PIWIL1 is recruited to centrosomes during mitosis in colorectal cancer cells and is linked to cell cycle progression.

PIWI proteins, traditionally associated with germline development, have recently gained attention for their expression in various cancers, including colorectal cancer. However, the molecular mechanisms underlying their reactivation and impact on cancer initiation and progression remain elusive. Here, we found that PIWIL1 is expressed at relatively high levels in CRC-derived samples and cell lines, where it undergoes a dynamic relocalization to the centrosome during mitosis. Knockdown of PIWIL1 induces G2/M arrest associated with disruption of the mitotic spindle and aberrant metaphase events, highlighting its role in cell cycle progression. We also found that the expression of PIWIL1 is lost during the differentiation of Caco-2 cells into enterocytes and that PIWIL1 is expressed in cells at the base of the intestinal crypts in normal human colon tissue, where intestinal stem cells are known to reside. Thus, it is possible that the presence of PIWIL1 in cancer cells reflects a physiological role of this protein in stem cell maintenance, which would argue in favor of the proposed stem cell origin of CRC. Supporting this view, dedifferentiation of human fibroblasts into induced pluripotent stem cells (iPSCs) involves the reactivation of PIWIL2 expression, another member of the PIWI protein family. Overall, our findings suggest a role of PIWIL1 in mediating cell cycle dynamics, both in colorectal cancer cells and possibly also in intestinal stem cells. In a broader aspect, we provide evidence supporting an involvement of PIWI proteins in somatic stem cell maintenance, thus expanding the known non-gonadal functions of this protein family.

Colorectal adenocarcinoma in children and adolescents.

INTRODUCTION: Colorectal adenocarcinoma is rare in children and adolescents and tends to present with nonspecific signs and symptoms, leading to late diagnoses. OBJECTIVES: Our aim was to describe the clinical presentation and progression in children and adolescents with colorectal adenocarcinoma treated at our hospital and detect possible predisposing conditions of this disease. MATERIALS AND METHODS: Eight patients with colorectal adenocarcinoma were followed at the Hospital Posadas within the time frame of January 2000 and December 2021. We searched for diseases predisposing to this cancer. RESULTS: The mean patient age was 16 years (between 11 and 17 years of age). Clinical presentation was abdominal pain in the 8 patients; 4 of them had pain in the right hypochondrium, 3 had abdominal tumor, 4 had rectal bleeding, and 3 had weight loss. Mean symptom duration was 9 weeks (range: 1-24 weeks). None of the patients showed predisposing illnesses. One patient presented with polyposis, with no cases in any other family member. Histology showed mucinous adenocarcinoma in all the patients, 4 of whom had the signet ring cell subtype. The primary tumor was located in the right colon in 6 patients. At diagnosis, staging according to the modified Dukes classification was: I: one patient; IIb: one patient; IIIb: one patient; IIIc: one patient; and IV: 4 patients. All patients except 2 received chemotherapy and one patient received radiotherapy. Overall survival at 3 years was 25%. CONCLUSIONS: All patients presented with mucinous adenocarcinoma, no predisposing diseases were found, and the children with colorectal cancer had a very poor prognosis. Colorectal cancer diagnosis should be considered in children presenting with acute abdominal pain, abdominal tumor, or lower gastrointestinal bleeding, especially if there is weight loss.

Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction.

LAH, an acetogenin from the Annonaceae family, has demonstrated antitumor activity in several cancer cell lines and in vivo models, where it reduced the tumor size and induced programmed cell death. We focused on the effects of LAH on mitochondrial dynamics, mTOR signaling, autophagy, and apoptosis in colorectal cancer (CRC) cells to explore its anticancer potential. METHODS: CRC cells were treated with LAH, and its effects on mitochondrial respiration and glycolysis were measured using Seahorse XF technology. The changes in mitochondrial dynamics were observed through fluorescent imaging, while Western blot analysis was used to examine key autophagy and apoptosis markers. RESULTS: LAH significantly inhibited mitochondrial complex I activity, inducing ATP depletion and a compensatory increase in glycolysis. This disruption caused mitochondrial fragmentation, a trigger for autophagy, as shown by increased LC3-II expression and mTOR suppression. Apoptosis was also confirmed through the cleavage of caspase-3, contributing to reduced cancer cell viability. CONCLUSIONS: LAH's anticancer effects in CRC cells are driven by its disruption of mitochondrial function, triggering both autophagy and apoptosis. These findings highlight its potential as a therapeutic compound for further exploration in cancer treatment.

