Indication of pre-surgical radiochemotherapy enhances psychosocial morbidity among patients with resectable locally advanced rectal cancer.

Patients with cancer experience stress-determined psychosocial comorbidities and behavioural alterations. Patients expectation to be cured by the first line surgery and their emotional status can be negatively influenced by the decision to include neoadjuvant long-course radiotherapy prior to surgical intervention. From the patient's perspective such treatment algorithmindicates incurability of the disease. The aim of this study was to analyse the extent and dynamics of stress and related psychosocial disturbances among patients with resectable rectal cancer to whom the neoadjuvant radiochemotherapy before surgery has been indicated.Three standardised assessment tools evaluating psychosocial morbidity of rectal cancer patients have been implemented: The EORTC QLQ C30-3, the EORTC QLQ CR29 module and the HADS questionnaires previously tested for internal consistency were answered by patients before and after long-course radiotherapy and after surgery and the scores of clinical and psychosocial values were evaluated by means of the EORTC and HADS manuals. The most profound psychosocial distress was experienced by patients after the decision to apply neoadjuvant radiotherapy and concomitant chemotherapy before surgical intervention. The involvement of pre-surgical radiotherapy into the treatment algorithm increased emotional disturbances (anxiety, feelings of hopelessness) and negatively influenced patient's treatment adherence and positive expectations from the healing process. The negative psychosocial consequences appeared to be more enhanced in female patients. Despite provided information about advances of neoadjuvant radiotherapy onto success of surgical intervention, the emotional and cognitive disorders improved only slightly. The results clearly indicate that addressed communication and targeted psychosocial support has to find place before pre-surgical radiochemotherapy and as a standard part through the trajectory of the entire multimodal rectal cancer treatment.

Universal mechanisms of sound production and control in birds and mammals.

As animals vocalize, their vocal organ transforms motor commands into vocalizations for social communication. In birds, the physical mechanisms by which vocalizations are produced and controlled remain unresolved because of the extreme difficulty in obtaining in vivo measurements. Here, we introduce an ex vivo preparation of the avian vocal organ that allows simultaneous high-speed imaging, muscle stimulation and kinematic and acoustic analyses to reveal the mechanisms of vocal production in birds across a wide range of taxa. Remarkably, we show that all species tested employ the myoelastic-aerodynamic (MEAD) mechanism, the same mechanism used to produce human speech. Furthermore, we show substantial redundancy in the control of key vocal parameters ex vivo, suggesting that in vivo vocalizations may also not be specified by unique motor commands. We propose that such motor redundancy can aid vocal learning and is common to MEAD sound production across birds and mammals, including humans.

[Anxio-depressive Syndrome -  Biopsychosocial Model of Supportive Care]. / Anxio-depresívny syndróm v onkológii -  biopsychosociálny model suportívnej terapie.

BACKGROUND: Acute stress in patients experiencing cancer diagnosis and the post-traumatic stress disorder in cancer survivors results in impaired overall quality of life mainly due to associated psychological and physical alterations, including anxiety, depression, sleep disturbances, cognitive dysfunctions, fatigue, pain, cachexia and others. Recent studies revealed a new insight into molecular mechanisms contributing to the development of cancer-related co morbidities. It has been shown that adverse psychosomatic reactions including cancer depression to emotional cancer distress result from neuroendocrinne dysfunctions, disruption of the hypothalamus- pituitary-adrenal axis and sympathetic nervous system, serotonin-dopamine interactions and circadian sleep- wake rhythm disruption. AIM: The aim of the present study was to evaluate clinical studies oriented toward elucidation of the hypothesis that cancer-related anxio- depressive syndrome is the major disorder leading to the development of accompanying psychosomatic disruptions. MATERIAL AND METHODS: The data of the biopsychosocial approach in the treatment of cancer presented in the current literature were collecting using appropriate electronic databases and were elaborated in the form of meta-analysis of 24 selected publications. RESULTS: According to relevant clinical studies, psychosocial interventions and psychopharmacological treatment has been shown to reduce cancer symptomatology and to improve the ability of patients to cope with the disease. Thus, one of the key pillars of supportive care in oncology is stress reduction. Cognitive- behavioral interventions and group psychosocial therapies have shown to reduce stress from the diagnosis and treatment, to palliate depression and to help in restoring the circadian rhythm. Psychopharamacological interventions are the most useful approaches in the reduction of stress-induced cancer comorbidities. In the presented study, a plausible role of stress reduction in the protection of cancer patients from posttraumatic and anxio- depressive syndrome, physical and psychical suffering, from decrease of patients quality of life, ability to cope with the disease and cooperate in cancer treatment has been analyzed. CONCLUSION: Implementation of the biopsychosocial model of cancer care needs further cooperation between behavioral scientists and clinical oncologists attempted to elucidate further possibilities of psychosocial and pharmacological interventions leading to the regulation of stress-induced alterations of the neurotransmitter system and neuroendocrinne dysfunctions reduction of cancer-related co morbidities and improvement of patients survival time.

