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Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The aim of the study was to perform a retrospective analysis of patients who had undergone laparoscopic resection for pancreatic cancer (PC) at the Department of Surgery of the Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic from 2010 to 2023., Methods: Forty-six patients with laparoscopic (n=19) or open (n=27) distal pancreatectomy (DP) for PC were included. Both groups were statistically evaluated and compared in the following parameters: clinical stage, tumor grade, nodes examined by the pathologist, blood loss, duration of surgery, three-month morbidity and mortality, length of ICU stay, overall length of hospital stay, readmission rate and overall survival., Results: There were more T3 tumors in the open DP group (81.5% vs 57.9%, p=0.035). The rate of dedifferentiated (G3) tumors was higher in the open DP group (18.5% vs 5.3%, p=0.354). The mean number of nodes examined by the pathologist was equal in both groups (open DP 15.1 (min- max, 3-39) vs lapDP 15.6 (min-max, 5-39). Laparotomy was associated with a higher mean blood loss (531 ml vs 198 ml, p=0.002). However, it was shorter on average (190 minutes vs 216 minutes, p=0.006). Clinically relevant complications (Dindo III and higher) and POPF (types B and C) were observed in 10/46 (21.7%) and 14/46 (30.5%) cases without any statistically significant difference between both groups (p=0.489 and p=0.241, respectively). The median ICU stay was similar for lapDP and open DP (median: 5.0 days vs 6.0 days, p=0.396). Overall length of hospital stay was identical in both groups (median: lapDP 12.0 days vs open DP 12 days, p=0.920). The three-month readmission rate was 5/46 (10.9%). One-, 2-, 3and 5-year overall survival probability after laparoscopic and open DP was 76.9% (95% CI 59.4-99.7%), 61.5% (95% CI 41,1-92.2%), 41.0% (95% CI 20,5-82.2%) and 20.5% (95% CI 6.2-68.2%), and 73.4% (95% CI 58.3-92.4%), 33.1% (95% CI 18,9-57.9%), 20.7% (95% CI 9.5-44.9%) and 20.7% (95% CI 9.5-44.9%), respectively. No statistically significant difference was observed between both groups (p=0.484)., Conclusion: When comparing lapDP and open DP performed for pancreatic cancer, our experience confirmed that lapDP was particularly suitable for patients with smaller tumors located further from the porto-mesenteric axis. The laparoscopic approach was associated with lower blood loss, reduced length of ICU stay, comparable morbidity and overall survival. The relatively long length of hospital stays, surprisingly identical in both groups, prompted us to implement the ERAS (Enhanced Recovery After Surgery) protocol in this surgical field.

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.

Background: Hepatocellular carcinoma (HCC) is a major contributor to the worldwide cancer burden. Recent studies on HCC have demonstrated dramatic alterations in expression of several cytochrome P450 (CYP) family members that play a crucial role in biotransformation of many drugs and other xenobiotics; however, the mechanisms responsible for their deregulation remain unclear., Methods: We investigated a potential involvement of miRNAs in downregulation of expression of CYPs observed in HCC tumors. We compared miRNA expression profiles (TaqMan Array Human MicroRNA v3.0 TLDA qPCR) between HCC human patient tumors with strong (CYP-) and weak/no (CYP+) downregulation of drug-metabolizing CYPs. The role of significantly deregulated miRNAs in modulation of expression of the CYPs and associated xenobiotic receptors was then investigated in human liver HepaRG cells transfected with relevant miRNA mimics or inhibitors., Results: We identified five differentially expressed miRNAs in CYP- versus CYP+ tumors, namely miR-29c, miR-125b1, miR-505, miR-653 and miR-675. The two most-upregulated miRNAs found in CYP- tumor samples, miR-29c and miR-653, were found to act as efficient suppressors of CYP1A2 or AHR expression., Conclusions: Our results revealed a novel role of miR-653 and miR-29c in regulation of expresion of CYPs involved in crucial biotransformation processes in liver, which are often deregulated during liver cancer progression., (© 2021. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Pancreatic ductal adenocarcinoma (PDAC) is now the 11th most common cancer and in 2018 there were 458,918 new cases worldwide. In the Czech Republic, a total of 2,173 patients were diagnosed in 2015, ranking the second in incidence worldwide. In contrast to other malignancies, recent research has not brought any major breakthrough in the treatment of PDAC and hence the prognosis remains very serious. Radical resection is the only curative approach, but after the initiation of the standard pathological evaluation of the resected tissue, according to the Leeds protocol, 80% of the resections are R1 (resections with microscopically positive margins). The results of studies in patients with borderline resectable or locally advanced PDAC prefer neoadjuvant chemotherapy or chemoradiotherapy. This approach leads to a higher number of radical R0 resections and better survival. For neoadjuvant treatment in patients with primarily resectable PDAC, most results come from retrospective analysis or phase II trials. However, recently, data from three randomized clinical trials with neoadjuvant therapy for resectable PDAC were presented. These results support the use of chemotherapy or chemoradiotherapy prior to surgery. In the trials published to date, there are differences in chemotherapeutic regimens, cytostatic doses, and the definition of resectability. Thus, up-front resection with adjuvant chemotherapy is still the standard of care and a well-designed randomized trial using neoadjuvant therapy is now necessary.

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.

