The importance of rectal washout for the oncological outcome after Hartmann's procedure for rectal cancer: analysis of population-based data from the Swedish Colorectal Cancer Registry.

BACKGROUND: During rectal cancer surgery the bowel may contain viable, exfoliated cancer cells, a potential source for local recurrence (LR). The amount and viability of these cells can be reduced using intraoperative rectal washout, a procedure that reduces the LR risk after anterior resection. The aim of this study was to analyse the impact of washout on oncological outcome when performed in Hartmann's procedure (HP) for rectal cancer. METHODS: A national cohort study on data for patients registered from 1995 to 2007 in the Swedish Colorectal Cancer Registry was carried out. The final analysis included patients belonging to TNM stages I-III who had undergone R0 HP with a registered 5-year follow-up. Multivariate analysis was performed. RESULTS: A total of 1188 patients were analysed (686 washout and 502 no washout). No differences were detected between the washout group and the no washout group concerning rates of LR [7% (49/686) vs. 10% (49/502); p = 0.13], distant metastasis (DM) [17% (119/686) vs. 18% (93/502); p = 0.65], and overall recurrence (OAR) [21% (145/686) vs. 24% (120/502); p = 0.29]. For both groups, the 5-year cancer-specific survival was below 50%. In multivariate analysis, washout neither decreased the risk of LR, DM, or OAR nor increased overall or the cancer-specific 5-year survival. CONCLUSIONS: The oncological outcome did not improve when washout was performed in HP for rectal cancer.

Does Internet-based guided-self-help for depression cause harm? An individual participant data meta-analysis on deterioration rates and its moderators in randomized controlled trials.

BACKGROUND: Almost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach. METHOD: Studies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data. RESULTS: A total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29-0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit-risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration. CONCLUSIONS: Internet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.

Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

AIM: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. METHOD: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. RESULTS: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. CONCLUSION: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

Temporal profile and amplitude of human masseter muscle activity is adapted to food properties during individual chewing cycles.

Jaw actions adapt to the changing properties of food that occur during a masticatory sequence. In the present study, we investigated how the time-varying activation profile of the masseter muscle changes during natural chewing in humans and how food hardness affects the profile. We recorded surface electromyography (EMG) of the masseter muscle together with the movement of the lower jaw in 14 healthy young adults (mean age 22) when chewing gelatin-based model food of two different hardness. The muscle activity and the jaw kinematics were analysed for different phases of the chewing cycles. The increase in the excitatory drive of the masseter muscle was biphasic during the jaw-closing phase showing early and late components. The transition between these components occurred approximately at the time of tooth-food contact. During the masticatory sequence, when the food was particularised, the size of the early component as well as the peak amplitude of the EMG significantly decreased along with a reduction in the duration of the jaw-closing phase. Except for amplitude scaling, food hardness did not appreciably affect the muscle's activation profile. In conclusion, when chewing food during natural conditions, masseter muscle activation adapted throughout the masticatory sequence, principally during the jaw-closing phase and influenced both early and late muscle activation components. Furthermore, the adaptation of jaw actions to food hardness was affected by amplitude scaling of the magnitude of the muscle activity throughout the masticatory sequence.

Hearing aid compliance in the elderly.

OBJECTIVES: A decreasing but still substantial proportion of elderly persons with hearing aids use them only occasionally. Because the prevalence of age-related hearing loss is increasing, it is important for the hearing rehabilitation process to be effective. The aim of this study was to use a mailed questionnaire to evaluate the rate of hearing aid use and the reasons for minimal use or nonuse. METHODS: Questions about hearing aid use and associated problems were included in a survey of hearing mailed to 4,067 people in age cohorts of 70, 75, 80 and 85 years in an industrialized urban community in Finland. RESULTS: In this sample of 249 hearing aid users, 55.4% used their hearing aid daily, and 27.3% used it > 6 hours a day. The percentage of subjects who never used their hearing aid was 10.7%. Use of hearing aids tended to decline with advancing age. The most common reasons for minimal use were disturbing background noise, acoustic feedback problems, battery cost, and a lack of motivation to use the hearing aid. CONCLUSIONS: Compliance with hearing aid use by the elderly is increasing, but a significant proportion of hearing aids are still used only occasionally or never. We discuss methods to improve compliance in this patient group. Our results may be used to reexamine existing procedures for fitting hearing aids for counseling, which may increase patient compliance with hearing aids, leading to greater benefits from their use.

