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Human epidermal growth factor receptor 2 (HER2) dysregulation is associated with tumorigenesis in gastric/gastroesophageal junction cancer; however, the number of patients with HER2-positive disease is unclear, possibly due to differing scoring criteria/assays. Data are also lacking for early disease. We aimed to assess the HER2-positivity rate using approved testing criteria in a large, real-life multinational population. HER2-positivity was defined as an immunohistochemistry staining score of 3+, or immunohistochemistry 2+ and HER2 amplification detected by in situ hybridization. A total of 4949 patients were enrolled and results showed that 14.2% of 4920 samples with immunohistochemistry results were HER2-positive. HER2-positivity was significantly higher in males (16.1% vs. 9.6% in females), in gastroesophageal versus stomach tumors (22.1% vs. 12.9%), in biopsy versus surgical samples (18.3% vs. 13.0%), in intestinal tumor subtypes versus diffuse (21.5% vs. 4.8%) and mixed types (21.5% vs. 8.5%) (P<0.001), in mixed versus diffuse types (8.5% vs. 4.8%), and in "other" versus diffuse types (11.7% vs. 4.8%; P=0.002). There were no significant differences between stages. Patients in the youngest age percentile had significantly lower HER2-positivity rates than patients in the remaining percentiles (9.2% vs. 15.9%, 15.7%, and 15.1%; P<0.001). HER2-positivity was highest in France (20.2%) and lowest in Hong Kong (10.4%). In conclusion, HER-EAGLE, the first study of its kind to be conducted in a large, multinational population of almost 5000 patients, gives valuable insights into the real-world HER2-positivity rate in a gastric/gastroesophageal junction cancer patient population not selected for disease stage or histology.

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OBJECTIVE: Although endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is the gold standard for diagnosing pancreatic lesions, its negative predictive value is suboptimal. Our aim was to evaluate the yield of contrast-enhanced EUS (CED-EUS) and of strain ratio EUS-elastography (SR-E-EUS) for differentiating pancreatic solid lesions. METHODS: Forty-seven patients (27 men, 20 women, 70 ± 11 years) were consecutively involved in this single-center, prospective study. They were submitted to EUS, SR-E-EUS, CED-EUS with Sonovue(®), and EUS-FNA. The final diagnosis was based on the histological assessment of EUS-FNA and/or surgical specimens when available, and on follow-up of at least 6 months. RESULTS: From the 47 focal pancreatic lesions included, 13 (28%) were benign and 34 (72%) malignant. Patients with malignancy were older (70 ± 11 vs. 61 ± 8, P = 0.003), and had larger lesions (34 ± 12 mm vs. 22 ± 11 mm, P = 0.03). Malignant lesions had higher SR-E-EUS (31 ± 32 vs. 8 ± 9, P = 0.001) and more hypovascular pattern (93% vs. 33%, P < 0.001). Logistic regression determined that only hypovascularity (OR = 2.6, 95%CI: 1.5-130, P = 0.02) was independently predictive of malignancy. ROC analysis for SR-E-EUS yielded an optimal cutoff of 8 (AUC 0.91, 95%CI: 0.74-0.98) for the best power distinction for malignancy. There was no significant difference concerning sensitivity (79%, 90%, 93%) and specificity rates (85%, 75%, 67%) of EUS-FNA, SR-E-EUS, and CED-EUS, respectively. By analysis of the inconclusive EUS-FNA subset (9 patients, 19%), SR-E-EUS > 8 and hypovascularity showed sensitivity of 80% and 100%, and specificity of 67% and 67%, respectively. CONCLUSION: The clinical utility of CED-EUS and SR-E-EUS remains questionable. The accuracies of CED-EUS and SR-E-EUS are similar to EUS-FNA. Hypovascularity was independently predictive of malignancy. Patients with inconclusive EUS-FNA could benefit from CED-EUS due to the high sensitivity of hypovascularity for diagnosing malignancy.

