Role of Multi-Parametric Magnetic Resonance Image and PIRADS Score in Patients with Prostate Cancer Eligible for Active Surveillance According PRIAS Criteria.

OBJECTIVE: To evaluate the prognostic role of multiparametric-MRI (mp-MRI) in patients with clinically localized prostate cancer (PCa) eligible for active surveillance (AS) according to Prostate Cancer Research International: Active Surveillance (PRIAS) criteria. PATIENTS AND METHODS: We analyzed prospectively 73 patients with PCa and PRIAS criteria for low-risk disease. All patients fitted criteria for AS but optioned surgery treatment. The mp-MRI was performed to define the likelihood of malignancy according to the Prostate Imaging Reporting and Data System (PIRADS) score (1-5). Patients were divided in 2 groups: non-visible cancer lesion on MRI (PIRADS 2-3) and visible cancer (PIRADS 4-5). Preoperative clinical data (age, body mass index, prostate specific antigen (PSA) level, positive core biopsy, PSA density (PSAD)) and definitive pathological findings (staging, upgrading, unfavorable disease) were compared between groups. PIRADS score was correlated with pathological data to evaluate the prognostic role of mp-MRI; and preoperative variables and definitive pathology (upgrading, upstaging and unfavorable disease) were also assessed. RESULTS: PSAD (p = 0.04) and pathological stage (p = 0.03) were significantly associated with the presence of visible disease. Visible disease was significantly associated with upstaging (p = 0.03). Correlation between PIRADS 5 and unfavorable disease was statistically significant (p = 0.02). The mp-MRI had adequate sensibility in detecting upstaging (92%), intermediate for upgrading (76%) and unfavorable disease (76%). Negative predictive value was higher for upstaging than for upgrading or unfavorable disease (96 vs. 68% and 64%). Multivariate logistic regression revealed that PIRADS 5 was a significant predictor of upstaging (p = 0.05, OR 16.12) and unfavorable disease (p = 0.01, OR 6.53). CONCLUSION: A visible lesion on mp-MRI strongly predicts significant PCa in patients eligible for AS according to PRIAS criteria, based on upstaging and unfavorable disease. We believe that mp-MRI is an important tool and should be added to clinical selection criteria for AS.

Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer.

Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for autoregulative tumor growth signaling in pancreatic cancer. We analyzed the expression of TLR2, -4, and -9 in primary human cancers and their impact on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth. The primary pancreatic cancers and cell lines expressed TLR2, -4, and -9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer. These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, -4, and -9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer.

External validation of EORTC risk scores to predict recurrence after transurethral resection of brazilian patients with non -muscle invasive bladder cancer stages Ta and T1.

Validate the EORTC risk tables in Brazilian patients with NMIBC. METHODS: 205 patients were analyzed. The 6 parameters analyzed were: histologic grading, pathologic stage, size and number of tumors, previous recurrence rate and concomitant CIS. The time for first recurrence (TFR), risk score and probability of re¬currence were calculated and compared to the probabilities obtained from EORTC risk tables. C-index was calculated and accuracy of EORTC tables was analyzed. RESULTS: pTa was presented in 91 (44.4%) patients and pT1 in 114 (55.6%). Ninety-seven (47.3%) patients had solitary tumor, and 108 (52.7%) multiple tumors. One hundred and three (50.2%) patients had tumors smaller than 3 cm and 102 (40.8%) had bigger than 3 cm. Concomitant CIS was observed in 21 (10.2%) patients. Low grade was presented in 95 (46.3%) patients, and high grade in 110 (53.7%). Intravesical therapy was utilized in 105 (56.1%) patients. Recurrence was observed in 117 (57.1%) patients and the mean TFR was 14,2 ± 7,3 months. C-index was 0,72 for 1 year and 0,7 for 5 years. The re¬currence risk was 28,8% in 1 year and 57,1% in 5 years, independently of the scoring risk. In our population, the EORTC risk tables overestimated the risk of recurrence in 1 year and underestimated in 5 years. CONCLUSION: The validation of the EORTC risk tables in Brazilian patients with NMIBC was satisfactory and should be stimulated to predict recurrence, although these may overestimated the risk of recurrence in 1 year and underestimated in 5 years.

MACROSCOPIC AND HISTOLOGICAL ANALYSIS ON ENDOSCOPICALLY RESECTED RECTAL LESIONS.