Purpose: Identification of prognostic survival factors of hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) in a single center in 2005-2018., Background: Transarterial chemoembolization in hepatocellular carcinoma is indicated in Barcelona Liver Cancer Clinic (BLCC) stage B. This stage includes a very large group of patients unsuitable for curative treatment, who are in a good clinical condition and do not show extra-hepatic spread. The aim of this retrospective analysis is to identify factors influencing patient survival and to divide the patients into subgroups based on these risk factors., Materials and Methods: All patients with HCC indicated for TACE in complex oncological center in 2005-2018 were included in the analysis. The survival rates from the 1st TACE were evaluated in relation to HCC on computed tomography/magnetic resonance prior to the 1st TACE (size of the biggest lesion, single/multiple lesions, unilobar/bilobar involvement), presence and severity of liver disease (cirrhosis, Child-Pugh, portal vein thrombosis) and a combination of other invasive treatment (resection, percutaneous ablation) (single and multivariate analysis). The survival of HCC patients was compared according to the year of the dia-gnosis and the year of the 1st TACE (log-rank test)., Results: Out of 382 patients, 157 (29 women) of them were treated with TACE (540 TACEs in total, median 3 TACEs per patient). The most important risk factors for survival were the presence of portal vein thrombosis (hazard ratio (HR) = 3.279), bilobar involvement (HR = 2.257), lesion size (HR = 1.125/cm) and Child-Pugh B in chronic liver disease (HR = 1.922). Based on these risk factors, the patients were divided into 3 prognostic groups with different median survival (52.1 vs. 21.5 vs. 9.0 months)., Conclusion: Based on the retrospective analysis, predictive factors of HCC survival after TACE were identified and the patients were divided into 3 prognostic groups based on these factors.

Background: Rectal cancer treatment advanced rapidly during last decades. The most important factors of this progress are new neoadjuvant therapy options, improvement in imaging (allowing for quality staging and restaging) and routine implementation of the total mesorectal excision technique. For the best outcomes, it is crucial to combine the treatment methods in the best way possible with ideal timing. It is necessary to keep in mind both advantages and complications of the individual kinds of approach. Therefore, interdisciplinary agreement is essential in the treatment of rectal cancer. Considering these new therapeutic possibilities, the debate about timing, indication and radicality of the surgical procedures is reopened. Surgical approaches are currently focused on mini-invasive methods and robotic surgery. New trend with promising potential seems to be clinical complete response achievement with watch and wait follow-up strategy. This approach, in the spirit of the organ sparing philosophy, however asks new questions about indication, timing and conception of this method. Proper answers are essential for sparing, yet radical oncotherapy of this disease.

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.

Angiomatosis is a term for multiple, gradually proliferating hemangiomas (angiodysplasia), affecting multiple organs or tissues at the same time. We describe a 12-year course of treatment of a patient with multiple hemangiomas located in the abdomen, retroperitoneum, oesophagus, mediastinum and also in vertebrae. The diagnosis was made in 2005 within probatory laparotomy, at the age of 28 years. The treatment was commenced right after making the diagnosis with interferon α. Due to its adverse effects (fatigue, anorexia), the use of interferon α was limited to the first year, after which the interferon dose was gradually being reduced until it was discontinued completely. From 2006 to 2011 the treatment was based on thalidomide and temporarily also on lenalidomide. By the end of the year 2011 the patient was stabilized through the effect of these drugs, without a need of repeated blood transfusions. In 2012 his condition got worse again, which required several transfusions in one month. We tested metronomic administration of cyclophosphamide and further administration of propranolol, however neither of them improved the patients situation. Injections of octreotide (Sandostatin 0.1 mg twice a day) helped reduce losses during bleeding into the alimentary tract. Still the patient continued to depend on blood transfusions. Therefore, in 2013, bevacizumab was added to the therapy (7.5 mg/kg in 3-week intervals). This treatment stabilized the patient, it reduced the use of transfusions for a period of 2 years, however after 2 years of a successful therapy with bevacizumab there was disease progression shown on CT imaging and hemorrhagic pleural effusion was also detected. After the treatment of hemorrhagic effusion, early in 2015 we transferred to the administration of aflibercept, at first at the dose of 4 mg/kg in 14-day intervals. Arising of massive proteinuria led to the dose reduction to 2 mg/kg while maintaining 14-day intervals. While receiving this dose, the patient tolerates aflibercept thera-py without significant adverse effects. At the time of publication, the patient has been treated with aflibercept for 24 months already, of that for the last ten months he has been fully independent of transfusions. Just before commencement of treatment with aflibercept his conditions required several transfusions in a week. This description demonstrates that the efficiency of individual medications for multiple angiomatosis is always time-limited and newly developed and more efficient drugs are needed to manage the disease. Bevacizumab and aflibercept are beneficial for patients with serious forms of multiple angiomatosis.Key words: aflibercept - angiomatosis - angiodysplasia - bevacizumab - hemangiomas.

Bisphosphonates have been used during the complete treatment of multiple myeloma for more than twenty years. They slow osteolysis and thereby contribute to the improvement of quality of life. Their long-term use, however, is related to 2 serious, usually later appearing complications: osteonecrosis of the jaw, occurring in 6-9 % of patients, and rarer atypical bone fractures. Both these complications are very difficult to heal, and all the more emphasis is therefore laid on prevention. This first of all includes discussion about the risk with the patient, followed by a dental checkup before the commencement of therapy and then repeated during its course, as well as reduced use of these drugs for a necessary period of time. However osteonecrosis of the jaw does not only develop as a consequence of bisphosphonate therapy. The complication is also caused by some new drugs (denosumab and others) used in cancer therapies. The text includes an overview of the drugs currently used in cancer treatment, which also increase the risk of appearance of osteonecrosis of the jaw. For patients with multiple myeloma, who achieve the complete or very good partial remission after chemotherapy, it is recommended to administer these drugs for more than 1 year after achieving the positive treatment response, but not longer than for 2 years. Only regarding those who do not reach the good treatment response, bisphosphonates are administered over the long term, as long as osteolytic activity of the disease lasts.Key words: atypical bone fractures - bisphosphonates - drug induced osteonecrosis of the jaw - multiple myeloma.

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.

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.