Biomarkers as prognostic and predictive factors in patients with hepatocellular carcinoma undergoing radiological oncological interventions.

BACKGROUND: Hepatocellular carcinoma is the most common malignant liver tumor in adults and thermal ablation and transarterial embolization are important methods of therapy. Thermal ablation can be used in early stages. Methods based on the transarterial approach, especially transarterial chemoembolization, play an important role in intermediate stage diseases. The success of procedures depends not only on the biological nature and the size of the tumor, on the technical design of the procedure and on the patient's response to treatment, but also on the molecular changes associated with these procedures. In addition to classic predictive and prognostic factors including age, patient comorbidities, Child-Pugh score, tumor characteristics, presence of large surrounding vessels, and portal vein thrombosis, molecular prognostic and predictive factors (serum biomarkers) are often mentioned in studies. Currently, only a-fetoprotein is routinely used as a prognostic biomarker; however, there are studies referring to new serum biomarkers that can potentially help to classical markers and imaging methods to determine the cancer prognosis and predict the success of therapy. These biomarkers most often include g-glutamyltranspeptidase, des- g-carboxyprothrombin, some types of microRNAs, inflammatory and hypoxic substances, whose serum levels are changed by the intervention therapies. Evaluation of these molecules could lead to the optimization of the medical intervention (choice of therapy method, timing of treatment) or change the management of patient follow-up after interventions. Although several biomarkers have shown promising results, most serum biomarkers still require validation in phase III studies. PURPOSE: The aim of this work is to present a comprehensive overview of classical and molecular biomarkers that could potentially help in the prognostic stratification of patients and better predict the success and effect of radiological intervention methods.

Correlation of survival length after pancreaticoduodenectomy for pancreatic head adenocarcinoma depending on tumor characteristics detected by means of computed tomography and resection margins status.

Pancreatic carcinoma is an aggressive tumor with a grim prognosis. Accurate staging is essential for indicating surgery in patients with borderline resectable tumors. This paper examines the correlation between pre-operation characteristics of tumors found on CT, infiltration of individual resection margins as confirmed by a pathologist, and the survival of patients with resectable pancreatic head ductal adenocarcinoma. This prospective cohort study involved patients operated on for pancreatic head adenocarcinoma, which was clearly resectable based on the staging CT and intraoperative observation between 2011-2014. Only patients without postoperative complications who underwent adjuvant chemotherapy were analyzed. Seventy-nine patients were assessed, of which 16 (20.3%) had R0 resection and 63 (79.7%) had R1 resection. Patients with R1 results had up to 2.7 times higher risk of death than patients with R0 resection. We found a trend towards shorter survival associated with a closer relationship of the tumor to the superior mesenteric vein/portal vein (SMV/PV) wall in the pre-operation CT examination. Patients with a tumor interface between the vein wall of up to 180 ° circumference had up to 1.97 times higher risk of death than patients without (p=0.131). The results of our work confirmed that in our center, even surgically treated, clearly resectable pancreatic head tumors still have a high occurrence of positive surgical margins (R1 resection) and that tumors with R1 resection had statistically significantly reduced survival compared to R0 resection. A trend for shorter overall survival was found after tumor resection depending on the increasing interface between the tumor and the SMV/PV wall, but this result was not statistically significant.

Our experience with transanal total mesorectal excision (TaTME) procedures in middle and distal rectal tumors.

INTRODUCTION: Transanal total mesorectal excision (TaTME) is a relatively new approach in surgical treatment of rectal cancer. There are no clear indications when to choose this strategy. It is a technically demanding procedure for the surgeon with a long learning curve, which should also be taken into account in evaluation of this method. The results of both oncological and postoperative complications must be properly evaluated to explore the benefit of TaTME. The aim of this study is to assess the potential benefit of TaTME compared to other alternatives in middle and distal rectal tumors. METHODS: Retrospective evaluation of patients undergoing TaTME procedure performed by one team of surgeons between October 2014 and June 2019. The authors analyzed demographic indicators of the group of patients, tumor characteristics, specimen quality, early postoperative complications and the possibility of stoma reversal. RESULTS: A total of 93 patients underwent TaTME procedure for middle and distal rectal cancer. Mean BMI was 27.6 (4.8). T3 or T4 tumor was found in 73 (78.5%) patients, 68 (73.1%) patients had positive lymph nodes and 12 (12.9%) patients were treated for synchronous metastatic rectal cancer. Neoadjuvant therapy was used in 80 (86%) patients. Conversion to open laparotomy was necessary in one case (1%). Stapled anastomosis was performed in 37 (39.7%) cases, handsewn in 56 (60.2%). A positive circumferential resection margin (CRM) was found in 10 (10.7%) cases. Distal resection margin (DRM) was positive in 3 (3.2%) patients. Pathological analysis showed a complete mesorectum in 18 patients (19.4%), nearly complete in 39 (41.9%) and an incomplete mesorectum in 36 (38.7%). Complications in the first 30 days after primary surgery were observed in 38 (40.8%) patients, mainly for anastomotic leak (19 patients, 20.4%). Reoperation was required in 7 (7.5%) patients. Permanent colostomy had to be performed in 4 (4.3%) cases. No patient died after surgery. CONCLUSION: In a selected group of patients it is possible to perform resection using this approach with acceptable postoperative morbidity and quality of the specimen. We used TaTME procedure in patients expected to have difficult TME due to obesity, size and distal localization of tumor. The incidence of conversion to open surgery was very low. Further studies for long term oncological outcomes are needed.