BACKGROUND: Colorectal cancer is among the most common malignancies worldwide. Colonoscopy is the examination of choice for the prevention of CRC because of its great diagnostic and, especially, therapeutic capacity in relation to adenomatous lesions. AIMS: This study aimed to analyze the prevalence, macroscopic, and histological characteristics of polypoid rectal lesions resected through endoscopic techniques and assess whether endoscopic therapy is safe and efficient for treating lesions located in the rectum. METHODS: This is a retrospective observational study with an analysis of the medical records of all patients undergoing resection of rectal polyps. RESULTS: A total of 123 patients with rectal lesions were evaluated, with 59 men and 64 women of mean age 56 years. All patients underwent endoscopic resection: 70% with polypectomy and 30% with wide mucosectomy. Complete colonoscopy with removal of the entire rectal lesion occurred in 91%, while in 5% the preparation was inadequate and poor clinical conditions were an impeditive factor, and in 4% surgical treatment was indicated because there was an infiltrative lesion with central ulceration. Histological evaluation showed adenomas in 3.25%, hyperplasia in 7.32%, and hamartoma in 0.81%; low-grade dysplasia was identified in 34.96%, high-grade dysplasia in 51.22%, and adenocarcinoma in 1.63%, while one case (0.81%) was classified as erosion. CONCLUSIONS: Polyps in the rectum are common and were found in 37% of these colonoscopies. Adenomas with dysplasia were the most common form of Colorectal cancer . Therapeutic colonoscopy proved to be a safe and efficient method for the complete treatment of rectal lesions.

Risk Factors for Persistence or Recurrence of High-Grade Cervical Squamous Intraepithelial Lesions.

OBJECTIVES: to evaluate whether the colposcopic lesion size , age, kind of surgery, the status of the surgical margins and the expression of the p16 and Ki-67 immunomarkers are risk factors for persistence or recurrence of the lesion. METHODS: a cross-sectional, observational, retrospective study of patients submitted to cold knife conization (CKC) or the loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2 or 3. The colposcopic lesion size, age, surgical method, involvement of the surgical margins, and p16/Ki-67 immunomarker expression were analyzed in relation to lesion persistence and recurrence. RESULTS: seventy-one women were treated with cold knife conization and 200 were treated with loop electrosurgical excision. Of these, 95 had cervical intraepithelial neoplasia 2, 173 had cervical intraepithelial neoplasia 3, 183 had free surgical margins, 76 had compromised margins, and 12 showed damage by processing artifact or fragments. Among the 76 cases with positive margins, 55, 11, and 10 showed endocervical margin involvement, ectocervical margin involvement, and both endocervial and ectocervical margin involvement, respectively. Of the 264 followed-up patients, 38 had persistent or recurrent disease. A multiple logistic regression indicated that positive endocervical margins are the only independent risk factor for the persistence/recurrence of cervical intraepithelial neoplasia. No significant association was identified between the colposcopic lesion size, age, surgery type, or p16/Ki-67 immunomarker expression and lesion persistence or recurrence.

The Nervous System Development Regulator Neuropilin-1 as a Potential Prognostic Marker and Therapeutic Target in Brain Cancer.

Neuropilins are transmembrane glycoproteins that regulate developmental processes in the nervous system and other tissues. Overexpression of neuropilin-1 (NRP1) occurs in many solid tumor types and, in several instances, may predict patient outcome in terms of overall survival. Experimental inhibition of NRP1 activity can display antitumor effects in different cancer models. Here, we review NRP1 expression and function in adult and pediatric brain cancers, particularly glioblastomas (GBMs) and medulloblastomas, and present analyses of NRP1 transcript levels and their association with patient survival in GBMs. The case of NRP1 highlights the potential of regulators of neurodevelopment as biomarkers and therapeutic targets in brain cancer.

Avoiding vascular complications in insular glioma surgery - A microsurgical anatomy study and critical reflections regarding intraoperative findings.

