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BACKGROUND Gastric cancer (GC) is a highly heterogeneous disease, and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups. However, the costs and technical complexity of molecular methodologies remains an obstacle to its adoption, and their clinical significance by other approaches needs further evidence. AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry (IHC) and in situ hybridization (ISH). METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent. Microsatellite instability (MSI) status, E-cadherin, and p53 expression were analyzed by IHC, and Epstein-Barr virus (EBV) by ISH. Tissue microarrays were constructed for analysis. Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas (TCGA) Research Network Group and Asian Cancer Research Group (ACRG) classification systems. RESULTS A total of 287 GC patients were included. Based on IHC and ISH analysis, five profiles were defined as follows: E-cadherin aberrant (9.1%), MSI (20.9%), p53 aberrant (36.6%), EBV positivity (10.5%), and p53 normal (31%), which corresponded to tumors that showed no alteration in another profile. A flowchart according to the TCGA and ACRG classifications were used to define the subtypes, where clinical and pathological characteristics associated with GC subtypes were evidenced. Proximal location (P < 0.001), total gastrectomy (P = 0.001), and intense inflammatory infiltrate (P < 0.001) were characteristics related to EBV subtype. MSI subtype was predominantly associated with advanced age (P = 0.017) and the presence of comorbidities (P = 0.011). While Lauren diffuse type (P < 0.001) and advanced stage (P = 0.029) were related to genomically stable (GS) subtype. GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival (DFS) and overall survival (OS) than other subtypes. Conversely, MSI subtype of GC had better survival in both classifications. Type of gastrectomy, pT and the TCGA subtypes were independent factors associated to DFS and OS. CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis, resembling the subtypes of the molecular classifications. Accordingly, this method of classification may represent a viable option for use in a clinical setting.

Background Epstein–Barr virus (EBV) positive gastric cancer (GC) has been described as a distinct molecular subtype of the disease, especially associated with gastric carcinoma with lymphoid stroma (GCLS). The possibility that EBV associated GC (EBVaGC) had better prognosis and may be susceptible to immunotherapy has increased the interest in this subtype. However, immune checkpoint and survival of EBVaGC are still controversial, especially with regard to GCLS and conventional gastric adenocarcinoma (CGA). This study aimed to evaluate the clinicopathological characteristics, immunohistochemical profiles and prognosis of EBVaGC according to the histological type GCLS and CGA. Methods we retrospectively evaluated a series of EBVaGC who underwent gastrectomy with D2-lymphadenectomy. Biomarkers and tumor-infiltrating cells were evaluated by immunohistochemistry. PD-L1 was evaluated using a combined positive score (CPS). Results From a total of 30 EBVaGC, 14 (46.7%) were identified as GCLS and 16 (53.3%) as CGA (9 Intestinal, 6 diffuse, 1 undetermined). There were no significant differences in age, sex, and pTNM between GCLS and CGA. CPS-positivity and high-CD8+ was significantly higher in GCLS compared with CGA (P = 0.007 and P = 0.005, respectively). Diffuse EBVaGC had worse survival than intestinal type (P = 0.020). There was no difference in survival between GCLS and intestinal CGA (P = 0.260). In multivariate analysis, CPS and pN status were related with survival in EBVaGC. Conclusions CGLS was associated with a predominance of CD8+ cell infiltration and PD-L1 expression. CPS and lymph node metastasis were independent factors associated with prognosis in EBVaGC. These results suggest that specifically EBV-positive GCLS may be prime candidates for PD-1 directed therapy.

Dioctophymosis is the disease caused by Dioctophyma renale, a large nematode, popularly known as giant kidney worm, and whose definitive hosts are the domestic dog and many wild mammal species. There are some reports of maned wolf parasitism by D. renale, however, in most cases the reports are restricted to the finding of the parasite during necropsy, without clinical assessment. The present report aimed to describe the clinical-therapeutic, ultrasonographic and pathological aspects of D. renale parasitism in a free-ranging maned wolf, emphasizing the treatment with an association of doramectin, praziquantel, pyrantel pamoate, and febantel that resulted in complete elimination of the parasite.

