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Objectives: Stroke volume (SV) and cardiac output monitoring is a cornerstone of hemodynamic assessment. Noninvasive technologies are increasingly used in children. This study compared SV measurements obtained by transcutaneous Doppler ultrasound techniques (ultrasonic cardiac output monitor [USCOM]), transthoracic echocardiography jugular (TTE-J), and parasternal (TTE-P) views performed by pediatric intensivists (OP-As) with limited training in cardiac sonography (20 previous examinations) and pediatric cardiologists (OP-Bs) with limited training in USCOM (30 previous examinations) in spontaneously ventilating children., Methods: A single-center study was conducted in 37 children. Each operator obtained 3 sets of USCOM SV measurements within a period of 3 to 5 minutes, followed with TTE measurements from both apical and jugular views. The investigators were blinded to each other's results to prevent visual and auditory bias., Results: Both USCOM and TTE methods were applicable in 89% of patients. The intraobserver variability of USCOM, TTE-J, and TTE-P were less than 10% in both investigators. The SV measurements by OP-As using USCOM, TTE-J, and TTE-P were 46.15 (25.48) mL, 39.45 (20.65) mL, and 33.42 (16.69) mL, respectively. The SV measurements by OP-Bs using USCOM, TTE-J, and TTE-P were 43.99 (25.24) mL, 38.91 (19.98) mL, and 37.58 (19.81) mL, respectively.The percentage error in SV with USCOM relative to TTE-J was 36% in OP-As and 37% in OP-Bs. The percentage error in SV with TTE-P was 33% relative to TTE-J in OP-As and 21% in OP-Bs., Conclusions: Our findings show that the methods are not interchangeable because SV values by USCOM are higher in comparison with the SV values obtained by TTE. Both methods have low level of intraobserver variability. The SV measurements obtained by TTE-P were significantly lower compared with the TTE-J for the operator with limited training in echocardiography. The TTE-P requires longer practice compared with the TTE-J; therefore, we recommend to prefer TTE-J to TTE-P for inexperienced operators., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Significance Statement: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches., Background: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined., Methods: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia., Results: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia., Conclusion: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy., Clinical Trial Registry Name and Registration Number: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 ., (Copyright © 2023 by the American Society of Nephrology.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Tonsillectomy is a routine surgery in otorhinolaryngology and the occurrence of postoperative bleeding is not a rare complication. The aim of this retrospective, observational, analytic, cohort study is to compare the incidence of this complication for the most common indications. A group of patients indicated for tonsillectomies for peritonsillar abscess (group I) was compared to a group of patients indicated for chronic and recurrent tonsillitis (group II). There are a lot of pathophysiological differences in patients indicated for acute tonsillectomy for peritonsillar abscess and in patients indicated for elective tonsillectomy for chronic or recurrent tonsillitis. No technique to minimize the risk of bleeding after tonsillectomy has been found and a large part of postoperative bleeding occurs in postoperative home-care, which makes this issue topical. In total, 2842 unilateral tonsillectomies from the years 2014-2019 were included in the study. Bleeding occurred in 10.03% and, surprisingly, despite completely different conditions in the field of surgery (oedema, acute inflammation in peritonsillar abscess), there was no statistically significant difference between incidence of postoperative bleeding in the studied groups ( p = 0.9920). The highest incidence of bleeding was found in the patients of group I on the eighth postoperative day, with those aged 20-24 years ( p = 0.0235) being the most at risk, and in group II, on the sixth postoperative day, with those aged 25-29 years ( p = 0.0128) and 45-49 years ( p = 0.0249) being the most at risk.