Analysis of radiation-induced angiosarcoma of the breast.

Breast angiosarcoma may occur de novo, or as a complication of radiation therapy, or chronic lymphedema secondary to axillary lymph node dissection for mammary carcinoma. Both primary and secondary angiosarcomas may present with bruise like skin discoloration, which may delay the diagnosis. Imaging findings are nonspecific. In case of high-grade tumours, MRI may be used effectively to determine lesion extent by showing rapid enhancement, nevertheless earliest possible diagnostics is crucial therefore any symptoms of angiosarcoma have to be carefully analysed. The case analysed here reports on results of 44-year old premenopausal woman who was treated for a T1N1M0 invasive ductal carcinoma. After a biopsy diagnosis of carcinoma, the patient underwent quadrantectomy with axillary lymph node dissection. She received partial 4 cycles of chemotherapy with adriamycin and cyclophosphamide, followed by radiation treatment. Thereafter, a standard postoperative radiotherapy was applied at our institution four months after chemotherapy (TD 46 Gy in 23 fractions followed by a 10 Gy electron boost to the tumour bed). Adjuvant chemotherapy was finished six months after operation, followed by tamoxifen. Follow up: no further complications were detected during regular check-ups. However, 12-years later, patient reported significant changes at breast region which was exposed to radiation during treatment of original tumour. In this article, we describe the clinical presentation, imaging and pathological findings of secondary angiosarcoma of the breast after radiotherapy (Fig. 2, Ref. 26).

[Relation between carbonic anhydrase IX serum level, hypoxia and radiation resistance of head and neck cancers]. / Vztah medzi sérovou hladinou karboanhydrázy IX, hypoxiou a rádiorezistenciou nádorov hlavy a krku.

BACKGROUND: Hypoxia of locally advanced head and neck cancers is one of the main causes of their radiation resistance that presents clinically as a persistence of residual tumor disease after radiation therapy. Therefore, detection of tumor hypoxia could be an important predictor of treatment efficacy. Carbonic anhydrase IX (CA IX) is a protein, coded by a homonymous gene, the expression of which increases in tumor tissues at hypoxic conditions. Hence, CA IX represents an endogenic marker of tumor hypoxia, identifiable in tumor tissues, and its soluble extracellular domain can also be detected in body fluids of the patient. The primary endpoint of this study was to explore whether a correlation exists between CA IX serum level and the residual tumor disease after therapy. The secondary endpoint was to find out how the serum concentration of CA IX changes during the course of fractionated radiation therapy. MATERIALS AND METHODS: The presented prospective monocentric clinical study evaluated a population of 30 patients with locally advanced squamous cell head and neck cancers, treated by radiation therapy or concurrent chemo radiation therapy with a curative intent. The serum concentration of the soluble form of CA IX was examined from a venous blood sample, using sandwich enzyme linked immunosorbent assay (ELISA). The blood samples were obtained before the treatment initiation, in the middle of radiation therapy, at the time of finishing radiation therapy and six weeks after the treatment completion. RESULTS: We found a substantial variability in the CA IX levels measured in the examined population, ranging 0- 1,696 pg/ ml. We found no significant changes in the mean value of CA IX concentration during the course of radiation therapy and after the treatment completion. In 11 patients (36.7%), the treatment resulted in complete remission of the disease. In these patients, lower average pretreatment levels of CA IX were noted when compared to patients with persistence of residual tumor disease (37.57 vs 77.47; p = 0.154). CONCLUSION: The results indicate that serum level of CA IX in patients with locally advanced head and neck cancers does not change significantly during the course of fractionated radiation therapy. The relation between CA IX serum level and residual tumor disease after radiation therapy requires verification on a larger population of patients.

