Locally advanced laryngeal cancer: Total laryngectomy or primary non-surgical treatment?

Between January 1997 and December 2013, the Charles University 3rd Medical School and Royal Vinohrady Teaching Hospital Ear, Nose and Throat oncology team treated 185 patients with advanced laryngeal cancer, which, from a surgical perspective, required a total laryngectomy. Overall, ~70% of these patients (n=129) underwent conventional treatment (i.e., total laryngectomy with post-operative radiotherapy), and ~30% (n=56) were treated with larynx preservation protocols (including primary radiotherapy, neoadjuvant chemotherapy followed by radiotherapy or chemoradiotherapy, or primary chemoradiotherapy). Patients treated with laryngeal preservation protocols had a 5-year survival probability of 48%, whereas those treated with total laryngectomy and post-operative radiotherapy had a 5-year survival probability of 63%. This difference was not statistically significant. However, patients who underwent primary surgical treatment survived for a significantly longer period (P<0.010). The sex of the patient did not have a statistically significant impact on patient survival probability. More extensive local disease and more advanced disease stages conferred a lower survival probability, but were not statistically significant; however, a lower survival probability in patients >70 years was identified to be statistically significant (P<0.010). Local disease recurrence and recurrent cervical nodal metastases had a statistically significant impact on the 5-year survival probability (P<0.001). A step wise Cox regression analysis was used to compare the parameters of sex, patient age, tumor extent, disease stage, choice of primary surgery, local recurrence and cervical nodal recurrence. In the first step, local recurrence was selected as the parameter having the greatest effect on survival (P<0.001); patient age >70 years (P<0.001) was selected in the second step; cervical nodal recurrence (P<0.001) in the third step; and disease stage (P<0.010) in the fourth step. Other parameters did not significantly affect survival. The results of the present study confirmed that primary non-surgical treatment is an alternative approach to total laryngectomy, and that an informed patient should determine the treatment approach. The decreased overall survival observed in more extensive tumors suggests that surgical treatment may be a better selection in these cases. Due to increased overall survival, primary non-surgical treatment may be recommended for younger patients. If the patient chooses primary non-surgical treatment, concomitant chemoradiotherapy is recommended. If the patient cannot tolerate cytostatic chemotherapy, radiotherapy alone is recommended.

Clinical and laboratory predictors of Infectious Complications in patients after Out-of-Hospital Cardiac Arrest.

PURPOSE: Identification of clinical and laboratory predictors related to Infectious Complications (ICs) in patients after Out-of-Hospital Cardiac Arrest (OHCA). METHODS: Patients, aged >18, after an OHCA between 9/2013 and 11/2015, surviving >24h, were studied. RESULTS: Study group consisted of 42 patients (mean age 63.4years, 88.1% men). Forty percent of patients had IC; lower respiratory tract infections were most common (87.5% of cases). ICs were more common in patients receiving Targeted Temperature Management (50% vs. 10%; p=0.032). Antibiotics were used in 85.7% of patients. The mean time to therapy initiation was 9.6 (SD 7.1) hours after admission. The mean course of treatment was 9.0 (SD 6.2) days. Fifty-three percent of patients receiving early antibiotic treatment didn't have IC. Initial antibiotic therapy was changed more often in patients with IC (75% vs. 38.9%; p=0.045). C-Reactive Protein, Procalcitonin, Troponin and White Blood Cell count values were higher in patients with IC. CONCLUSION: Early initiated antibiotic treatment is overused in patients after OHCA. This practice is associated with necessitating antibiotic change in the majority of patients with IC. Assessment of clinical and laboratory parameters in the first days after OHCA increases the likelihood of appropriate ATB therapy.

The natural evolution of idiophatic epimacular membrane.

