Neoadjuvant Chemotherapy and Pathologic Complete Response in HR+/HER2- Breast Cancer: Impact of Tumor Ki67 and ER Status.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is extensively employed in breast cancer (BC), primarily for aggressive subtypes like triple-negative and human epidermal growth factor receptor 2 (HER2) positive BC, and in estrogen receptor-positive (ER+)/ HER2- BC with high-risk features. In ER+/HER2- breast cancer, pathological complet rates are much lower (<10%), while axillary dissection rates are higher. This study focuses on hormone receptor positive (HR+)/HER2- BC patients undergoing NAC, examining its impact on pathological complete response (pCR) rates, with specific attention to tumor Ki67 and ER status. METHODS: Retrospective data analysis from Kartal Dr. Lütfi Kirdar City Hospital included HR+/HER2- BC patients who received NAC. Clinicopathological factors, NAC response, and surgical outcomes were assessed. Statistical analyses evaluated the association between Ki67, ER status, and pCR. RESULTS: Of 203 patients, 11.8% achieved pCR. Ki67 (p<0.001) and ER percentage (p<0.001) significantly correlated with pCR. Higher Ki67 was associated with increased pCR likelihood (HR: 1.03, 95% CI: 1.01-1.05). A Ki67-pCR probability curve revealed a cutoff of 23.5%. ER%-pCR analysis showed decreasing pCR rates with higher ER percentages. Multivariate analysis confirmed Ki67 (p=0.003, HR: 1.02) and ER percentage (p=0.019, HR: 0.97) as independent predictors of pCR probability. CONCLUSION: Consideration of Ki67 and ER percentage aids in NAC decisions for HR+/HER2- BC, identifying patients with high NAC response rates, facilitating axillary preservation, and potentially avoiding axillary dissection. The pCR rates in patients with Ki67 ≤ 24 are particularly low, especially in patients with a high ER percentage. In these cases, upfront surgery and adjuvant treatment should be considered instead of NAC.

Pericardial hydatid cyst and tuberculosis co-existence.

Tuberculosis and hydatid cyst are still major health problems in developing countries. Co-existence of these two infections is also seen commonly. In this article, we present a 15-year-old-girl patient who applied with cardiac tamponade accompanied by pleural and pericardial effusion and was diagnosed as pericardial hydatid cyst and pericardial tuberculosis. To the best of our knowledge, this is the first case with such feature reported in the literature.

Histopathological and Immunohistochemical Evaluation of Pannus Tissue in Patients with Prosthetic Valve Dysfunction.

BACKGROUND: Prosthetic valve dysfunction due to pannus formation is a rare but serious complication. Currently, limited data are available concerning the pathogenesis and immunohistochemical properties of pannus. The study aim was to investigate the morphological, histopathological and immunohistochemical characteristics of pannus formation in patients with prosthetic valve dysfunction. METHODS: A total of 35 patients (10 males, 25 females; mean age 44 ± 16 years) who had undergone re-do valve surgery due to prosthetic valve obstruction was enrolled in the study. Immunohistochemical studies were aimed at evaluating the expression of alphasmooth muscle actin (α-SMA) and desmin in myofibroblasts and smooth muscle cells; epithelial membrane antigen (EMA) in epithelial cells; and CD34, Factor VIII and vascular endothelial growth factor (VEGF) in endothelial cells. Matrix metalloproteinases (MMPs) -2 and -9, and transforming growth factor-beta (TGF-ß) were used to demonstrate cytokine release from macrophages, leukocytes, fibroblasts and myofibroblasts. RESULTS: Pannus appeared as a tough and thick tissue hyperplasia which began from outside the suture ring in the periannular region and extended to the inflow and outflow surfaces of the prosthetic valves. Histopathological analysis showed the pannus tissue to consist of chronic inflammatory cells (lymphocytes, plasma cells, macrophages and foreign body giant cells), spindle cells such as myofibroblasts, capillary blood vessels and endothelial cells laying down the lumens. Calcification was present in the pannus tissue of 19 explanted prostheses. Immunohistochemical studies revealed positive α-SMA expression in all patients, whereas 60.5% of patients were positive for desmin, 50% for EMA, 42.1% for VEGF, 39.5% for TBF-ß, 42.1% for MMP-2, 86.8% for CD34, and 97.4% for Factor VIII. MMP-9 was negative in all patients. CONCLUSIONS: Pannus tissue appears to be formed as the result of a neointimal response in periannular regions of prosthetic valves that consist of periannular tissue migration, myofibroblast and extracellular matrix proliferation with vascular components. It is a chronic active process in which mediators such as TGF-ß, VEGF and MMP-2 play roles in both matrix formation and degradation.

Alternative causes of bioreaction to prosthetic heart valves: three cases with pannus formation.

Pannus formation is an infrequent but serious complication of prosthetic heart valve surgery. The cause of pannus is recognized as a bioreaction to the prostheses; histological investigations have shown that pannus comprises collagen and elastic tissues containing endothelial cells, chronic inflammatory cells, and myofibroblasts. However, the detailed mechanism of its formation has not been fully demonstrated. We aimed to evaluate the potential role of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in the pathogenesis of pannus formation in three patients with mechanical prosthetic heart valves. Pannus specimens removed from the prostheses were fixed in 10% neutral-buffered formalin for 24 hours after surgical removal and paraffin-embedded using standard procedures. Serial sections were cut at 4 µm for immunohistochemistry analysis. Hematoxylin and eosin (HE) was used in the histological analysis. VEGF and MMP-2 were studied in the immunohistochemistry analysis. Three patients with mechanical prosthetic obstruction due to pannus overgrowth underwent redo valve surgery. In the first and second patients, the mitral prosthesis was explanted along with the pannus overgrowth. The third patient had both aortic and mitral prostheses; the aortic prosthesis was explanted with obstructive pannus formation, whereas the mitral valve was spared with excision of the nonobstructive pannus. The immunohistochemical study demonstrated the expressions of MMP-2 and VEGF in all of the pannus specimens acquired from these cases. VEGF and MMP-2 may play a role in the mechanism of pannus formation as the elements of the chronic active inflammatory process.