Tongue Metastasis of Mucinous Colorectal Adenocarcinoma: Report of a Rare Case.

Metastases in the oral and maxillofacial region, particularly in soft tissues, are exceedingly rare. Such metastases can present as swelling in older individuals, especially in the tongue and gingiva. Furthermore, colorectal metastases at this site are commonly found in the mandible and gingiva and usually share the same morphology as the primary tumor. Herein, we report the case of a 61-year-old woman with a metastatic nodule in the tongue covered by normal mucosa. The clinical, histopathological, and immunohistochemical findings were essential for the final diagnosis of colorectal metastasis, consistent with adenocarcinoma with mucinous differentiation and intestinal phenotype. Metastases of colorectal adenocarcinoma to the tongue are rare but should be included in the differential diagnosis of nodular lesions at this site. The diagnosis can therefore be made based on meticulous clinical and histopathological examination complemented by immunohistochemistry.

Impact of the Early Phase of the COVID-19 Pandemic on the Quality of Care for Colorectal and Anal Cancers at Comprehensive Cancer Centers on Two Continents.

PURPOSE: The early phase of the COVID-19 pandemic affected cancer care globally. Evaluating the impact of the pandemic on the quality of cancer care delivery is crucial for understanding how changes in care delivery may influence outcomes. Our study compared care delivered during the early phase of the pandemic with the same period in the previous year at two institutions across continents (Princess Margaret Cancer Center [PM] in Canada and A.C. Camargo Cancer Center [AC] in Brazil). METHODS: Patients newly diagnosed with colorectal or anal cancer between February and December 2019 and the same period in 2020 were analyzed. Sociodemographic and clinical characteristics and performance of individual indicators within and between centers and between the peri-COVID-19 and control cohorts were tested using Cohen's h test to assess the standardized differences between the two groups. RESULTS: Among 925 patients, distinct effects of the early COVID-19 pandemic on oncology services were observed. AC experienced a 50% reduction in patient consultations (98 v 197) versus a 12.5% reduction at PM (294 v 336). Similarly, AC experienced a higher proportion of stage IV disease presentations (42.9% v 29.9%; P = .015) and an increase in treatment delay (61.9% v 9.7%; P < .001) compared with prepandemic. At PM, a 10% increase in treatment interruption (32.4% v 22.3%; P < .001) and a higher rate of discontinuation of radiotherapy (9.4% v 1.1%; P < .001) were observed during the pandemic. Postsurgical readmission rates increased in both AC (20.9% v 2.6%; P < .001) and PM (10.5% v 3.6%; P < .01). CONCLUSION: The early phase of the COVID-19 pandemic affected the quality of care delivery for colorectal and anal cancers at both centers. However, the magnitude of this impact was greater in Brazil.

Phytochemicals and colorectal cancer: about polyphenols / Fitoquímicos y cáncer colorrectal: acerca de los polifenoles

Dietary consumption of polyphenols, found in fruits and vegetables, has been associated with a potentially protective role in colorectal cancer (CRC). To establish the state of knowledge regarding advances in polyphenols, CCR and action mechanisms a systematic review and an analysis of information available until 2021 were made. Results indicate that only some polyphenols have in vitro, preclinical and clinical studies. These studies showed that polyphenols will inhibit human CRC cell invasion, migration, metastasis formation, tumor growth. Action mechanisms involve signaling pathways that modulate genes, proteins, markers or cell death inductors, like the AMPK pathway, caspases, Bcl-2, p-Akt, and NF-kB, lysosomal and mitochondrial dysfunction, cellular cycle arrest, among the best known and implied in CRC. Overall, in vitro, preclinical and clinical data on phytochemicals against CRC are still not sufficient and therefore the preventive or therapeutic impacts of dietary phytochemicals on CRC development deserve further research.