[The dynamics of psychosocial burden development in breast cancer survivors: clinical success with psychosocial consequences]. / Dynamika vývoja psychosociálnej zát'aze prezívajúcich pacientok s karcinómom prsníka: klinický uspech s psychosociálnymi dôsledkami.

BACKGROUNDS: Modified radical mastectomy (MRM) and breast-conserving surgery (lumpectomy, quadrantectomy - BCS) have shown equivalent clinical outcome in early stage breast cancer. On the other hand, quality of life and, probably, survival time of these patients are negatively influenced by fear of cancer recurrence, leading to episodes of anxiety, depression, and frustration, and, subsequently, physical, marital, sexual, and social functioning disorders. The aim of the present study was to analyze the dynamics and qualitative changes in psychosocial morbidity outcomes in breast cancer survivors one and three years after MRM versus BCS. METHODS: A survey evaluating psychosocial morbidity of patients was performed by distributing Slovak version of the standardised EORTC-QLQ.C30:3 and EORTC-QLQ-BR23 questionnaires provided by the European Organisation for Research and Treatment of Cancer. The survey was performed in both arms of breast cancer patients surviving one and three years after MRM versus BCS. RESULTS: Patients surviving one year post MRM or BCS scored their quality of life rather low (2-4, very bad - acceptable), while 78% patients surviving three years after BSC scored considerably higher (5-6, good - very good). However, 22% of patients in this arm considered their quality of life bad, scoring comparably with patients in the MRM arm. While psychosocial burden and behavioural risk profile remain fully expressed in MRM-treated breast cancer patients three years post surgery, the patients surviving three years after BCS suffer from significant emotional dysfunction. CONCLUSION: The shift in the quality and intensity of psychosocial dysfunction symptoms in breast cancer patients surviving three years after BCS requires greater attention related to the need for appropriate community-based psychosocial interventions and psychosocial prevention due to the negative impact of continuing and even accelerated psychosocial distress on the quality of life of surviving patients and remission period of the malignant disease.

Circulating tumour cells in breast cancer--review.

Disseminated malignancies are responsible for the majority of cancer-related deaths. During the metastatic process, circulating tumour cells (CTCs) are generated. The presence of CTCs, epithelial cells found in the peripheral blood, is an essential step in establishing distant metastases. Circulating epithelial cells have the morphology of malignant cells and their number in the blood correlates with tumour burden. To identify CTCs in peripheral blood, two major approaches are used involving additional antibodies and nucleic acid-based techniques. Tumour cells with HER-2 overexpression are frequently resistant to cytotoxic drugs and radiotherapy. Wider clinical application of the detection of minimal residual disease is partly limited by the lack of standardized methods for detection. Recent studies suggest that in addition to the prognostic significance of tumour cells, determination of CTCs may be important in therapy monitoring or as potential targets for targeted therapy. Persistence of minimal residual disease after primary treatment may be an indication for extensive adjuvant treatment in order to prevent relapse of the disease. Detection of CTCs and the use of prognostic markers such as HER-2 overexpression may help us to better understand the biology and clinical significance of the presence of CTCs in breast cancer patients.