The present study aimed to analyze the association between 18F-fluorodeoxyglucose (FDG) uptake and histologic panel in esophagogastric adenocarcinoma.We retrospectively enrolled 26 patients with histologically confirmed esophageal, gastroesophageal junction and gastric adenocarcinoma that have been submitted to pretreatment FDG-PET/CT. We collected the cancer tissue sample of each patient and performed immunohistochemical analyses of the glucose transport protein 1 (GLUT-1), Ki-67, cysteine aspartate-specific proteinases (Caspase)-3 and hexokinase-1, and evaluated the association of these parameters with FDG uptake. The FDG uptake was measured by tumor standardized uptake value (SUV), metabolic tumor volume (MTV), and Total Lesion Glycolysis (TLG). Besides, we analyzed the association of FDG uptake and tumor location, Lauren's histologic subtype, grade of cellular differentiation and intratumoral inflammatory infiltrate.We found a positive association between GLUT-1 with SUV and TLG, Caspase-3 and SUV and inflammation grade with SUV.Tumor inflammation infiltrate, GLUT-1 and Caspase-3 correlated with 18F-FDG uptake in PET/CT in esophagogastric adenocarcinoma. These findings may help understand the pathologic PET/CT significance in cancer. Understanding the meaning of the 18F-FDG uptake in the field of tumor histologic and immunohistochemistry features is essential to allow the evolution of PET/CT application in esophageal and gastric carcinomas.

Aim: The PHLDA (pleckstrin homology like domain, family A) gene family encodes proteins capable of inhibiting AKT (serine/threonine kinase) signaling through phosphoinositol binding competition. Results & methodology: Using in silico analysis, we found that Luminal A and B patients' short relapse-free survival was associated with low PHLDA1 or PHLDA3 and high PHLDA2 expression. In a cohort of 393 patients with luminal breast cancer evaluated by immunohistochemistry on tissue microarrays, we found a direct association of PHLDA3 expression with hormonal therapy response (p = 0.013). Conclusion: Our findings provide new information on the role played by the PHLDA family members as prognostic markers in breast cancer, and more importantly, we provide evidence that they might also predict a response to endocrine therapy.

The combined positive score (CPS) and tumor proportion score (TPS) have been developed to evaluate programmed death ligand-1 (PD-L1) expression, especially due to the potential benefit of the targeted therapy. However, the prognostic value of PD-L1 scoring systems in gastric cancer (GC) remains unclear. This study aimed to evaluate PD-L1 expression according to CPS and TPS in curative resected GC patients and its correlation with prognosis. We retrospectively evaluated 284 GC patients who underwent D2-gastrectomy by tissue microarray. PD-L1 expression was analyzed by immunohistochemistry. PD-L1 positivity by CPS and TPS was observed in 45 (15.8%) and 34 (12%) patients, respectively. Larger tumor size (p = 0.028), undetermined Lauren type (p < 0.001), and heavy inflammatory infiltrate (p = 0.009) were associated with CPS-positive GC. TPS-positive were more frequent in patients with larger tumor size (p = 0.004), undetermined type (p < 0.001), moderate/severe inflammatory infiltrate (p = 0.001), total gastrectomy (p = 0.036), and poorly differentiated histology (p = 0.025). No differences were observed in the pT, pN, and pTNM status according to the PD-L1 scores. Both scores were associated with Epstein-Barr virus positivity, microsatellite instability and p53-normal expression. The disease-free survival (DFS) was worse for CPS-negative compared to CPS-positive group (p = 0.052). No difference was observed between TPS-positive and negative groups (p = 0.436). Total gastrectomy, advanced pT status, and CPS-negative were independent factor for worse survival in GC. CPS was an independent prognostic factor for survival and could be used as a prognostic biomarker in patients with resectable GC.

The importance of targeted therapy and interest in the study of predictive markers in gastric cancer (GC) have increased in recent years with the use of anti-HER2 therapy and immunotherapy with anti-PD1/PD-L1 for microsatellite instability (MSI) and PD-L1 + tumors. However, the behavior of remnant GC (RGC) in this scenario is poorly reported. Thus, this study aims to evaluate the clinicopathological characteristics and prognosis of RGC and its association with the expression of current markers for targeted therapy. All RGC resections performed in a single center from 2009 to 2019 were retrospectively reviewed. As a comparison group, 53 primary proximal GC (PGC) who underwent total D2-gastrectomy were selected. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry. Combined Positive Score (CPS) was used to determine PD-L1 positivity. A total of 40 RGC were included. RGC patients were older (p = 0.001), had lower BMI (p = 0.001) and number of resected lymph nodes (p