BACKGROUND AND AIMS: Epiretinal membrane (ERM) refers to a semi-translucent tissue layer found on the inner surface of the retina especially in older people. Surgical treatment remains controversial, optimal timing for such treatment is difficult to determine and data on the natural evolution of this disorder are limited. In this study we evaluated the natural course of idiopathic epimacular membrane in 49 patients (53 eyes). MATERIALS AND METHODS: Retrospective evaluation of a group of 49 patients (53 eyes) with idiopathic epimacular membrane confirmed by biomicroscopy, photography and optical coherence tomography (OCT). RESULTS: Patient age ranged from 51-85 years (median 72). The average follow-up was 21.3 months (± 14). Between the initial and final best corrected visual acuity (BCVA) there was no statistically significant difference although there was a significant tendency to decrease in BCVA (Spearman P=0.05) during the follow-up. Initial BCVA correlated with initial central retinal thickness (CRT), final CRT, final volume, and age. The final BCVA significantly correlated with all parameters measured. CONCLUSION: BCVA during follow-up tended to decrease: difference of starting BCVA and final BCVA values depending on the time of monitoring is significant. This we attribute to a slow gradual progression of macular changes. But, initial and final BCVA measurements were not substantially different at the end. Thus, in the absence of any clear signs of ERM progression, we can safely postpone the decision whether to perform PPV.

High thoracic anesthesia offers no major benefit over general anesthesia in on-pump cardiac surgery patients: a retrospective study.

BACKGROUND: Thoracic epidural anesthesia (TEA) has been proposed to improve and facilitate early postoperative outcome in cardiac surgery. The aim of our study was to analyze early postoperative outcome data of patients undergoing cardiac surgery under general anesthesia (GA) with comparison to patients receiving combined TEA and GA. METHODS: Medical records data from 288 patients who underwent elective on-pump cardiac surgery were retrieved and analyzed. Patients were divided into two study groups according to the type of anesthesia used: GA group (n = 141) and TEA group (n = 147). Early postoperative outcome data including quality of analgesia and major organ outcome parameters were compared between the study groups. RESULTS: There was no major difference in early postoperative outcome data between the study groups, except for shorter time to extubation (6.0 ± 10.0 vs. 6.9 ± 8.8 h, respectively, P < 0.05) and hospital stay (10.7 ± 5.9 vs. 12.9 ± 8.8 days, respectively, P < 0.05) in TEA group compared to GA group. Also TEA group as compared to GA group had lower pain numeric rating scale scores (1 ± 1.1 vs. 1.4 ± 1.5 at 24 h, respectively, P < 0.05) and morphine requirements during the first 24 h after surgery (148.2 vs. 193 ± 85.4 µg/kg, respectively, P < 0.05). CONCLUSION: Both anesthetic methods were equivalent in most postoperative outcome measures. Thoracic epidural analgesia provided superior pain relief, shorter time to extubation and earlier hospital discharge.

Genetic and epigenetic characterization of low-grade gliomas reveals frequent methylation of the MLH3 gene.

Diffuse astrocytomas and oligodendrogliomas (WHO grade II) are the most common histological subtypes of low-grade gliomas (LGGs). Several molecular and epigenetic markers have been identified that predict tumor progression. Our aim was in detail to investigate the genetic and epigenetic background of LGGs and to identify new markers that might play a role in tumor behavior. Twenty-three patients with oligodendroglioma or oligoastrocytoma (LGO) and 22 patients with diffuse astrocytoma (LGA) were investigated using several molecular-cytogenetic and molecular methods to assess their copy number variations, mutational status and level of promoter methylation. The most frequent findings were a 1p/19q codeletion in 83% of LGO and copy-neutral loss of heterozygosity (CN-LOH) of 17p in 72% of LGA. Somatic mutations in the isocitrate dehydrogenase 1 or 2 (IDH1/IDH2) genes were detected in 96% of LGO and 91% of LGA. The O-6-methylguanine-DNA-methyltransferase (MGMT) promoter was methylated in 83% of LGO and 59% of LGA. MutL homolog 3 (MLH3) promoter methylation was observed in 61% of LGO and 27% of LGA. Methylation of the MGMT promoter, 1p/19q codeletion, mutated IDH1, and CN-LOH of 17p were the most frequent genetic aberrations in LGGs. The findings were more diverse in LGA than in LGO. To the best of our knowledge, this is the first time description of methylation of the MLH3 gene promoter in LGGs. Further studies are required to determine the role of the methylated MLH3 promoter and the other aberrations detected.

Diseases caused by defects of energy level and loss of coherence in living cells.