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., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Polyomavirus BK (BKV) infection of the renal allograft causes destructive tissue injury with inflammation and subsequent fibrosis., Methods: Using a prospective cohort of patients after kidney transplantation performed between 2003 and 2012, we investigated the role of BKV viraemia in the development and progression of interstitial fibrosis and tubular atrophy (IFTA). The primary outcome was moderate-to-severe IFTA assessed by protocol biopsy at 36 months., Results: A total of 207 consecutive recipients were enrolled. Of these, 57 (28%) developed BKV viraemia with 10 (5%) cases of polyomavirus-associated nephropathy (PVAN). Transient (<3 months) BKV viraemia occurred in 70% of patients, and persistent (≥3 months) BKV viraemia in 30%. A high viral load (≥10 000 copies/mL) was detected in 18% and a low viral load (<10 000 copies/mL) in 61%, while the viral load could not be determined in 21%. Moderate-to-severe IFTA was significantly increased in high [71%; odds ratio (OR) = 12.1; 95% confidence interval (CI) 1.62-90.0; P = 0.015] or persistent BKV viraemia (67%; OR = 6.33; 95% CI 1.19-33.7; P = 0.031) with corresponding rise in 'interstitial fibrosis + tubular atrophy' scores. Only patients with transient low BKV viraemia showed similar incidence and progression of IFTA to the no-BKV group. Persistent low BKV viraemia was uncommon yet the progression of fibrosis was significant. Only recipients with PVAN experienced inferior graft survival at 5 years., Conclusions: These data suggest that only transient low BKV viraemia does not negatively affect the progression of allograft fibrosis in contrast to excessive risk of severe fibrosis after high or persistent BKV viraemia., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft., Methods: From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir (n = 60) or valacyclovir (n = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population., Results: Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.90; P = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P = 0.115) and CMV DNAemia (36% versus 42%; P = 0.361) were not different at 3 years., Conclusions: Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation., Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007.

Background: Concerns regarding postoperative complications following liver resection for colorectal liver metastases (CLMs) in elderly patients may lead to preference for conservative therapy. The aim of this study was to evaluate the role of patient age in the development of postoperative complications., Patients and Methods: Surgical complications were evaluated in 712 patients who underwent surgery for CLMs over the past 13 years. Seventy-two patients (10.1%) were aged ≥75 years and 640 (89.9%) <75 years. The significance of the type of liver resection, preoperative American Society of Anesthesiologists classification (ASA), Child-Pugh classification,body mass index, quality of liver tissue and preoperative oncological treatment for the development of postoperative complications were evaluated., Results: We did not find any difference in the incidence of early postoperative complications between the two groups of patients. A preoperative ASA score of 3.4 (p<0.001) was the principal factor for developing postoperative complications in patients aged ≥75 years. Postoperative complications in patients with an ASA score of 3.4 were more frequent when the body mass index was >26 kg/m 2 (p<0.02)., Conclusion: Patient age does not represent a contraindication to liver resection for CLMs. An ASA score of 3 or 4 and a body mass index >26 kg/m 2 are risk factors for development of early postoperative complications., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: The objective of this study was to assess the impact of weather phenomena on the occurrence of spontaneous pneumothorax (SP) in the Plzeň region (Czech Republic)., Methods: A retrospective analysis of 450 cases of SP in 394 patients between 1991 and 2013. We observed changes in average daily values of atmospheric pressure, air temperature and daily maximum wind gust for each day of that period and their effect on the development of SP., Results: The risk of developing SP is 1.41 times higher (P=.0017) with air pressure changes of more than±6.1hPa. When the absolute value of the air temperature changes by more than±0.9°C, the risk of developing SP is 1.55 times higher (P=.0002). When the wind speed difference over the 5 days prior to onset of SP is less than 13m/sec, then the risk of SP is 2.16 times higher (P=.0004). If the pressure difference is greater than±6.1hPa and the temperature difference is greater than±0.9°C or the wind speed difference during the 5 days prior to onset of SP is less than 10.7m/s, the risk of SP is 2.04 times higher (P≤.0001)., Conclusion: Changes in atmospheric pressure, air temperature and wind speed are undoubtedly involved in the development of SP, but don't seem to be the only factors causing rupture of blebs or emphysematous bullae., (Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.)