Highlights • Ménétrier’s disease (MD) is a rare condition. Its incidence remains undetermined. • MD is frequently associated with H. pylori infection, hypergastrinemia and hypoalbuminaemia. • The gastric mucosal usually presents giant rugal folds with polypoid appearance on upper endoscopy. • Clinical, laboratory, endoscopic and histopathological findings are paramount for reaching the diagnosis of MD. • MD should be suspected in all cases of upper gastrointestinal symptoms and hypertrophied gastric mucosa., Introduction Ménétrier’s disease is a rare condition, frequently associated with Helicobacter pylori infection, hypergastrinemia and hypoalbuminaemia. Presentation of the case A case of a 55 years-old female patient with a previous diagnosis of pernicious anemia complaining of epigastric discomfort, hyporexia, vomiting, and weight loss is reported. Endoscopy showed multiple gastric polyploid formations and Helicobacter pylori infection was detected. Laboratory tests showed elevated gastrin serum levels and presence of antibodies antiparietal cells, as well as microcytic hypochromic anemia compatible with chronic iron deficiency. Albumin serum level was slightly decreased. Full thickness biopsy performed via echoendoscopy reported gastritis cystica/polyposa profunda. Given the association of diffuse involvement of the entire stomach, the possibility of developing malignant disease and the clinical symptoms, the patient underwent laparoscopic total gastrectomy with Roux-en-Y reconstruction. The surgical specimen showed the mucosa hyperemic and swollen, with prominent gastric folds. Hyperplastic elongation of gastric foveolas associated with disappearance of oxyntic glands was compatible with Ménétrier’s disease. Discussion The Ménétrier’s disease diagnosis may be tricky, especially when an unusual endoscopic presentation is associated with other conditions that may mislead the diagnostic evaluation. The differential diagnoses were gastric malignancies, Zollinger-Ellison syndrome, massive gastric polyposis and gastritis cystica/polyposa profunda. Conclusion Clinical, laboratory, endoscopic and histopathological findings are paramount for reaching the diagnosis of Ménétrier’s disease, but it should be suspected in all cases of upper gastrointestinal symptoms and hypertrophied gastric mucosa.

Introduction: Papillary thyroid carcinoma (PTC) have high node metastasis rates. Occasionally after thyroidectomy, the pathological report reveals node metastasis unintentionally resected. The present study aimed to evaluate the prognosis of these patients. Methods: A retrospective cohort of patients submitted to thyroidectomy with or without central compartment neck dissection (CCND) due to PTC with a minimum follow-up of five years. Results: A total of 698 patients were included: 320 Nx, 264 pN0-incidental, 37 pN1a-incidental, 32 pN0-CCND and 45 pN1a-CCND. Patients with node metastasis were younger, had larger tumors, higher rates of microscopic extra-thyroidal extension, and angiolymphatic invasion and most received radioiodine therapy. Treatment failure was higher in patients pN1a-incidental and pN1a-CCND (32% and 16%, respectively; p < 0.001—Chi-square test). Disease-free survival (DFS) was lower in patients pN1a-incidental compared to patients Nx and pN0-incidental (p < 0.001 vs. Nx and pN0-incidental and p = 0.005 vs. pN0-CCND) but similar when compared to patients pN1a-CCND (p = 0.091)—Log-Rank test. Multivariate analysis demonstrated as independent risk factors: pT4a (HR = 5.524; 95%CI: 1.380–22.113; p = 0.016), pN1a-incidental (HR = 3.691; 95%CI: 1.556–8.755; p = 0.003), microscopic extra-thyroidal extension (HR = 2.560; 95%CI: 1.303–5.030; p = 0.006) and angiolymphatic invasion (HR = 2.240; 95%CI: 1.077–4.510; p = 0.030). Conclusion: Patients that were pN1a-incidental were independently associated with lower DFS.

The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC). We aimed to investigate the clinicopathological characteristics and prognosis of GC patients according to these profiles. GC patients who underwent gastrectomy with D2 lymphadenectomy were eligible. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry (IHC). Patients were grouped as follows: HER2+ group, immunotherapy (IT) group (MSI and/or PD-L1+), and non-targeted therapy (NTT) group (stable microsatellite and HER2/PD-L1−). Among 282 patients, 50 (17.7%) were HER2+ and 79 (28%) MSI/PD-L1+. Fifteen had HER2+ and MSI/PD-L1+, while 168 (59.6%) were in the NTT group. HER2+ GCs were related to male gender (p = 0.007), intestinal type (p = 0.001) and less advanced pTNM stage (p = 0.029). Older age (p = 0.003), subtotal gastrectomy (p = 0.025), intestinal type (p = 0.008), pN0 status (p = 0.002) and less advanced pTNM stage (p = 0.001) were associated with the IT group. IT GC had better disease-free survival (DFS) and overall survival than the NTT group (p = 0.015 and p = 0.027, respectively). Concerning patients eligible for the standard adjuvant therapy, the treatment impacted positively on DFS for HER2+ and NTT groups (p = 0.003 and p = 0.042, respectively). No difference in DFS was seen between IT patients who received perioperative/adjuvant therapy and those treated only with surgery (p = 0.160). GC patients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs.

