMARCB1 mutations were statistically linked to this group. The P group, including mainly early-diagnosed tumors, was linked with the most frequent and differential altered chromosomal regions in the array comparative genomic hybridization. The two most frequent groups according to the follow-up were the NP group (40%), and patients developing polyps in the first 5 years of follow-up (P < 5FU) (34%) (these last groups predominantly diagnosed at the earliest stage and with adenomatous polyps (45%)). EOCRC with polyps that developed during the entire follow-up (PDFU group) were mainly located in the right colon (53%), diagnosed in earlier stages, and 75% had a familial history of CRC. Patients developing polyps after the first 5 years (P > 5FU) showed a mucinous component (50%). Our results show that the absence or presence of polyps in EOCRC is an important prognostic factor with differential phenotypes. The development of polyps during surveillance shows that it is necessary to extend the follow-up time, also in those cases with microsatellite-stable EOCRC.

Differential clinicopathological and molecular features within late-onset colorectal cancer according to tumor location.

BACKGROUND: Since there is a predilection of some clinical and molecular features for a given tumor location, we assessed whether this can be confirmed in late-onset colorectal cancer (LOCRC). RESULTS: Right colon cancers showed features associated with sporadic Microsatellite Instability: predominance of female cases and BRAF mutations, and an important mucinous component. Left colon cancers developed a higher number of polyps and multiple primary CRCs, showed the strongest familial component, and had better prognosis. Rectal cancers showed a predominantly sporadic phenotype, with worse prognosis and a CpG Island Methylator Phenotype (CIMP)-High. No copy number alterations (CNAs) greater than or equal to 50% were observed in this LOCRC group, and the most recurrent alterations were losses at 5q13 and 14q11, and gains at 7q11, 7q21-q22, 19p13-p12, 19q13 and 20p11-q11. KRAS and PIK3CA were the only mutated genes showing differences according to the tumor location, mainly for right colon cancers. MATERIALS AND METHODS: We analyzed clinical and molecular characteristics of LOCRC at different tumor locations in order to determine if there are differential phenotypes related with the location in the colon. CONCLUSIONS: Categorizing LOCRC according to tumor location appears to be an adequate first step to resolving the heterogeneity of this subset of CRC.

Guía de práctica clínica para el tratamiento de la rinosinusitis crónica: versión completa / Clinical practice guideline for the treatment of chronic rhinosinusitis: full version

La rinosinusitis (RS) se define como la inflamación de la nariz y los senos paranasales con dos o más síntomas como bloqueo/obstrucción/congestión o secreción nasal (goteo nasal anterior/posterior) más dolor/presión facial y/o reducción o pérdida del sentido del olfato. Adicional, se tienen en cuenta los hallazgos objetivos como la presencia de pólipos nasales y/o descarga mucopurulenta en meato medio y/o edema u obstrucción de la mucosa en el meato medio en la endoscopia nasal. Se pueden considerar o no, los cambios tomográficos como cambios mucosos en el complejo osteomeatal y la mucosa de los senos paranasales. Se reconoce que los síntomas tienen alta sensibilidad, pero baja especificidad, de ahí la necesidad de hallazgos objetivos.

Rhinosinusitis (RS) is defined as inflammation of the nose and sinuses with two or more symptoms such as blockage/obstruction/congestion or nasal discharge. with two or more symptoms such as nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior runny nose) plus facial pain/pressure and/or reduction or loss of the sense of smell. sense of smell. In addition, objective findings such as the presence of nasal polyps and/or nasal presence of nasal polyps and/or mucopurulent discharge from the middle meatus and/or edema or mucosal obstruction or mucosal obstruction in the middle meatus on nasal endoscopy. Tomographic changes may or may not tomographic changes may or may not be considered as mucosal changes in the osteomeatal complex and mucosal osteomeatal complex and the mucosa of the paranasal sinuses. It is recognized that the symptoms symptoms have high sensitivity but low specificity, hence the need for objective findings. findings.

Guía de práctica clínica para el tratamiento de la rinosinusitis crónica: versión corta para profesionales de la salud. Colombia-2023 / Clinical practice guideline for the management of chronic rhinosinusitis: short version for health care professionals. Colombia-2023

La rinosinusitis (RS) se define como la inflamación de la nariz y los senos paranasales con dos o más síntomas como bloqueo/obstrucción/congestión o secreción nasal (goteo nasal anterior/posterior) más dolor/presión facial y/o reducción o pérdida del sentido del olfato. Adicional, se tienen en cuenta los hallazgos objetivos como la presencia de pólipos nasales y/o descarga mucopurulenta en meato medio y/o edema u obstrucción de la mucosa en el meato medio en la endoscopia nasal.

Rhinosinusitis (RS) is defined as inflammation of the nose and sinuses with two or more symptoms such as blockage/obstruction/congestion or nasal discharge with two or more symptoms such as nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior runny nose) plus facial pain/pressure and/or reduced or lost sense of smell sense of smell. Additionally, objective findings such as the presence of nasal polyps and/or nasal presence of nasal polyps and/or mucopurulent discharge in the middle meatus and/or edema or mucous or mucosal obstruction in the middle meatus on nasal endoscopy.