Background/aims: Portal vein ligation (PVL) could multiply the future liver remnant volume (FLRV). Tumor necrosis factor- alpha (TNF-α) is a pleiotropic cytokine that is connected with initial phase of liver regeneration. The aim of this basic pilot study was to accelerate regeneration of liver parenchyma after PVL. The experimental porcine model was developed to be as much compatible as possible with portal vein embolization (PVE) in human medicine., Methodology: After ligation of portal branches of caudate and right lateral and right medial liver lobes recombinant porcine TNF-α (TNF-α group) or physiological solution (control group) were applied into non-occluded portal vein branches. The biochemical and immunoanalytical parameters were assessed. The compensatory hypertrophy was evaluated by periodic ultrasonography. The histological examination of liver was performed., Results: The acceleration of growth of hypertrophic liver lobes was maximal at the 7th postoperative day in comparison with the control group (p<0.05); nevertheless this stimulating effect was lost at the end of experiment. The important differences in biochemical or histological studied parametres between study groups were not proved., Conclusions: The achieved acceleration of growth of hypertrophic liver lobes after application of TNF-α confirms the role of studied cytokine in priming of liver regeneration.

Objectives: Classical and proliferative tumour markers and matrix metalloproteinases and their tissue inhibitors reflect the features of malignancy and are useful in prediction of prognosis in patients with colorectal liver metastases. There is very limited information about their physiological functions during regeneration and healing of liver parenchyma after any type of liver surgery for malignancy., Methods: The presented study included the patients, who underwent following surgical procedures for CLM, benign liver lesions and inguinal hernias: Group A: 22 patients with inguinal hernias, Group B: 26 patients with benign liver lesions, Group C: 30 patients with colorectal liver metastases (CLM) who were treated by radiofrequency ablation, Group D: 41 patients with CLM who underwent a radical surgical therapy - resection, and Group E: 22 patients with inoperable CLM who underwent an explorative laparotomy without any surgical procedure., Results: The preoperative and postoperative serum levels of CEA, CA 19-9, TK, TPA, TPS, MMP-2, MMP-9, TIMP-1, and TIMP-2 were statistically analyzed and compared within the groups to estimate the influence of a surgical procedure type. These results reflect the influence of surgical procedure on the serum levels of studied tumour markers during operation., Conclusions: It was the first description using these types of comparison to all metalloproteinases, their inhibitors, and proliferative and classical tumour markers. It could help us to estimate the critical relations of these tumour markers in prognoses of disease free survival or overall survival in patients after a surgical procedure for CLM (Tab. 5, Ref. 26).

Purpose of the Study: The aim of the study was to find out whether the frequency and intensity of patellar pain can be affected by individual rotational alignment of the femoral component in total knee arthroplasty, as compared with the standard 3 degrees of external femoral rotation in conventional procedures., Material and Methods: In randomly selected patients treated for knee osteoarthritis by total joint replacement between January 2007 and January 2011, the occurrence of patellar pain was assessed. The evaluated knees were allocated to two groups. Group 1 included 350 knee joints with conventional femoral rotational alignment, i.e., 3 degrees of external rotation. Group 2 comprised 380 knee joints with an individual rotational alignment of the femoral component based on the condylar twist angle. Post-operative anterior knee pain was assessed on the following scale: 1, no pain; 2, occasional mild pain; 3, moderate pain; 4, severe pain., Results: In group 1, 312 knee joints were free from pain, 15 occasionally experienced mild pain, 15 had moderate and eight had severe pain. A total of 23 revision operations were performed for patellar pain at the anterior knee and pain around the patella refractory to non-steroidal anti-rheumatic and rehabilitation therapy. In group 2, there were 331 pain-free knees, 48 with occasional mild pain, one with moderate pain and no knee with severe pain. No revision surgery was required. One patient with moderate patellar pain underwent surgery for spinal canal stenosis; after that knee pain was only mild. The groups were compared, as to pain assessment results, using the test of equality of relative frequencies, i.e., score categories 1+2 versus 3+4 of 350 (group 1) equalled 23 (6.57%) were compared with 1 (0.26%) of 380 (group 2); the difference was significant (p < 0.001). Using the same test for comparison of the frequency of repeat operations, i.e., 23 (0.57%) of 350 (group 1) versus 0 (0%) of 380 (group 2), also gave a significant result (p = 0.001)., Discussion: Mild and occasional pain was recorded in both groups, suggesting that femoral component malrotation is not the only cause of patellar pain following total knee arthroplasty. A markedly lower incidence of moderate and severe pain and no need for revision surgery found in group 2 provides evidence that the use of individual rotational alignment of the femoral component is fully justified., Conclusions: An individual rotational alignment of the femoral component can significantly reduce the incidence of moderate to severe patellar pain or even need for revision surgery.