BACKGROUND Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. METHODS All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. RESULTS Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p

The pathologic classification of pseudomyxoma peritonei is controversial. This study aimed to standardize the histopathological evaluation of pseudomyxoma peritonei and identify the clinicopathological factors associated with survival.A pathologic review was performed to systematize the pathology report and verify the relationship between clinical features and survival. Terminology was based on the World Health Organization and Peritoneal Surface Oncology Group International definitions. Preoperative serum levels of carcinoembryonic antigen, CA19-9, and CA-125 were evaluated to determine their association with overall survival (OS) and ability to predict CC0-1 cytoreduction.Among 109 patients with carcinomas resulting from primary appendiceal neoplasms, 72 had pseudomyxoma peritonei of appendiceal origin and underwent debulking surgery. CC0-1 cytoreduction and CC2-3 cytoreduction were achieved in 61% and 39% of patients, respectively. Patients in the CC0-1 and CC2-3 groups had an OS of 122.80 and 32.92 mo, respectively. The histologic grade was associated with CC0-1 cytoreduction; however, it did not influence OS. Patients with CC0-1 cytoreduction, acellular mucin, and low-grade lesions had better disease-free survival. Higher preoperative CA19-9 levels were associated with poor OS. Normal carcinoembryonic antigen values were associated with 100% sensitivity for predicting CC0-1. CA19-9 levels of 625 U/mL were associated with a low possibility of predicting CC0-1.Histologic grades are associated with disease-free survival when CC0-1 cytoreduction is achieved. Normal preoperative CA19-9 levels were associated with a better OS. CC0-1 cytoreduction is the main determinant of longer survival.

Despite advances in therapies, the prognosis of patients with advanced gastric cancer (GC) remains poor. Several studies have demonstrated the expression of estrogen receptor alpha (ERa); however, its significance in GC remains controversial. The present study aims to report a case series of GC with ERa-positive expression and describe their clinicopathological characteristics and prognosis.We retrospectively evaluated patients with GC who underwent gastrectomy with curative intent between 2009 and 2019. ERa expression was assessed by immunohistochemistry through tissue microarray construction. Patients with ERa-negative gastric adenocarcinoma served as a comparison group.During the selected period, 6 (1.8%) ERa-positive GC were identified among the 345 GC patients analyzed. All ERa-positive patients were men, aged 34-78 years, and had Lauren diffuse GC and pN+ status. Compared with ERa-negative patients, ERa-positive patients had larger tumor size (p=0.031), total gastrectomy (p=0.012), diffuse/mixed Lauren type (p=0.012), presence of perineural invasion (p=0.030), and lymph node metastasis (p=0.215). The final stage was IIA in one case, IIIA in three cases, and IIIB in two cases. Among the six ERa-positive patients, three had disease recurrence (peritoneal) and died. There was no significant difference in survival between ERa-positive and ERa-negative groups.ERa expression is less common in GC, is associated with diffuse histology and presence of lymph node metastasis, and may be a marker related to tumor progression and worse prognosis. Also, a high rate of peritoneal recurrence was observed in ERa-positive patients.Apesar do avanço nas terapias, o prognóstico de pacientes com câncer gástrico (CG) avançado permanece ruim. Vários estudos demonstraram a expressão do receptor de estrogênio alfa (REa), porém seu significado no CG permanece controverso. relatar uma série de casos de CG com expressão de REa-positivo, e descrever suas características clínicopatológicas e prognóstico.Avaliamos retrospectivamente os pacientes com CG submetidos à gastrectomia com intenção curativa entre 2009 e 2019. A expressão do REa foi avaliada por imuno-histoquímica por meio da construção de microarranjos de tecido (TMA). Pacientes com adenocarcinoma gástrico ERa-negativos serviram como grupo comparação.No período selecionado, foram identificados 6 (1,8%) CG REa-positivos entre os 345 CG analisados. Todos os ERa-positivos eram homens, com idades entre 34-78 anos, tinham CG do tipo difuso de Lauren e pN+. Comparado aos REa-negativos, os CG REa-positivos associaram-se a maior diâmetro (p=0,031), gastrectomia total (p=0,012), tipo de Lauren difuso/misto (p=0,012), presença de invasão perineural (p=0,030) e metástase linfonodal (p=0,215). O estágio final foi o IIA em um caso; IIIA em três e IIIB em dois casos. Entre os 6 pacientes REa -positivos, 3 tiveram recorrência da doença (peritoneal) e morreram. Não houve diferença significativa na sobrevida entre os grupos REa-positivo e negativo.A expressão do REa é menos comum no CG, estando associada à histologia difusa e presença de metástases linfonodal, podendo servir como um marcador relacionado à progressão tumoral e pior prognóstico. Além disso, uma alta taxa de recorrência peritoneal foi observada em pacientes ERa-positivos.