Synchronous liver metastases of rectal cancer and the possibility of simultaneous resection.

Treatment of metastatic rectal cancer and liver metastases continues to pose a major challenge. Synchronous liver metastases are present in up to one fifth of patients diagnosed with rectal carcinoma. Multidisciplinary cooperation is essential for determination of the consequent diagnostic and therapeutic plan. Only tight collaboration of experts from different medical fields allows for optimal timing of various medical procedures leading to a maximal benefit for the patient. Given the complexity of the problem, different specific methods and combinations thereof are applied in the course of the therapy, making the design of straightforward guidelines impossible. Since open surgery is complicated by the vastly distant locations of the rectum and liver, minimally invasive approach brings more perspectives in simultaneous surgery. A novel possibility of robotic and/or laparoscopic surgery performed by two teams is currently being developed. Despite the progress in surgical technology, optimal strategy has not yet been established.

[Molecular biological diagnostics of KRAS and BRAF mutations in patients with colorectal cancer - laboratory experience]. / Molekulárne biologická diagnostika mutací genu KRAS a BRAF u pacientu s kolorektálním karcinomem - zkusenosti laboratorního pracoviste

BACKGROUND: Targeted biological therapy based on blocking growth factor receptors and inhibition of cancer-inducing signaling pathways is a new treatment facility for patients with colorectal cancer (CRC). Therapeutic agents are monoclonal antibodies targeting epidermal growth factor receptor (EGFR). Gene aberrations in the EGFR-induced pathways are negative predictors of therapeutic response. Determination of -non-mutated KRAS is a requirement for the indication of targeted anti-EGFR therapy in the present time, BRAF mutation analysis is recommended. Comparison of our results with published data and verification of routine laboratory methods in relation to diagnostic kits were the purposes of this study. PATIENTS AND METHODS: In addition to routine methods based on PCR, direct sequencing as well as two diagnostic kits for KRAS (codon 12 and 13) and BRAF (codon 600) mutation analysis were used for 132 patients. RESULTS: KRAS mutations were detected in 45 patients (34%), V600E mutation of the BRAF gene in 9 patients (7%). Both mutations simultaneously were not detected. Tissues from primary tumor and metastases were available from 33 patients. KRAS mutation was detected in 13 cases of this group. KRAS mutations in tumor and metastasis were of the same type in 9 patients; types of mutation in both tissues were different in one case. KRAS mutation only in one tissue was detected in 3 cases. BRAF mutation in both tissues was detected in the 4 patients. A low percentage of tumor cells in 17 patients specimen did not allow performance of routine analysis and diagnostic kit was used. CONCLUSION: The frequency of KRAS and BRAF mutations in our cohort of patients corresponds to published data. The suitability of metastatic tissue analysis due to tumor heterogeneity was confirmed. KRAS analysis requires a comprehensive methodological approach with regard to reduced DNA quality and different percentage of tumor cells in tissue. For this reason, commercial diagnostic kits constitute a suitable supplement to standard methods.

[A case report: patient with advanced ovarial tumour and supporting care]. / Kazuistika: Podpurná lécba u pacientky s rozsáhlým tumorem ovaria.

BACKGROUND: The primary aim of palliative treatment is to improve the quality of life, followed by prolongation of overall survival. The effective regimens are usually complicated by increased side effects, particularly hematologic. Under these conditions, useful treatment is difficult and less effective. CASE: We present the case of a patient with cancer of the abdominal and pelvic cavity (the origin was likely an ovary). The patient was treated with intensive chemotherapy (15 cycles of carboplatin and paclitaxel) and supportive care (30 doses of epoetin alpha and 2 doses of 48MIU G-CSF for neutropenia G4). CONCLUSION: A good quality of life and long-term persistent complete remission (6 months) was achieved, no transfusion, no hospitalization. Overall survival was 61 months.

Cetuximab-induced cutaneous toxicity.

BACKGROUND: Epidermal growth factor receptor inhibitors are recently utilized by oncologists in advanced cases of certain malignancies. However, these agents are associated with numerous cutaneous adverse reactions. OBJECTIVE: To systematically review the cutaneous toxicity of cetuximab-treated patients. METHODS: An analysis of a series of 24 patients (20 men and 4 women) treated with cetuximab (12 patients with head and neck cancer and 12 patients with colorectal cancer) was performed with respect to relevant clinical characteristics. RESULTS: A total of 22 patients (91.7%) developed pustular or maculopapular follicular eruption, often referred to as acneiform rash. One patient (4.2%) developed paronychia in the course of cetuximab therapy. All patients with head and neck cancer had a combination treatment with radiotherapy and experienced radiation dermatitis accompanied by skin xerosis. Anaphylactic reaction was observed in three patients (12.5%). CONCLUSIONS: The most frequent cutaneous side effect reported in this series was acneiform eruption. The authors observed that all women with acneiform rash had only limited facial involvement, whereas all but one man experienced more widespread lesions of the face, the back and the chest. We found no association between the extent and severity of cutaneous eruptions (grade 1 vs. grade 2) and patients' response to therapy.