Human and animal diseases are brought about by pathological alterations of production, composition, and conformation of macromolecules and structures in cells. Additional contributing factors include changes in physiological states caused by disturbances of energy supply, energy transduction, energy dissipation in moving or oscillating parts, and parasitic energy consumption. Disturbances of energy states may endanger existence of the system. The cell-mediated immunity (CMI) response of T lymphocytes correlating with their adherence properties was examined using antigen prepared from the serum of inbred laboratory mice strain C3H H(2k) infected with lactate dehydrogenase elevating (LDH) virus. LDH virus is a parasite on the cellular energy system. Significant CMI response was elicited in T lymphocytes prepared from the blood of patients with cancer of different phenotypes, acute myocardial infarctions, schizophrenia, and recurrent spontaneous abortions in early pregnancy from unknown reasons. The CMI response is assumed to monitor transferred information about decreased levels of energy states and decoherence in the cells caused by mitochondrial malfunction, parasitic consumption, production of lactate, and possibly other disturbances. The LDH virus infection or similar pathological processes caused by different agents might be connected with the diseases and monitored by the examined CMI response. A large amount of mitoses with chromosome defects in aborted fetuses suggest increased mutability of genomes caused by defective energy states.

The effect of adjusting tracheal tube cuff pressure during deep hypothermic circulatory arrest: a randomised trial.

BACKGROUND: Regular endotracheal tube cuff monitoring may prevent silent aspiration. OBJECTIVES: We hypothesised that active management of the cuff of the tracheal tube during deep hypothermic cardiac arrest would reduce silent subglottic aspiration. We also determined to study its effect on postoperative mechanical ventilation and the incidence of postoperative positive tracheal cultures. DESIGN: A randomised clinical trial. SETTING: The study was conducted in a University Teaching Hospital from September 2008 to November 2009. PATIENTS: Twenty-four patients undergoing elective pulmonary endarterectomy were included in the study. INTERVENTION: After induction of general anaesthesia and tracheal intubation, the cuff of the tracheal tube was inflated to 25 cmH2O. Following this, 1 ml of methylene blue dye diluted in 2 ml of physiological saline was injected into the hypopharynx. Patients were randomly assigned to active cuff management during cooling and warming (where cuff pressure was monitored and the cuff was reinflated if it dropped below 20 cmH2O, or deflated if pressure exceeded 30 cmH2O) or passive monitoring (where cuff pressure was monitored but volume was not altered). Before weaning from cardiopulmonary bypass, fibreoptic bronchoscopy was performed. Silent aspiration was then diagnosed if blue dye was seen in the trachea below the cuff of the tube. MAIN OUTCOME MEASURES: The primary aim of this study was to determine the incidence of silent aspiration. Secondary outcomes included duration of postoperative mechanical ventilation of the lungs and incidence of positive culture of tracheal aspirate. RESULTS: Active cuff management patients were younger than controls (51.2 ±â€Š11.6 vs. 63.2 ±â€Š9 years, P = 0.028), but otherwise the two groups were similar. The primary endpoint was reached because we showed that silent aspiration was significantly less frequent in the study group (0/12 vs. 8/12 patients, P = 0.001). Significantly lower intracuff pressures were measured in the control group patients at several timepoints during cooling, just before hypothermic arrest and at all timepoints during rewarming. CONCLUSION: We recommend that the cuff of the tracheal tube should be checked regularly during surgery under deep hypothermia, and the cuff pressure adjusted as required.

Involvement of deleted chromosome 5 in complex chromosomal aberrations in newly diagnosed myelodysplastic syndromes (MDS) is correlated with extremely adverse prognosis.

MDS with complex chromosomal aberrations (CCA) are characterized by short survival and a high rate of transformation to AML. A comprehensive genome-wide analysis of bone-marrow cells of 157 adults with newly diagnosed MDS and CCA revealed a large spectrum of nonrandom genomic changes related to the advanced stages of MDS. Chromosome shattering, probably resulting from chromothripsis, was found in 47% of patients. Deleted chromosome 5 was unstable and often involved in different types of cryptic unbalanced rearrangements. No true monosomy 5 was observed. Patients with CCA involving deleted chromosome 5 had an extremely poor prognosis (median overall survival, 2 months).

The impact of lower induction values of 50 Hz external electromagnetic fields on in vitro T lymphocyte adherence capabilities.