OBJECTIVE To determine the implication of the new AJCC staging system for pT classification in a cohort of patients with SCC of the lip mucosa and compare it to other oral cavity sites. METHODS Retrospective cohort of 744 patients treated between 2002 and 2017, by the Head and Neck Surgery Department of the University of Sao Paulo. RESULTS Of 95 lip patients, 42 had pT upstage (58.1% of pT1 to pT2-3 and 50% of pT2 to pT3). Similar DFS/OS observed for those pT1 maintained or upstaged to pT2-3, pT2 patients upstaged to pT3 presented worse OS (49.4% versus 92.3%, P = .032). The comparison between lip and other mouth topographies, denoted better prognosis for pT1-2, but not for pT3-4a. Lip tumors had lower DOI, rates of perineural/angiolymphatic invasion, nodal metastasis, recurrence, and death. CONCLUSION The inclusion of DOI to the new pT classification better stratifies patients with SCC of the lip mucosa upstaged to pT3 by assessing inferior OS. LEVEL OF EVIDENCE 3 Laryngoscope, 131:E2770-E2776, 2021.

Background: It has been demonstrated that for oral cavity squamous cell carcinoma (SCC) as tumor thickness increases, there are lower rates of survival. Several molecular factors have been studied to determine this invasive behavior, including microRNAs, that play a role in the tumor microenvironment. Methods: The aim of this study is evaluate the role of extracellular matrix remodeling, as well as the involvement of microRNAs, in the process of oral cavity SCC carcinogenesis. This was a retrospective study with patients operated on for SCC of the oral cavity, in addition to a group of oral mucosa samples from paired patients. RNA extraction was performed, followed by complementary DNA amplification of microRNAs related to adhesion, migration, cell proliferation, apoptosis, and constituents of the extracellular matrix. We also performed immunohistochemical reactions for markers involved in the same biological processes. Results: High expression of miR-21-5p and miR-106-5p and low expression of miR-320a and miR-222-3p were predictors of malignancies and mir21-5p, individually, showed the best differentiation between the groups (AUC = 0.972). Regarding the immunohistochemical markers, there was greater expression of p53, EGFR, metalloproteinase-2 (MMP-2), laminin beta, Ki-67 and CD34 in the tumor cells than in the healthy mucosa. Furthermore, increased expression of MMP-2, metalloproteinase-9 (MMP-9), laminin alpha and laminin beta in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane were observed. Conclusions: These results demonstrate the biological effects of microRNAs on the carcinogenesis of SCC of the oral cavity as well as the intense modification of the tumor microenvironment.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

