Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes.

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

Duodenal Pseudolipomatosis. Literature review and case report of a very unusual finding.

Pseudolipomatosis (PL) is a rare, benign, iatrogenic condition first described in colorectal mucosa. This condition is thought to arise from gas penetration into the mucosa due to mechanical or chemical injury during endoscopy. Despite these associations and its characteristic appearence, the definitive pathogenesis remains unclear and it continues to be underrecognized by some pathologists and endoscopists, which is crucial to avoid any further unnecessary treatments. Immunohistochemistry techniques play a role in differentiating PL from similar conditions such as cystic intestinal pneumatosis, intestinal lipomatosis, or lymphangiectasia. A 70-year-old man with a family history of colon adenocarcinoma was diagnosed with duodenal pseudolipomatosis after a routine endoscopic assessment. To the best of our knowledge, there have been only two reports of PL diagnosed in the duodenum. A review of over 500 duodenal biopsies at our centre revealed that no other instances were identified, emphasizing the unusual occurrence of this particular location.

Anogenital Distance, a Biomarker of Prenatal Androgen Exposure Is Associated With Prostate Cancer Severity.

BACKGROUND: Anogenital distance (AGD), the distance from the centre of the anus to the genitals, is a sexually dimorphic phenotype in mammals. Experimental studies have shown that AGD is a biomarker of prenatal androgen exposure during the masculinisation period of development. The aim of this study is to assess the relationship between anogenital distance (AGD), as an indirect marker of prenatal hormonal environment, and prostate cancer (PCa) severity. MATERIALS: We conducted a cross-sectional study with a total of 120 PCa patients with confirmed biopsy of the tumour from April 2007 to July 2015. Two variants of the anogenital distance were assessed, from the anus to the posterior base of the scrotum (AGDAS ) and to the cephalad insertion of the penis (AGDAP ). We compared differences in groups to evaluate the association between AGD measurements and severity of the preoperative biopsy and clinical scores. RESULTS: Longer AGDAS was significantly associated with the highest Gleason score (P = 0.015) and D'Amico nomogram (P = 0.048). In contrast, no statistical differences were found in the AGDAP and severity of the preoperative biopsy. CONCLUSIONS: These findings are consistent with the hypothesis that a higher prenatal androgen exposure is associated with higher severity of PCa. Prostate 77: 406-411, 2017. © 2016 Wiley Periodicals, Inc.

The therapeutic effects of apigenin and dexamethasone on 5-fluorouracil-induced oral mucositis - a pilot study using a Syrian hamster model.

OBJECTIVE: Oral mucositis (OM) is a common complication of chemotherapy and radiotherapy. The aim of this study was to evaluate the effects of treating 5-fluorouracil-induced OM with apigenin and dexamethasone. METHODS: Thirty-six male Syrian hamsters were randomly assigned to one of three groups: control (50% acetic acid + 5-FU), 50% acetic acid + 5-FU + potassium Apigenin (KA), and 50% acetic acid + 5-FU + dexamethasone. The animals from each group were sacrificed 5, 7, 10, and 14 days after inducing the mucositis, and two samples collected from each animal, accounting a total of 72 samples. Macroscopic changes were assessed by histomorphometric analysis, with ulcers being assessed by imaging analysis and the number of inflammatory cells in the ulcerated region quantified in all periods through histomorphometric analysis (H&E). Furthermore, immunohistochemical changes were evaluated by proliferating cell nuclear antigen. RESULTS: All groups presented an increased inflammatory infiltrate after 7 days, compared to other evaluation times (P ≥ 0.05). There was significant difference between apigenin and control group in the 10-days period. Lower quantity of inflammatory cells in the apigenin-treated group in comparison with control group in the 7- and 10-days periods was observed (P < 0.05). No statistically significant difference was verified among the groups in 5- and 14-days periods. The healing process of the control group was slower than that of apigenin and dexamethasone-treated groups, with an overall significant difference between apigenin and the control group in the 10-days period. CONCLUSIONS: Apigenin treatment may enhance healing of OM induced by 5-fluorouracil, thus suggesting that more extensive research in this area may be useful to assess the role of agents of natural origin capable of preventing OM. Hence, further studies involving broader samples are need to confirm the therapeutic potential shown by this study.