Our research thus far has concerned the impact of external electromagnetic fields (50 Hz) and low (0.01-10 mT) induction on adherence capabilities of T lymphocytes obtained from the blood of patients with head and neck tumors. We know that the in vitro adherence capability of T lymphocytes towards surfaces in cancer patients is less than that of control. Previously, we have found that exposure to electromagnetic fields (50 Hz/0.01-10 mT) increases the capability of T lymphocytes, in larynx/pharynx cancer patients, to adhere in vitro to surfaces, achieving almost physiological values, in not only pre-treatment patients but also those receiving treatment in the course of follow-up. The capability of T lymphocytes in controls (voluntary blood donors) to adhere to surfaces was also increased (50 Hz/0.01-0.5 mT). The present study concentrates on the significance of the level of electromagnetic field induction in order to determine whether low induction values can restore T lymphocytes adherence capabilities. Testing a subset of 20 patients showed a statistically significant difference (p<0.05) in the in vitro adherence capacity of T lymphocytes between both 0.01 and 0.05, and 0.1 mT induction levels. In the control group (patients diagnosed with chronic sensorineural hearing loss) there was even a statistically significant difference between induction values of 0.05 and 0.01 mT. A statistically significant difference (p<0.05) was also achieved with induction levels of 1 and 10 mT compared to 0.5, 0.1, and 0.05 mT, respectively. Therefore, we concluded that lower induction values resulted in a more biologically significant response.

Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic risk profile acute myeloid leukemia.

OBJECTIVES: Recently, mutations in DNMT3A gene have been described in about 25% acute myeloid leukemia (AML) cases, preferentially in monocytic AML. They were found to predict worse overall survival (OS) of mutated patients. PATIENTS AND METHODS: RT-PCR followed by direct sequencing was used to test the presence of DNMT3A mutations in 226 AML patients with an intermediate-risk (IR) cytogenetics. RESULTS: Sixty-seven patients of 226 (29.6%) carried a mutation in the DNMT3A gene. Occurrence of DNMT3A mutations was associated with female sex (P = 0.027) and with the presence of FLT3/ITD (P = 0.003), but not with particular FAB subtypes. Patients with DNMT3A mutation had higher initial WBC counts than those without it (P = 0.064) only because of higher incidence of FLT3/ITD within these cases. There was no difference between mutated and wild-type groups in reaching complete remission (CR) (P = 0.380). OS was not affected by DNMT3A mutation (P = 0.251), but OS of patients who reached CR was longer in DNMT3A negative cases (P = 0.025). Patients with DNMT3A mutation had a higher relapse rate (P = 0.007). Patients carrying both the DNMT3A mutation and FLT3/ITD relapsed more often than either patients with single DNMT3A mutation (P = 0.044) or patients with FLT3/ITD only (P = 0.058). DNMT3A mutations were associated with higher relapse rate even within the FLT3/ITD-negative group (P = 0.072). After reaching CR, these two genetic factors were independent predictors of relapse at multivariate analysis (P < 0.001). Only three of 30 'double-mutated' (FLT3/ITD+, DNMT3A+) patients are still alive, all of them having undergone hematopoietic stem cell transplant. CONCLUSIONS: We have confirmed the high incidence of DNMT3A mutations in patients with AML with IR cytogenetics. Patients with DNMT3A mutations relapse more often and have inferior OS when only patients achieving CR are analyzed. 'Double-mutated' patients have a very poor prognosis.

Reproduction after myomectomy: comparison of patients with and without second-look laparoscopy.

Myomectomy is associated with a high risk of de-novo adhesion formation that may decrease fertility. The purpose of this study was to compare the reproductive outcome of patients after laparoscopic or open myomectomy who underwent second-look (SL) hysteroscopy and laparoscopy including adhesiolysis with patients with no SL intervention. A total of 170 patients underwent open or laparoscopic myomectomy at one centre. All patients were recommended SL. Reproductive results were analyzed in 12 and 24 months intervals following myomectomy. Out of 170 post-myomectomy patients 96 signed informed consent with SL (group A) and 74 withheld (group B). The cumulative pregnancy rate in the 24-months follow-up was: 61.4% and 66.7% (p = 0.535) in group A and group B respectively. Adhesions of adnexa were observed and lysed in the overall of 34.0% of patients at the time of SL. Intrauterine synechiae were present in 1.56% of patients at the SL hysteroscopy. No case of uterine rupture during pregnancy or delivery was recorded. Our results show that the pregnancy rate of patients after myomectomy who underwent SL hysteroscopy and laparoscopy is similar to that of patients with no SL procedure. Adhesiolysis performed during SL does not seem to improve the reproductive outcome of post-myomectomy patients.