RESUMO - RACIONAL: Apesar do avanço nas terapias, o prognóstico de pacientes com câncer gástrico (CG) avançado permanece ruim. Vários estudos demonstraram a expressão do receptor de estrogênio alfa (REa), porém seu significado no CG permanece controverso. OBJETIVO: relatar uma série de casos de CG com expressão de REa-positivo, e descrever suas características clínicopatológicas e prognóstico. MÉTODOS: Avaliamos retrospectivamente os pacientes com CG submetidos à gastrectomia com intenção curativa entre 2009 e 2019. A expressão do REa foi avaliada por imuno-histoquímica por meio da construção de microarranjos de tecido (TMA). Pacientes com adenocarcinoma gástrico ERa-negativos serviram como grupo comparação. RESULTADOS: No período selecionado, foram identificados 6 (1,8%) CG REa-positivos entre os 345 CG analisados. Todos os ERa-positivos eram homens, com idades entre 34-78 anos, tinham CG do tipo difuso de Lauren e pN+. Comparado aos REa-negativos, os CG REa-positivos associaram-se a maior diâmetro (p=0,031), gastrectomia total (p=0,012), tipo de Lauren difuso/misto (p=0,012), presença de invasão perineural (p=0,030) e metástase linfonodal (p=0,215). O estágio final foi o IIA em um caso; IIIA em três e IIIB em dois casos. Entre os 6 pacientes REa -positivos, 3 tiveram recorrência da doença (peritoneal) e morreram. Não houve diferença significativa na sobrevida entre os grupos REa-positivo e negativo. CONCLUSÃO: A expressão do REa é menos comum no CG, estando associada à histologia difusa e presença de metástases linfonodal, podendo servir como um marcador relacionado à progressão tumoral e pior prognóstico. Além disso, uma alta taxa de recorrência peritoneal foi observada em pacientes ERa-positivos. ABSTRACT - BACKGROUND: Despite advances in therapies, the prognosis of patients with advanced gastric cancer (GC) remains poor. Several studies have demonstrated the expression of estrogen receptor alpha (ERa); however, its significance in GC remains controversial. AIM: The present study aims to report a case series of GC with ERa-positive expression and describe their clinicopathological characteristics and prognosis. METHODS: We retrospectively evaluated patients with GC who underwent gastrectomy with curative intent between 2009 and 2019. ERa expression was assessed by immunohistochemistry through tissue microarray construction. Patients with ERa-negative gastric adenocarcinoma served as a comparison group. RESULTS: During the selected period, 6 (1.8%) ERa-positive GC were identified among the 345 GC patients analyzed. All ERa-positive patients were men, aged 34-78 years, and had Lauren diffuse GC and pN+ status. Compared with ERa-negative patients, ERa-positive patients had larger tumor size (p=0.031), total gastrectomy (p=0.012), diffuse/mixed Lauren type (p=0.012), presence of perineural invasion (p=0.030), and lymph node metastasis (p=0.215). The final stage was IIA in one case, IIIA in three cases, and IIIB in two cases. Among the six ERa-positive patients, three had disease recurrence (peritoneal) and died. There was no significant difference in survival between ERa-positive and ERa-negative groups. CONCLUSIONS: ERa expression is less common in GC, is associated with diffuse histology and presence of lymph node metastasis, and may be a marker related to tumor progression and worse prognosis. Also, a high rate of peritoneal recurrence was observed in ERa-positive patients.

SARS-CoV-2 pandemics have been massively characterized on a global scale by the rapid generation of in-depth genomic information. The main entry gate of SARS-CoV-2 in human cells is the angiotensin-converting enzyme 2 (ACE2) receptor. The expression of this protein has been reported in several human tissues, suggesting a correlation between SARS-CoV-2 organotropism and ACE2 distribution. In this study, we selected (a series of) 90 patients who were submitted to surgery for tumor removal between the beginning of the SARS-CoV-2 pandemic and the closure of operating rooms (by the end of March 2020) in two different countries—Portugal and Brazil. We evaluated the expressions of ACE2 and furin (another important factor for virus internalization) in colon (n = 60), gastric (n = 19), and thyroid (n = 11) carcinomas. In a subseries of cases with PCR results for SARS-CoV-2 detection in the peri-operatory window (n = 18), we performed different methodological approaches for viral detections in patient tumor samples. Our results show that colon and gastric carcinomas display favorable microenvironments to SARS-CoV-2 tropism, presenting high expression levels of ACE2 and furin. From the subseries of 18 cases, 11 tested positive via PCR detection performed in tumor blocks; however, a direct association between the ACE2 expression and SARS-CoV-2 infection was not demonstrated in cancer cells using histology-based techniques, such as immunohistochemistry or in situ hybridization. This study raises the possibility of ACE2-mediated viral tropism in cancer tissues to be clarified in future studies.