El consumo dietético de polifenoles, que se encuentran en frutas y verduras, se ha asociado con un papel potencialmente protector contra el cáncer colorrectal (CCR). Para establecer el estado del conocimiento respecto a los avances en polifenoles, CCR y mecanismos de acción, se realizó una revisión sistemática y un análisis de la información disponible hasta el año 2021. Los resultados indican que sólo algunos polifenoles cuentan con estudios in vitro, preclínicos y clínicos. Estos estudios demostraron que los polifenoles inhiben la invasión, migración, formación de metástasis y crecimiento de tumores de células de CCR humanas. Los mecanismos de acción involucran vías de señalización que modulan genes, proteínas, marcadores o inductores de muerte celular, como la vía AMPK, caspasas, Bcl-2, p-Akt y NF-kB, disfunción lisosomal y mitocondrial, parada del ciclo celular, entre los más conocidos e implicados en el CCR. En general, los datos in vitro, preclínicos y clínicos sobre fitoquímicos contra el CCR aún no son suficientes y, por lo tanto, los impactos preventivos o terapéuticos de los fitoquímicos dietéticos en el desarrollo del CCR requieren más investigación.

Clinical profile of early- and late-onset colorectal cancer patients in a referral medical center in Medellín, Colombia: A comparative analysis / Perfil clínico de pacientes con cáncer colorrectal de aparición temprana y tardía en un centro médico de referencia en Medellín, Colombia: Un análisis comparativo

Introduction. Incidence of early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) in individuals aged < 50 years, is rising worldwide. Despite the increasing international scientific production on EOCRC, research is limited in Colombia. The objective of this study was to characterize the clinical features of adults with EOCRC and late-onset CRC (LOCRC, CRC in individuals aged ≥ 50 years). Methods. An observational, retrospective, cross-sectional study was conducted with CRC patients ≥ 18 years old at one medical center in Medellín, Colombia. Clinical and pathological data were retrieved from the Institutional Cancer Registry. Two analysis groups were established: EOCRC and LOCRC. The Chi-Square test was applied to compare the variables of interest between both groups. Results. The sample included 1,202 patients, 53.5% were female (N=643) and the median age was 65 years (interquartile range: 55-73). EOCRC represented 15.9% (N=192). LOCRC tended to have more history of cardiometabolic diseases and smoking (p<0.001) than EOCRC. CRC family history was proportionally more frequent in EOCRC (7.3% vs 3.8%; p=0.028) than in LOCRC. Right-sided tumors were more common in LOCRC (30.4% vs 21.9%; p=0.041) and left-sided tumors in EOCRC (30.7% vs 23.2%; p=0.041). Only one patient had inflammatory bowel disease history. Conclusion. EOCRC is clinically distinct from LOCRC regarding pathological and toxicological history as well as tumor location. Our findings provide valuable insights for enhancing clinical decision-making, particularly in relation to age at onset in Colombian CRC patients.

Introducción. La incidencia de cáncer colorrectal (CCR) de aparición temprana (CCR-ATem), definido como CCR en individuos menores de 50 años, está aumentando en todo el mundo. A pesar del incremento en la producción científica internacional sobre CCR-ATem, la investigación es limitada en Colombia. El objetivo de este estudio fue caracterizar clínicamente los adultos con CCR-ATem y CCR de aparición tardía (CCR-ATar, CCR en individuos ≥ 50 años). Métodos. Estudio observacional, retrospectivo, transversal, en el que se incluyeron los pacientes adultos con CCR atendidos en un centro médico de Medellín, Colombia. Los datos se obtuvieron del Registro Institucional de Cáncer. Se establecieron dos grupos de análisis: CCR-ATem y CCR-ATar. Se aplicó la prueba de Chi cuadrado para comparar las variables de interés entre ambos grupos. Resultados. La muestra incluyó 1.202 pacientes, 53,5 % fueron mujeres (N=643), y la mediana de edad fue de 65 años (rango intercuartil: 55-73). CCR-ATem representó el 15,9 % (N=192). CCR-ATar tuvo más casos de enfermedades cardiometabólicas y tabaquismo (p<0,001). El antecedente familiar de CCR fue proporcionalmente más frecuente en CCR-ATem (7,3 % vs. 3,8 %; p=0,028). Los tumores del colon derecho fueron más frecuentes en CCR-ATar (30,4 % vs. 21,9 %; p=0,041) y los del colon izquierdo en CCR-ATem (30,7 % vs. 23,2 %; p=0,041). Solo un paciente tuvo antecedente de enfermedad inflamatoria intestinal. Conclusión. CCR-ATem es clínicamente distinto de CCR-ATar con respecto a antecedentes patológicos y toxicológicos, y localización tumoral. Nuestros hallazgos proporcionan información útil para mejorar la toma de decisiones clínicas, particularmente en relación con la edad de inicio en pacientes colombianos con CCR.

