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BACKGROUND: The European Thyroid Imaging and Reporting Data System (EU-TIRADS) aims to reduce the overdiagnosis of thyroid cancer (TC) by guiding the selection of nodules for fine-needle aspiration biopsy (FNAB). This study sought to validate EU-TIRADS nodule selection criteria using data from EUROCRINE, an extensive international endocrine surgery registry. METHOD: We reviewed indications for FNAB among patients with TC compared to those with benign disease who underwent surgery between March 2020 and March 2022, considering preoperative EU-TIRADS scores and dominant nodule size (FNAB is recommended in Category 5 (Ë10 mm or Ë10 mm with suspicious lymph nodes), 4 (Ë15 mm), and 3 (Ë20 mm)). Patients were categorized into three risk groups: minimal risk (patients with papillary microcarcinoma), high risk (patients with pT3b stage or higher, pN1b, or pM1), and low-moderate risk (all other patients). We conducted a Receiver Operating Characteristic (ROC) analysis to assess the diagnostic accuracy of the EU-TIRADS. RESULTS: We analyzed 32,008 operations. Approximately 68% of the surgical records included EU-TIRADS classifications. The EU-TIRADS exhibited diagnostic accuracy across high-volume sites, with a median ROC Area Under the ROC Curve (AUC) of 0.752, indicating its effectiveness in identifying malignancy. Among the cases, 7907 patients had TC. Notably, 55% of patients with TC underwent FNAB despite not initially meeting the EU-TIRADS criteria. These patients were distributed across the minimal- (58%), low-moderate- (36%), and high-risk (5.8%) categories. Of the patients with TC recommended for FNAB, 78% were deemed low-moderate risk, 21% high risk, and only 0.7% minimal risk. CONCLUSION: The EU-TIRADS offers effective preoperative malignancy risk stratification. Promoting the proper use of the EU-TIRADS in clinical practice is essential to mitigate the overdiagnosis and overtreatment of low-risk TC.
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Colorectal cancer (CRC) cells show some alterations in lipid metabolism, including an increased fatty acid elongation. This study was focused on investigating the effect of a small interfering RNA (siRNA)-mediated decrease in fatty acid elongation on CRC cells' survival and migration. In our study, the elongase 4 (ELOVL4) and elongase 6 (ELOVL6) genes were observed to be highly overexpressed in both the CRC tissue obtained from patients and the CRC cells cultured in vitro (HT-29 and WiDr cell lines). The use of the siRNAs for ELOVL4 and ELOVL6 reduced cancer cell proliferation and migration rates. These findings indicate that the altered elongation process decreased the survival of CRC cells, and in the future, fatty acid elongases can be potentially good targets in novel CRC therapy.
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Acetiltransferasas , Neoplasias Colorrectales , Humanos , Elongasas de Ácidos Grasos/genética , Elongasas de Ácidos Grasos/metabolismo , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Proliferación Celular/genética , Ácidos Grasos/metabolismo , Neoplasias Colorrectales/genéticaRESUMEN
Prehabilitation is a comprehensive preparation of a patient for primarily surgical treatments. Its aim is to improve the patient'sgeneral condition so as to reduce the risk of complications and ensure the fastest possible recovery to full health. Thebasic components of prehabilitation include: improvement of nutritional status, appropriate exercises to improve functioning,psychological support, and help in eliminating addictions. Other important aspects of prehabilitation are: increasinghemoglobin levels in patients with anemia, achieving good glycemic control in patients with diabetes, treatment or stabilizationof any concurrent disorders, or specialist treatment associated with a specific procedure (endoprostheses, ostomyprocedure). This article organizes and outlines the indications for prehabilitation, its scope, duration, and the method to conductit. Experts of various specialties related to prehabilitation agree that it should be an element of surgery preparationwhenever possible, especially in patients with co-existing medical conditions who have been qualified for major procedures.Prehabilitation should be carried out by interdisciplinary teams, including family physicians and various specialists in thetreatment of comorbidities. Prehabilitation requires urgent systemic and reimbursement solutions.