BACKGROUND Remnant gastric cancer (RGC) is a carcinoma arising in the stomach remnant after previous gastric resection. It is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer (PGC). However, as it is less frequent, its profile regarding the current molecular classifications of gastric cancer has not been evaluated. AIM To evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and RGC. METHODS Consecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels: Epstein-Barr virus in situ hybridization, immunohistochemistry for mismatch repair proteins (MutL homolog 1, MutS homolog 2, MutS homolog 6, and PMS1 homolog 2), p53 protein, and E-cadherin expression. Clinicopathological characteristics and survival of these patients were compared to 284 PGC patients. RESULTS A total of 40 RGC patients were enrolled in this study. Compared to PGC, older age (P < 0.001), male (P < 0.001), lower body mass index (P = 0.010), and lower hemoglobin level (P < 0.001) were associated with RGC patients. No difference was observed regarding Lauren's type and pathologic Tumor Node Metastasis stage between the groups. Regarding the profiles evaluated, EBV-positive tumors were higher in RGC compared to PGC (P = 0.039). The frequency of microsatellite instability, aberrant p53 immunostaining, and loss of E-cadherin expression were similar between RGC and PGC. Higher rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC (P < 0.001). According to the molecular classification, the subtypes were defined as EBV in nine (22.5%) cases, microsatellite instability in nine (22.5%) cases, genomically stable in one (2.5%) case, and chromosomal instability in 21 (52.5%) cases. There was no significant difference in survival between molecular subtypes in RGC patients. CONCLUSION RGC was associated with EBV positivity and higher rates of co-altered expression profiles compared to PGC. According to the molecular classification, there was no significant difference in survival between the subtypes of RGC.

Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLMs). Despite an improvement in results following resection, recurrence rates remain high. Many histopathological features have been reported as prognostic factors. Infiltrative borders are known to be associated with worse prognosis; however, margin size has never been evaluated together with the type of tumor border. In the present study, we analyzed the prognosis of patients with resected CRLM according to tumor growth pattern (TGP) and whether a larger margin size would bring any prognostic benefit.Medical records from a prospective database of 645 patients who underwent hepatic resection for CRLM between January 2004 and December 2019 at a single center were reviewed, and 266 patients were included in the analytic cohort. TGP (pushing or infiltrative) was evaluated regarding the impact in overall and disease-free survival. The impact of margin size (≤ or1 cm) on survival and hepatic recurrence according to TGP was also evaluated.TGP was defined as infiltrative in 182 cases (68.4%) and pushing in 84 patients (31.6%). Patients with infiltrative-type border presented worse overall survival and disease-free survival, as well as higher intrahepatic recurrence (p0.05). Larger margin size did not impact the prognosis of patients with infiltrative borders.Patients with infiltrative-type border present worse prognosis and higher intrahepatic recurrence. Larger margin size (1 cm) does not change the prognosis in patients with infiltrative border, showing that tumor biology is the most important factor for survival.

Resection is the mainstay of treatment for colorectal liver metastases (CRLMs). Many different histopathological factors related to the primary colorectal tumour have been well studied; however, histopathological prognostic factors related to CRLMs are still under evaluation.To identify histopathological factors related to overall survival (OS) and disease-free survival (DFS) in patients with resected CRLMs.A systematic review was performed with the following databases up to August 2020: PubMed, EMBASE, Web of Science, SciELO, and LILACS. The GRADE approach was used to rate the overall certainty of evidence by outcome.Thirty-three studies including 4,641 patients were eligible. We found very low certainty evidence that the following histopathological prognostic factors are associated with a statistically significant decrease in OS: presence of portal vein invasion (HR, 0,50 [95% CI, 0,37 to 0,68]; I²=0%), presence of perineural invasion (HR, 0,55 [95% CI, 0,36 to 0,83]; I²=0%), absence of pseudocapsule (HR, 0,41 [CI 95%, 0,29 to 0,57], p0,00001; I²=0%), presence of satellite nodules (OR, 0,45 [95% CI, 0,26 to 0,80]; I²=0%), and the absence of peritumoural inflammatory infiltrate (OR, 0,20 [95% CI, 0,08 to 0,54]; I²=0%). Outcome data on DFS were scarce, except for tumour borders, which did not present a significant impact, precluding the meta-analysis.Of the histopathological prognostic factors studied, low- to moderate-certainty evidence shows that vascular invasion, perineural invasion, absence of pseudocapsule, presence of satellite nodules, and absence of peritumoral inflammatory infiltrate are associated with shorter overall survival in CRLMs.

The objective of the present study was to evaluate the role of microRNA-mediated remodeling of the extracellular matrix in the process of tumor invasion of oral squamous cell carcinoma and to evaluate its relationship with the prognosis of these patients. This was a retrospective study on material from the paraffin blocks of patients operated on for oral squamous cell carcinoma, in addition to a group of healthy oral mucosa samples of paired patients. miR-1-3p, miR-133-3p, and miR-21-5p were differentially expressed between the superficial and deep tumor groups. miR-21-5p was the one with the greatest accuracy in the differentiation between superficial and deep tumors. By immunohistochemistry, the group of deep tumors showed greater immunoreactivity to matrix metalloproteinases 2 and 9 and laminin α in tumor-associated fibroblasts, with consequent degradation of the basal membrane, measured by greater loss of continuity of type IV collagen. This process was also associated with lower and higher expression of miR-1-3p and miR-21-5p, respectively. There was also a trend toward better overall and disease-free survival rates in patients with higher miR-133a-3p. The present study showed the interaction between microRNAs and extracellular matrix remodeling in oral squamous cell carcinoma.