Obesity and Colorectal Cancer: A Narrative Review.

Background and Objectives: Cancer is a multicausal disease, and environmental, cultural, socioeconomic, lifestyle, and genetic factors can influence the risk of developing cancer. Colorectal cancer (CRC) stands as the third most common cancer globally. Some countries have observed a rise in the incidence of CRC, especially among young people. This increase is associated with lifestyle changes over the last few decades, including changes in diet patterns, a sedentary lifestyle, and obesity. Currently, obesity and overweight account for approximately 39% of the world's population and increase the risk of overall mortality of certain cancer types. This study aims to conduct a literature review examining the association between obesity and CRC. Materials and Methods: This narrative review explored the pathophysiological mechanisms, treatment strategies, and challenges related to obesity and CRC. Results: Several studies have established a clear causal relationship between obesity and CRC, showing that individuals with morbid obesity are at a higher risk of developing colorectal cancer. The adipose tissue, particularly the visceral, secretes proinflammatory cytokines, such as TNF-alpha, interleukin-6, and C-reactive protein. Chronic inflammation is closely linked to cancer initiation and progression, with a complex interplay of molecular mechanisms underlying this association. Obesity can complicate the treatment of CRC due to several factors, reducing the therapeutic effectiveness and increasing the risk for adverse events during treatment. Dietary modification, calorie restriction, and other types of weight-control strategies can reduce the risk of CRC development and improve treatment outcomes. Conclusions: Obesity is intricately linked to CRC development and progression, making it a crucial target for intervention, whether through diet therapy, physical exercises, medical therapy, or bariatric surgery.

Cytotoxic Activity of Lepidium virginicum L. Methanolic Extract on Human Colorectal Cancer Cells, Caco-2, through p53-Mediated Apoptosis.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Its treatment options have had a limited impact on cancer remission prognosis. Therefore, there is an ongoing need to discover novel anti-cancer agents. Medicinal plants have gained recognition as a source of anti-cancer bioactive compounds. Recently, ethanolic extract of L. virginicum stems ameliorated dinitrobenzene sulfonic acid (DNBS)-induced colitis by modulating the intestinal immune response. However, no scientific study has demonstrated this potential cytotoxic impact on colon cancer cells. The objective of this study was to evaluate the cytotoxic effect of the methanolic extract of L. virginicum (ELv) on a human colorectal adenocarcinoma cell line (Caco-2) and to identify and quantify the phenolic compounds present in ELv extracts by liquid chromatography-mass spectrometry analysis. The cytotoxic activity was assessed using cell viability assays by reduction in the compound 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH). MTT and LDH assays revealed that the ELv decreases cell viability in the Caco-2 cell line in a concentration-dependent manner. Cell death was a result of DNA fragmentation and p53-mediated apoptosis. Eight phenolic acids and five flavonoids were identified and quantified in the stems. In conclusion, our findings demonstrate that the extract of L. virginicum possesses cytotoxic properties on Caco-2 cell line, suggesting that it could be a potential source of new drugs against CRC.

EVALUATION OF QUALITY INDICATORS OF SCREENING COLONOSCOPY PERFORMED IN A PRIVATE QUARTERNARY HOSPITAL IN BRAZIL.

