The purposes of this study were to examine the therapeutic response of advanced cervical cancer to Ki-67 proliferative index (Ki-67 PI) dependent cisplatin chemotherapy, and to determine Ki-67 PI referential value that is expected to provide a satisfactory therapeutic response of cervical cancer to cisplatin chemotherapy.This prospective study enrolled 59 patients treated for cervical cancer at Clinic for Oncology, Clinical Center Nis, Serbia. According to the obtained Ki-67 PI values, patients were divided into three groups, and all the patients received the same cytostatic, cisplatin. Therapeutic response to chemotherapy was evaluated in relation to disease progression presence or absence and progression-free survival after a year follow-up since the first chemotherapy.Survival rate increases with an increase of Ki-67 PI by Kaplan-Meier survival analysis, meaning that survival rate is statistically significantly shorter in the group of patients with Ki-67 PI < 40% in comparison to patients from other two groups (p=0.010). Mann-Whitney test confirmed a statistically significant increase in survival rate among the groups of patients formed according to Ki-67 PI (p<0.05). Kaplan-Meier survival analysis confirmed that the mean survival rate in the group of patients with Ki-67 PI values over 60% is statistically significantly longer in comparison to patients with Ki-67 PI values below or equal 60% (p<0.001).Advanced cervical cancer with a high Ki-67 PI expression responds better to cisplatin-based chemotherapy, thus resulting in a longer survival rate. The values of Ki-67 PI were determined: high Ki-67 PI (≥ 60%), moderate Ki-67 PI (40-60%), and low Ki-67 PI (≤ 40%).
The purpose of this study was to assess the immunohistochemistry and chromogenic in situ hybridization (CISH) inter-laboratory consensus between national pathology laboratories in Serbia.This study was conducted between 2013 and 2016. In 2013, HER2 results were evaluated using two sets of four different breast cancer specimens in five laboratories. A total of 20 immunohistochemistry and 20 CISH cases were tested. In 2014, there were 6 testing rounds, and a total of 24 specimens were analyzed, whereas in 2015 and 2016, seven testing rounds were conducted, with four additional cases (i.e. a total of 28 specimens). In 2014, 2015 and 2016, all institutions performed immunohistochemical analysis only.We found discrepan¬cies in HER2 immunohistochemical (IHC) results in all four surveys. IHC testing resulted in diagnostic discordance between participating centers in two (2/17) cases in 2013, two (2/24) in 2014, four (4/27) cases in 2015 and three cases (3/27) in 2016. The overall agreement among the centers was 79%, 85.5%, 83.5% and 89.4%, respectively. For CISH analyses, the results for 16 (84.2%) of 19 samples were consistent for all participants. Three results were found to be discordant, indicating a misdiagnosis rate of 15.8%. In all the discrepant cases, interinstitutional discordances were related to technical and evaluation issues.Our study highlights the difficulty encountered during HER2 testing using immunohistochemistry and CISH. This also emphasizes the need for rigorous quality control procedures for specimen preparation and analysis.
Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.
Abstract The formation of amyloid-β (Aβ) plaques is a neuropathological hallmark of Alzheimer’s disease (AD), however, these pathological aggregates can also be found in the brains of cognitively unimpaired elderly population. In that context, individual variations in the Aβ-specific immune response could be key factors that determine the level of Aβ-induced neuroinflammation and thus the propensity to develop AD. CD4 + T cells are the cornerstone of the immune response that coordinate the effector functions of both adaptive and innate immunity. However, despite intensive research efforts, the precise role of these cells during AD pathogenesis is still not fully elucidated. Both pathogenic and beneficial effects have been observed in various animal models of AD, as well as in humans with AD. Although this functional duality of CD4 + T cells in AD can be simply attributed to the vast phenotype heterogeneity of this cell lineage, disease stage-specific effect have also been proposed. Therefore, in this review, we summarized the current understanding of the role of CD4 + T cells in the pathophysiology of AD, from the aspect of their antigen specificity, activation, and phenotype characteristics. Such knowledge is of practical importance as it paves the way for immunomodulation as a therapeutic option for AD treatment, given that currently available therapies have not yielded satisfactory results.