[Neo-adjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer treatment--a retrospective study]. / Neo-adjuvantná chemoterapia s následnou IDS (interval debulking surgery) v liecbe pokrocilého karcinómu ovária--retrospektívna analýza.

BACKGROUNDS: Primary debulking surgery and chemotherapy (paclitaxel and carboplatin) remain the standard treatment for advanced ovarian cancer. The size of the residual tumour after primary debulking surgery has proved to be an important prognostic determinant. Complete tumour debulking without any macroscopic residual disease is considered the optimal primary debulking surgery. It is not possible to perform such an aggressive operation in patients with advanced ovarian cancer due to the bad performance status and extensive disease. Neo-adjuvant chemotherapy and interval debulking surgery seem to be an effective treatment strategy in this group of patients. MATERIAL AND METHODS: The retrospective analysis evaluated the efficiency of interval debulking surgery in correlation with progression-free and overall survival in patients with advanced ovarian cancer. 38 patients were treated with standard chemotherapy: paclitaxel 175 mg/m2 and carboplatin 5-6 AUC every three weeks. According to the clinical response, surgical debulking was considered, after which postoperative chemotherapy was given. Ineligible patients for interval debulking were treated with 2nd line chemotherapy. RESULTS: After neo-adjuvant chemotherapy, 24 patients of the group of 38 achieved partial remission and interval debulking surgery was indicated. Optimal interval debulking surgery was performed in 12 patients, suboptimal debulking surgery in 12 patients. Of the entire group, 14 patients did not show any adequate response to the primary treatment, they did not have interval debulking surgery indicated and they were treated with 2nd line chemotherapy. Progression-free survival in patients after optimal debulking was 11 months, median overall survival was not achieved (OS > 42.5 months). Progression-free survival in patients after suboptimal debulking was 6 months and median overall survival was 33 months. Median overall survival in patients without surgical treatment was 21.5 months. CONCLUSION: The results of the study confirm that neo-adjuvant chemotherapy with subsequent interval debulking surgery is a suitable therapeutic approach in primary inoperable patients with advanced ovarian cancer.

An unusual presentation of testicular cancer.

We report two rare cases of patients presenting with unusual symptoms, which led to the diagnosis of a germ cell tumor. Metastatic germ cell tumor of testis involving the gastrointestinal tract and causing the occult gastrointestinal bleeding is described in the first case. The second patient is reported to have limbic encephalitis with positive serum for Ma2 antibodies (antibodies against neuronal proteins) and parallel malignant germ cell tumor diagnosis (Fig. 4, Scheme 2, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

Specialisation studies in medicine: formal or non-formal education?

The intention of authors of this article was not to interprete or even to criticise the official documents of the Europen Commission. We just want to put a flash onto unsolved problems in higher education which seem to hamper the ongoing process of harmonisation of higher education internal structure within the European Union leading to the European Higher Education Area. Bologna process as a backbone of this organism of knowledge might consider tertiary professional higher education in specialised medicine as part of its internal structure. It is just to hope that despite the critical distance and uniqueness of some policymakers in higher education, attention will be focused on this issue in thinking about a further progress in the preparation of a common European Qualification Framework (Ref 5). Full Text (Free, PDF) www.bmj.sk.

Chemoprevention of colorectal cancer.

Colorectal cancer is the 3rd most common form of cancer and the 2nd leading cause of death among all cancer diseases in Europe. The risk of developing colon cancer in the lifetime is about 7% and is gradually increasing with age. Mutation of protooncogenes, tumor-suppresor genes (particularly APC 1 and 2, k-RAS, P53 e.i.) and DNA repair genes (hMSH-2 and -6, hMLH-1, MMR) is leading to unrestricted cell division. Most colorectal cancers should be preventable by an increased surveillance, improved lifestyle, dietary protective agents, and probably, by a targeted chemoprevention. A re-evaluation of the colon cancer chemoprevention in the light of the recent results of clinical data is presented (Ref. 12).