Combining Oxidative Stress Markers and Expression of Surfactant Protein A in Lungs in the Diagnosis of Seawater Drowning.

BACKGROUND AND OBJECTIVES: The diagnosis of seawater drowning (SWD) remains one of the most complex and contentious. It is one of the leading causes of unintentional death around the world. In most cases, the forensic pathologist must reach an accurate diagnosis from the autopsy findings and a series of complementary tests such as histopathological, biological, and chemical studies. Despite the lung being the most affected organ in death by submersion, there are few studies on this type of death's impact on this organ. The aim was to investigate human lung cadavers of forensic cases due to different causes of death, the concentration of the oxidative stress markers malondialdehyde (MDA) and γ-glutamyl-l-cysteinyl glycine (GSH), and the relationship with the expression of surfactant protein A (SP-A) to try to discriminate SWD from other types of causes of death. MATERIALS AND METHODS: A total of 93 forensic autopsy cases were analyzed. Deaths were classified into three major groups based on the scene, cause of death, and autopsy findings (external foam, frothy fluid in airways, overlapping medial edges of the lungs): (a) drowning in seawater (n = 35), (b) other asphyxia (n = 33), such as hangings (n = 23), suffocations (n = 6), and strangulation (n = 4), and (c) other causes (n = 25), such as multiple suffocations. Oxidative stress markers (MDA and GSH) and the immunohistochemical expression of SP-A were determined in both lungs. RESULTS: MDA levels were statistically higher in both lungs in cases of SWD than in other causes of death (p = 0.023). Similarly, significantly higher levels of GSH were observed in SWD compared to the rest of the deaths (p = 0.002), which was more significant in the right lung. Higher immunohistochemical expression of SP-A was obtained in the cases of SWD than in the other causes of death, with higher levels in both lungs. The correlation analysis between the levels of oxidative stress (MDA and GSH) in the lung tissue and the expression level of SP-A showed positive and significant results in SWD, both in the alveolar membrane and the alveolar space. CONCLUSIONS: Determining the levels of MDA and GSH in lung tissue and the expression level of SP-A can be of great importance in diagnosing SWD and the circumstances of death. A better understanding of the physiology of submersion is essential for its possible repercussions in adopting measures in the approach to patients who have survived a submersion process. It is also necessary for forensic pathology to correctly interpret the events that lead to submersion.

[Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients]. / Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos.

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.

Clinical Meaning of Stromal Tumor Infiltrating Lymphocytes (sTIL) in Early Luminal B Breast Cancer.

Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5% (Q1-Q3 range (IQR), 0-10). We found that sTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02-1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33-17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC.

Localized neurofibromatosis of the female genital system: a case report and review of the literature.

Neurofibromatosis within the female genital tract is uncommon. The vulva is the most frequent genital location, but it has rarely been reported in the context of the vagina, uterine cervix or ovaries. In spite of its rarity, neurofibroma is a neoplasm that should be considered in the differential diagnosis of pelvic masses, especially in patients with neurofibromatosis. In this paper we describe the case of a 71-year-old patient with pelvic pain and a uterine mass who underwent a hysterectomy after having been diagnosed with an 11-cm neurofibroma occupying the myometrium of the entire uterine corpus. There were no neurofibromas in the endometrium, serosa, fallopian tubes or ovaries. The patient had an unknown von Recklinghausen's disease.

Study of the Effect of Photobiomodulation on a Skin Repair Model in SKH-1 Mice.