BACKGROUND: Colorectal cancer is the third most common type of cancer in Brazil, despite the availability of screening methods that reduce its risk. Colonoscopy is the only screening method that also allows therapeutic procedures. The proper screening through colonoscopy is linked to the quality of the exam, which can be evaluated according to quality criteria recommended by various institutions. Among the factors, the most used is the Adenoma Detection Rate, which should be at least 25% for general population. AIMS: To evaluate the quality of the screening colonoscopies performed in a quarternary private Brazilian hospital. METHODS: This is a retrospective study evaluating the quality indicators of colonoscopies performed at a private center since its inauguration. Only asymptomatic patients aged over 45 years who underwent screening colonoscopy were included. The primary outcome was the Adenoma Detection Rate, and secondary outcomes included polyps detection rate and safety profile. Subanalyses evaluated the correlation of endoscopic findings with gender and age and the evolution of detection rates over the years. RESULTS: A total of 2,144 patients were include with a mean age of 60.54 years-old. Polyps were diagnosed in 68.6% of the procedures. Adenoma detection rate was 46.8%, with an increasing rate over the years, mainly in males. A low rate of adverse events was reported in 0.23% of the cases, with no need for surgical intervention and no deaths. CONCLUSIONS: This study shows that high quality screening colonoscopy is possible when performed by experienced endoscopists and trained nurses, under an adequate infrastructure.

Dermatology-related quality-of-life outcomes in patients with RAS wild-type metastatic colorectal cancer treated with fluorouracil and folinic acid with or without panitumumab (Pmab) maintenance after FOLFOX + Pmab induction: a prespecified secondary analysis of the phase II randomized PanaMa (AIO KRK 0212) trial.

BACKGROUND: The key endpoints for the assessment of the effect of maintenance therapy for metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed to compare dermatology-related quality of life (DRQOL) in patients with RAS wild-type (wt) mCRC treated with fluorouracil and folinic acid (FU/FA) + panitumumab (Pmab) versus FU/FA alone as maintenance therapy after folinic acid, fluorouracil and oxaliplatin + Pmab induction. PATIENTS AND METHODS: The phase II randomized PanaMa (AIO KRK 0212; NCT01991873) trial included 387 patients at 70 community/academic sites in Germany. For this prespecified secondary analysis, DRQOL outcomes were assessed using the Functional Assessment of Cancer Therapy-epidermal growth factor receptor inhibitor (FACT-EGFRI), Dermatology Life Quality Index (DLQI), and Skindex-16 questionnaires at every second cycle of therapy until disease progression/death. RESULTS: At least one DRQOL questionnaire was completed by a total of 310/377 (82%) patients who received induction therapy, and by 216/248 (87%) patients who were randomized and received maintenance therapy. Patients who experienced skin toxicity according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) during induction therapy had significantly worse DRQOL according to all three measures, compared to those who did not [i.e. Skindex-16, mean difference at cycle 2 -12.87; 95% confidence interval (CI) -20.01 to -5.73; P < 0.001]. During maintenance therapy, significantly improved recovery was observed in all DRQOL measures for patients receiving FU/FA, compared to those receiving additional Pmab (i.e. Skindex-16, mean difference at cycle 6 -16.53; 95% CI -22.68 to -10.38; P < 0.001). CONCLUSIONS: In this secondary analysis of a phase II randomized clinical trial, patient-reported DRQOL outcomes correlated with skin toxicity according to NCI-CTCAE during induction therapy. Maintenance therapy with FU/FA + Pmab was associated with deteriorated DRQOL versus FU/FA alone in patients with RAS wt mCRC.

Enhancing Colorectal Cancer Screening with Droplet Digital PCR Analysis of Fusobacterium nucleatum in Fecal Immunochemical Test Samples.

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a colorectal cancer screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a colorectal cancer screening program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients' clinicopathological features and accuracy measurements was calculated. Fn-high levels were more prevalent in FIT-positive (47.2%, n = 34 of 72) than FIT-negative samples (28.9%, n = 66 of 228; P < 0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in patients with cancer (CA, n = 8) when compared to normal (NT, n = 16; P = 0.02), non-advanced adenomas (NAA, n = 36; P = 0.01), and advanced adenomas (AA, n = 12; P = 0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 [confidence interval (CI), 0.6464-0.9942], with high sensitivity (100%) and specificity of 50%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate colorectal cancer detection. Prevention Relevance: Fusobacterium nucleatum detection by droplet digital PCR could prioritize the selection of fecal immunochemical test-positive individuals who might benefit the most from the colonoscopy procedure.