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Cuidados Preoperatorios , Ejercicio Preoperatorio , Humanos , Cuidados Preoperatorios/métodos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Estado NutricionalRESUMEN
The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
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Neoplasias de la Mama , Carcinoma , Neoplasias Colorrectales , Bancos de Muestras Biológicas , Neoplasias de la Mama/genética , Variación Genética , Humanos , Masculino , Mastectomía , Neoplasias Pancreáticas , Neoplasias PancreáticasRESUMEN
Colorectal cancer (CRC) is often diagnosed at an advanced stage due to the invasiveness of colonoscopy; thus, non-invasive CRC diagnostics are desirable. CRC is associated with lipid alterations. We aimed to verify whether fatty acid (FA) profiles in CRC patients may serve as a potential diagnostic tool for CRC diagnosis. FA profiles were assayed by GC-MS in cancer tissue, paired normal mucosa and serum from CRC patients and healthy controls. The levels of very long FAs - VLCFAs (26:0, 28:0 and 26:1) were the most highly increased FAs in cancer tissue compared to normal colon mucosa. Moreover, these FA were present in serum of CRC patients, they were absent in the serum of healthy subjects, or present in only trace amounts. To verify if cancer cells are the source of small amounts of these VLCFAs in the serum of patients we performed experiment in HT-29 CRC cells, which proved that CRC cells can produce and release VLCFAs into the blood. Most importantly, we defined a panel of FAs that may be assayed in a single analysis that definitely distinguishes CRC patients and healthy subjects, which was confirmed by PLS-DA and multivariate ROC analysis (AUC = 0.985). This study shows that selected FA panel may serve as a diagnostic marker for CRC.
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BACKGROUND: The number of morbidly obese kidney transplant candidates is growing. They have limited access to kidney transplantation and are at a higher risk of postoperative complications. Bariatric surgery is considered as a safe weight loss method in those patients. OBJECTIVES: Matched pair analysis was designed to analyze the preparatory and postoperative weight loss after bariatric procedures in end-stage kidney disease (ESKD) and non-ESKD morbidly obese patients. METHODS: Twenty patients with ESKD underwent bariatric surgery in our Centre of Excellence for Bariatric and Metabolic Surgery between 2015 and 2019 (nine one-anastomosis gastric bypasses, nine Roux-en-Y gastric bypasses, and two sleeve gastrectomies). They were compared with matched pairs from a dataset of 1199 morbidly obese patients without ESKD. Data on demographic factors and comorbidities was recorded. BMI was obtained at the start of the preparatory period preceding the bariatric procedure, at the time of procedure, and during the 1-year follow-up. RESULTS: The ESKD and non-ESKD patients did not differ significantly in preoperative weight loss (13.00 ± 11.69 kg and 15.22 ± 15.96 kg respectively, p = 0.619). During the 1-year follow-up, the weight loss was similar to the non-ESKD group. In the first 3 months, faster weight loss in ESKD was observed. Initial and follow-up BMI values did not differ significantly between groups. We demonstrated that obese patients with ESKD can lose weight as effectively as non-ESKD patients. CONCLUSION: Morbidly obese ESKD patients have an equal weight loss to patients without ESKD. Bariatric surgery could improve access to kidney transplantation and may potentially improve transplantation outcomes of obese patients with ESKD.
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Cirugía Bariátrica , Fallo Renal Crónico , Trasplante de Riñón , Obesidad Mórbida , Humanos , Fallo Renal Crónico/cirugía , Análisis por Apareamiento , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Although a growing body of evidence suggests that colorectal cancer (CRC) is associated with alterations of fatty acid (FA) profiles in serum and tumor tissues, available data about polyunsaturated fatty acid (PUFA) content in CRC patients are inconclusive. Our study showed that CRC tissues contained more PUFAs than normal large intestinal mucosa. However, serum levels of PUFAs in CRC patients were lower than in healthy controls. To explain the mechanism of PUFA alterations in CRC, we measured FA uptake by the colon cancer cells and normal colon cells. The levels of PUFAs in colon cancer cell culture medium decreased significantly with incubation time, while no changes were observed in the medium in which normal colon cells were incubated. Our findings suggest that the alterations in tumor and serum PUFA profiles result from preferential uptake of these FAs by cancer cells; indeed, PUFAs are essential for formation of cell membrane phospholipids during rapid proliferation of cancer cells. This observation puts into question potential benefits of PUFA supplementation in CRC patients.