Introduction: Vascular lesions in insular glioma surgery can severely impact patients' quality of life. This study aims to present the results of our dissections and authors' reflections on the insular vascular anatomy. Matherials and Methods: The insular vascularization was examined using ×3 to ×40 magnification in 20 cadaveric cerebral hemispheres in which the arteries and veins had been perfused with colored silicone. Results: In insular gliomas, this individualization of the anatomical structures is rarely possible, as the gyri are swollen by the tumor and lose their individuality. In the transsylvian approaches, the anatomical parameters for delimiting the insula in tumors are best provided by the superior and inferior circular sulci. The branches of the MCA are easily identified in the transcortical approach, but only at the end of the surgery after the tumor is resected.). One of the factors under-discussed in the literature is the involvement of the lenticulostriate arteries by the medial part of the tumor. In our experience of 52 patients (article submitted to publishing), LSTa were founded to be involved by the tumor in 13 cases. In 39 patients, there was no involvement of the LSTa, which allowed a more aggressive resection. Early preoperative identification of the anterior perforated substance on the MRI and its proximity to the tumor may help determine the route of the LSTa over the medial tumor boundaries. Discussion: Our reflections introduced our imaging and anatomical concept regarding LSTa in insular glioma surgery. Accurate identification of origin, route, and distribution of the LSTa is pivotal to surgical success, especially in the lateral group. The anatomical knowledge of their path directly impacts the extent of tumor resection and functional preservation. Conclusion: Knowledge of microsurgical anatomy, brain mapping, and surgical experience counts a lot in this type of surgery, creating a reasonable procedure flowchart to be taken intraoperatively.

Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer.

Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression. We have recently provided evidence for upregulation of PDGF expression in UICC stage I-IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. The present study sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC. Our analysis of primary human colon tumor samples demonstrated upregulation of the PDGFRß, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors. Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding partners, VEGFR2 and EGFR. We then analyzed several CRC cell lines for PDGFRα, PDGFRß, VEGFR1, and VEGFR2 protein expression and found these receptors to be variably expressed amongst the investigated cell lines. Interestingly, whereas Caco-2 and SW480 cells showed expression of all analyzed receptors, HT29 cells expressed only VEGFR1 and VEGFR2. However, stimulation of HT29 cells with PDGF resulted in upregulation of VEGFR1 and VEGFR2 expression despite the absence of PDGFR expression and mimicked the effect of VEGF stimulation. Moreover, PDGF recovered HT29 cell proliferation under simultaneous treatment with a VEGFR or EGFR inhibitor. Our results provide some of the first evidence for PDGF cross-signaling through alternative receptors in colorectal cancer and support anti-PDGF therapy as a combination strategy alongside VEGF and EGF targeting even in tumors lacking PDGFR expression.

ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER?

BACKGROUND: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). AIM: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. METHODS: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. RESULTS: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. CONCLUSIONS: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER?

BACKGROUND: A) CD133+ cytoplasmic B) AXL+ combined C) c-MYC+ nuclear. CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). AIM: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. METHODS: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. RESULTS: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. CONCLUSIONS: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

IS THERE A CLINICAL PATHOLOGICAL CORRELATION OF COLORECTAL ADENOCARCINOMA WITH THE IMMUNOHISTOCHEMICAL EXPRESSION OF OPN AND ABCB5?

BACKGROUND: OPN ABCB5. Studies with biomarkers in TMA (tissue microarray) have been showing important results regarding its expression in colon cancer. AIM: Correlate the expression profile of the OPN and ABCB5 biomarkers with the epidemiological and clinicopathological characteristics of the patients, the impact on the progression of the disease and the death. METHOD: A total of 122 CRC patients who underwent surgical resection, immunomarking and their relationship with progression and death events were evaluated. RESULT: The average age was 61.9 (±13.4) years. The cases were distributed in 42 (35.9%) in the ascending/transverse colon, 31 (26.5%) in the sigmoid, 27 in the rectum (23.1%), 17 (14.5%) in the descending colon. Most patients had advanced disease (stages III and IV) in 74 cases (60.9%). There was a predominance of moderately differentiated tumors in 101 samples (82.8%); despite this, the poorly differentiated subtype proved to be an independent risk factor for death in 70%. Metastasis to the liver proved to be an independent risk factor for death in 75% (18/24), as well as patients with primary rectal tumors in 81.5% (22/27). CONCLUSION: The immunohistochemical expression of the OPN and ABCB5 markers was not associated with epidemiological and clinicopathological characteristics. Regarding the progression of disease and death, it was not possible to observe a correspondence relationship with the evaluated markers.

Expression of Parkin, APC, APE1, and Bcl-xL in Colorectal Polyps.