Schistosomiasis is a cutaneously acquired infection caused by trematodes (fla¬tworms from the phylum Platyhelminthes), due to swimming in contaminated waters. The central nervous system (CNS) schistosomiasis is a rare presen¬tation of the disease. Brain infection due to S. Mansoni has been rarely reported, in anedoctal fashion. It should be early recognized , since an available treatment may prevent neurological deterioration. A high index of sus¬picion is necessary, mainly in patients coming from endemic areas, with brain or spinal cord lesions associated with eosino¬philia and inflammatory CSF. The finding schistosoma eggs in stools or in a CNS biopsy confirms the diagnosis. We re¬port on a 35-year old brazilian man harboring an isolated brain infection due to S. mansoni.

Objective Adjuvant chemotherapy with 5-fluorouracil (5-FU) has been widely used in gastric cancer (GC) patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase (TS), and high levels of TS correlate with resistance to treatment with fluoropyrimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. Methods We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry (IHC) in tumor cells by tissue microarray (TMA). TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score: negative, low and high. Results TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age (P=0.007), high neutrophil/lymphocyte ratio (P=0.048), well/moderately differentiated histology (P=0.001), intestinal Lauren type (P

Thyroid carcinomas are the most common endocrine malignancy. Inconclusive results for the analysis of malignancies are an issue in the diagnosis of thyroid carcinomas; 20% of thyroid cancer diagnoses are indeterminate or suspicious, resulting in a surgical procedure without immediate need. The use of Raman spectroscopy may help improve the diagnosis of thyroid carcinoma. In this study, 30 thyroid samples, including normal thyroid, goiter and thyroid cancer, were analyzed by confocal Raman spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA) with cross validation and binary logistic regression (BLR) analysis were applied to discriminate among tissues. Significant discrimination was observed, with a consistent rate of concordant pairs of 89.2% for normal thyroid versus cancer, 85.7% for goiter versus cancer and 80.6% for normal thyroid versus goiter using just the amide III region. Raman spectroscopy was thus proven to be an important and fast tool for the diagnosis of thyroid tissues. The spectral region of 1200-1400cm-1 discriminated normal versus goiter tissues despite the great similarity of these tissues.

The purpose of the present study was to investigate the predictive factors for shorter disease-specific survival in patients with pulmonary disease secondary to differentiated thyroid cancer (DTC).This was a retrospective cohort study conducted over a 5-year period that included 54 patients with pulmonary disease secondary to DTC during the follow-up. Among these patients, 13 (24.1%) died from the disease. Dedifferentiation characteristics were identified at pathological examination of the metastatic disease (lymph node or distant metastases) and was defined as the abrupt transformation of a well-differentiated tumor into high-grade morphology lacking the original distinct histologic characteristics.Tumor dedifferentiation marked by cellular aberrations and radioiodine (RAI) therapy resistance occurred in 5 (9.3%) patients. Four of them died due to pulmonary progression (80.0%), and the median survival of this group was 30 months compared to 279 months in the patients without dedifferentiation. The cumulative disease-specific survival was 20.0% in the patients with dedifferentiation during the follow-up versus 46.1% among the cases without this condition (P = .003, log-rank test). Moreover, dedifferentiation was independently associated with shorter disease-specific survival (hazard ratio [HR] = 31.607; 95% confidence interval [CI]: 4.815-207.478; P.0001, Cox regression model) as were age over 45 years (HR = 10.904; 95% CI: 1.145-103.853; P = .038) and male sex (HR = 4.210; 95% CI: 1.056-16.783; P = .042).DTC patients with pulmonary disease exhibited shorter disease-specific survival, particularly those who developed tumor dedifferentiation, and these patients require special attention during follow-up.CI = confidence interval DTC = differentiated thyroid cancer FTC = follicular thyroid carcinoma HR = hazard ratio IQR = interquartile range LN = lymph node LR = likelihood ratio PTC = papillary thyroid carcinoma RAI = radioiodine pTNM = pathologic tumor-node-metastasis stage system.