Hormone receptor conversion in metastatic breast cancer.

Background/Objective: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer. Materials and methods: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019. Results: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039). Conclusions: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions.

The Role of Serum Tumor Markers in Follow-up After Surgical Treatment of Malignant Lung Tumors.

AIM: The aim of this study was to evaluate the utility of selected tumor markers for the detection of lung cancer recurrence during follow-up. PATIENTS AND METHODS: The study group consisted of 109 patients and 109 healthy controls. The following biomarkers were selected: Carcinoembryonic antigen; cytokeratin fragment 19; neuron-specific enolase; tissue polypeptide-specific antigen; cytokeratin fragments 8, 18 and 19; insulin-like growth factor 1; pro-gastrin-releasing peptide; and 25-hydroxyvitamin D. The biomarkers were assessed individually or using a multivariate analysis. RESULTS: Carcinoembryonic antigen [area under the receiver operating characteristics curve (AUC)=0.6857, p<0.0001] and cytokeratin fragment 19 (AUC=0.6882, p<0.0001) proved best in detecting relapse. The multivariate model indicated insulin-like growth factor 1 (p=0.0006, AUC=0.6225) as the third most useful biomarker. The multivariate model using these three markers achieved the best AUC value of 0.7730 (p=0.0050). CONCLUSION: We demonstrated that carcinoembryonic antigen and cytokeratin fragment 19 play a key role in the detection of lung cancer recurrence. A multivariate approach can increase the effectiveness of detection.

[Descending Necrotising Mediastinitis: the Choice of Drainage]. / Deszendierende nekrotisierende Mediastinitis: Wahl der Drainage.

INTRODUCTION: Descending necrotising mediastinitis (DNM) is a rare, but very severe, septic condition, caused by the spread of infection from the neck to the mediastinum. Delay in diagnosis and inadequate surgical procedures may lead to a life-threatening situation. MATERIAL: We retrospectively evaluated a group of patients who suffered from DNM and were treated in our department by mediastinal drainage in the last 10 years (2010 - 2019). All patients required one of the following methods of drainage: cervicomediastinal, mediastinothoracic or cervicomediastinothoracic "Rendevouz" drainage (MTC-D). In the group, we evaluated the source of infection, microbiologic findings, method of mediastinal drainage, length of hospitalisation, ventilation duration and inflammatory laboratory parameters. RESULTS: In total, we treated 22 patients with DNM, including 14 men and 8 women, aged 23 - 85 years, with a mean age of 54.1 years. After the spread of infection, in 8 cases the initial cervicomediastinal type of drainage had to be followed by one of the types of thoracic drainage. As the final method, in 8 patients we chose irrigation drainage from the cervical approach, from thoracotomy in 6 cases and in 8 cases irrigation CMT-D. The method of mediastinal drainage was chosen according to the initial CT findings, and further intervention was chosen according to CT signs during the treatment. Four patients died of DNM (mortality 18.2%). Pharyngeal focus was responsible for 15 cases of DNM; odontogenic infection caused 6 DNM cases; in 1 case the origin was unclear. Although we always chose the method individually and CMT-D for the most difficult cases, there were no statistically significant (p < 0.05) differences between the evaluated parameters. For CMT-D, there was even a shorter hospital stay (not significant) and ventilation duration. CONCLUSION: In cases of DNM with severe inflammation of caudal and distal compartments of the mediastinum we consider CMT-D as an ideal method of treatment. This appraoch is radical enough and in our group of patients, despite the severity of this illness, both the length of treatment and mortality were sufficient.

Outcomes and Prognostic Factors Following Surgical Treatment of Pulmonary Metastases from Colorectal Carcinoma.

BACKGROUND/AIM: The lungs are the second most common site of cancer dissemination. The aim of this study was to analyze a cohort of patients operated for pulmonary metastases from colorectal carcinoma over a period of 18 years. PATIENTS AND METHODS: In a group of 104 patients, relations were sought between overall survival or disease-free survival and preoperative levels of selected biomarkers, number of metastases and the condition of the intrathoracic lymphatic nodes. Median observation period was 63 months. RESULTS: The 5-year survival rate was 54.3%. Risk of disease progression and risk of death increases in case of occurrence of 2 or more metastases, affection of intrathoracic lymph nodes and levels of CA 19-9, TPS or CEA above cut-off value. CONCLUSION: Prognostic factors that determine overall survival as well as disease-free survival are the number of metastases, the condition of intrathoracic lymphatic nodes and the preoperative levels of biomarkers.

Prognostic Significance of Lymph Node Examination by the OSNA Method in Lung Cancer Patients-Comparison with the Standard Histopathological Procedure.