Purpose of the Study: The aim of this prospective randomised study was to compare and statistically analyse two methods of condylar twist angle (CTA) measurement in total knee arthroplasty in order to assess their applicability in routine practice., Material and Methods: The study included 238 patients with 256 sites undergoing total knee arthroplasty (TKA) in the period from January 2009 to May 2011. There were 93 men (nine with bilateral TKA) and 145 women (nine with bilateral TKA) with an average age of 69.3 years and a range of 47 to 88 years. The implants NexGen (Zimmer) and ADVANCE® Medial-Pivot Knee (Wright) were used. In each patient, CTA was measured before surgery by the radiologist on a multidetector CT SOMATOM 64 (Siemens) using the Yoshioki method. The other CTA measurement was made intra-operatively by the surgeon using our modification of the Hofmann method which involved the identification of a reference line for optimal rotational alignment of the femoral component. A STATISTICA 9.0 software package was used for statistical analysis. In addition to basic statistical data, selected data were presented in graphical forms as Box and Whisker's plots and histograms. Changes in CTA and differences between the groups were evaluated using the Wilcoxon signed-rank test. Relationships among the variables were studied using Spearman's correlation coefficient., Results: The statistical analysis showed that the pre-operative CTA value obtained from CT scans was, on the average, higher by 0.5 degrees than the value from intra-operative measurement, as assessed at the level of significance p = 0.001 (signed- rank test). The intra-individual variability was lower than the inter-individual one (14.4% and 30.8%, respectively). This means that both methods are suitable for CTA measurement in the knee joint replacement procedures. Spearman's correlation coefficient was 0.6, which is the value of medium strong correlation. The post-operative CTA assessed on CT scans was in the range of 0 to 2 degrees in 87.5% of the patients. Both the pre-operative and intra-operative CTA values were significantly higher in women than in men (Wilcoxon two-sample test). There was no statistical difference between the left and the right side., Discussion: Malrotation of the femoral component is one of the causes leading to patellar subluxation and pain in the front part of the knee. The post-operative CTA value should be zero. Optimal rotational alignment of the femoral component varies with each patient; in our study it was found in the range of 0 to 7 degrees on the basis of CTA values. We do not recommend 7 degrees of external rotation to be exceeded because of the risk associated with balancing the flexion gaps; nor do we recommend to set internal rotation of the femoral component for the risk of patellar complications. The difference of 0.5 degree found in the CTA value between the two measuring methods can be explained by individual differences in the anatomy of the medial epicondylar region, and by the use of only selected whole numbers (0, 3, 5, 7) in intra-operative measurements. This difference does not play any role in routine surgical procedures., Conclusions: The statistical evaluation of the results of CTA measurement with the two methods showed that both were equally suitable for routine total knee arthroplasty. The results of intra-operative CTA measurements are comparable with those obtained on CT scans; in addition, the intra-operative method is less expensive and eliminates exposure of the patient to radiation. CT-based CTA measurements are useful in the patients with chronic problems after TKA in whom femoral component malrotation needs to be either confirmed or ruled out.

Background: An impairment of the 5-fluorouracil (5-FU) catabolic pathway, represented by alterations in the dihydropyrimidine dehydrogenase (DPYD) gene, is considered a crucial factor contributing to the development of 5-FU-related toxicity. The β-ureidopropionase (BUP1) enzyme catalyzes the final step in the 5-FU catabolic pathway; however, alterations in the UPB1 gene coding for the BUP1 enzyme have not yet been analyzed in fluoropyrimidine (FP)-treated patients suffering from 5-FU-related toxicity., Methods: We have performed a mutation analysis of the entire coding sequence of UPB1 based on denaturing high-performance liquid chromatography in 113 cancer patients treated by FP-containing regimes. These patients included 67 individuals suffering from severe 5-FU-related toxicity and 46 individuals with excellent tolerance of chemotherapy., Results: Nine UPB1 variants were detected in the subpopulation of patients with severe toxicity, including a novel mutation affecting the coding sequence (c.872&#95;873+11del13). An analysis of UPB1 variants on 5-FU-related toxicity in the population of all analyzed patients revealed an association between the c.-80C>G (rs2070474) variant and gastrointestinal toxicity. A strong positive correlation was found between the carriers of the c.-80 GG genotype and the development of severe (grade 3-4) mucositis (OR = 7.5; 95% CI = 2.60 - 21.60; p = 0.0002)., Conclusion: Our results suggest that UPB1 variants may contribute to the development of 5-FU-related toxicity in some FP-treated patients; however, the role of UPB1 alterations is probably less significant than that of DPYD alterations.