Dense tumor-infiltrating lymphocytes (TILs) in liver metastasis from colorectal cancer are related to improved overall survival.

BACKGROUND AND OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) represent a host-tumor interaction, frequently signifying an augmented immunological response. Nonetheless, implications with survival outcomes in patients with colorectal carcinoma liver metastasis (CRLM) warrant rigorous validation. The objective was to demonstrate the association between TILs and survival in patients with CRLM. METHOD: In a retrospective evaluation conducted in a single institution, we assessed all patients who underwent hepatectomy due to CRLM between 2014 and 2018. Comprehensive medical documentation reviews were executed. TILs were assessed by a liver pathologist, blinded to the clinical information, in all surgical slides. RESULTS: This retrospective cohort included 112 patients. Median overall survival (OS) was 58 months and disease-free survival (DFS) was 12 months for the entire cohort. Comparison between groups showed a median OS of 81 months in the dense TILs group and 40 months in the weak/absent group (p = 0.001), and DFS was 14 months versus 9 months (p = 0.041). Multivariable analysis showed that TILs were an independent predictor of OS (HR 1.95; p = 0.031). CONCLUSIONS: Dense TILs are a pivotal prognostic indicator, correlating with enhanced OS. Including TILs information in histopathological evaluations should refine the clinical decision-making process for this group of patients.

Outcomes of repeat conventional transarterial chemoembolization in patients with liver metastases.

INTRODUCTION AND OBJECTIVES: Although unlimited sessions of conventional transarterial chemoembolization (cTACE) may be performed for liver metastases, there is no data indicating when treatment becomes ineffective. This study aimed to determine the optimal number of repeat cTACE sessions for nonresponding patients before abandoning cTACE in patients with liver metastases. MATERIALS AND METHODS: In this retrospective, single-institutional analysis, patients with liver metastases from neuroendocrine tumors (NET), colorectal carcinoma (CRC), and lung cancer who underwent consecutive cTACE sessions from 2001 to 2015 were studied. Quantitative European Association for Study of the Liver (qEASL) criteria were utilized for response assessment. The association between the number of cTACE and 2-year, 5-year, and overall survival was evaluated to estimate the optimal number of cTACE for each survival outcome. RESULTS: Eighty-five patients underwent a total of 186 cTACE sessions for 117 liver metastases, of which 30.7 % responded to the first cTACE. For the target lesions that did not respond to the first, second, and third cTACE sessions, response rates after the second, third, and fourth cTACE sessions were 33.3 %, 23 %, and 25 %, respectively. The fourth cTACE session was the optimal number for 2-year survival (HR 0.40; 95 %CI: 0.16-0.97; p = 0.04), 5-year survival (HR 0.31; 95 %CI: 0.11-0.87; p = 0.02), and overall survival (HR 0.35; 95 %CI: 0.13-0.89; p = 0.02). CONCLUSIONS: Repeat cTACE in the management of liver metastases from NET, CRC, and lung cancer was associated with improved patient survival. We recommend at least four cTACE sessions before switching to another treatment for nonresponding metastatic liver lesions.

A REVIEW TO HONOR THE HISTORICAL CONTRIBUTIONS OF PAULINE GROSS, ALDRED WARTHIN, AND HENRY LYNCH IN THE DESCRIPTION AND RECOGNITION OF INHERITANCE IN COLORECTAL CANCER.

The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a century ago. In 1895, a reputed pathologist from Michigan University, Dr. Aldred Scott Warthin, got intrigued by the family history of a local seamstress called Pauline Gross. According to her prevision, she would present an early death due to cancer, which actually happened (from the uterus). Historically, her family was designated "Family G", comprising a group recognized as the longest and most detailed cancer genealogy that has ever been studied. Warthin concluded that its members had genetic susceptibility for cancer, and they are, nowadays, considered the first reported Lynch Syndrome family. At that time, however, the medical cancer community was far less receptive to the association between heredity and cancer, despite the description of other families with similar heredograms. Unfortunately, this historical fact remained somewhat dormant until another investigator inaugurated a new era in the understanding of family cancer clusters. After reports and studies from this family and many others, the condition initially called Cancer Family Syndrome was changed to the eponym Lynch Syndrome. This was a recognition of the extensive and dedicated work developed by Dr. Henry Lynch in describing various characteristics of the disease, and his efforts to establish the correct recommendations for its diagnosis and treatment. Although the future announces there is still far to go for a complete understanding of Lynch Syndrome, the remarkable contributions of Pauline's intuition, Warthin's perseverance, and Lynch's work consistency must never be forgotten by those who already have or will still benefit from this knowledge.