Foam posturography: standing on foam is not equivalent to standing with decreased rapidly adapting mechanoreceptive sensation.

Standing on a foam surface is believed to exaggerate balance deficits by decreasing the reliability of somatosensory information from cutaneous mechanoreceptors on the plantar soles (i.e. base of feet) and by altering the effectiveness of ankle torque. The aim was to further document the nature of foam posturography testing by comparing between standing on foam and standing with decreased Rapidly Adapting Mechanoreceptive Sensation (RAMS). Sixteen healthy adults (mean age 20.8 years) were tested with posturography, standing with eyes open and closed on a solid surface and on foam, with and without decreased plantar RAMS. Standing balance was measured as torque variance and further analyzed by being divided into three spectral categories. Plantar cutaneous hypothermic anesthesia by ice-cooling was used to decrease RAMS. Plantar mechanoreceptive sensation was precisely determined with tactile sensitivity and vibration perception tests. Vibration perception was significantly decreased by hypothermic anesthesia, but tactile sensitivity was not. The anterior-posterior torque variance was significantly larger for frequencies less than 0.1 Hz under eyes closed conditions when standing on a solid surface with decreased RAMS compared to normal sensation. No effect of decreased RAMS was seen with eyes open on a solid surface, nor on foam with eyes open or closed. Decreased RAMS produced body sway responses on a solid surface that were different in spectral composition, amplitude, direction and that responded differently to vision compared with standing on foam. Hence, this study showed that RAMS contributes to postural control but reduction in RAMS does not produce a similar challenge as standing on foam.

Anastomotic leakage after surgery for rectal cancer: a risk factor for local recurrence, distant metastasis and reduced cancer-specific survival?

AIM: The impact of anastomic leakage (AL) on the oncological outcome after anterior resection (AR) for rectal cancer is still controversial. We explored the impact of AL regarding local recurrence (LR), distant metastasis and overall recurrence (OAR). Overall and cancer-specific survival was analysed. METHOD: Patients undergoing AR for rectal cancer with a registered AL between 1995 and 1997 and a control group were identified in the Swedish Rectal Cancer Registry. The medical records were retrieved for additional data and validation. Differences in the oncological outcome at 5-year follow-up were analysed with multivariate methods. RESULTS: After validation, 114 patients with AL and 136 control patients with locally radical surgery for tumours in tumour-node-metastasis stages I-III were analysed. There was no difference detected between patients with AL and control patients regarding rates of LR [8% (9 of 114) vs 9% (12 of 136); P = 0.97], distant metastasis [18% (20 of 114) vs 23% (31 of 136); P = 0.37] and OAR [19% (22 of 114) vs 28% (38 of 136); P = 0.15]. The 5-year cancer-specific survival was almost 80% in both groups. In multivariate analysis, AL was not a risk factor of LR, distant metastasis or OAR and had no impact on 5-year overall or 5-year cancer-specific survival. Irrespective of the occurrence of AL, preoperative radiotherapy (P = 0.055) and rectal washout (P = 0.046) reduced the LR rate, but did not influence survival. CONCLUSION: Anastomotic leakage was not proved to be a risk factor of worse oncological outcome. Hence, additional adjuvant treatment or extended follow-up on the basis of the occurrence of AL after AR might not be justified.

Risk factors of rectal cancer local recurrence: population-based survey and validation of the Swedish rectal cancer registry.