Background and objective: Laser applied at low power (400-1100 nm), currently named photobiomodulation (PBM), is a noninvasive therapy to speed up wound healing. The purpose of this study was whether two different laser PBM delivery protocols would impact the skin wound healing in a mouse model. Materials and methods: A total of 24 SKH-1 mice were divided into three groups: Group 1 (control: untreated ulcers), Group 2 (a single postsurgical laser application), and Group 3 (laser each other day for 10 days; total five applications). Laser parameters were 940 nm, 0.4 W, 10 mm spot size, 0.008 J/cm2, 300 sec/wound. Each animal received two skin wounds which were photographed on days 0, 5, and 10 to determine wound closure (ImageJ). Half of the animals in each group were sacrificed on day 5 and the other half on day 10. Samples were routinely processed for histological analysis (re-epithelization, angiogenesis, granulation tissue formation, inflammation, and collagen deposition). Results: The closure of the wounds at the end of the experiment in the animals photobiostimulated each other day was more advanced than in the controls and in those treated only once, in both the macroscopic and microscopic studies. Angiogenesis was higher in both treated groups than in the control in the first study time (day 5). However, inflammation, maturation of the granulation tissue, and collagen deposition only improved when the laser was applied each other day. Conclusions: In our study, with the parameters used, PBM improved the healing of skin wounds when applied every other day and not in a single dose.

Cytologic and histologic features of COVID-19 post-vaccination lymphadenopathy.

In this study, we present six cases of axillary or supraclavicular lymphadenopathies in the days following to the Pfizer-BioNTech vaccine's first dose and its study for fine-needle aspiration cytology (two patients), biopsy with a gross needle (two patients), and the evolution of two other patients. Cytological smears and histological sections reveal reactive nodes, predominantly T, CD8, and the presence of atypia with striking mitosis. Differential diagnosis with viral lymphadenopathies and lymphoma is important, so the clinical correlation, in a vaccination context, sudden appearance, and progressive decrease in days of the adenopathy, is essential. In this article, we have studied the cytohistological manifestations of post-Pfizer-BioNTech vaccination lymphadenopathy and discussed its differential diagnosis.

Disposition of Dietary Polyphenols in Breast Cancer Patients' Tumors, and Their Associated Anticancer Activity: The Particular Case of Curcumin.

SCOPE: Some polyphenol-derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and the tissue-occurring metabolites' anticancer activity are evaluated. METHODS AND RESULTS: Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC-QTOF-MS using targeted metabolomics. Anticancer activity was tested in MCF-7 and MDA-MB-231 BC cells. Mainly phase-II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L-1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L-1 in NT and MT, respectively). Breast tissue-occurring metabolites' antiproliferation was mainly exerted in p53-wild-type MCF-7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone-derived metabolites exerted estrogenic-like activity. CONCLUSION: Curcuminoids could be coadjuvants that might help fight BC upon regular consumption.

Chemopreventive effect of pomegranate and cocoa extracts on ultraviolet radiation-induced photocarcinogenesis in SKH-1 mice.

Non-melanoma skin cancer (NMSC) has a high and increasing incidence all over the world. Solar radiation is the main aetiology for humans. Although most research into photocarcinogenesis uses UVB as a source of radiation, UVA is also carcinogenic in long term. Pomegranate (PGE) and cocoa (CE) extracts have been used for medicinal purposes for time immemorial. Recently, it has been claimed that some of their properties may be an effective preventative measure against photocarcinogenesis and photoaging, but to date in vivo models have not been tested using RUVA, the objective of the present work. A lower incidence of lesions was observed in SKH-1 mice treated with PGE (p<0.001), and lower incidence of invasive squamous carcinoma in both treatment groups (p<0.001 for PGE and p<0.05 for CE); the PGE group also showed a lower level of cell proliferation than the control group (p<0.001). Significantly greater p53 alteration was observed in the control group than the treatment groups (p<0.001 for PGE and p = 0.05 for CE). No significant differences were found in relation to TIMP-1 and MMP-9. Taken together, the results suggest that oral feeding of PGE and CE to SKH-1 mice affords substantial protection against the adverse effects of RUVA, especially PGE.

Metabolic Profiling of Dietary Polyphenols and Methylxanthines in Normal and Malignant Mammary Tissues from Breast Cancer Patients.

