1531. Oral treatment with etoposide in small cell lung cancer - dilemmas and solutionRenata Režonja, Lea Knez, Tanja Čufer, Aleš Mrhar, 2013, review article Abstract: Background. Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be atrisk for excess toxicity. Conclusions. The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice. Keywords: oral etoposide, bioavailability, pharmacokinetic variability, small cell lung cancer, treatment Published in DiRROS: 22.03.2024; Views: 265; Downloads: 101
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1532. A review of the treatment options for skin rash induced by EGFR-targeted therapies : evidence from randomized clinical trials and a meta-analysisJanja Ocvirk, Steffen Heeger, Philip McCloud, Ralf-Dieter Hofheinz, 2013, original scientific article Abstract: Background. Agents targeting the epidermal growth factor receptor (EGFR) are amongst the most extensively used of the targeted agents in the therapy of some of the most common solid tumors. Although they avoid many of the classic side effects associated with cytotoxic chemotherapy, they are associated with unpleasant cutaneous toxicities which can affect treatment compliance and impinge on patient quality of life. To date, despite a plethora of consensus recommendations, expert opinions and reviews, there is a paucity of evidence-based guidance for the management of the skin rash that occurs in the treatment of patients receiving EGFR-targeted therapies. Methods. A literature search was conducted as a first step towards investigating not only an evidence-based approach to the management of skin rash, but also with a view to designing future randomized trials. Results. The literature search identified seven randomized trials and a meta-analysis was conducted using the data from four of these trials involving oral antibiotics. The meta-analysis of the data from these four trials suggests that prophylactic antibiotics might reduce the relative risk of severe rash associated with EGFR-targeted agents by 4277%. Vitamin K cream was also identified as having a potential role in the management EGFR-targeted agent induced rash. Conclusions. This review and meta-analysis clearly identify the need for further randomized studies of the role of oral antibiotics in this setting. The results of the ongoing randomized trials of the topical application of vitamin K cream plus or minus doxycycline and employing prophylactic versus reactive strategies are eagerly awaited. Keywords: acne-like skin rash, cetuximab, erlotinib, gefitinib, panitumumab, vitamin K Published in DiRROS: 22.03.2024; Views: 396; Downloads: 285
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1533. Long term follow-up report of cardiac toxicity in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantationMirta Koželj, Samo Zver, Vesna Zadnik, 2013, original scientific article Abstract: Background. Tandem autologous hematopoietic stem cell transplantation (ta-HSCT) is a standard treatment for multiple myeloma (MM). Patients receive a high-dose cyclophosphamide (CY), followed by two myeloablative cycles of melphalan (MEL). There are scarce data about long term cardiotoxicity. Patients and methods. We studied 12 patients (62.25 8.55 years) six years after the completion of MM treatment with ta-HCST. Late cardiotoxic effects were evaluated clinically and echocardiographically. Results. None of the patients developed clinical signs of heart failure, all were in sinus rhythm and NT-pro BNP concentration was elevated (778 902.76 pg/mL). The left ventricular (LV) size remained normal. The LV ejection fraction did not decrease (73.75 5.67%, 69.27 6.13%, p = NS). The LV diastolic function parameters (E, A, ratio E/A and A/a) did not change significantly. In tissue Doppler parameters we observed a nonsignificant decrease in Em (10.26 2.63 cm/s, 7.57 1.43 cm/s) and Sm velocities (8.7 0.87 cm/s, 7.14 1.17 cm/s, p = NS). The E/Em values were in an abnormal range (8.66 1.05, 10.55 2.03). Conclusions. The treatment of MM with ta-HSCT, during which patients receive a high dose CY followed by two myeloablative cycles of MEL, causes mild, chronic, partially reversible and clinically silent cardiotoxic side-effects. However, ta-HSCT in patients with MM is a safe regarding cardiotoxic side effects, but, because of increasing life expectancy needs long term attention. Keywords: cardiotoxicity, echocardiography, myeloma Published in DiRROS: 22.03.2024; Views: 343; Downloads: 88
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1534. Comparison of continuous local anaesthetic and systemic pain treatment after axillary lymphadenectomy in breast carcinoma patients - a prospective randomized studyBranka Stražišar, Nikola Bešić, 2013, original scientific article Abstract: Background. Acute pain after axillary lymphadenectomy is often related mainly to axillary surgery. The aim of the prospective randomized study was to find out if continuous wound infusion of local anaesthetic reduces postoperative pain, consumption of opioids and the incidence of chronic pain compared to the standard intravenous piritramide analgesia after axillary lymphadenectomy in breast carcinoma patients. Methods. Altogether 60 patients were enrolled in the prospective randomized study; half in wound infusion of local anaesthetic and half in the standard (piritramide) group. Results. In the recovery room and on the first day after surgical procedure, the wound infusion of local anaesthetic group reported less acute and chronic pain, a lower consumption of piritramide and metoclopramide, but their alertness after the surgical procedure was higher compared to the standard group. Conclusions. After axillary lymphadenectomy in breast carcinoma patients, wound infusion of local anaesthetic reduces acute pain and enables reduced opioid consumption, resulting in less postoperative sedation and a reduced need for antiemetic drugs. After wound infusion of local anaesthetic there is a statistical trend for reduction of chronic pain. Keywords: breast carcinoma, pain treatment, acute pain Published in DiRROS: 22.03.2024; Views: 369; Downloads: 90