The aim of the study was to compare the prognostic significance of lymph node status of patients with lung cancer analyzed by three different methods: hematoxylin and eosin (H&E), immunohistochemistry of cytokeratin 19 (IHC CK19), and One-Step Nucleic Acid Amplification (OSNA). The clinical relevance of the results was evaluated based on relation to prognosis; the disease-free interval (DFI) and overall survival (OS) were analyzed. During radical surgical treatment, a total of 1426 lymph nodes were obtained from 100 patients, creating 472 groups of nodes (4-5 groups per patient) and examined by H&E, IHC CK19 and OSNA. The median follow-up was 44 months. Concordant results on the lymph node status of the H&E, IHC CK19 and OSNA examinations were reported in 78% of patients. We recorded shorter OS in patients with positive results provided by both OSNA and H&E. The study demonstrated a higher percentage of detected micrometastases in lymph nodes by the OSNA method. However, the higher sensitivity of the OSNA, with the cut-off value 250 copies of mRNA of CK19/µL, resulted in a lower association of OSNA positivity with progress of the disease compared to H&E. Increasing the cut-off to 615 copies resulted in an increase in concordance between the OSNA and H&E, which means that the higher cut-off is more relevant in the case of lung tumors.

Long-term Results of Surgery for Colorectal Liver Metastases in Terms of Primary Tumour Location and Clinical Risk Factors.

BACKGROUND/AIM: The aim of the study was to evaluate the influence of primary tumour location and clinical risk factors for long-term results of surgery for colorectal liver metastases (CLMs). PATIENTS AND METHODS: Overall survival (OS) and recurrence-free survival (RFS) were evaluated in 636 patients. Patients were divided by tumour location (right-/left-sided colorectal cancer: RCRC/LCRC; rectal cancer), and age, gender, number and size of CLMs, type of liver surgery and interval from primary operation were evaluated. RESULTS: One-, 3- and 5-year OS and RFS were independent of primary tumour location (p<0.59). CLM diameter was negatively associated with OS for the whole cohort (p<0.002), and RCRC (p<0.03) and LCRC (p<0.04) groups, as well as for RFS of those with LCRC (p<0.04). CLM number was negatively associated with RFS for the whole cohort (p<0.0001), RCRC (p<0.02), LCRC (p<0.0001) and RC (p<0.02). Radiofrequency ablation and combined procedures led to worse OS for the whole cohort (p<0.03), and to worse RFS for the whole cohort (p<0.0003) and for those with LCRC (p<0.03). A shorter interval between primary colorectal cancer surgery and CLMs procedure was risky for poor OS and RFS of patients with CLMs from RCRC (p<0.05), LCRC (p<0.05) and RC (p<0.02). CONCLUSION: Primary tumour location together with clinical risk factors are important for long-term results of surgery CLMs.

Monoclonal antibody against transforming growth factor Beta 1 does not influence liver regeneration after resection in large animal experiments.

BACKGROUND: Steatohepatitis is a type of histopathological liver injury that can be caused by chemotherapy [chemotherapy-associated steatohepatitis (CASH)] and can progress to liver fibrosis or cirrhosis. CASH impairs liver functions, including liver regeneration. Impaired liver regeneration reduces the number of patients who can undergo liver resection and reduces opportunities for curative therapies. Transforming growth factor-beta (TGFß) is a potent mitotic inhibitor that participates during the last phase of liver regeneration. TGFß has been studied as a potential solution to the development of liver fibrosis or hepatocellular carcinoma. AIM: The first aim of our study was to establish a large animal model of toxic liver injury and test the ability of a monoclonal antibody against TGFß (MAB-TGFß) to increase liver-regeneration capacity. The second aim was to evaluate the degree to which early preoperative administration of MAB-TGFß influenced hepatic parenchyma regeneration following healthy liver resection in a swine experimental model. MATERIALS AND METHODS: Toxic liver injury was induced by alcohol consumption and regular intraperitoneal administration of carbon tetrachloride (CCl4) to piglets for 10 weeks. After 10 weeks, the piglets underwent liver resection of the left lateral and left medial liver lobes. Twenty-four hours after liver resection, MAB-TGFß was administered to the experimental group (10 piglets) and a physiological solution to the control group (10 piglets) through an implemented port-a-cath. In the second part of the study, either MAB-TGFß or a saline solution control were administered at 12 and 4 days prior to resection of the right lobes of healthy liver (six experimental and 10 control group subjects). Observation and follow-up was performed throughout the entire experiment. Ultrasound and biochemical tests (for albumin, cholinesterase, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, bilirubin, urea, creatinine and ammonia levels) were performed on postoperative days 1, 3, 7, 10 and 14. A histopathological examination was performed after sacrificing the animals on the 14th postoperative day. RESULTS: No significant differences were observed between groups when using ultrasound volumetry to assess the regenerative volume of the liver in both experiments. The only significant differences found when comparing biochemical parameters between groups were higher serum levels of both creatinine and γ-glutamyl transferase in the experimental group with preoperative administration of MAB-TGFß. There were no differences in the histological analyses of hepatic lobule cross-sectional area nor in the proliferative index between animals receiving MAB-TGFß and those treated with physiological saline solution before resection. Hepatocytic cross-sectional areas were larger in animals treated with physiological solution versus those treated with MAB-TGFß on the operative day; however, these values were comparable between groups by 14 days following resection. CONCLUSION: We established a large animal model of toxic liver injury that is comparable with CASH. The toxic injury that was induced without pause between administrations was probably more extensive than occurs in CASH, and there was no effect of MAB-TGFß administration on liver regeneration. MAB-TGFß administration did not lead to any observable side-effects, indicating that it could be a promising solution for use as an oncologic-targeted treatment.