SCOPE: Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer. METHODS AND RESULTS: Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g-1 ) are urolithin-A-3-O-glucuronide (26.2; 3.2-66.5), 2,5-dihydroxybenzoic acid (40.2; 27.7-52.2), resveratrol-3-O-sulfate (86.4; 7.8-224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3-229.4), and theobromine (715.0; 153.9-3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells. CONCLUSION: This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively. Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.

Nurse's A-Phase-Silicocarnotite Ceramic-Bone Tissue Interaction in a Rabbit Tibia Defect Model.

Calcium phosphate materials are widely used as bone substitutes due to their bioactive and biodegradable properties. Also, the presence of silicon in their composition seems to improve the bioactivity of the implant and promote bone tissue repair. The aim of this study was to develop a novel ceramic scaffold by partial solid-state sintering method with a composition lying in the field of the Nurse's A-phase-silicocarnotite, in the tricalcium phosphate-dicalcium silicate (TCP-C2S) binary system. Also, we evaluated its osteogenic and osteoconductive properties after being implanted into tibia defects in New Zealand rabbits. X-ray, microcomputer tomography, and histomorphometry studies demonstrated that this porous ceramic is highly biocompatible and it has excellent osteointegration. The material was being progressively reabsorbed throughout the study and there was no unspecified local or systemic inflammatory response observed. These results suggest that ceramic imitates the physicochemical characteristics of bone substitutes used in bone reconstruction.

Cáncer neuroendocrino de mama, presentación de un caso y técnicas diagnósticas / Neuroendocrine breast cancer, case report and diagnosis

El cáncer neuroendocrino de mama es una forma poco frecuente de aparición del cáncer de mama. Se presenta como un nódulo mamario asociado generalmente a una sintomatología general; por lo que también se debe realizar el diagnóstico diferencial con metástasis de cáncer neuroendocrino primario. En este artículo, presentamos el caso clínico de una paciente con cáncer de mama neuroendocrino, el tratamiento recibido y la detección e identificación del ganglio centinela mediante la utilización del trazador Magtrace® y del detector SentiMag®. Finalmente, se realiza una breve revisión de los pocos casos publicados en la literatura. (AU)

Neuroendocrine breast cancer is a rare form of breast cancer. It appears as a breast nodule, generally associated with general symptoms; therefore, the differential diagnosis should also be made with metastases from a primary neuroendocrine form. In this article, we present the clinical case of a patient with neuroendocrine breast cancer, the treatment and the detection and identification of the sentinel node using the Magtrace® tracer and the SentiMag® detector. Finally, a brief review of the few cases published in the literature is made. (AU)

Consumption of pomegranate decreases plasma lipopolysaccharide-binding protein levels, a marker of metabolic endotoxemia, in patients with newly diagnosed colorectal cancer: a randomized controlled clinical trial.

Gut microbiota dysbiosis alters the intestinal barrier function, increases plasma lipopolysaccharide (LPS) levels, which promotes endotoxemia, and contributes to the onset and development of colorectal cancer (CRC). We report here for the first time the reduction of plasma LPS-binding protein (LBP) levels, a marker of endotoxemia, after pomegranate consumption in newly diagnosed CRC patients.

[Relationship between anogenital distance and prognosis of prostate cancer.] / Relación entre distancia anogenital y pronóstico del cáncer de próstata.

OBJECTIVE: Anogenital distance (AGD), the distance from the centre of the anus to the genitals, is a sexually dimorphic phenotype in mammals. Several experimental studies have demonstrated that AGD is a biomarker of prenatal androgen exposure during the masculinisation period of development. The objective of this study was to assess the relationship between AGD (as an indirect marker of prenatal hormonal environment) and severity of the surgical specimen and prostate cancer (PCa) prognosis. METHODS: We conducted a cross-sectional study with a total of 119 PCa patients with confirmed biopsy of the tumour. Every participant underwent a physical examination where two variants of the AGD were assessed, a) from the anus to the cephalad insertion of the penis (AGDAP) and b) to the posterior base of the scrotum (AGDAS). To assess the association between both AGD and severity and PCa prognosis multiple logistic regression analysis was used. RESULTS: Longer AGDAS was significantly associated with biochemical recurrence and affected margins of the surgical specimen (OR: 2.5; IC 95%:1.2-5.5, and 2.8; IC 95%: 1.1-7.5, respectively). CONCLUSIONS: Our findings suggest that a higher prenatal androgen exposure, resulting in a longer AGD, is associated with worse prognosis of PCa.