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BACKGROUND: There are situations in which the specimens obtained after endoscopic mucosal resection of superficial adenocarcinoma arising from Barrett's esophagus are not adequate for histopathological assessment of the margins. In these cases, immunohistochemistry might be an useful tool for predicting cancer recurrence. AIM: To evaluate the value of p53 and Ki-67 immunohistochemistry in predicting the cancer recurrence in patients with Barrett's esophagus-related cancer referred to circumferential endoscopic mucosal resection. METHODS: Mucosectomy specimens from 41 patients were analyzed. All endoscopic biopsies prior to endoscopic mucosal resection presented high-grade dysplasia and cancer was detected in 23 of them. Positive reactions were considered the intense coloration in the nuclei of at least 90 percent of the cells in each high-power magnification field, and immunostaining could be classified as superficial or diffuse according to the mucosal distribution of the stained nuclei. RESULTS: Endoscopic mucosal resection samples detected cancer in 21 cases. In these cases, p53 immunohistochemistry revealed a diffuse positivity for the great majority of these cancers (90.5 percent vs. 20 percent), and Ki-67 showed a diffuse pattern for all cases (100 percent vs. 30 percent); conversely, patients without cancer revealed a superficial or negative pattern for p53 (80 percent vs. 9.5 percent) and Ki-67 (70 percent vs. 0 percent). During a mean follow-up of 31.6 months, 5 (12.2 percent) patients developed six episodes of recurrent cancer. Endoscopic mucosal resection specimens did not show any significant difference in the p53 and Ki-67 expression for patients developing cancer after endoscopic treatment. CONCLUSIONS: p53 and Ki-67 immunohistochemistry were useful to confirm the cancer; however, they had not value for predicting the recurrent carcinoma after circumferential endoscopic mucosal resection of Barrett's carcinoma.

RACIONAL: Há situações nas quais o material obtido após mucosectomia endoscópica do adenocarcinoma superficial do esôfago de Barrett é inadequado para avaliação histopatológica de suas margens. Nesses casos, a imunoistoquímica poderia ser de auxílio para predição da recurrência tumoral. OBJETIVO: Avaliar o valor da detecção imunoistoquímica da p53 e do Ki-67 na predição da recurrência tumoral após mucosectomia endoscópica circunferencial do câncer no esôfago de Barrett. MÉTODOS: Foi analisado o material proveniente de mucosectomias de 41 pacientes. Todas as biopsias endoscópicas pré-mucosectomia apresentavam displasia de alto grau e câncer foi detectado em 23 casos. A imunorreatividade foi definida pela coloração de, pelo menos, 90 por cento dos núcleos em cada campo de grande aumento, podendo ser classificada como superficial ou difusa, conforme a distribuição celular dos núcleos corados. RESULTADOS: A mucosectomia detectou o câncer em 21 casos. Nesses casos, a p53 revelou padrão difuso de positividade para a maioria dos casos (90,5 por cento vs. 20 por cento) e o Ki-67 demonstrou padrão difuso para todos os portadores de câncer (100 por cento vs. 30 por cento). Por sua vez, pacientes sem câncer revelaram padrão negativo ou apenas superficial para a p53 (80 por cento vs. 9,5 por cento) e para o Ki-67 (70 por cento vs. 0 por cento). Durante seguimento médio de 31,6 meses, cinco (12,2 por cento) pacientes apresentaram seis episódios de câncer recurrente. Neste grupo, os fragmentos de mucosectomia não demonstraram nenhuma diferença significativa na expressão imunoistoquímica da p53 e do Ki-67 nos pacientes desenvolvendo câncer após o tratamento endoscópico. CONCLUSÕES: A imunoistoquímica da p53 e do Ki-67 é útil na confirmação do câncer; contudo não demonstra nenhum valor na predição da recurrência tumoral após mucosectomia endoscópica circunferencial do esôfago de Barrett com adenocarcinoma.

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BACKGROUND: There are situations in which the specimens obtained after endoscopic mucosal resection of superficial adenocarcinoma arising from Barrett's esophagus are not adequate for histopathological assessment of the margins. In these cases, immunohistochemistry might be an useful tool for predicting cancer recurrence. AIM: To evaluate the value of p53 and Ki-67 immunohistochemistry in predicting the cancer recurrence in patients with Barrett's esophagus-related cancer referred to circumferential endoscopic mucosal resection. METHODS: Mucosectomy specimens from 41 patients were analyzed. All endoscopic biopsies prior to endoscopic mucosal resection presented high-grade dysplasia and cancer was detected in 23 of them. Positive reactions were considered the intense coloration in the nuclei of at least 90% of the cells in each high-power magnification field, and immunostaining could be classified as superficial or diffuse according to the mucosal distribution of the stained nuclei. RESULTS: Endoscopic mucosal resection samples detected cancer in 21 cases. In these cases, p53 immunohistochemistry revealed a diffuse positivity for the great majority of these cancers (90.5% vs. 20%), and Ki-67 showed a diffuse pattern for all cases (100% vs. 30%); conversely, patients without cancer revealed a superficial or negative pattern for p53 (80% vs. 9.5%) and Ki-67 (70% vs. 0%). During a mean follow-up of 31.6 months, 5 (12.2%) patients developed six episodes of recurrent cancer. Endoscopic mucosal resection specimens did not show any significant difference in the p53 and Ki-67 expression for patients developing cancer after endoscopic treatment. CONCLUSIONS: p53 and Ki-67 immunohistochemistry were useful to confirm the cancer; however, they had not value for predicting the recurrent carcinoma after circumferential endoscopic mucosal resection of Barrett's carcinoma.

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