Colorectal cancer can develop through molecular, chromosomal, and epigenetic cumulative changes that transform the normal intestinal epithelium into the colorectal polyps, called conventional adenomas (CAs) or serrated polyps (SPs), recognized as precursors of invasive colorectal neoplasia. These benign lesions need to explore the morphology, histological diagnosis, and biomarkers profile to accurately characterize lesions with potential for evolution to cancer. This study aimed to correlate the immunohistochemical expression of Parkin and Adenomatous Polyposis Coli (APC; tumor suppressors), Human Apurinic/Apyrimidinic endonuclease 1 (APE1), and B-cell lymphoma-extra-large (Bcl-xL; oncogenic proteins) in sporadic colorectal polyps with clinical, endoscopic, and diagnostic data. Immunohistochemical analysis was performed on tissue microarray samples of 306 polyps. Based on the Allred score, the expressions were graduated in the cytoplasm and nucleus of superficial and cryptic cells. There was higher Parkin nuclear expression (p=0.006 and 0.010) and APC cytoplasmic expression in cryptic cells (p<0.001) in SPs. CAs, APE1 (p<0.001) and Bcl-xL (p<0.001) were more expressed in the nuclei and cytoplasms, respectively. These results are related to the biological role proposed for these proteins in cellular functions. They can contribute to the diagnosis criteria for polyps and improve the knowledge of biomarkers that could predict cancer development.

IS THERE CORRELATION BETWEEN HUMAN PAPILLOMAVIRUS (HPV) AND ESOPHAGEAL EPIDERMOID CARCINOMA?

BACKGROUND: Currently, persistent human papillomavirus (HPV) infection has been related in some geographic regions as a risk factor for esophageal squamous cell carcinoma. It results in the immunoexpression of the p16 protein, which has been used as marker of the oncogenic lineage by this etiological agent. AIM: To correlate epidemiological aspects of esophageal squamous cell carcinoma with the prevalence of HPV infection. METHODS: Fifty-eight cases were analyzed and submitted to histopathological and immunohistochemical analysis by p16. RESULTS: Of the 58 cases evaluated, 40 were men and 18 women, with a mean age of 63.2 years. p16 immunoexpression was positive in 46.55%. CONCLUSION: The prevalence of HPV infection is high in esophageal squamous cell carcinoma presenting in almost half of the cases (46.55%), without gender differentiation.

THE ROLE OF CONVENTIONAL ECHOENDOSCOPY (EUS) IN THERAPEUTIC DECISIONS IN PATIENTS WITH NEUROENDOCRINE GASTROINTESTINAL TUMORS.

BACKGROUND: Gastrointestinal neuroendocrine tumors are rare, usually presented as subepithelial or polypoid tumors. Accurate diagnosis and indication of the type of resection are still challenging. AIM: To determine the effectiveness of echoendoscopy in determining the depth of the lesions (T) identified by endoscopy in order to evaluate surgical and/or endoscopic indication, and to evaluate the results of endoscopic removal in the medium term. METHODS: Twenty-seven patients were included, all of whom underwent echoendoscopy for TN tumor staging and the evaluation of possible endoscopic resection. The parameters were: lesion size, origin layer, depth of involvement and identified perilesional adenopathies. The inclusion criteria for endoscopic resection were: 1) high surgical risk; 2) those with NET <2 cm; 3) absence of impairment of the muscle itself; and 4) absence of perilesional adenopathies in echoendoscopy and in others without distant metastases. Exclusion criteria were TNE> 2 cm; those with infiltration of the muscle itself; with perilesional adenopathies and distant metastases. The techniques used were: resection with polypectomy loop; mucosectomy with saline injection; and mucosectomy after ligation with an elastic band. The anatomopathological study of the specimens included evaluation of the margins and immunohistochemistry (chromogranin, synaptophysin and Ki 67) to characterize the tumor. Follow-up was done at 1, 6 and 12 months. RESULTS: Resections with polypectomy loop were performed in 15 patients; mucosectomy in five; mucosectomy and ligation with elastic band in three and the remaining four were referred for surgery. The anatomopathological specimens and immunohistochemical analyzes showed positive chromogranin and synaptophysin, while Ki 67 was less than 5% among all cases. The medium-term follow-up revealed three recurrences. The average size of tumors in the stomach was 7.6 mm and in the duodenum 7.2 mm. Well-demarcated, hypoechoic, homogeneous lesions occurred in 75%; mucous layer in 80%; and the deep and submucosal mucosa in 70%. CONCLUSIONS: Echoendoscopy proved to be a good method for the study of subepithelial lesions, being able to identify the layer affected by the neoplasm, degree of invasion, echogenicity, heterogeneity, size of the lesion and perilesional lymph node involvement and better indicate the treatment option.