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Neoplasias Colorrectales/metabolismo , Ácidos Grasos Insaturados/metabolismo , Anciano , Línea Celular Tumoral , Membrana Celular/metabolismo , Proliferación Celular/fisiología , Colon/metabolismo , Femenino , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Masculino , Fosfolípidos/metabolismoRESUMEN
BACKGROUND/AIM: Fatty acid synthase (FASN) provides palmitate for cell membrane formation in colorectal cancer (CRC) cells, however, palmitate is also available in the blood of CRC patients. The aim of this study was to examine whether orlistat, a FASN inhibitor, is able to attenuate CRC cell growth despite the availability of extracellular palmitate. MATERIALS AND METHODS: Palmitate concentrations were measured in serum from CRC patients and healthy controls. HT-29 CRC cells were treated with orlistat and palmitate. RESULTS: Treatment of CRC cells with orlistat caused a dose-dependent inhibition of cell proliferation. In turn, delivery of extracellular palmitate at doses lower than those found in the serum of CRC patients reversed inhibition by orlistat concentrations of up to 10 µM. CONCLUSION: Inhibition of CRC cell proliferation by orlistat is reversed by palmitate which is present at high levels in the serum. Therefore, orlistat may be effective in vivo only at high concentrations.
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Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Orlistat/farmacología , Palmitatos/sangre , Adulto , Anciano , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/sangre , Acido Graso Sintasa Tipo I/antagonistas & inhibidores , Acido Graso Sintasa Tipo I/genética , Femenino , Células HT29 , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The aim of this study was to evaluate the impact of low-volume vs. standard-volume bowel preparation on participation in screening colonoscopy, bowel preparation quality, and lesion detection rates. METHODS: This was a multicenter, randomized, health services study within the population-based primary colonoscopy screening program in Poland. Individuals aged 55â-â62 years were randomized in a 1:1 ratio to bowel preparation with a low-volume (0.3âL sodium picosulfate with magnesium citrate) or standard-volume (4âL polyethylene glycol) regimen and then invited to participate in screening colonoscopy. The primary outcome measure was the rate of participation in screening colonoscopy. Compliance with the assigned bowel preparation, bowel preparation quality, and lesion detection rates were also evaluated. RESULTS: A total of 13â 621 individuals were randomized and 13â 497 were analyzed (6752 in the low-volume group and 6745 in the standard-volume group). The participation rate (16.6â% vs. 15.5â%; Pâ=â0.08) and compliance rate (93.3â% vs. 94.1â%; Pâ=â0.39) did not differ significantly between the groups. In the low-volume group, fewer participants had adequate bowel preparation compared with the standard-volume group (whole colon 79.0â% vs. 86.4â%, Pâ<â0.001; proximal colon 80.1â% vs. 87.3â%, Pâ<â0.001). Detection rates of advanced adenoma (AADR) and advanced serrated polyps (ASPDR) were lower in the low-volume group than in the standard-volume group (AADR in the proximal colon 2.6â% vs. 4.3â%, Pâ=â0.02; ASPDR in the whole colon 2.0â% vs. 3.3â%, Pâ=â0.04; ASPDR in the proximal colon 1.0â% vs. 1.9â%, Pâ=â0.048). CONCLUSION: When compared with a standard-volume bowel preparation with polyethylene glycol, low-volume bowel preparation with sodium picosulfate/magnesium citrate did not improve participation rate or lesion detection rates, and negatively affected bowel preparation quality.
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Catárticos/administración & dosificación , Colonoscopía , Tamizaje Masivo , Cooperación del Paciente , Citratos/administración & dosificación , Ácido Cítrico/administración & dosificación , Femenino , Investigación sobre Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organometálicos/administración & dosificación , Picolinas/administración & dosificación , Polonia , Polietilenglicoles/administración & dosificaciónRESUMEN
Altered metabolism of lipids is currently considered a hallmark characteristic of many malignancies, including colorectal cancer (CRC). Lipids are a large group of metabolites that differ in terms of their fatty acid composition. This review summarizes recent evidence, documenting many alterations in the content and composition of fatty acids, polar lipids, oxylipins and triacylglycerols in CRC patients' sera, tumor tissues and adipose tissue. Some of altered lipid molecules may be potential biomarkers of CRC risk, development and progression. Owing to a significant role of many lipids in cancer cell metabolism, some of lipid metabolism pathways may also constitute specific targets for anti-CRC therapy.
