Feasibility and Colonoscopy Yield Using the Fecal Immunochemical Test (FIT)-Based Colorectal Cancer Screening in a Latin America Country.

BACKGROUND & AIMS: Organized colorectal cancer (CRC) screening is not widely practiced in Latin America and the results of regional studies may help overcome barriers for implementation of national screening programs. We aimed to describe the implementation and findings of a fecal immunochemical test (FIT)-based program in Brazil. METHODS: In a prospective population-based study, asymptomatic individuals (50-75 years old) from Sao Paulo city were invited to undergo FIT for CRC screening. Participants with positive FIT (≥10 µg Hb/g feces) were referred for colonoscopy. Subjects were classified into groups according to the presence of CRC, precursor lesions, and other benign findings, possibly related to bleeding. RESULTS: Of a total of 9881 subjects, 7.8% had positive FIT and colonoscopy compliance was 68.9% (n = 535). Boston scale was considered adequate in 99% and cecal intubation rate was 99.4%. CRC was diagnosed in 5.9% of the cases, adenoma in 63.2%, advanced adenoma in 31.4%, and advanced neoplasia in 33.0%. Age was positively associated with CRC (P = .03). Higher FIT concentrations were associated with increased detection of CRC (P < .008), advanced adenoma (P < .001), and advanced neoplasia (P < .001). CONCLUSIONS: Implementation of a FIT-based CRC screening program was feasible in a low-resource setting, and there was a high yield for neoplasia in individuals with a positive FIT. This approach could be used as a model to plan and disseminate organized CRC screening more broadly in Brazil and Latin America.

Prognostic Impact of Pathology, Cytoreduction, and Tumor Markers in Pseudomyxoma Peritonei.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer.

Objective: Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune-related score. Methods: Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC). Results: A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival. Conclusions: A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.

Infiltrative Tumor Borders in Colorectal Liver Metastasis: Should We Enlarge Margin Size?

BACKGROUND: 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. PATIENTS AND METHODS: 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 (≤ or > 1 cm) on survival and hepatic recurrence according to TGP was also evaluated. RESULTS: 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 (p < 0.05). Larger margin size did not impact the prognosis of patients with infiltrative borders. CONCLUSIONS: 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.

Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression.

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 < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. CONCLUSION: CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients.

Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer.

BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT. METHODS: Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve. RESULTS: Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS. CONCLUSION: High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.

Risk assessment of lymph node metastases in early gastric adenocarcinoma fulfilling expanded endoscopic resection criteria.

BACKGROUND AND AIMS: Early gastric cancer (EGC) is known to present a low rate of lymph node metastases (LNMs). Gastrectomy with D2 lymphadenectomy is usually curative for EGC. Endoscopic submucosal dissection (ESD) is a well-accepted treatment modality for lesions that meet the classic criteria: those mucosal differentiated adenocarcinoma measuring 20 mm or less, without ulceration. Expanded criteria for ESD have been proposed based on a null LNM rate from large gastrectomy series from Japan. Patients with LNM have been reported in Western centers, heightening the need for validation of expanded criteria. Our aim was to assess the risk of LNM in gastrectomy specimens of patients with EGC who met the expanded criteria for ESD. METHODS: We conducted an evaluation of gastrectomy specimens including LNM staging of patients submitted to gastrectomy for EGC in a 39-year retrospective cohort. RESULTS: A total of 389 surgical specimens were included. From them, 135 fulfilled criteria for endoscopic resection. None of the 31 patients with classic criteria had LNM. From the 104 patients with expanded criteria, 3 had LNM (n = 104 [2.9%], 95% confidence interval, .7%-8.6%), all of them with undifferentiated tumors without ulceration, measuring less than 20 mm. CONCLUSIONS: There is a small risk of LNM in EGC when expanded criteria for ESD are met. Refinement of the expanded criteria for the risk of LNM may be desirable in a Brazilian cohort. Meanwhile, the decision to complement the endoscopic treatment with gastrectomy will have to take into consideration the individual risk of perioperative morbidity and mortality.