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1535. Uterine perforation - 5-year experience in 3-D image guided gynaecological brachytherapy at Institute of Oncology LjubljanaBarbara Šegedin, Jasenka Gugić Kevo, Primož Petrič, 2013, original scientific article Abstract: Background. Accurate applicator placement is a precondition for the success of gynaecological brachytherapy (BT). Unrecognized uterine perforation can lead to bleeding, infection, high doses to pelvic organs and underdosage of the target volume, resulting in acute morbidity, long-term complications and reduced chance of cure. We aimed to assess the incidence and clinical characteristics of our cases with uterine perforation, review their management and impact on the treatment course. Patinets and methods. In all patients, treated with utero-vaginal image guided BT for gynaecological cancer between January 2006 and December 2011, the CT/MR images with the applicator in place were reviewed. The incidence of uterine perforations was recorded. Clinical factors that may have predisposed to increased risk of perforation were recorded. Management of perforations and their impact on treatment course was assessed. Results. 219 patients (428 applications) were suitable for analysis. Uterine perforation was found in 13 (3.0%) applications in 10 (4.6%) patients. The most frequent perforation site was posterior uterine wall (n = 9), followed by anterior wall (n = 2) and fundus (n = 2). All cases were managed conservatively, without complications. Prophylactic antibiotics were administered in 8 cases. In 4 patients, abdominal and/or transrectal ultrasound (US) guidance was used on subsequent applications for applicator insertion; adequate applicator placement was achieved and treatment completed as planned in all cases. Conclusions. 3D imaging for BT planning enables accurate identification of uterine perforations. The incidence of perforations at our department is one of the lowest reported in the literature. US guidance of applicator insertion is useful and feasible, allowing to complete the planned treatment even in challenging cases. Keywords: uterine perforation, brachytherapy, 3D imaging, ultrasound guidance Published in DiRROS: 22.03.2024; Views: 285; Downloads: 90
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1536. The correlation between the levels of tissue inhibitor of metalloproteinases 1 in plasma and tumour response and survival after preoperattive radiochemotherapy in patients with rectal cancerIrena Oblak, Vaneja Velenik, Franc Anderluh, Barbara Možina, Janja Ocvirk, 2013, original scientific article Abstract: Background. The aim of this study was to analyse whether the level of tissue inhibitor of metalloproteinases (TIMP) 1 is associated with the tumour response and survival to preoperative radiochemotherapy in rectal cancer patients. Patients and methods. Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I- III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA). Results. Median follow-up time was 68 months (range: 3-93 months) while in survivors it was 80 months (range: 68-93 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22-523 ng/mL) and the mean level (standard deviation) was 192 (87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP>12 mg/L and in those who died from rectal cancer or had cT4 tumours. No correlation was established for age, gender, carcinoembriogenic antigene (CEA) level, platelets count, histopathological grade, response to preoperative therapy, resectability and disease reappearance. On univariate analysis, various parameters favourably influenced one or more survival endpoints: TIMP-1 <170 ng/mL, CRP <12 mg/L, platelets count <290 10E9/L, CEA <3.4mg/L, age <69 years, male gender, early stage disease (cN0 and/or cT2-3), radical surgery (R0) and response to preoperative radiochemotherapy. In multivariate model, LRC was favourably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage. Conclusions. Although we did not find any association between pretreatment serum TIMP-1 levels and primary tumour response to preoperative radiochemotherapy in our cohort of patients with rectal cancer, TIMP-1 levels were recognized as an independent prognostic factor for OS in these patients. Keywords: rectal cancer, radiochemotherapy, tissue inhibitor of metalloproteinases Published in DiRROS: 22.03.2024; Views: 312; Downloads: 84
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1539. Early outcome in endoscopic extended endonasal approach for removal of supradiaphragmatic craniopharyngiomas : a case series and a comprehensive reviewRoman Bošnjak, Mitja Benedičič, Alenka Vittori, 2013, original scientific article Abstract: Background. The choice of endoscopic expanded endonasal approach introduces the possibility of improved gross total resection of craniopharyngioma while minimizing surgical morbidity in a significant subset of patients. Methods. From our trans-sphenoidal surgical series of 331 cases, we retrospectively reviewed visual, endocrine and neuro-cognitive outcomes in the first consecutive eight patients (median age 63 years; range 4773 years) with newly diagnosed supradiaphragmatic craniopharyngioma (median tumour height 23 mm; range 1534 mm), removed by expanded endonasal approach (median follow-up 27 months; range 1069 months). Gross total resection was attempted in all patients. Results. Gross total resection was achieved in 6 of 8 patients. Visual improvement was present in 6 of 8 patients of patients or in 14 of 16 eyes. New endocrinopathy, including diabetes insipidus, appeared in 5 of 8 patients. Stalk was preserved in 4 patients. Cognitive decline was present in 2 cases. Five of 8 patients retained previous quality of life. Conclusions. Our early outcome results are comparable to the recent few expanded endonasal approach series, except for the incidence of new endocrinopathy and cerebrospinal fluid leak rate. This was influenced by higher number of transinfundibular tumours in our series, where stalk preservation is less likely, and not using nasoseptal flap or gasket closure in the first half of cases. Including data from the literature and ours, expanded endonasal approach shows a trend for improved gross total resection rate with less morbidity, more obviously for visual outcome and quality of life than for endocrine outcome. However, validity of expanded endonasal approach should be confirmed in a larger number of patients with a longer follow-up period. Published in DiRROS: 22.03.2024; Views: 256; Downloads: 91
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1540. Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patientsAleš Rozman, Mira Šilar, Mitja Košnik, 2012, original scientific article Abstract: Background. Lung cancer is the leading cause of cancer deaths. Angiogenesis iscrucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. Patients and methods. Clinical data, blood samples and broncho-alveolar lavage(BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. Results. We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affectedside of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage ofdisease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. Conclusion. Angiogenin and VEGF concentrations insystemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF. Published in DiRROS: 22.03.2024; Views: 357; Downloads: 104
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