Aim: The liver is the site of breast cancer metastasis in 50% of patients with advanced disease. Tumour markers have been demonstrated as being useful in follow-up of patients with breast cancer, in early detection of recurrence of breast cancer after radical surgical treatments, and in assessing oncologic therapy effect, but no study has been carried out on their usefullness in distinguishing benign liver lesions from breast cancer metastases. The aim of this study was therefore to evaluate the importance of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen CA19-9 (CA19-9), thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin 19 fragment (CYFRA 21-1) in differential diagnosis between benign liver lesions and liver metastases of breast cancer., Patients and Methods: The study includes 3 groups: 22 patients with liver metastases of breast cancer; 39 patients with benign liver lesions (hemangioma, focal nodular hyperplasia, liver cyst, hepatocellular adenoma); and 21 patients without any liver disease or lesion that were operated on for benign extrahepatic diseases (groin hernia, varices of lower limbs) as a control group. The serum levels of tumour markers were assessed by means of immunoanalytical methods., Results: Preoperative serum levels of CYFRA 21-1, TPA, TPS and CEA were significantly higher in patients with liver metastases of breast cancer in contrast to healthy controls and patients with benign liver lesions (p-value<0.05). Serum levels of CA19-9 and TK were higher in patients with malignancy in comparison with benign liver disease and healthy controls but these differences were not statistically significant., Conclusion: Tumour markers CEA, CYFRA 21-1, TPA and TPS can be recommended as a good tool for differential diagnosis between liver metastases of breast cancer and benign liver lesions.

Purpose: Carriers of BRCA1/2 mutations are at high lifetime risk of breast cancer (BC); however, the BC onset broadly vary in individual patients. Recently, polyglutamine (poly-Q) repeat length polymorphism of the amplified in breast cancer 1 (AIB1) gene was analyzed as a risk factor influencing BC onset in BRCA1/2 mutation carriers with contradictory results., Methods: We genotyped AIB1 poly-Q repeat in 243 BRCA1/2 mutation carriers, 61 patients with familial BC (negatively tested for the presence of BRCA1/2 mutation), 221 patients with sporadic BC, and 176 non-cancer controls using denaturing high-performance liquid chromatography and statistically evaluated the effect of AIB1 poly-Q repeat length polymorphism on BC onset., Results: Having used previously published statistical analyses of AIB1 poly-Q repeat length (≥28 and ≥29 repeat cutpoints or analysis of AIB1 poly-Q repeat length as continuous variable), we did not find any association between AIB1 poly-Q repeat length and BC development in analyzed BC groups. However, the analysis of individual genotypes revealed that AIB1 genotype consisting of 28/28 glutamine repeats served as a protective factor in BRCA1 mutation carriers (HR = 0.64; 95% CI 0.41-0.99; P = 0.045) and as a risk factor in carriers of mutation in exon 11 of the BRCA2 gene (HR = 3.50; 95% CI 1.25-9.78; P = 0.017)., Conclusions: Our results confirm that AIB1 poly-Q repeat length polymorphism does not influence the BC risk in general but suggest that the specific AIB1 genotypes should be considered in patients with BC carrying mutation in the BRCA1/2 genes.