Resonance properties of the vocal folds: in vivo laryngoscopic investigation of the externally excited laryngeal vibrations.

The study presents the first attempt to investigate resonance properties of the living vocal folds by means of laryngoscopy. Laryngeal vibrations were excited via a shaker placed on the neck of a male subject and observed by means of videostroboscopy and videokymography (VKG). When the vocal folds were tuned to the phonation frequency of 110 Hz and sinusoidal vibration with sweeping frequency (in the range 50-400 Hz) was delivered to the larynx, three clearly pronounced resonance peaks at frequencies around 110, 170, and 240 Hz were identified in the vocal fold tissues. Different modes of vibration of the vocal folds, observed as distinct lateral-medial oscillations with one, two, and three half-wavelengths along the glottal length, respectively, were associated with these resonance frequencies. At the external excitation frequencies below 100 Hz, vibrations of the ventricular folds, aryepiglottic folds and arytenoid cartilages were dominant in the larynx.

Doppler flowmetry in the differentiation of biological characteristics of ovarian cancer.

On basis of ultrasonographic structural criteria and Doppler flowmetry in a group of 76 patients with ovarian cancer, benign lesions were discovered in 59 patients and malignant lesions in 17 patients (77.6% and 22.4%, respectively). Surgical intervention was indicated according to the clinical findings and following of the trend of organ-specific oncomarkers in 32 out of 76 patients (42.1%). The stratification involved 17 patients with sonomorphologically/Doppler-flowmetry - diagnosed malignancy as well as 15 patients with sonographically diagnosed benign ovarian tumor. The clinical findings were histologically verified in all 32 patients. Histology confirmed malignant tumor in 16 patients, 1 histologically borderline malignancy and 15 benign tumors. The Doppler-flowmetry showed 94.1% sensitivity, 93.3% specificity, 93.3% positive predictive value, and 93.75% accuracy.

Relevance of the Doppler flowmetry in the diagnosis of pathological alterations in the post-menopausal endometrium.

The sonopathomorphology of the menopausal endometrium was investigated by measuring the endometrium thickness using the Doppler flowmetry technique. The endometrium thickness extending five millimeters has been considered critical, indicating possible neoplastic disorders. Such clinical status has been discovered in 21 out of 58 post-menopausal patients inspected (36.2%). Furthermore, the Doppler blood-flow analysis, based on the evaluation of the resistance indices (RI) in the ascendent branches of uterine arteries bilaterally, and - in case of the vascularization analysis - in the edometrial and perimetrial regions, has been performed. These investigations brought evidence indicating full capacity of the method in detecting blood flow through the uterine arteries, while significant differences in the endometrial flow-through parameters were detected only in 14 (66.7%) patients. In all 21 patients with endometrium thickness extending 5 millimeters, bioptic examination followed by histology confirmed endometrial cancer in 9 patients, epidermoid cancer in 3 patients, and cystic hyperplasia in 3 patients, respectively. The remaining 6 patients showed either secretory or quiet endometrium (5 cases), or necrotic endometrial regions (1 case). In all 12 cases of malignant endometrial cancer and in 2 out of 3 cases of histologically verified benign hyperplasia, intra- and periendometrial vascularization has been confirmed. It is to note that the mean RI values measured in the intra- and periendometrial vessels in case of endometrial cancer were significantly lower than in patients with benign cystic hyperplasia of the endometrium. Our results brought evidence indicating that the estimation of differences in the RI values in patients with detectable intra- and periendometrial vascularization has a significant relevance in the distinction of endometrial cancer from nonmalignant endometrial lesions, predominantly the benign atypical hyperplasia. The reliability of the test was 100%, however - in case of malignant disorders - a significant decrease in the RI values has been seen in the intratumoral vs. peritumoral vascularization.

On pitch jumps between chest and falsetto registers in voice: data from living and excised human larynges.