Prognostic significance of CD133 and ABCB5 expression in papillary thyroid carcinoma.

Expression of CD133 and ABCB5 is associated with tumor aggressiveness, but evidence in papillary thyroid cancer (PTC) is lacking. We correlated CD133 and ABCB5 expression with pathological characteristics and factors of worse prognosis in PTC. Samples of 119 PTCs and 40 controls (goiters) were distributed in 8 tissue microarray blocks and evaluated with immunohistochemistry using anti-CD133 and anti-ABCB5 antibodies. The expression of each marker alone and combined was analyzed against pathological characteristics and factors of worse prognosis in PTC. Expression of CD133 alone (19 tumors, 16.0%) was more frequent in patients with versus without lymph node metastases (P=0.024). Expression of ABCB5 alone (n=95, 83.3%) was associated with larger tumor size (P=0.045). CD133-ABCB5 coexpression was not associated with pathological characteristics or factors of worse prognosis in PTC.

Development of an application for mobile phones (App) based on the collaboration between the Spanish Society of Rheumatology and Spanish Society of Family Medicine for the referral of systemic autoimmune diseases from primary care to rheumatology. / Desarrollo de una aplicación para teléfonos móviles (app) basada en la colaboración Sociedad Española de Reumatología/Sociedad Española de Medicina de Familia y Comunitaria para derivación de enfermedades autoinmunes sistémicas.

Management of systemic autoimmune diseases is challenging for physicians in their clinical practice. Although not common, they affect thousands of patients in Spain. The family doctor faces patients with symptoms and non-specific cutaneous, mucous, joint, vascular signs or abnormal laboratory findings at the start of the disease process and has to determine when to refer patients to the specialist. To aid in disease detection and better referral, the Spanish Society of Rheumatology and the Spanish Society of Family Medicine has created a group of experts who selected 26 symptoms, key signs and abnormal laboratory findings which were organized by organ and apparatus. Family doctors and rheumatologists with an interest in autoimmune systemic diseases were selected and formed mixed groups of two that then elaborated algorithms for diagnostic guidelines and referral. The algorithms were then reviewed, homogenized and adapted to the algorithm format and application for cell phone (apps) download. The result is the current Referral document of systemic autoimmune diseases for the family doctor in paper format and app (download). It contains easy-to-use algorithms using data from anamnesis, physical examination and laboratory results usually available to primary care, that help diagnose and refer patients to rheumatology or other specialties if needed.

MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY (MRCP) VERSUS ENDOSONOGRAPHY-GUIDED FINE NEEDLE ASPIRATION (EUS-FNA) FOR DIAGNOSIS AND FOLLOW-UP OF PANCREATIC INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS.

BACKGROUND: Intraductal papillary mucinous tumor (IPMN) are being diagnosed with increasing frequency. Computerized tomography scanning is commonly used as the primary imaging modality before surgery nonetheless magnetic resonance cholangiopancreatography (MRCP) provides better characterization. Endosonography-guided fine needle aspiration (EUS-FNA) has emerged as a way to reach pathological diagnose. AIM: To compare results of both methods with surgical pathology findings for classification of IPMN. METHODS: Thirty-six patients submitted to surgical resection with preoperative suspect of IPMN were submitted preoperatively to MRCP and EUS-FNA. Images obtained were analyzed according to a classification determined for each method. ROC curve was used for statistical analysis, that compared the images tests with the purpose of finding the best method for diagnosis and classification of IPMN. RESULTS: Sixteen patients underwent pancreatoduodenectomy, 16 to subtotal pancreatectomy and only four laparotomy. Pathological diagnosis was IPMN (n=33) and pancreatic intraepithelial neoplasia type 2 (n=3). Twenty-nine revealed non-invasive neoplasia and invasive form in four patients. MRCP and EUS-FNA have correctly diagnosed and classified (type of IPMN), in 62.5% and 83.3% (p=0.811), the affected segment location in 69% and 92% (p=0.638) and identification of nodules and/or vegetation presence in 45% and 90% (p=0.5). Regarding to histopathological diagnosis by EUS-FNA the sensitivity was 83.3%; specificity was 100%; positive predictive value was 100%; negative predictive value was 33.3% and accuracy was 91.7%. CONCLUSIONS: There was no significant difference in the diagnosis of IPMN. However, EUS-FNA showed better absolute results than MRCP to identify nodule and/or vegetation.

Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects.

CD137-targeting immune therapy, which activates anti-tumor T effector cell responses, seems to be an attractive concept in clinical oncology. Recent evidence has demonstrated that tumor cells besides T cells and antigen-presenting cells are able to express CD137 and CD137L. Here we aimed to identify CD137/CD137L expression in established colon cancer cell lines and primary tumors (UICC stages I-IV) from patients with documented long-term follow-up. CD137/CD137L expression was highly upregulated in early to late-stage tumors while the inverse was observed in patient-derived peripheral blood mononuclear cells. High CD137L expression within primary tumors was mediated by tumor cells and significantly correlated with the occurrence of distant metastases and shortened survival in advanced stages of disease (UICC stage IV). Interestingly, induced tumor cell signaling via CD137L on its surface in vitro resulted in dual effects: (i) reduced tumor cell proliferation suggesting inhibitory signaling in all investigated cancers and (ii) increased epithelial-to-mesenchymal transition signaling events. Taken together CD137/CD137L expression was stage-dependently upregulated with shortened survival in patients with highly CD137L-expressing tumors. Our clinical and experimental data suggest that colon cancer cells predominantly express CD137L and thereby have negative impact on overall survival through a process of reverse signaling. Beside agonistic CD137 antibody therapy to foster T effector cell responses, CD137L-mediated intervention strategies may become instrumental to circumvent relapsed tumor growth through induced epithelial-to-mesenchymal transition and consecutive metastases formation.

Risk Factors for Persistence or Recurrence of High-Grade Cervical Squamous Intraepithelial Lesions / Fatores de risco na persistência ou recidiva da Lesão escamosa intraepitelial de alto grau (LIEAG)

ABSTRACT Objectives: to evaluate whether the colposcopic lesion size , age, kind of surgery, the status of the surgical margins and the expression of the p16 and Ki-67 immunomarkers are risk factors for persistence or recurrence of the lesion. Methods: a cross-sectional, observational, retrospective study of patients submitted to cold knife conization (CKC) or the loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2 or 3. The colposcopic lesion size, age, surgical method, involvement of the surgical margins, and p16/Ki-67 immunomarker expression were analyzed in relation to lesion persistence and recurrence. Results: seventy-one women were treated with cold knife conization and 200 were treated with loop electrosurgical excision. Of these, 95 had cervical intraepithelial neoplasia 2, 173 had cervical intraepithelial neoplasia 3, 183 had free surgical margins, 76 had compromised margins, and 12 showed damage by processing artifact or fragments. Among the 76 cases with positive margins, 55, 11, and 10 showed endocervical margin involvement, ectocervical margin involvement, and both endocervial and ectocervical margin involvement, respectively. Of the 264 followed-up patients, 38 had persistent or recurrent disease. A multiple logistic regression indicated that positive endocervical margins are the only independent risk factor for the persistence/recurrence of cervical intraepithelial neoplasia. No significant association was identified between the colposcopic lesion size, age, surgery type, or p16/Ki-67 immunomarker expression and lesion persistence or recurrence.