Hyperbaric oxygen therapy increases the effect of 5-fluorouracil chemotherapy on experimental colorectal cancer in mice.

Tumor hypoxia may compromise the results of chemotherapy for treating colorectal cancer because it stimulates angiogenesis and the release of tumor growth factors. Hyperbaric oxygen (HBO) supplementation may potentiate the effects of chemotherapy in such cases. This study aimed to assess the effect of HBO therapy combined with chemotherapy on the treatment of colorectal cancer in mice. C57BL6 mice were submitted to the intrarectal instillation of N-methyl-N-nitrosoguanidine (MNNG) and treated with 5-fluorouracil (5FU) and/or HBO therapy. The MNNG group presented the highest dysplastic crypt rate. The 5FU + HBO group presented the highest rate of apoptotic cells per dysplastic crypt. The 5FU group presented the highest expression of hypoxia-inducible factor-1 alpha and CD44. HBO therapy increased the effect of 5FU on the treatment of the experimental colorectal neoplasia in mice.

Thigh muscle by CT images as a predictor of mortality in patients with newly diagnosed colorectal cancer.

This study aimed to evaluate the prognostic value of thigh muscle assessed by CT images to predict overall mortality in patients with colorectal cancer (CRC). This was a multicenter cohort study including adults (≥ 18 years old) newly diagnosed with CRC, who performed a diagnostic computed tomography (CT) exam including thigh regions. CT images were analyzed to evaluate skeletal muscle (SM in cm2), skeletal muscle index (SMI in cm2/m2), and skeletal muscle density (SMD in HU). Muscle abnormalities (low SM, SMI, and SMD) were defined as the values below the median by sex. Kaplan-Meyer curves and hazard ratios (HRs) for low SM, SMI and SMD were evaluated for overall mortality, stratified by sex. A total of 257 patients were included in the final analysis. Patients' mean age was 62.6 ± 12.1 years, and 50.2% (n = 129) were females. In males, low thigh SMI was associated with shorter survival (log-rank P = .02). Furthermore, this low thigh SMI (cm2/m2) was independently associated with higher mortality rates (HR adjusted 2.08, 95% CI 1.03-4.18). Our additional findings demonstrated that low SMD was independently associated with overall mortality among early-stage patients (I-III) (HR adjusted 2.78, 95% CI 1.26-6.15).

Efficacy of probiotics, paraprobiotics, and postbiotics in colorectal cancer cell line and their role in immune response.

OBJECTIVE: The aim of this study was to reveal certain features (anti-tumor/microbial activities) of postbiotics and heat-inactivated paraprobiotics obtained from two different bacteria with determined probiotic properties, which are thought to contribute to human health. METHODS: In the study, Lactobacillus reuteri ENA31 and L. rhamnosus GAA6 strains were used. Supernatants of postbiotically active cultures were used. Paraprobiotics were obtained by exposing probiotic bacteria to high temperatures. The cytotoxic effects of probiotics, paraprobiotics, and postbiotics were evaluated by the MTT method. IL-1/-10/-12/-13, TNF-α, IFN-γ, and neopterin parameters were determined via the ELISA method in immunity studies. RESULTS: It was detected that biotics had a cytotoxic effect on cancer cells with rising concentrations (paraprobiotic

Age-adjusted Charlson comorbidity index and its association with body composition and overall survival in patients with colorectal cancer.

OBJECTIVE: To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). RESEARCH METHODS AND PROCEDURES: In this cohort study, patients (≥ 18 years old) with CRC were followed for 36 months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. RESULTS: A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2 years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). CONCLUSION: The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.