GRANULOMA PIOGÊNICO EM LÁBIO SUPERIOR: RELATO DE CASO

This article is based at the diagnosis of pyogenic granuloma, which is characterized as a benign simple hyperplastic tumor and has an inflammatory reactive component that increases in size as a connective tissue reaction, forming a repair tissue as a protective mechanism. Clinically, pyogenic granuloma is seen as a red or purplish lesion (similar to the adjacent mucosa), too vascular, with a sessile or pedunculated base, with slow growth, reaching a size that rarely exceeds 2,5 cm, the surface of which can be rough or smooth. It occurs more frequently in adulthood, with a predominance in females (mainly during pregnancy), between the second and seventh life's decades. This aim of this paper is to report a case of pyogenic granuloma on the upper lip of a patient at the FAESA's Dental Clinic.

Transoral Endoscopic Examination of the Oropharynx With Tongue Protrusion, Phonation, and Open Mouth

Background/Aim: We examined the diagnostic performance of the tongue protrusion with phonation and open mouth (TOPPOM) method for visualizing structures of the oropharynx. Patients and Methods: Transoral endoscopy was performed on 20 healthy participants to evaluate 12 oropharynx subsites under three conditions: open mouth (OM), phonation with open mouth (POM), and TOPPOM. Each subsite was scored from 0 to 2 depending on subsite visualization, and the scores were summed. Images of subsite-adjacent mucosa were similarly scored. Results: The total scores were significantly higher for TOPPOM than for POM and for POM than for OM. Such scores were observed for both the palatine arches, both palatine tonsils, the left lingual tonsillar sulcus, and the vallecula. Conclusion: TOPPOM enables visualization of the oropharynx through transoral endoscopic examination, and TOPPOM with conventional transnasal endoscopy may enable early detection of oropharyngeal carcinomas and lesions and improve the performance of pre- and post-treatment evaluations.

A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4–6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51–1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50–1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.

Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients

Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A, and IL1R1). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes CXCL3, IL1B, MET and TNS1 genes (p = 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of TNS1 and MET were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these TNS1 and MET are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.

Gastric Hyperplastic Polyps: A Benign Entity? Analysis of Recurrence and Neoplastic Transformation in a Cohort Study

<b><i>Introduction:</i></b> Hyperplastic polyps represent 30–93% of all gastric epithelial polyps. They are generally detected as innocuous incidental findings; however, they have a risk of neoplastic transformation and recurrence. Frequency and risk factors for neoplastic transformation and recurrence are not well established and are fields of ongoing interest. This study aims to evaluate the frequency of and identify the risk factors for recurrence and neoplastic change of gastric hyperplastic polyps (GHP). <b><i>Methods:</i></b> A single-centre retrospective cohort study including consecutive patients who underwent endoscopic resection of GHP from January 2009 to June 2020. Demographic, endoscopic, and histopathologic data was retrieved from the electronic medical records. <b><i>Results:</i></b> A total of 195 patients were included (56% women; median age 67 [35–87] years). The median size of GHP was 10 (3–50) mm, 62% (<i>n</i> = 120) were sessile, 61% (<i>n</i> = 119) were located in the antrum, and 36% (<i>n</i> = 71) had synchronous lesions. Recurrence rate after endoscopic resection was 23% (<i>n</i> = 26). In multivariate analysis, antrum location was the only risk factor for recurrence (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.1–8.1). Overall, 5.1% (<i>n</i> = 10) GHP showed neoplastic transformation, with low-grade dysplasia in 5, high-grade dysplasia in 4, and adenocarcinoma in 1. In multivariate analysis, a size &#x3e;25 mm (OR 84; 95% CI 7.4–954) and the presence of intestinal metaplasia (OR 7.6; 95% CI 1.0–55) and dysplasia (OR 86; 95% CI 10–741) in adjacent mucosa were associated with an increased risk of neoplastic transformation. Recurrence was not associated with neoplastic transformation (OR 1.1; 95% CI 0.2–5.9). <b><i>Discussion:</i></b> Our results confirmed the risk of recurrence and neoplastic transformation of GHP. Antrum location was a predictor of recurrence. The risk of neoplastic change was increased in large lesions and with intestinal metaplasia and dysplasia in adjacent mucosa. More frequent endoscopic surveillance may be required in these subgroups of GHP.