AIM: Despite advances in rectal cancer treatment, local recurrence (LR) remains a significant problem. To select high-risk patients for different treatment options aimed at reducing LR, it is essential to identify LR risk factors. METHOD: Local recurrence and survival rates of 4153 patients registered 1995-1997 in the Swedish Rectal Cancer Registry were analysed. LR risk factors were analysed by multivariate methods. For LR patients the registry was validated and additional data retrieved. RESULTS: The 5-year overall and cancer-specific survival rates were 45% and 62% respectively. LR was registered in 326 (8%) patients. After R0-resections for tumours in TNM stages I-III, LR developed in 10% of tumours at 0-5 cm, 8% at 6-10 cm and 6% at 11-15 cm above the anal verge. Preoperative radiotherapy (RT) reduced the LR rate irrespective of height [0-5 cm: OR 0.50 (0.30-0.83), 6-10 cm: OR 0.42 (0.25-0.71), and 11-15 cm: OR 0.29 (0.13-0.64)]. Patients without preoperative RT had significantly higher LR risk after rectal perforation [OR 2.50 (1.48-4.24)], and almost significantly decreased LR risk when rectal washout was performed [OR 0.65 (0.43-1.00)]. Preoperative RT prolonged time to LR but did not significantly influence the survival among LR patients. LR was an isolated tumour manifestation in 103 (39%) patients with validated LR. CONCLUSION: Preoperative RT should be considered for rectal cancer also in the upper third of the rectum. Intraoperative perforation should be avoided, and rectal washout is indicated as valuable. Follow-up for the detection of isolated LR is important. Extended follow up should be considered for patients treated with RT.

Diabetes mellitus modeling and short-term prediction based on blood glucose measurements.

Insulin-Dependent Diabetes Mellitus (IDDM) is a chronic disease characterized by the inability of the pancreas to produce sufficient amounts of insulin. Daily compensation of the deficiency requires 4-6 insulin injections to be taken daily, the aim of this insulin therapy being to maintain normoglycemia - i.e., a blood glucose level between 4 and 7mmol/l. To determine the quantity and timing of these injections, various different approaches are used. Currently, mostly qualitative and semi-quantitative models and reasoning are used to design such a therapy. Here, an attempt is made to show how system identification and control may be used to estimate predictive quantitative models to be used in design of optimal insulin regimens. The system was divided into three subsystems, the insulin subsystem, the glucose subsystem and the insulin-glucose interaction. The insulin subsystem aims to describe the absorption of injected insulin from the subcutaneous depots and the glucose subsystem the absorption of glucose from the gut following a meal. These subsystems were modeled using compartment models and proposed models found in the literature. Several black-box models and grey-box models describing the insulin/glucose interaction were developed and analyzed. These models were fitted to real data monitored by an IDDM patient. Many difficulties were encountered, typical of biomedical systems: Non-uniform and scarce sampling, time-varying dynamics and severe nonlinearities were some of the difficulties encountered during the modeling. None of the proposed models were able to describe the system accurately in all aspects during all conditions. However, all the linear models shared some dynamics. Based on the estimated models, short-term blood glucose predictors for up to two-hour-ahead blood glucose prediction were designed. Furthermore, we explored the issues that arise when applying prediction theory and control to short-term blood glucose prediction.

Time trends of short-term mortality for octogenarians undergoing a colorectal resection in North Europe.

BACKGROUND: Decreased cancer specific survival in older colorectal patients is mainly due to mortality in the first year, emphasizing the importance of the first postoperative year. This study aims to gain an overview and time trends of short-term mortality in octogenarians (≥80 years) with colorectal cancer across four North European countries. METHODS: Patients of 80 years or older, operated for colorectal cancer (stage I-III) between 2005 and 2014, were included. Population-based cohorts from Belgium, Denmark, the Netherlands, and Sweden were collected. Separately for colon- and rectal cancer, 30-day, 90-day, one-year, and excess one-year mortality were calculated. Also, short-term mortality over three time periods (2005-2008, 2009-2011, 2012-2014) was analyzed. RESULTS: In total, 35,158 colon cancer patients and 10,144 rectal cancer patients were included. For colon cancer, 90-day mortality rate was highest in Denmark (15%) and lowest in Sweden (8%). For rectal cancer, 90-day mortality rate was highest in Belgium (11%) and lowest in Sweden (7%). One-year excess mortality rate of colon cancer patients decreased from 2005 to 2008 to 2012-2014 for all countries (Belgium: 17%-11%, Denmark: 21%-15%, the Netherlands: 18%-10%, and Sweden: 10%-8%). For rectal cancer, from 2005 to 2008 to 2012-2014 one-year excess mortality rate decreased in the Netherlands from 16% to 7% and Sweden: 8%-2%). CONCLUSIONS: Short-term mortality rates were high in octogenarians operated for colorectal cancer. Short-term mortality rates differ across four North European countries, but decreased over time for both colon and rectal cancer patients in all countries.