Purpose: Decreased 5-fluorouracil catabolism has been considered a major factor contributing to fluoropyrimidine (FP)-related toxicity. Alterations in the dihydropyrimidine dehydrogenase gene coding for the first and rate-limiting enzyme of FP catabolic pathway could explain toxicity in only a limited proportion of FP-treated patients. The importance of gene variants in dihydropyrimidinase (DPYS) coding for subsequent catabolic enzyme of FP degradation is not fully understood., Methods: We performed genotyping of DPYS based on denaturing high-performance liquid chromatography in 113 cancer patients including 67 with severe FP-related toxicity and 46 without toxicity excellently tolerating FPs treatment., Results: We detected nine DPYS variants including four located in non-coding sequence (c.-1T>C, IVS1+34C>G, IVS1-58T>C, and novel IVS4+11G>T), four silent (c.15G>A, c.216C>T, and novel c.105C>T and c.324C>A), and one novel missense variant c.1441C>T (p.R481W). All novel alterations were detected once only in patients without toxicity. The c.-1T>C and IVS1-58T>C variants were found to modify the risk of toxicity. The CC carriers of the c.-1C alleles were at higher risk of mucositis (OR = 4.13; 95% CI = 1.51-11.31; P = 0.006) and gastrointestinal toxicity (OR = 3.54; 95% CI = 1.59-7.88; P = 0.002), whereas the presence of the IVS1-58C allele decreased the risk of gastrointestinal toxicity (OR = 0.4; 95% CI = 0.17-0.93; P = 0.03) and leucopenia (OR = 0.29; 95% CI = 0.08-1.01; P = 0.05)., Conclusions: Our results indicate that missense and nonsense variants in DPYS are infrequent, however, the development of serious primarily gastrointestinal toxicity could be influenced by non-coding DPYS sequence variants c.-1T>C and IVS1-58T>C.

Background: Cytomegalovirus (CMV) is a risk factor for acute renal allograft rejection. The aim of this study was to determine the impact of CMV viremia on subclinical rejection (SCR) and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 3 months after transplantation., Methods: A total of 118 consecutive renal transplant recipients at risk for CMV (donor and recipient CMV seropositive) were included and followed up prospectively. Protocol biopsies with sufficient tissue were obtained in 102 patients. CMV activity was monitored using real-time polymerase chain reaction in whole blood. Three-month prophylaxis with valacyclovir or ganciclovir was given in 60 patients, whereas the remaining 42 patients were managed by preemptive therapy. Multivariate logistic stepwise regression analysis was used to estimate the effect of CMV viremia and other covariates on SCR and IF/TA., Results: CMV viremia occurred in 41% of the patients with a median peak viral load of 1300 copies/mL. The incidence of SCR and IF/TA was 29% and 28%, respectively. CMV viremia was not a risk factor for SCR (OR=0.77, P=0.551); however, viremia of more than or equal to 2000 copies/mL increased the risk of IF/TA (OR=3.83, P=0.023). Biopsy-proven acute rejection (OR=3.34, P=0.009) and sirolimus-based immunosuppression (OR=6.13, P=0.008) were independent predictors of SCR. Delayed-graft function (OR=6.02, P=0.001) and donor age (OR=1.53 per 10-year increase, P=0.009) were associated with IF/TA., Conclusions: CMV viremia is not an independent risk factor for SCR. CMV viremia with viral load of more than or equal to 2000 copies/mL is associated with increased risk of IF/TA in protocol biopsy at 3 months after transplantation.

Background: Optimal chemotherapy (CT) for advanced breast treatment should be effective, well tolerated and convenient. In this study the efficacy and safety of the fully oral combination of oral vinorelbine (Navelbine Oral) plus capecitabine (Xeloda) in metastatic breast cancer (MBC) patients pretreated with anthracycline, was evaluated., Patients and Methods: In this phase II multicenter study, this combination CT was given as a first- or second-line therapy for MBC. The treatment schedule was: oral vinorelbine 60 mg/m2 day 1 and day 8 plus capecitabine 1,000 mg/m2 twice daily from day 1 to day 14, every 21 days., Results: One hundred and fifteen patients were included in this trial. The median age was 58 years (range: 40-75). All the patients had received prior anthracycline-based chemotherapy. The combination was well tolerated, with, in particular, only 0.8% of patients presenting with febrile neutropenia. In the intention-to-treat (ITT) population, an objective response was achieved in 65 patients (56.5%). A complete response was achieved in 22 patients (19.1%); partial response in 43 patients (37.4%); stable disease in 36 patients (31.3%), and progressive disease was observed in 14 patients (12.2%). After a median follow-up of 10.0 months, the median progression-free survival (PFS) was 10.5 months and the median survival was 17.5 months., Conclusion: Oral vinorelbine-capecitabine shows very promising activity and low toxicity in MBC treatment, with high compliance of the patients.