The paper offers a new concept of studying abrupt chest-falsetto register transitions (jumps) based on the theory of nonlinear dynamics. The jumps were studied in an excised human larynx and in three living subjects (one female and two male). Data from the excised larynx revealed that a small and gradual change in tension of the vocal folds can cause an abrupt change of register and pitch. This gives evidence that the register jumps are manifestations of bifurcations in the vocal-fold vibratory mechanism. A hysteresis was observed; the upward register jump occurred at higher pitches and tensions than the downward jump. Due to the hysteresis, the chest and falsetto registers can be produced with practically identical laryngeal adjustments within a certain range of longitudinal tensions. The magnitude of the frequency jump was measured as the "leap ratio" F0F:F0C (fundamental frequency of the falsetto related to that of the chest register) and alternatively expressed as a corresponding musical interval, termed the "leap interval." Ranges of this leap interval were found to be different for the three living subjects (0-5 semitones for the female, 5-10 and 10-17 for the two males, respectively). These differences are considered to reflect different biomechanical properties of the vocal folds of the examined subjects. A small magnitude of the leap interval was associated with a smooth chest-falsetto transition in the female subject.

First results of clinical application of videokymography.

OBJECTIVES: Stroboscopy is based on the assumption that the vibration of the vocal folds is stable and regular. Irregular vibrations, which are common in voice pathology, cannot easily be studied and described in a reliable way. Videokymography overcomes most of these drawbacks. DESIGN: The use of the recently invented videokymography for studying vocal fold vibrations in patients is introduced. METHOD: Videokymography, using a modified CCD-video camera, works in two modes: standard and high speed. In standard mode the vocal folds are displayed on a video monitor in the usual way, providing 50 images per second (or 60 in the National Television Standards Committee (NTSC) system). This is used for routine laryngoscopic and stroboscopic examination of the larynx. In high-speed mode (nearly 8000 images per second) only one line from the whole image is selected and displayed on the x-axis of the monitor; the y-axis represents the time dimension. RESULTS: All kinds of vocal fold vibrations, including those leading to pathological rough, breathy, hoarse, or diplophonic voice productions can be observed. Videokymography visualizes small left-right asymmetries, open quotient differences along the glottis, lateral propagation of mucosal waves, and movements of the upper margin and, sometimes in the closing phase, the lower margin of the vocal folds. CONCLUSION: Videokymography is advantageous for a more accurate diagnosis of voice disorders. Videokymography provides a simple way to study irregular vibrations of the vocal folds. Information is directly available for further processing and allows a first-time quantification of vibrations registered.

Risk factors, aetiology, therapy and outcome in 123 episodes of breakthrough bacteraemia and fungaemia during antimicrobial prophylaxis and therapy in cancer patients.

One hundred and twenty-three breakthrough bacteraemias (BB) were defined during a 5-year period in a National Cancer Centre, among 9986 admissions and a total of 979 bacteraemic episodes analysed. Of 123 bacteraemias in 103 patients, 77 were polymicrobial and 116 of the 323 organisms isolated were resistant to currently administered antimicrobial agents. Sixty-seven of the bacteraemic episodes were catheter-associated, as confirmed by the isolation of the same organisms from both blood and catheter tip. The strains isolated most frequently were coagulase-negative staphylococci (30.5%), corynebacteria (10%), Pseudomonas aeruginosa (10%), Enterococcus faecalis (9%) and viridans streptococci (8.5%). Gram-positive aerobes accounted for two-thirds of all micro-organisms isolated during breakthrough bacteraemic and fungaemic episodes. Polymicrobial episodes were associated more frequently with vascular catheters and neutropenia, and had a less favourable outcome than monomicrobial infections. Relapse was associated more frequently with catheter-related episodes, but the overall mortality rate was similar and independent of catheter insertion. Breakthrough bacteraemic and fungaemic episodes were associated more frequently with acute leukaemia. Catheter removal, as an independent variable, and modification of antimicrobial therapy were essential for better outcome.