Effects of proprioceptive vibratory stimulation on body movement at 24 and 36h of sleep deprivation.

OBJECTIVE: To investigate whether postural stability and adaptation differed after a normal night of sleep, after 24h (24 SDep) and 36h (36 SDep) of sleep deprivation while subjected to repeated balance perturbations. Also, to determine whether there was any correlation between subjective alertness scores and objective posturographic measurements. Lastly, to investigate the effects of vision on the stability during sleep deprivation. METHODS: Body movements at five locations were recorded in 18 subjects (mean age 23.8years) using a 3D movement measurement system while subjected with eyes open and closed to vibratory proprioceptive calf stimulation after a normal night of sleep, 24 and 36 SDep. RESULTS: The clearest sleep deprivation effect was reduced ability to adapt head, shoulder and hip movements, both with eyes open and eyes closed. Additionally, several near falls occurred after being subjected to balance perturbations for 2-3min while sleep deprived. Unexpectedly, postural performance did not continue to deteriorate between 24 and 36h of sleep deprivation, but showed some signs of improvement. Subjective scores of sleepiness correlated poorly with actual changes in postural control performance. CONCLUSIONS: Sleep deprivation might affect postural stability through reduced adaptation ability and lapses in attention. Subjective alertness might not be an accurate indicator of the physiological effects of sleep deprivation. SIGNIFICANCE: Sleep deprivation could increase the risk of accidents in attention demanding tasks. There is a need for objective evaluation methods to determine actual performance capacity during sleep deprivation.

Effects of 24-h and 36-h sleep deprivation on human postural control and adaptation.

This study investigated whether human postural stability and adaptation were affected by sleep deprivation and the relationship between motor performance and subjective scores of sleepiness (visuo-anlogue sleepiness scores, VAS). Postural stability and subjective sleepiness were examined in 18 healthy subjects (mean age 23.8 years) following 24 and 36 h of continued wakefulness, ensured by portable EEG recordings, and compared to a control test where the assessments were made after a normal night of sleep. The responses were assessed using posturography with eyes open and closed, and vibratory proprioceptive stimulations were used to challenge postural control. Postural control was significantly affected after 24 h of sleep deprivation both in anteroposterior and in lateral directions, but less so after 36 h. Subjective VAS scores showed poor correlation with indicators of postural control performance. The clearest evidence that sleep deprivation decreased postural control was the reduction of adaptation. Also several near falls after 2-3 min during the posturographic tests showed that sleep deprivation might affect stability through momentary lapses of attention. Access to vision, somewhat, but not entirely reduced the effect of sleep deprivation. In conclusion, sleep deprivation can be a contributing factor to decreased postural control and falls.

The effects of foam surface properties on standing body movement.

CONCLUSION: The properties of a foam surface significantly affect body movement variance. Therefore, studies where different kinds of foam have been used may not provide congruent results. OBJECTIVES: To investigate whether different properties of foam affect body movement variance (32 subjects, mean age 22.5 years) in terms of linear head, shoulder, hip and knee movements. Subjects repeated tests with eyes open and closed, to also determine the effect of vision on the different surfaces. SUBJECTS AND METHODS: Body movement was captured on three different foam surfaces and on a control solid surface over 2 min using a Zebris ultrasound measuring system. The foam surfaces were categorized by their firmness as firm foam, medium foam and soft foam. RESULTS: Body movement variance increased significantly when standing on all foam surfaces compared with the solid surface. However, movement variance was larger when standing on the firm foam compared with the softer foams, except in the anteroposterior total and low frequency ranges. We also found that the body movement pattern differed when standing on foam and firm surfaces, with greater reliance on movements at the knee to give postural stability on foam than on the solid surface. Vision clearly reduced all body movement variances, but particularly within the high frequency range.

Oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer - A EURECCA international comparison between the Netherlands, Belgium, Denmark, Sweden, England, Ireland, Spain, and Lithuania.

INTRODUCTION: The aim of this EURECCA international comparison is to compare oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer between European countries. MATERIAL AND METHODS: Population-based national cohort data from the Netherlands (NL), Belgium (BE), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), Spain (ES), and single-centre data from Lithuania (LT) were obtained. All operated patients with (y)pTNM stage I-III rectal cancer diagnosed between 2004 and 2009 were included. Oncologic treatment strategies and relative survival were calculated and compared between neighbouring countries. RESULTS: We included 57,120 patients. Treatment strategies differed between NL and BE (p < 0.001), DK and SE (p < 0.001), and ENG and IE (p < 0.001). More preoperative radiotherapy as single treatment before surgery was administered in NL compared with BE (59.7% vs. 13.1%), in SE compared with DK (55.1% vs. 10.4%), and in ENG compared with IE (15.2% vs. 9.6%). Less postoperative chemotherapy was given in NL (9.6% vs. 39.1%), in SE (7.9% vs. 14.1%), and in IE (12.6% vs. 18.5%) compared with their neighbouring country. In ES, 55.1% of patients received preoperative chemoradiation and 62.3% postoperative chemotherapy. There were no significant differences in relative survival between neighbouring countries. CONCLUSION: Large differences in oncologic treatment strategies for patients with (y)pTNM I-III rectal cancer were observed across European countries. No clear relation between oncologic treatment strategies and relative survival was observed. Further research into selection criteria for specific treatments could eventually lead to individualised and optimal treatment for patients with non-metastasised rectal cancer.

Population-based study of local surgery for rectal cancer.

BACKGROUND: The aim was to determine long-term survival and recurrence rates after local excision of rectal cancer from a prospectively registered population-based database. METHODS: Swedish Rectal Cancer Registry data from 1995 to 2001, including 10 181 patients of whom 643 (6.3 per cent) had a local excision, were analysed. Complete 5-year follow-up data from 1995 to 1998 were available. Cumulative relative and cancer-specific survival rates, and rates of local recurrence and distant metastases, were calculated by actuarial methods. RESULTS: The 5-year cancer-specific survival rate for 256 patients with stage I disease who had local excision was 95.3 (95 per cent confidence interval 91.5 to 99.1) per cent. The 5-year local recurrence rate was 7.2 per cent. After adjustment for age, sex, tumour stage and preoperative radiotherapy, the relative risk of death from cancer was the same as that after major resection. CONCLUSION: Population-based results after local excision of rectal cancer are the same as those reported in controlled series for early-stage tumours after abdominal resection. A low relative survival and a high median age indicate the use of local excision in patients with a high level of co-morbidity. To achieve acceptable long-term results, optimal preoperative and postoperative staging is needed.

The Swedish rectal cancer registry.