Background: This prospective non-randomized single center study evaluated the predictive significance of various factors to the treatment outcomes of the prosthetic vascular graft infections., Methods: 46 patients with the prosthetic vascular graft infection underwent the treatment. The prosthesis extirpation was performed in 37 cases. The extra-anatomical reconstruction was implanted in 18 and the in situ reconstruction in 12 patients. In 9 patients, only local treatment was applied. The influence of the preoperative factors (patient's age, type of primary procedure, type of infection, positive hemoculture, diabetes mellitus, comorbidity, C-reactive protein, leucocytosis, repeated interventions) on the result of the treatment was evaluated with the multivariate analysis., Results: On the 30 day, the postoperative mortality was 23.9%. One and three years after the treatment, 72.1 and 57.8% of patients, respectively, survived. C-reactive protein above 90 mg/l (Wilcoxon test p<0.02, Log-rank test p<0.01), and leucocytosis >13 x 10(9)/l (Wilcoxon test p<0.0001, Log-rank test p<0.0004) were significant factors for patients morbidity and mortality. There were no preoperative factors with a statistically significant cut-off value which should be important for the long-term graft patency., Conclusion: C-reactive protein and leucocytosis are simple preoperative predictive markers of the treatment results of the prosthetic vascular graft infections. An early and aggressive diagnostic and therapeutic procedure is recommended in patients with the pre-operative levels of CRP higher than 90 mg/l and leucocytosis of 13 x 10(9)/l (Tab. 5, Fig. 3, Ref. 30). Full Text (Free, PDF) www.bmj.sk.

Background/aims: The authors evaluated the significance of various factors regarding the recurrence of colorectal liver metastases (CLM) after liver resection or radiofrequency ablation., Methodology: 82 patients were operated on for CLM at our department between 1998 and 2003. Radical surgery was performed in 58 patients (74.4%), an palliative surgery in 20 (25.6%). Recurrence of the disease was recorded in 53 patients (71.6%), 21 (28.4%) were without any sign of recurrence. The factors examined in the multifactorial analysis were: age and sex, localization of the primary carcinoma, Dukes classification, grading, histology, microscopically free resection line, chemotherapy and radiotherapy after colorectal or liver surgery, different types of liver resection, radical versus palliative liver surgery, complication after liver surgery, laterality of metastatic process, number of metastases, blood transfusion, staging, repeated liver surgery. Long-rank and Wilcoxon test were used for the statistical evaluation., Results: The factors statistically significant for disease-free interval after liver surgery were: unilaterality of metastatic process, microscopically free resection line, radical versus palliative surgical treatment. The survival rates after liver surgery and after the primary operation were dependent on grading, age, radical versus palliative resection, Dukes classification and staging., Conclusions: These factors could play an important role as predictors of colorectal cancer recurrence in patients' follow-up period after liver surgery for CLM.

Background: The authors present a statistical analysis of the dynamics of tumour markers and compare these with single serum levels in patients before and after liver surgery for colorectal liver metastases (CLM)., Patients and Methods: The serum levels of tumor markers conventionally used in clinical practice (CA19-9, CEA, CA72-4) and markers informing of the proliferation activity of malignancy (TKI TPA, TPS) were statistically analysed. The authors studied 144 patients who underwent liver surgery for colorectal liver metastases between September 1999 and June 2005. Serum levels of tumor markers before surgery (maximally two weeks before the operation), after surgery (maximally one month after the operation - usually on the day of dismission), six months (+/- one month) and twelve months after the surgery (+/- one month) were determined. The Log Rank test and the Wilcoxon test were used for statistical evaluation. The survival rate and disease-free intervals (DFI) were computed using the Kaplan-Meier method., Results: The statistical analysis of tumour marker dynamic after liver surgery (speed and power of recurrence) supported the dynamics of CA 19-9 and CEA as excellent prognostic factors of early recurrence of CLM in contrast to proliferative tumor markers., Conclusion: The results of the study suggest the importance of tumour markers for the prediction of a short survival rate or DFI. This approach would be very helpful for the planning of palliative oncological treatment for patients with liver malignancies that cannot be treated by surgical therapy. Current patients with a high tendency of recurrence of CLM after liver surgery should be followed up more thoroughly to increase the possibility of successful reoperation.