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Neoplasias Colorrectales/genética , Metabolismo de los Lípidos/genética , Lípidos/genética , Tejido Adiposo/metabolismo , Biomarcadores/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Lípidos/química , Triglicéridos/metabolismoRESUMEN
BACKGROUND: To date there is scarce published evidence reporting the dual blood supply reaching anterior papillary muscle (APM), which descends from both major coronary arteries. Such a vascular configuration can prevent the dysfunction of right ventricular entire valvular system in case of the occlusion of proximal part of either right coronary artery (RCA) or left coronary artery (LCA). The aim of our study was to determine the vascular pattern of APM blood supply which originates from two main coronary arteries, in the context of the APM and septomarginal trabecula (SMT) topography. METHODS: The study was carried out using tissue obtained from 36 human hearts. The material was divided into four morphological types of SMT/APM arrangement. Vascularization and blood supply pattern of papillary muscle was investigated following the analysis of multiple tissue cross sections. The origin of APM arterial supply was traced back to both main coronary arteries. Cross-sectional area of the arteries was estimated at the base of APM and compared within mixed male-female population, aged 18-76. RESULTS: We noted that as much as 78% of entire APM material had a blood supply vasculature originating from both LCA and RCA branches. In contrast, 22% of cases APM was supplied by a single coronary artery, while in each case it proved to be LCA. We have never found APM arterial supply provided exclusively by RCA. In case of double AMP blood supply an average of total cross-section area of the arteries branching from LCA, was noted to be in excess of two and a half times bigger in type III and more than two times bigger in type IV, as compared with the arteries originating from RCA. CONCLUSIONS: Our research confirm the possibility of double blood supply which vascularizes APM, but the finding does not necessarily apply in all cases. However, APM seems to be predominantly vascularized by arteries deriving from LCA, regardless of their morphological type.
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Vasos Coronarios/anatomía & histología , Ventrículos Cardíacos/anatomía & histología , Músculos Papilares/anatomía & histología , Adolescente , Adulto , Anciano , Circulación Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The therapy of colorectal cancer (CRC) patients is often unsuccessful because of the presence of cancer stem cells (CSCs) resistant to conventional approaches. Dendritic cells (DC)-based protocols are believed to effectively supplement CRC therapy. Our study was aimed to assess how the number and properties of CSCs isolated from tumor tissue of CRC patients will affect the biological characteristics of in vitro modified DCs. Similar procedures were conducted with the using of CRC HCT116 and HT29 cell lines. We found that the detailed configuration of CSC-like markers significantly influenced the maturation and activation of DCs after stimulation with cancer cells lysates or culture supernatants. This basic stimulatory effect was enhanced by LPS that is normally present in CRC CSCs niche. The increased number of CD29+ and CD44+ CSCs presented the opposite impact on treated DCs as showed by many significant correlations. The CD133+ CSCs seemed to impair the functions of DCs. The more CD133+ CSCs in tumor sample the lower number of activated DCs evidenced after stimulation. Moreover, our results showed superiority of the spherical culture model over the adherent one since spherical HCT116 and HT29 cells presented similar influence on DCs properties as CRC patients cancer cells. We concluded that the DCs features may depend directly on the properties of CSCs affected by progression status of tumor.
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Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Neoplasias Colorrectales/terapia , Células Dendríticas/trasplante , Células Madre Neoplásicas/trasplante , Antígeno AC133/metabolismo , Anciano , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Técnicas de Cocultivo , Neoplasias Colorrectales/patología , Femenino , Células HCT116 , Células HT29 , Humanos , Receptores de Hialuranos/metabolismo , Integrina beta1/metabolismo , MasculinoRESUMEN
INTRODUCTION: Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. AIM: The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. RESULTS: In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. CONCLUSIONS: From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.
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Neoplasias de las Glándulas Suprarrenales/cirugía , Feocromocitoma/cirugía , Complicaciones Neoplásicas del Embarazo/cirugía , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Adulto , Femenino , Humanos , Feocromocitoma/diagnóstico por imagen , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Colorectal cancer (CRC) is the third most frequent malignancy and represents the fourth most common cause of cancer-associated mortalities in the world. Despite many advances in the treatment of CRC, the 5-year survival rate of patients with CRC remains unsatisfactory due to tumor recurrence and metastases. Recently, cancer stem cells (CSCs), have been suggested to be responsible for the initiation and relapse of the disease, and have been identified in CRC. Due to their basic biological features, which include self-renewal and pluripotency, CSCs may be novel therapeutic targets for CRC and other cancer types. Conventional therapeutics only act on proliferating and mature cancer cells, while quiescent CSCs survive and often become resistant to chemotherapy. In this review, markers of CRC-CSCs are evaluated and the recently introduced experimental therapies that specifically target these cells by inducing CSC proliferation, differentiation and sensitization to apoptotic signals via molecules including Dickkopf-1, bone morphogenetic protein 4, Kindlin-1, tankyrases, and p21-activated kinase 1, are discussed. In addition, novel strategies aimed at inhibiting some crucial processes engaged in cancer progression regulated by the Wnt, transforming growth factor ß and Notch signaling pathways (pyrvinium pamoate, silibinin, PRI-724, P17, and P144 peptides) are also evaluated. Although the metabolic alterations in cancer were first described decades ago, it is only recently that the concept of targeting key regulatory molecules of cell metabolism, such as sirtuin 1 (miR-34a) and AMPK (metformin), has emerged. In conclusion, the discovery of CSCs has resulted in the definition of novel therapeutic targets and the development of novel experimental therapies for CRC. However, further investigations are required in order to apply these novel drugs in human CRC.