Postoperative outcome in awake, on-pump, cardiac surgery patients.

PURPOSE: Thoracic epidural anesthesia (TEA) alone or combined with general anesthesia (TEA-GA) has been assumed to improve early postoperative outcome in cardiac surgery. The aim of our study was to investigate data of early and late postoperative outcome results of awake TEA patients undergoing cardiac surgery with comparison to patients under combined and general anesthesia (GA). METHODS: Forty-seven patients undergoing elective on-pump cardiac surgery were assigned to receive either epidural (group TEA, n = 17), combined (group TEA-GA, n = 15), or general (group GA, n = 15) anesthesia. Early and late postoperative outcome data, including hospital and 3-year mortality rates, were recorded and compared among the study groups. RESULTS: There was no major difference in early or late postoperative outcome data across all study groups, except for lower incidence of atrial fibrillation in the TEA group compared with the GA group (23.5% vs. 66.7%, respectively, P < 0.05). Also, TEA and TEA-GA groups compared with the GA group had lower pain visual analogue scale scores at 24 h postoperatively (4 ± 7, 6 ± 7, 14.7 ± 11, respectively, P < 0.05) and morphine requirements during the first 24 h after surgery (30 ± 6, 30 ± 6, 250 ± 140 µg/kg, respectively, P < 0.05). CONCLUSIONS: Based on our data, all three anesthetic methods were equivalent in terms of major determinants of postoperative outcome, except for lower incidence of atrial fibrillation in awake patients compared with patients under general anesthesia. Methods using postoperative epidural analgesia provided superior pain relief.

Standard blood flow rates of cardiopulmonary bypass are adequate in awake on-pump cardiac surgery.

OBJECTIVE: Standard blood flow rates for cardiopulmonary bypass have been assumed to be the same for awake cardiac surgery with thoracic epidural anesthesia (TEA) as for general anesthesia. However, compared with general anesthesia, awake cardiac surgery with epidural anesthesia may be associated with higher oxygen consumption and may result in lactic acidosis when standard blood flow rates were used. The aim of our study was to investigate if standard blood flow rates are adequate in awake cardiac surgery. METHODS: Forty-five patients undergoing elective on-pump cardiac surgery were assigned to receive either epidural (Group TEA, n=15), combined (Group TEA-GA, n=15) or general (Group GA, n=15) anesthesia. To monitor the adequacy of standard blood flow rates, arterial lactate, acid base parameters, and central venous and jugular bulb saturation were measured at six time points (before, during, and after the surgery) in all groups. Blood flow rates were adjusted when needed. RESULTS: No lactic acidosis has developed in any group (p=NS). TEA as compared with TEA-GA and GA groups had lower central venous (67±4%, 75±11%, and 72±13%, respectively, p<0.05) and jugular bulb oxygen saturations during cardiopulmonary bypass (60±7%, 68±9%, and 75±12%, respectively, p<0.05) during the post-cardiopulmonary bypass period. The TEA group as compared with the TEA-GA and GA groups also had mild hypercapnic respiratory acidosis (56±10, 42±8, and 37±4 mmHg, respectively, p<0.05) and mild decrease of arterial oxygen saturation (93±4%, 97±2%, and 96±1%, respectively, p<0.05) at the end of surgery without any clinical consequences. Thus, no additional blood flow rates adjustments in any study group and no ventilatory support in TEA group were required. CONCLUSIONS: Under careful monitoring, the use of standard blood flow rates is adequate for patients undergoing awake on-pump normothermic cardiac surgery.

Cytosine-Adenosine (CA)n repeats polymorphism in IGF-I gene and early growth in infants born appropriate and small for gestational age.