Background: Thymidine kinase (TK) is involved in nucleic acid synthesis and is therefore considered to be an important proliferation tumor marker. Our main goal was to determine the significance of elevated TK levels as a relapse marker during follow-up with child patients suffering from acute leukemia., Patients and Methods: TK serum levels in 38 children with acute leukemia (34 lymphoblastic, 4 myeloblastic) were determined using radio-receptor analysis (RRA, Immunotech, Prague, USA). All patients included in this study had had TK examined before the start of the treatment and at least twice during the follow-up., Results: Our results showed that TK serum levels at the time of diagnosis were extremely high (78-5826 U/l, median value 403 U/l, normal < 8 U/l), while in remission TK serum levels were much lower (5-80 U/l, median value 31 U/l). During relapse of acute leukemia (5 cases), TK levels increased considerably to measurements between 120-800 U/l (median value 324 U/l). The study showed that the elevation of TK serum levels during follow-up was a helpful marker for the recognition of an early stage of relapse and in some cases occurred as early as one month before the appearance of clinical signs. Sensitivity in this case was 87% and thus TK serum levels seem to be a very good parameter during follow-up because of acceptable sensitivity, low cost (4 $/sample) and the elimination of a requirement for screening of bone marrow samples., Conclusion: While TK serum levels were helpful in predicting relapse during follow-up, it is necessary to note that they did not correlate with prognosis in our group of patients during the time of the initial diagnosis of acute leukemia.

Background: Tumor markers are used for the prediction of relapse and in determining the effect of postoperative or post-oncological therapy as a standard component of follow-up. Metastatic processes of the liver and primary malignancies of the liver and gall bladder are very common in the European population. The aim of this study was to demonstrate the behaviour of malignancy in patients who have not undergone surgical therapy and to study serum levels of the monitored tumor markers in relation to the life expectancy of these patients., Patients and Methods: The Log-rank test and Wilcoxon test were used for statistical evaluation. Survival was computed using the Kaplan-Meier method. Serum levels of the tumor markers conventionally used in clinical practice in patients with gastrointestinal tumors (CEA, CA19-9, C724) and the markers of the proliferation activity in malignancy (TK, TPA, TPS) were studied., Results: One hundred and nine patients who underwent exploratory laparotomy without any surgical therapy between September 1999 and June 2005 were studied. For patients with a serum level of CEA, CA19-9 and CA72-4 that was higher than the calculated cut-off hazard ratios of early death were respectively 3-, 5- and 9-fold higher than for patients with serum levels of the same tumor markers below the calculated cut-off. Preoperative serum levels of proliferative tumor markers (TK, TPA and TPS) were not statistically significant for the prediction of early death., Conclusion: The results of the pilot study suggest the importance of tumor markers for the prediction of the short-term survival rate. These markers could be used to supplement classic clinical, laboratory and radiodiagnostic parameters. It would be very helpful for the planning of palliative oncological therapy for patients with liver malignancies who cannot be treated by surgical therapy.

Aim: To evaluate CEA and CA19-9 in a long-term follow-up after radical surgery for colorectal cancer., Patients and Methods: A total of 1,090 patients were operated on for colorectal cancer, 716 patients underwent R0 resection, 631 patients were under further surveillance, relapse was diagnosed in 122 patients (20%), 74 patients were indicated for reoperation The resectability of the relapse was 35%. An AxSYM instrument (Abbott) was used for analysis., Results: At the time of relapse both markers were normal in 31% of the patients. When relapse was diagnosed, in patients with normal preoperative levels, CEA and CA19-9 were below cut-off in 48% and 79%, respectively, and in those with primary elevation, they were again elevated in 78% and 64%, respectively., Conclusion: The surveillance based only on CEA and/or CA19-9 was cost-effective, but failed to disclose 1/3 of patients suffering from relapse; these markers must be combined with liver and chest imaging methods and colonoscopy.