Prognostic and Clinical Significance of PD-L1, EGFR and Androgen Receptor (AR) Expression in Triple-Negative Breast Cancer (TNBC) Patients.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, a high incidence of distant metastases and poor overall survival. The aim of this study was to investigate the role of PD-L1, EGFR and AR expression in TNBC promotion and progression. To that end, we analyzed the immunohistochemical expression of these genes in 125 TNBC patients and their relation to clinicopathological parameters and survival. An elevated expression of PD-L1 was significantly correlated with higher tumor and nuclear grade, while a low expression was correlated with loco-regional recurrence without any influence on survival. Contrary to this, the expression of AR showed a positive impact on the DFI and a negative association with tumor grade. Furthermore, PD-L1 and AR demonstrated simultaneous expression, and further co-expression analysis revealed that a positive expression of PD-L1/AR notably correlates with tumor and nuclear grade and has a significant impact on a longer DFI and OS, while a negative PD-L1/AR expression is significantly associated with metastases. Therefore, our results suggest that positive PD-L1/AR expression is beneficial for TNBC patients. In addition, an elevated expression of EGFR contributes to metastases and a worse DFI and OS. In conclusion, we think that low PD-L1/low AR/high EGFR expression followed by high Ki67 expression constitutes a 'high risk' profile of TNBC.

IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients.

Regional lymph nodes (LN)s represent important immunological barriers in spreading of malignant tumors. However, they are the most frequent early metastatic site in melanoma. Immunomodulatory agents including cytokines have been included in therapy of melanoma and have shown severe side effects and toxicity. In this sense, there is a growing need for bringing these agents to further in vitro testing that may enlighten aspects of their regional application. Therefore, the aim of this study was to investigate the effect of interleukin (IL)-2 and IL-15, the two cytokines with similar immune-enhancing effects, on the expression of activating NKG2D, inhibitory CD158a and CD158b receptors on CD8+ T, NKT-like and NK cell lymphocyte subsets from regional LNs of melanoma patients. In this study, we showed significant effects of IL-2 and IL-15 cytokine treatments on the expression of activating NKG2D and on inhibitory CD158a and CD158b receptors on lymphocytes, CD8+ T, NKT-like and NK cell lymphocyte subsets originating from regional LNs of melanoma patients. Furthermore, IL-2 and IL-15 by inducing the expression of NKG2D activating receptor on innate and on adaptive lymphocyte subsets and by augmenting NK cell antitumor cytotoxicity that correlated with the cytokine-induced NKG2D expression, increased antitumor potential of immune cells in regional LNs of melanoma patients irrespective of LN involvement. These findings indicate the importance of immune cell population from regional LNs of melanoma patients in the development of immune intervention strategies that may if applied locally increase antitumor potential to the level that controls tumor progressions.

Predictors of sentinel lymph node status of cutaneous melanoma in Serbian patients.

PURPOSE: Presence of metastasis in sentinel lymph node (SLN) is considered to be the most important factor in terms of patient survival. The main aim of this study was to identify predictors of positive SLN in Serbian patients with melanoma. METHODS: This retrospective study was conducted on 147 patients. Univariate chi-square and univariate logistic regression analyses were used to identify the association between prognostic factors and positive SLN. Receiver Operating Characteristics (ROC) was conducted to find the Breslow thickness cutoff point at which to perform SLN biopsy (SLNB). Kaplan-Meier analysis was used to evaluate disease-free survival (DFS), and log rank test was applied to compare differences between groups. RESULTS: Breslow thickness and Clark level (p≤0.05), presence of ulceration and a high mitotic rate (>6 mitoses/mm2) (p<0.001) were significant independent predictors of SLN metastasis. ROC curve showed that Breslow thickness of 2.8 mm was the most suitable cutoff point for SLN positivity (sensitivity 86%, specificity 67%). Furthermore, Breslow thickness and presence of ulceration were found to be associated with DFS (p<0.05). CONCLUSIONS: Patients with Breslow thickness ≥2.8 mm, ulceration, and high mitotic rate are at higher risk for SLN metastasis. In addition, high Breslow thickness and presence of ulceration are associated with decreased DFS. These results indicate that multiple selection criteria should be used when performing and predicting SLN metastasis and disease recurrence.

Hyperthermic intrathoracic chemotherapy (HITHOC) in ovarian carcinoma - a propos of a case.

A female patient aged 42, started chemotherapy for advanced ovarian carcinoma in June 2016. Considering intraoperative findings, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) were performed, followed by adjuvant chemotherapy. In March 2018, computed tomography (CT) examination showed disease progression in the form of pleural carcinomatosis with increased levels of tumor markers. In April 2018, total parietal pleurectomy, partial visceral pleurectomy, and then hyperthermic intrathoracic chemotherapy (HITHOC) with cisplatin were performed. The procedure was uneventful, as was the postoperative course. The patient was discharged on the 13th postoperative day with no major postoperative complications. Three months after surgery, CT showed no signs of disease relapse. Since this is a relatively new method of treating pleural carcinomatosis, real results are to be expected with larger series of patients and longer postoperative follow-up.

Acceptable adverse outcomes after delayed breast reconstruction using abdominal advancement flap - a 15-year experience.