Histopathological Changes in Adjacent Non-Tumour Mucosa in Trans Urethral Resection of Bladder Tumour Specimens of Bladder Carcinoma

BACKGROUND Urinary bladder cancer is associated with high morbidity and mortality rates if not treated optimally. One of the causes of tumour recurrence is undiscovered residual tumour, and the existence of macroscopically invisible premalignant and malignant lesions of urothelium during the primary resection which can be detected by taking biopsy from apparently normal mucosa in the vicinity of the tumour during trans urethral resection of bladder tumour (TURBT). The primary objective was to estimate the proportion of bladder tumour showing changes in adjacent non tumour mucosa in TURBT specimens, within a period of six months. The secondary objectives were to study the association between changes in non-tumour bladder mucosa with the recurrence, seen after six months, and to study the expression of P53 in adjacent non tumour mucosa of bladder cancer. METHODS All cases of bladder carcinoma from trans urethral resection of bladder tumour which were sent along with adjacent non tumour mucosa and received at Department of Pathology, MCH, Trivandrum, for a period of six months were included in the study. Adjacent mucosa sent along with TURBT specimen received at our department was collected. After processing, tissue is embedded in paraffin blocks and thin sections of 4 - 5 m thickness was taken and stained with haematoxylin and eosin (H & E). Using light microscopy, changes in adjacent mucosa were assessed for any abnormal changes and findings were correlated with collected data. P53 expression was studied in the adjacent mucosa. All details were entered in the proforma. Details collected were entered in Excel and analysed using SPSS software. RESULTS Out of 37 TURBT cases that were sent along with adjacent mucosa, 12 cases showed changes in adjacent mucosa accounting for 32.4 %. P53 positivity accounting for 18.9 %, was seen in abnormal mucosa change with carcinoma in situ and dysplasia. On follow up, 8 % of cases with positive biopsy finding showed recurrence. CONCLUSIONS Multiple biopsies from adjacent non tumour mucosa is not necessary for all patients with superficial bladder tumour. Positive findings in adjacent mucosa does not have significant correlation with tumour stage / grade, and tumour size, number of lesions or histopathological findings. Adjacent mucosa may be useful in detecting concomitant carcinoma in situ (CIS), which can be helpful in therapeutic approach. KEY WORDS Normal Looking Mucosa, TURBT, Bladder Cancer

Downregulation of PAICS due to loss of chromosome 4q is associated with poor survival in stage III colorectal cancer

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) encodes an enzyme that catalyzes de novo purine biosynthesis. Although PAICS has been implicated as a potential therapeutic target in several cancers, its clinical and prognostic significance in colorectal cancer (CRC) is not fully understood. To elucidate the roles of PAICS in CRC, we investigated PAICS expression in four cohorts consisting of a total of 1659 samples based on quantitative RT-PCR, microarray and RNA-seq analysis. Despite upregulated PAICS levels in tumor compared to those of normal mucosa, we found a decreasing trend of PAICS expression during tumor progression and metastasis. We conducted immunohistochemistry on 252 specimens, showing that PAICS protein was strongly expressed in the majority of CRCs, but not in adjacent mucosa. Notably, 29.0% of tumors lacked PAICS staining, and PAICS-negative expression in tumor had significant prognostic impact on poor cancer-specific survival in stage III CRC. Correspondingly, decreased levels of PAICS transcript were also correlated with poor relapse-free survival particularly in stage III patients, and this finding was robustly confirmed in three microarray datasets of a total of 802 stage II-III patients. Bioinformatics analysis of CRC tissues and cell lines consistently indicated a correlation between decreased PAICS expression and copy number loss of chromosome arm 4q. In conclusion, our results suggest that PAICS expression is downregulated during tumor progression due to genetic deletion of chromosome 4q in microsatellite stable but chromosomally unstable tumors. Furthermore, decreased expression of PAICS transcript or loss of PAICS protein may provide prognostic stratification for postoperative patients with stage III CRC.

Macrophages produce and functionally respond to interleukin-34 in colon cancer

In colorectal cancer (CRC), macrophages represent a major component of the tumor mass and exert mostly functions promoting tumor cell survival, proliferation, and dissemination. Interleukin-34 (IL-34) is a cytokine overproduced by colon cancer (CRC) cells and supposed to make a valid contribution to the growth and diffusion of CRC cells. The biological functions of IL-34 are mediated by the macrophage colony-stimulating factor receptor (M-CSFR-1), which controls monocyte/macrophage differentiation, growth, and survival. We here investigated whether, in CRC, tumor-associated macrophages (TAMs) express M-CSFR-1 and functionally respond to IL-34. By flow-cytometry analysis of tumor-infiltrating cells (TICs) and lamina propria mononuclear cells (LPMCs) isolated from normal, adjacent mucosa of CRC patients, we showed that CD68/HLA-DRII-expressing TICs and LPMCs expressed M-CSFR-1. Both these cell types produced IL-34 even though the expression of the cytokine was more pronounced in TICs as compared to normal LPMCs. Moreover, in CRC samples, there was a positive correlation between IL-34-producing cells and CD68-positive cells. Stimulation of LPMCs and TICs with IL-34 resulted in enhanced expression of CD163 and CD206, two markers of type II-polarized macrophages, and this was evident at both RNA and protein level. In the same cell cultures, IL-34 stimulated expression and production of IL-6, a cytokine known to promote CRC cell growth and diffusion. Finally, knockdown of IL-34 in TICs with specific antisense oligonucleotides with: a specific antisesne oligonucleotide decreased IL-6 production and the number of TAMs producing this cytokine. This is the first to show a positive role of IL-34 in the control of TAMs in CRC, further supporting the notion that IL-34 sustains colon tumorigenesis.