RESUMO Objetivos: avaliar se o status das margens, idade, tamanho da lesão colposcópica, tipo de cirurgia e expressão dos marcadores p16/Ki-67 são fatores de risco na persistência ou recidiva da LIEAG. Métodos: um estudo de corte transversal, observacional com coleta de dados retrospectivos de pacientes submetidas a conização a frio (CF) ou exérese da zona de transformação por cirurgia de alta frequência EZT por NIC2/3. Foram analisados os seguintes fatores em relação a persistência ou recidiva: comprometimento das margens, idade, tamanho da lesão, tipo de cirurgia e coexpressão dos imunomarcadores p16 e Ki-67. Resultados: 271 mulheres tratadas com CF (71) e EZT (200), onde 95 apresentavam NIC 2 e 173 NIC 3, 183 apresentaram margens cirúrgicas livres, 76 comprometidas e 12 prejudicadas por artefatos ou fragmentação. Das 76 pacientes com margens comprometidas, 55 foram endocervical, 11 ectocervical e 10 ambas as margens. Das 264 pacientes que tiveram seguimento, 38 persistiram ou recidivaram a doença. A regressão logística múltipla indicou ser a margem endocervical comprometida o único fator independente de risco de persistência/recorrência da NIC (p<0,001). Não houve associação significativa entre a idade, o tamanho da lesão colposcópica, o tipo de cirurgia e a expressão dos imunomarcadores p16/Ki-67 e a persistência ou recorrência da doença. Conclusão: entre os fatores estudados associados com persistência ou recorrência, somente a margem endocervical comprometida provou ser significativamente um fator risco para persistência ou recorrência da lesão.

Macroscopic and histological analysis on endoscopically resected rectal lesions / Análise macroscópica e histológica de lesões retais endoscopicamente ressecadas

ABSTRACT BACKGROUND: Colorectal cancer is among the most common malignancies worldwide. Colonoscopy is the examination of choice for the prevention of CRC because of its great diagnostic and, especially, therapeutic capacity in relation to adenomatous lesions. AIMS: This study aimed to analyze the prevalence, macroscopic, and histological characteristics of polypoid rectal lesions resected through endoscopic techniques and assess whether endoscopic therapy is safe and efficient for treating lesions located in the rectum. METHODS: This is a retrospective observational study with an analysis of the medical records of all patients undergoing resection of rectal polyps. RESULTS: A total of 123 patients with rectal lesions were evaluated, with 59 men and 64 women of mean age 56 years. All patients underwent endoscopic resection: 70% with polypectomy and 30% with wide mucosectomy. Complete colonoscopy with removal of the entire rectal lesion occurred in 91%, while in 5% the preparation was inadequate and poor clinical conditions were an impeditive factor, and in 4% surgical treatment was indicated because there was an infiltrative lesion with central ulceration. Histological evaluation showed adenomas in 3.25%, hyperplasia in 7.32%, and hamartoma in 0.81%; low-grade dysplasia was identified in 34.96%, high-grade dysplasia in 51.22%, and adenocarcinoma in 1.63%, while one case (0.81%) was classified as erosion. CONCLUSIONS: Polyps in the rectum are common and were found in 37% of these colonoscopies. Adenomas with dysplasia were the most common form of Colorectal cancer . Therapeutic colonoscopy proved to be a safe and efficient method for the complete treatment of rectal lesions.

RESUMO RACIONAL: O câncer colorretal (CCR) está entre as neoplasias mais comuns em todo o mundo. A colonoscopia é o exame de escolha para prevenção por sua grande capacidade diagnóstica e, principalmente, terapêutica em relação às lesões adenomatosas. OBJETIVOS: Analisar a prevalência, as características macroscópicas e histológicas das lesões polipoides retais ressecadas por técnicas endoscópicas e avaliar se a terapia endoscópica é segura e eficaz para o tratamento de lesões localizadas no reto. MÉTODOS: Estudo observacional retrospectivo com análise dos prontuários de todos os pacientes submetidos à ressecção de pólipos retais. RESULTADOS: Foram avaliados 123 pacientes com lesões retais: 59 homens e 64 mulheres com idade média de 56 anos. Todos os pacientes foram submetidos à ressecção endoscópica: 70% com polipectomia e 30% com mucosectomia ampla. A colonoscopia completa com retirada de toda a lesão retal ocorreu em 91%, enquanto em 5% o preparo foi inadequado e as más condições clínicas foram fator impeditivo, e em 4% o tratamento cirúrgico foi indicado por haver lesão infiltrativa com ulceração central. A avaliação histológica mostrou adenomas em 3,25%, hiperplasia em 7,32% e hamartoma em 0,81%; displasia de baixo grau foi identificada em 34,96%, displasia de alto grau em 51,22% e adenocarcinoma em 1,63%, enquanto um caso (0,81%) foi classificado como erosão. CONCLUSÕES: Pólipos no reto são comuns e foram encontrados em 37% das colonoscopias. Adenomas com displasia foram a forma mais comum de câncer colorretal. A colonoscopia terapêutica mostrou-se método seguro e eficiente para o tratamento completo das lesões retais.