Lymph Node Yield After Neoadjuvant Chemoradiotherapy in Rectal Cancer Specimens: A Randomized Trial Comparing Two Fixatives.

BACKGROUND: It is widely reported that neoadjuvant chemoradiation reduces lymph node yield in rectal cancer specimens. Some have questioned the adequacy of finding ≥12 lymph nodes for accurate staging, and fewer nodes were correlated with good response. Others reported that low lymph node count raises the chance for understaging and correlates with worse survival. In addition, a few studies demonstrated that diligent specimen analysis increases lymph node count. OBJECTIVE: The aim of this study was to compare Carnoy's solution and formalin concerning lymph node yield in specimens of patients with rectal cancer after neoadjuvant chemoradiation. DESIGN: This is a prospective randomized trial that was conducted from 2012 to 2015. SETTINGS: This study was performed in a reference cancer center in Brazil. PATIENTS: Patients who underwent low anterior resection with total mesorectal excision after neoadjuvant chemoradiation for rectal adenocarcinoma were included. INTERVENTION: Rectosigmoid specimens were randomized for fixation with Carnoy's solution or formalin. MAIN OUTCOME MEASURES: A total of 130 specimens were randomized. After dissection, the residual fat from the formalin group was immersed in Carnoy's solution in search for missed lymph nodes (Revision). RESULTS: The Carnoy's solution group had superior lymph node count (24.0 vs 16.3, p < 0.01) and fewer cases with <12 lymph nodes (6 vs 22, p = 0.001). The Revision group found lymph nodes in all cases (mean, 11.1), retrieving metastatic lymph nodes in 6 patients. It reduced the formalin cases with <12 lymph nodes from 33.8% to 4.6% and upstaged 2 patients. Tumor response to neoadjuvant chemoradiotherapy was not associated with lymph node count. LIMITATIONS: This was a unicentric study. CONCLUSIONS: Compared with formalin, the Carnoy's solution increases lymph node count and reduces the cases with <12 lymph nodes. Harvested lymph nodes are missed following routine analysis and this is clinically relevant. Finding <12 lymph nodes is not a sign of good response to neoadjuvant chemoradiation (www.clinicaltrials.gov. Unique identifier: NCT02629315). See Video Abstract at http://links.lww.com/DCR/A694.

Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy.

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<0.001) and absence of perineural invasion (P=0.003). Among 285 patients, 133 stage II/III patients (46.7%) received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival (DFS) in stage III GC patients who received 5-FU-based chemotherapy (P=0.007). Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. CONCLUSIONS: High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy.

Lymphoepithelioma-like gastric carcinoma: clinicopathological characteristics and infection status.

BACKGROUND: Lymphoepithelioma-like gastric carcinoma (LLGC) is a rare subtype of gastric carcinoma (GC) characterized by prominent lymphocytic infiltration. LLGC may be associated with latent Epstein-Barr virus (EBV) infection or microsatellite instability (MSI). This study aims to assess the clinicopathological characteristics, EBV infection, and MSI status in LLGC. METHODS: A retrospective analysis of GC patients submitted to potentially curative resection between 2009 and 2014 was performed. The LLGC subtype specimens were examined for EBV by in situ hybridization and MSI by immunohistochemical analysis. The LLGC profile was analyzed accordingly to clinicopathological parameters. RESULTS: From 255 patients, seven were identified on the pathological report as LLGC. Six cases were EBV-positive and one had MSI, showing loss of MLH1 and PMS2 expression. LLGC was more frequently seen in men, and the mean age was 69 years. When compared to non-LLGC, LLGC cases were larger (∼5.8 cm) poorly differentiated tumors and had lower incidence of lymph node metastasis (P = 0.045). Mean number of lymph nodes dissected in the LLGC group was 39.5, and only one patient had a single positive lymph node. In addition, two patients presented associated lesions. LLGC was not associated with HER-2, chromogranin and synaptophysin positivity or Helicobacter pylori infection. CONCLUSIONS: Distinct pathological aspects and clinical behavior of LLGC reinforce the need for proper recognition of this histological subtype to choose better therapeutic approaches.

DEATH RELATED TO PULMONARY METASTASIS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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. ABBREVIATIONS: 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.