BACKGROUND: IGF-I gene polymorphisms might alter IGF-I level resulting in decreased foetal and postnatal growth and increased risk for diabetes mellitus type 2 and cardiovascular diseases in adulthood. OBJECTIVES: We analyzed the association between Cytosine-Adenosine (CA)10-24 repeats polymorphism in promoter region of the IGF-I gene and early growth in infants with birth weight appropriate for gestational age (AGA) and small for gestational age (SGA). DESIGN AND METHODS: All neonates were born at term, 196 of them were AGA and 26 SGA. Blood for DNA analyses was obtained from placental part of umbilical vein. Genotyping was performed using fragment analyses of IGF-I gene promoter region. The data about postnatal growth in the group of AGA children were obtained at the age of 18 months, in SGA children at 12 months. RESULTS: No differences in the frequency of wild type allele with (CA)19 repeats and polymorphisms with (CA)<19 or (CA)>19 repeats were observed between AGA and SGA children. The average birth weight and length in AGA wild type (CA)19 homozygotes were lower in comparison with AGA carriers of various (CA)n polymorphisms but all observed anthropometric differences disappeared at the age of 18 months. In SGA children, no differences were found between number of (CA)n repeats and anthropometric parameters both at birth and at the age of 12 months. CONCLUSIONS: Although (CA)n repeats polymorphism in IGF-I gene might affect prenatal growth in AGA children, our results have not shown any impact of variable number of (CA) n repeats in IGF-I gene on postnatal growth.

Lifestyle decreases risk factors for cardiovascular diseases.

The morbidity and mortality of cardiovascular diseases is high in the developed countries. The lifestyle changes are capable to decrease it by 50%. The aim of the present study was to measure the parameters of some risk factors before and after a one-week NEW START rehabilitative retreat. 1349 volunteers, 320 men, 1029 woman, mean age 51 +/- 14.5 (SD) years participated in 30 rehabilitative retreats from 1999-2006 in the Czech Republic, using a low-fat, low-energy, lacto-ovo-vegetarian diet and exercise, in a stress-free environment. Body weight, height, BMI, blood pressure, heart rate, serum cholesterol and blood glucose were measured. Body weight decreased in 1223 measured persons from 71.2 +/- 14.38 (SD) to 70.6 +/- 14.02 kg (p<0.0001), BMI (1,046 measured persons) from 25.1 +/- 4.60 (SD) to 24.8+4.49 (SD) kg/m2 (p<0.0001), systolic blood pressure (1,218 persons) from 129.8 +/- 23.02 (SD) to 123.8 +/- 21.52 (SD) mmHg (p<0.0001), diastolic blood pressure (1210 persons) from 79.8 +/- 12.7 (SD) to 77.5 +/- 11.6 (SD) mmHg (p<0.0001), serum cholesterol (998 persons) from 4.86 +/- 0.95 (SD) to 4.32 +/- 0.77 (SD) mmol (p<0.0001), blood glucose (544 persons) from 4.31 +/- 1.59 (SD) to 3.88 +/- 1.33 (SD) mmol (p<0.0001). Heart rate was not significantly decreased. The parameters were lower in lacto-ovo vegetarians and Seventh-day Adventists than in controls who never observed the diet and avail the lifestyle programs. The parameters were nonsignificantly changed one year after finishing the retreat in the sample of 68 persons showing the positive effect of retreats. Our results showed, that the intake of a low-fat, low-energy diet, over the course of one week in a stress-free environment, had positive impact on the risk factors of cardiovascular diseases.

Prognostic value of structural chromosomal rearrangements and small cell clones with high hyperdiploidy in children with acute lymphoblastic leukemia.

In this study, 107 children with acute lymphoblastic leukemia (ALL) were analysed for the presence of hyperdiploidy by cytogenetics and interphase fluorescence in situ hybridisation (I-FISH). Structural aberrations in hyperdiploid cells were investigated by multiple colour FISH (mFISH). Clones with high hyperdiploidy (>50 chromosomes) (HeH) were found in 46 patients (43%). In nine of these (20%), the abnormal clone was present in <20% of the total cell population. There was no significant difference in EFS between those patients with HeH in 2.5-20% or >20% of cells. Structural rearrangements in the HeH clone were found in 10 patients (22%). In this study, HeH karyotypes containing structural aberrations were an indication of a poor prognosis in childhood ALL.