Introduction/Objective. Nasolacrimal duct obstruction with consequent epiphora and the development of dacryocystitis (DC) represents a common pathological entity in the clinical practice of ophthalmologists and maxillofacial surgeons. The etiology of DC is multifactorial and still has not been clarified in detail. It is considered that ascending infections from the nasal cavity and paranasal sinuses, injuries and surgical interventions in the middle third of the face, dacryoliths, tumors of the lacrimal sac and surrounding structures may be some of the etiological factors of nasolacrimal duct obstruction. The aim of this study is to present clinical characteristics and surgical treatment of DC. Methods. A retrospective study was carried out. It covered a period of 10 years during which 49 patients with clinically verified DC were treated after surgical examination and complete diagnostics. Out of the total number, 37 patients underwent surgery. Results. The occurrence of predisposing factors was present in 80% of the patients ? rhinitis and the inflammation of paranasal sinuses in 27 patients (72%), injuries and surgical interventions in the middle third of the face in nine patients (24%), whereas lacrimal sac and nasolacrimal duct tumors were noted in three patients (8%). Surgical failure, which was manifested in terms of recurrent DC and epiphora, was noted in six cases (16%). Conclusion. Regarding the possible complications of inadequately administered antibiotic therapy and a broad spectrum of pathological entities which comprise the differential diagnosis, dacryocystorhinostomy with an adequate histopathological analysis and appropriate antibiotic therapy in the acute stage represents a right way for the treatment of DC.
Introduction. Colorectal cancer is the third most common cancer and metastatic disease is an important and frequent clinical problem. Metastases in the oral and maxillofacial region are rare, comprising 1-2% of all malignant lesions, and clinically resemble common benign conditions. Case report. A 59-year-old woman diagnosed with rectal cancer developed perimandibular lesion as a first sign of metastatic process. Metastasis manifested clinically during the curative intent treatment of rectal cancer (preoperative chemo-irradiation) as a rapidly growing tumefaction close to the mandible angle. After the biopsy and histopathological examination of the lesion that clinically resembled abscess, metastasis of rectal cancer was diagnosed. Incidentally, a cerebral metastasis was diagnosed as well. Although it was oligometastatic rectal cancer, surgical treatment was not indicated due to extensive infiltrative characteristics of the perimandibular lesion. The patient was treated with chemotherapy, with good clinical response. Biological therapy was not available at that moment. Cerebral metastasis was treated with stereotactic neuroradiosurgery with gamma knife. Unfortunately, the patient died from cerebrovascular insult. Conclusion. Lesions in the oral and maxillofacial region may be the first manifestation of metastatic disease. Since early diagnosis of metastatic process has prognostic implications, any new formation in the oral and maxillofacial region in a patient with colorectal cancer requires cautious observation and histological examination.
Abstract Background Recent evidence brought by novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates is leading to significant changes in HER2-negative breast cancer (BC) best practices. A new targetable category termed ‘HER2-low’ has been identified in tumors previously classified as ‘HER2-negative’. Daily practice in pathology and medical oncology is expected to align to current recommendations, but patient access to novel anticancer drugs across geographies might be impeded due to local challenges. Materials and methods An expert meeting involving ten regional pathology and oncology opinion leaders experienced in BC management in four Central and Eastern Europe (CEE) countries (Bulgaria, Croatia, Serbia, Slovenia) was held. Herein we summarized the current situation of HER2-low metastatic BC (mBC), local challenges, and action plans to prevent delays in patient access to testing and treatment based on expert opinion. Results Gaps and differences at multiple levels were identified across the four countries. These included variability in the local HER2-low epidemiology data, certification of pathology laboratories and quality control, and reimbursement conditions of testing and anticancer drugs for HER2-negative mBC. While clinical decisions were aligned to international guidelines in use, optimal access to testing and innovative treatment was restricted due to significant delays in reimbursement or limitative reimbursement conditions. Conclusions Preventing delays in HER2-low mBC patient access to diagnosis and novel treatments is crucial to optimize outcomes. Multidisciplinary joint efforts and pro-active discussions between clinicians and decision makers are needed to improve care of HER2-low mBC patients in CEE countries.