Tumor thickness as an independent risk factor of early recurrence in oral cavity squamous cell carcinoma.

The aim is to determine if tumor thickness is a risk factor related to the development of early recurrences in surgically treated oral cavity squamous cell carcinoma (SCC). Retrospective cohort study conducted at Instituto do Câncer do Estado de São Paulo (ICESP). Fifty-seven patients with oral cavity SCC (excluding lip tumors and patients previously submitted to any treatment) were analyzed regarding the occurrence of an early disease progression (locoregional or distant metastasis) within the first 12 months after initial treatment. Tumor thickness and other histological characteristics related to the development of recurrence up to 1 year after treatment were tested. Results demonstrated that tumor thickness greater than 10 mm (P = 0.034), as well as angiolymphatic invasion (P = 0.001), perineural invasion (P = 0.041) and lymph-node metastasis (P = 0.021) was associated with a worse 12-month disease-free survival (Log-Rank test). In multivariate analysis, tumor thickness greater than 10 mm emerged as an independent risk factor for early recurrence in oral cavity tumors (HR = 3.4, 95% CI: 1.005-11.690; P = 0.049--Cox regression). Post-operative radiotherapy seems to be a protective factor for early recurrences in patients with tumor thickness greater than 10 mm (P = 0.017--Log-Rank test; HR = 0.32, 95% CI: 0.12-0.87, P = 0.026--Cox regression). The results of the present research suggest that tumor thickness greater than 10 mm may be an independent adverse factor for early progression of surgically treated oral cavity SCC. Adjuvant therapies, in particular post-operative radiotherapy, should be advocated in this group of patients, regardless of the co-existence of other well-described histological risk factors.

Effects of tacrolimus and insulin in a liver regeneration model in growing animals with portal vein stenosis: immunohistochemical and molecular studies.

The aim of the present investigation was to describe a new model of liver regeneration in growing rats with reduced portal flow. In addition, it was studied whether tacrolimus and insulin could have any pro-regenerative effect under such conditions. Ninety-five rats were divided into five groups: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + PV stenosis; Group 4, 70% hepatectomy + portal vein stenosis + insulin; and Group 5, 70% hepatectomy + portal vein stenosis + tacrolimus. The remnant liver lobes were harvested for analyses. The liver weight decreased in the PV stenosis group and it increased with the use of insulin and tacrolimus. The mitotic activity was higher in the hepatectomy, insulin and tacrolimus groups and this parameter was reduced by portal stenosis. Levels of interleukin 6 (IL-6) were higher in the hepatectomy group compared to the sham and PV stenosis groups. The expression of IL-6 and Ki67 was significantly increased in the insulin and tacrolimus groups compared to the portal stenosis group. A highly reproducible model was standardized to study liver regeneration with portal blood inflow reduction in weaning rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of PV stenosis.

Utility of a Low-Cost 3-D Printed Microscope for Evaluating Esophageal Biopsies.

In this manuscript we assessed the utility of a low-cost 3D printed microscope to evaluate esophageal biopsies. We conducted a comparative analysis between the traditional microscope and our 3-D printed microscope, utilizing a set of esophageal biopsy samples obtained from patients undergoing screening endoscopy. Two pathologists independently examined 30 esophageal biopsies by light microscopy and digital images obtained using a low-cost 3D printed microscope (Observer 1 and 2). The glass slide consensus diagnosis was compared to the findings of 2 additional pathologist who independently just reviewed the digital images (Observer 3 and 4). The intra-observer agreement was substantial to almost perfect for observer 1 (k:0.64) and 2 (k:0.84). All four observers had 100% sensitivity and negative predictive value, whereas specificity ranged from 59% to 100% and positive predictive value ranged from 21% to 100%. The PPV and specificity were lower for the two Observers (3 and 4) who just examined the digital images. Overall, our results suggest that telepathology may be used with high sensitivity and specificity, utilizing the pictures produced by our 3D-printed microscope.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma.