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Colorectal cancer (CRC) is one of the most common solid organ cancers prevalent worldwide causing, in spite of advancing therapeutic methodology, high rate of patient mortality, especially due to metastasis development. The cancer stem cell (CSC) theory of tumor growth indicates that CSCs within the tumor mass have great capacity to initiate and sustain tumor growth. Following the suggestion that Fas signaling can be engaged in apoptosis, tumor maintenance, senescence or DICE (death induced by CD95 or CD95L elimination), the attempts to broaden the knowledge concerning the relationships between CSCs features and FasR/FasL appeared to be necessary. The most important advantage of our study was the simultaneously analysis of CSCs from commonly used CRC lines (HCT116 and HT29) and tumor fragments collected from CRC patients. Moreover, the sphere-promoting expansion of CRC lines brought a specific three-dimensional specific environment for CSC exploration. We further investigated the function of Fas signaling in CRC lines depending on the culture mode as we incubated HCT116 and HT29 cells with anti-FasR agonistic antibodies. It appeared to act in a line-dependent and culture mode-dependent manner and influenced some particular features of CSCs such as spherogenicity, proliferation and phenotype. Additionally, the analysis of mRNA level showed that disease progression is associated with significantly increased expression of FasR and/or FasL. In conclusion, our observation seems to confirm that spherical model of cancer lines is more reliable for some sophisticated analysis because of their greater resemblance to the CSCs from human CRC samples in comparison to commonly used adherent cells, at least according to aspects of their biology analyzed in this study. That can be extended to the resemblance of in vitro sphere forming conditions to the in vivo environment. However, the greatest difference concerns the level of apoptosis, thus, this issue require further experiments.
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Proliferación Celular/genética , Neoplasias Colorrectales/genética , Proteína Ligando Fas/genética , Receptor fas/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Senescencia Celular/genética , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células HCT116 , Humanos , Masculino , Persona de Mediana Edad , Células Madre Neoplásicas , ARN Mensajero/genética , Transducción de Señal/genéticaRESUMEN
BACKGROUND & AIMS: The quality of endoscopists' colonoscopy performance is measured by adenoma detection rate (ADR). Although ADR is associated inversely with interval colorectal cancer and colorectal cancer death, the effects of an increasing ADR have not been shown. We investigated whether increasing ADRs from individual endoscopists is associated with reduced risks of interval colorectal cancer and subsequent death. METHODS: We performed a prospective cohort study of individuals who underwent a screening colonoscopy within the National Colorectal Cancer Screening Program in Poland, from January 1, 2004, through December 31, 2008. We collected data from 146,860 colonoscopies performed by 294 endoscopists, with each endoscopist having participated at least twice in annual editions of primary colonoscopy screening. We used annual feedback and quality benchmark indicators to improve colonoscopy performance. We used ADR quintiles in the whole data set to categorize the annual ADRs for each endoscopist. An increased ADR was defined as an increase by at least 1 quintile category, or the maintenance of the highest category in subsequent screening years. Multivariate frailty models were used to evaluate the effects of increased ADR on the risk of interval colorectal cancer and death. RESULTS: Throughout the enrollment period, 219 endoscopists (74.5%) increased their annual ADR category. During 895,916 person-years of follow-up evaluation through the National Cancer Registry, we identified 168 interval colorectal cancers and 44 interval cancer deaths. An increased ADR was associated with an adjusted hazard ratio for interval colorectal cancer of 0.63 (95% confidence interval [CI], 0.45-0.88; P = .006), and for cancer death of 0.50 (95% CI, 0.27-0.95; P = .035). Compared with no increase in ADR, reaching or maintaining the highest quintile ADR category (such as an ADR > 24.56%) decreased the adjusted hazard ratios for interval colorectal cancer to 0.27 (95% CI, 0.12-0.63; P = .003), and 0.18 (95% CI, 0.06-0.56; P = .003), respectively. CONCLUSIONS: In a prospective study of individuals who underwent screening colonoscopy within a National Colorectal Cancer Screening Program, we associated increased ADR with a reduced risk of interval colorectal cancer and death.