Metástasis parotídea de carcinoma de células claras renal con presencia simultánea de pseudoaneurisma arterial. Caso clínico y revisión de la literatura / Parotid metastasis of clear cell renal carcinoma with simultaneous presence of arterial pseudoaneurysm. Case report and review of literature

Las metástasis en glándula parótida son muy poco frecuentes. Presentamos el caso de una mujer de 73 años cuyos antecedentes oncológicos principales a destacar son carcinoma ductal infiltrante de mama tratado con mastectomía y linfadenectomía axilar y, posteriormente, carcinoma de células renales de célula clara bilaterales metacrónicos tratados con nefrectomía radical. Desde entonces la mujer se encuentra en diálisis. Presenta tumoración en parótida de 4 cm, que radiológicamente es catalogada como pseudoaneurisma arterial intraparotídeo. Tras la extirpación de la parótida, seis años después de la última nefrectomía, en el estudio anatomopatológico se observa, junto a vasos dilatados, lesión neoplásica compatible morfológica e inmunohistoquímicamente con metástasis de carcinoma de células renales de célula clara. Se ha realizado una profunda revisión de la literatura encontrando menos de 60 casos descritos de metástasis parotídea de carcinoma de células renales de célula clara. Analizándolos observamos metástasis en otros lugares en el 61 % de los mismos, principalmente pulmonares, óseas y en glándulas adrenales, existiendo mayor porcentaje de segundas metástasis (70 %) cuando hay sincronía entre carcinoma renal y metástasis parotídea. En conclusión, presentamos un caso inusual de metástasis tardía de carcinoma renal de célula clara en parótida, y el primero, según nuestro conocimiento, que se diagnostica como hallazgo incidental en la extirpación de un aneurisma intraparotídeo. (AU)

Parotid gland metastases are very rare. We present the case of a 73-year-old woman whose main oncological history to highlight is infiltrating ductal carcinoma of the breast treated with mastectomy and axillary lymphadenectomy and after that. metachronous bilateral clear cell renal cell carcinoma treated with radical nephrectomy. Since then, the woman has been on dialysis. It presents a 4 cm parotid tumor, which is radiologically classified as an intraparotid arterial pseudoaneurysm. After extirpation of the parotid gland, six years after the last nephrectomy, in the pathological study, together with dilated vessels, a neoplastic lesion compatible morphologically and immunohistochemically with metastasis of clear cell renal cell carcinoma is observed. A thorough review of the literature has been carried out, finding less than 60 reported cases of parotid metastasis from clear cell renal cell carcinoma. Analyzing them, we observed metastases in other places in 61 % of them, mainly lung, bone and adrenal glands, with a higher percentage of second metastases (70 %) when there was a synchrony between renal carcinoma and parotid metastasis. In conclusion, we have presented an unusual case of late metastasis of clear cell renal carcinoma in the parotid, and the first –to our knowledge–, which is diagnosed as an incidental finding in the removal of an intraparotid aneurysm. (AU)

Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial.

The clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5-35 days of supplementation. Tissues were also obtained from 10 control patients (no supplementation) that confirmed a large, gene- and tissue-specific interindividual variability and impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3) and others not affected (KRAS). Despite these issues, the consumption of the PE was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR and TYMs, suggesting that the intake of this PE modulated the impact of the protocol on gene expression in a gene- and tissue-specific manner. These effects were not associated with the individuals' capacity to produce specific urolithins (i.e., metabotypes) or the levels of urolithins and EA in the colon tissues and did not reproduce in vitro effects evidencing the difficulty of demonstrating in vivo the in vitro results.