BACKGROUND: Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has demonstrated promising results on gastric cancer (GC). However, PD-L1 can express differently between metastatic sites and primary tumors (PT). AIM: To compare PD-L1 status in PT and matched lymph node metastases (LNM) of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics. METHODS: We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy. PD-L1 was evaluated by immunohistochemistry (clone SP142) using the combined positive score. All PD-L1+ PT staged as pN+ were also tested for PD-L1 expression in their LNM. PD-L1(-) GC with pN+ served as the comparison group. RESULTS: Among 284 GC patients included, 45 had PD-L1+ PT and 24 of them had pN+. For comparison, 44 PD-L1(-) cases with pN+ were included (sample loss of 4 cases). Of the PD-L1+ PT, 54.2% (13/24 cases) were also PD-L1+ in the LNM. Regarding PD-L1(-) PT, 9.1% (4/44) had PD-L1+ in the LNM. The agreement between PT and LNM had a kappa value of 0.483. Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites. There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status (P = 0.166 and P = 0.837, respectively). CONCLUSION: Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM. This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Prognostic implications of tumor-infiltrating lymphocytes within the tumor microenvironment in gastric cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) play a regulatory role in the tumor-associated immune response and are important in the prognosis and treatment response of several cancers. However, because of its heterogeneity, the prognostic value of TILs in gastric cancer (GC) is still controversial. Thus, this study aimed to investigate the association between the density of TILs and patients' outcomes in GC. METHODS: Patients with gastric adenocarcinoma who underwent curative intent gastrectomy were retrospectively investigated. The groups for analysis were determined on the basis of TIL intensity and percentage of CD3+ T-cell infiltration by immunohistochemical. Furthermore, Epstein-Barr virus (EBV), microsatellite instability (MSI), T-cell ratio of CD4 to CD8, and programmed death protein ligand 1 (PD-L1) status were evaluated. RESULTS: A total of 345 patients were enrolled: 124 patients with GCs (35.9%) were classified as the low-CD3+ TIL group, and 221 patients with GCs (64.1%) were classified as the high-CD3+ TIL group. Poorly differentiated histology (P = .014), EBV-positive status (P < .001), PD-L1-positive status (P = .001), and CD4 < CD8 (P < .001) were associated with high-CD3+ GC. There was no difference regarding MSI status, the degree of tumor invasion (pT), the presence of lymph node metastasis, and pTNM stage between low- and high-CD3+ groups. In survival analysis, the high-CD3+ group had better disease-free survival and overall survival rates than had the low-CD3+ group (P = .055 and P = .041, respectively). In the multivariate analysis, total gastrectomy, lymph node metastasis, advanced pT stage, and low CD3+ levels were independent factors related to worse survival. CONCLUSION: High CD3+ TILs levels were significantly associated with improved survival and could serve as prognostic biomarkers in GC. In addition, CD3+ T-cell infiltration was related to both EBV-positive and PD-L1-positive GC and may assist in the investigation of targets in immunotherapy.

Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Incidental Node Metastasis as an Independent Factor of Worse Disease-Free Survival in Patients with Papillary Thyroid Carcinoma.

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.

Transmission of clear cell tumor in a graft liver from cadaveric donor: case report.

Neoplasms in children after organ transplantation are related to the type and intensity of immunosuppression and the donor-recipient serostatus, especially in relation to the Epstein-Barr virus. The patient was a two-yr-old female child with biliary atresia who underwent a liver transplantation from a female cadaver donor. Two adults received kidney transplants from the same donor. Nine months after transplantation, one of the adult recipients developed an urothelial tumor in the kidney graft. Imaging tests were repeated monthly in the liver-transplanted child and revealed no abnormalities. However, one yr and two months after the transplantation, the patient developed episodes of fever. At that time, imaging and liver biopsy showed a clear cell tumor of urothelial origin in the graft and the disease was limited to the liver. The patient underwent liver retransplantation, and she is currently free of tumor recurrence. Although rare, the occurrence of tumors in the post-transplant period from cadaver donors, without previously diagnosed tumors, is one of the many problems encountered in the complex world of organ transplantation.

Searching for SARS-CoV-2 in Cancer Tissues: Results of an Extensive Methodologic Approach based on ACE2 and Furin Expression.

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.