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Adenocarcinoma/epidemiología , Adenoma/diagnóstico , Colonoscopía/normas , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Adenocarcinoma/mortalidad , Benchmarking , Neoplasias Colorrectales/mortalidad , Detección Precoz del Cáncer , Retroalimentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Estudios Prospectivos , Mejoramiento de la Calidad , Factores de RiesgoRESUMEN
BACKGROUNDS/AIMS: Colorectal cancer (CRC) cells show some alterations of lipid metabolism. Elongation of fatty acids (FA) has not been studied in CRC tissues thus far. The aim of this study was to verify if CRC specimens and normal colon mucosa differ in terms of their levels of very long-chain FAs, a product of FA elongation. Moreover, the expression of elongase genes has been studied in normal tissue and CRC. Finally, we searched for some specific products of FA elongation in serum of CRC patients. METHODS: The specimens of normal colon mucosa and CRC were obtained from nineteen CRC patients differ in terms of FA elongation. We also searched for some specific products of FA elongation in serum of CRC patients and from healthy volunteers. Tissue and serum FA profiles were determined by means of gas chromatography-mass spectrometry (GC/MS), and the tissue expression of elongases (ELOVLs) was analyzed with real-time PCR. RESULTS: Compared to normal colon tissue, CRC specimens showed significantly higher levels of 22-, 24- and 26-carbon FAs, stronger expressions of ELOVL1 and ELOVL6 (4- and 9-fold elevated respectively), and higher values of 18: 0/16: 0 elongation index. We also demonstrated presence of cerotic acid (26: 0) in serum of all CRC patients but in none of the healthy controls. CONCLUSIONS: CRC tissue seems to be characterized by enhanced FA elongation (hyper-elongation). Presence of cerotic acid in CRC patients sera and absence of this FA in healthy subjects points to this compound as a strong candidate for specific metabolic marker of colorectal malignancies.
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Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Ácidos Grasos/metabolismo , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Colon/metabolismo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/metabolismo , Elongasas de Ácidos Grasos , Ácidos Grasos/análisis , Ácidos Grasos/sangre , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
INTRODUCTION: The colorectal cancer (CRC) is one of the most frequent cancer in Poland and worldwide. This disease is characterized by distinct genetic alterations. p73 belongs to the p53 gene family; however, its role in the pathogenesis of CRC has not been completely understood. p73 gene encodes several mRNA variants and protein isoforms with its longest and fully functional p73a (mRNA) and TAp73a (protein) isoform. The aim of the study was to investigate p73 gene expression at the mRNA (p73a) and protein (TAp73a) levels in CRC. MATERIAL AND METHODS: Small sections of the crc tumor tissue and macroscopically unchanged colon mucosa and submucosa from the dissection margin were collected from 23 patients diagnosed with CRC. p73 mRNA levels were measured by Real-time PCR (QPCR) method and the expression level of TAp73a protein was assessed by Western blotting (WB) and immunohistochemical (IHC) staining. RESULTS: We found a 37% decrease in the level of p73a mRNA in neoplastically changed (tumor) compared with unchanged normal colon tissue from the surgical margin (p = 0.041). No correlations were found between mRNA levels in cancer tissue and clinical-pathological parameters. The semi-quantification of TAp73a protein revealed lower and higher TAp73a protein contents in 11/23 and 12/23 of tumor samples, respectively, when compared with the median value of TAp73a protein in normal colon tissue (p = 0.61). The level of TAp73a protein level was 5 times lower in poorly differentiated cancer cells (G3) in comparison to moderately differentiated ones (G2; p = 0.02). No statistically significant correlations were observed between the level of the TAp73a protein and clinical-pathological patients' characteristics. The IHC analysis of TAp73a protein presence in CRC samples showed decreased immunoreactivity when compared with matched sections of the unchanged colon wall in 4/9 patients, similar intensity of the IHC reaction in 4/9 patients and increased immunoreactivity in 1/9 patients. The TAp73a protein was localized mainly in the cytoplasm of the cancer cells. No statistically significant correlations between IHC results and clinical-pathological features of the patients were found. CONCLUSIONS: The obtained results suggest that the p73 gene may play a role as a tumor suppressor in the CRC progression.