PURPOSE: To evaluate the adverse outcomes after delayed breast reconstruction (DBR) by abdominal advancement flap (AAF) and permanent prosthesis in patients treated with mastectomy due to unilateral breast carcinoma, as well as to determine which factors are predictive for their occurrence. METHODS: The study included 155 patients operated at the Institute for Oncology and Radiology of Serbia from 1996 to 2010. All patients had total mastectomy and axillary lymph node dissection, followed by specific oncological treatment. Patients were selected for DBR after complete diagnostic evaluation. Adverse events were evaluated in regard to patient, disease and prostheses-related factors. RESULTS: During follow-up, DBR adverse events were observed in 23.237percnt; of the patients - the majority (91.67%) had only one. The most frequent was capsule contracture (47.22%), followed by asymmetry (22.22%), infection (16.67%) and prosthesis rupture (16.67%). There were isolated cases of prosthesis prolapse and local disease recurrence. Infections were treated conservatively in all but one patient. Other events were managed by additional operation. Statistical analysis showed that complications occurred significantly more often in patients ?51 years (vs 18-40, vs 41-50), disease stage IIb (vs Ia), T2 (vs T1) tumors and adjuvant radiotherapy (vs without). Prostheses-related factors were not significant for DBR complications, neither body mass index (BMI), nor smoking habits. CONCLUSIONS: DBR using AAF and permanent prosthesis is a safe technique with acceptable complication rate. It provides one-time surgery with satisfactory aesthetic results and good postoperative recovery. Most frequent complication is capsule contracture. Patients' age and irradiation of the chest wall after mastectomy are predictive factors for complications.

Factors related to local recurrence of non small cell lung cancer and its operability.

PURPOSE: To analyze the correlation of primary tumor (PT) pathological characteristics (size, stage, type and grade) and the extent of initial surgical treatment of non small cell lung cancer (NSCLC) with the incidence and time to local recurrence (LR) and disease-free survival (DFS), as well as to determine in what way these parameters and LR localizations affect the possibility for surgical retreatment. METHODS: The research was conducted on 114 patients with NSCLC and LR that had initial surgery in two reference institutes in Serbia from January 2002 to December 2010. PT size and disease stage were defined according to the revised 2004 WHO classification. PTs were grouped by size into 3 categories. Due to great diversity, surgical procedures were sorted into 6 operation types. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analyses showed significant difference in DFS and LR reoperability that were related to PT size, disease stage and the extent of initial surgery. LR localization on the chest wall was favorable for secondary surgery due to LR. CONCLUSIONS: Squamous cell lung carcinoma relapses locally more frequently than other lung tumor types, and the commonest LR site is the chest wall. This localization provides high possibility for surgical retreatment. Adequate staging, proper indications for surgical treatment and quality surgery provide longer DFS in patients with NSCLC. All these suggest that the surgeon may be considered as the most significant factor of prognosis.

HUMAN SUBCUTANEOUS DIROFILARIASIS - CASE REPORT.

INTRODUCTION: Human dirofilariasis is a zoonotic disease caused by Dirofilaria repens and Dirofilaria immitis. It usually presents as a nodular lesion in the lung, subcutaneous tissues or eyes. In animals, dirofilariasis is a very common disease with serious cardiovascular and respiratory manifestations. If adequate therapy is not given at the beginning ofthe disease, dirofilariasis can lead to animal death. On the contrary, human dirofilariasis is frequently mild, sporadic and asymptomatic disease. Complications in humans are very rare. In Europe, human dirofilariasis is a very rare zoonotic disease even in endemic areas such as Italy, Spain and the Mediterranean. CASE REPORT: The authors reported the case of a 43-year-old male with a subcutaneous nodule caused by Dirofilaria repens. The patient who lives in Budva, Montenegro, had a nodule in the right-hand side of the anterior abdominal walljust below the sternum with maximum diameter of 3 cm. His health condition was good and all laboratory analyses were normal. The lesion was surgically removed and the histopathological examination confirmed the parasitic infection by Dirofilaria repens. After surgical excision, the patient was treated with dual antimicrobial therapy (100 mg doxycycline per os twice a day for 28 days and 200 mg albendazole per os twice a day for 10 days). CONCLUSION: It is very difficult to make the diagnosis of a subcutaneous nodule. The difficulties arise in the differential diagnosis because subcutaneous nodules are suspected to be malignant neoplasm or other pathologies such as tuberculosis, fungal infections, sebaceous cysts, hamartomas, abscesses, and so on. Although human dirofilariasis is a rare disease, the number of reported cases has recently been increasing worldwide.

Decreased Interferon γ Production in CD3+ and CD3- CD56+ Lymphocyte Subsets in Metastatic Regional Lymph Nodes of Melanoma Patients.

As lymphogenic dissemination is very common in melanoma, regional lymph nodes (LN)s represent first immunological barriers to tumor invasion and play a complex role in antitumor immune defense. In this sense, their most prominent role is the presentation of tumor-derived antigens to naïve T cells and generation of cell-mediated adaptive immune response. Since tumor micro-environment affects immune cell function in this study we have evaluated the ability of T cells and NK cells in metastatic (involved) and non-metastatic regional LNs to produce interferon γ (IFNγ), a pleiotropic cytokine that regulates adaptive antitumor immune response. Our results show reduced IFNγ production in both T and NK lymphocyte subsets and decreased prevalence of T cells in metastatic regional LNs of melanoma patients. The decrease of IFNγ production in T cells was more pronounced with increased number of involved regional LNs indicating tumor-induced functional impairment of both T and NK cell lymphocyte subsets in involved regional LNs. Therefore, shown low IFNγ production in metastatic LNs may represent an obstacle in adaptive cell-mediated antitumor immune response and hence may enable tumor progression.