BACKGROUND: An audit of all patients with rectal cancer in Sweden was launched in 1995. This is the first report from the Swedish Rectal Cancer Registry (SRCR). METHODS: Between 1995 and 2003, 13 434 patients treated for adenocarcinoma of the rectum were registered with the SRCR; there were approximately 1500 new patients annually. RESULTS: Approximately half had an anterior resection, a quarter an abdominoperineal resection and 15 per cent a Hartmann's procedure. The median 30-day postoperative mortality rate was 2.4 per cent and the overall postoperative morbidity rate was 35.0 per cent. The 5-year cancer-specific survival rate was 62.3 per cent. The 5-year relative survival rate was 70.1 per cent after anterior resection, 59.8 per cent after abdominoperineal resection and 39.8 per cent after a Hartmann's procedure. The crude 5-year local recurrence rate was 9.5 per cent overall, 6.1 per cent after preoperative radiotherapy and 11.4 per cent after surgery alone. For 3868 patients who had a locally curative procedure the local recurrence rate was 7.4 per cent overall, 5.9 per cent for those who had radiotherapy and 10.2 per cent for those who did not. The local recurrence rate was 2.9 per cent (28 of 968) for stage I disease, 7.9 per cent (112 of 1418) for stage II, 13.9 per cent (188 of 1357) for stage III and 8.5 per cent (45 of 532) for stage IV. CONCLUSION: These good population-based results are due, in part, to the nationwide prospective quality assurance registration.

Biological and prognostic role of acid cysteine proteinase inhibitor (ACPI, cystatin A) in non-small-cell lung cancer.

BACKGROUND: Acid cysteine protease inhibitor (ACPI) is an intracellular protein, often linked to neoplastic changes in epithelium and thought to have an inhibitory role in malignant transformation. AIM: To analyse the expression and prognostic role of ACPI in non-small-cell lung cancer (NSCLC). METHOD: Histological samples from 199 patients with resected NSCLC were stained immunohistochemically for the expression of ACPI in normal and preneoplastic bronchial epithelium, and in various types of lung carcinomas. RESULTS: A normal bronchial epithelium showed positive staining for ACPI in the basal cells, whereas the upper two-thirds of the dysplastic epithelium was ACPI positive. High staining for ACPI was found in 74% (91/123) of squamous-cell carcinomas, whereas 16% (8/49) of adenocarcinomas and 30% of (8/27) large-cell carcinomas showed the high expression of ACPI (p<0.001). Among squamous-cell carcinomas, low expression of ACPI was correlated with poor tumour differentiation (p=0.032). In the whole tissue, reduced expression of ACPI was associated with tumour recurrence (p=0.024). In overall survival (OS) and disease-free survival (DFS) analyses, the histological type of the tumour (both p<0.001) and stage of the tumour (p=0.001, p=0.013, respectively) were related to patient outcome. Low expression of ACPI in tumour cells was associated with poor OS and DFS (p<0.041, p=0.004, respectively). In multivariate analysis, ACPI did not retain its prognostic value, whereas the traditional factors were the most important prognostic factors. CONCLUSIONS: ACPI expression is linked with the malignant transformation of the bronchial epithelium and predicts a risk of tumour recurrence as well as poor rate of survival for the patients. However, ACPI does not have any independent prognostic value in NSCLC.

CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma.

We investigated the expression of CD44 and MMP-9 in primary oral squamous cell carcinoma (OSCC) and evaluated their association with each other and clinicopathological factors as well as their prognostic value during long term follow up. Histological samples from 138 OSCC patients were immunohistochemically stained for the expression of CD44 and MMP-9. The staining results were compared with conventional prognostic factors and their impacts to patients' prognosis were also studied with survival analyses. Irregular staining of CD44 in tumour cells was associated with poor tumour differentiation (p=0.003), higher clinical stage (III-IV) (p=0.049), and the presence of T3-4 tumour stage (p=0.03). Strong stromal MMP-9 staining intensity was correlated with poor tumour differentiation (p=0.03). In univariate survival analysis irregular staining of CD44 in tumour cells was related to poor disease free and overall survival (p=0.001 and p<0.001, respectively). In multivariate analysis CD44 staining was a significant independent predictor for overall (p=0.03) and disease free survival (p=0.003). MMP-9 expression showed no statistical significance in survival analyses. Strong stromal staining intensity of MMP-9 correlated with irregular staining of CD44 in tumour cells, but had no prognostic significance in the present cohort. However, irregular staining of CD44 predicted more advanced disease and shortened survival of the patients.

Sensory-motor coordination during grasping and manipulative actions.

Goal-directed grasping and manipulation of objects are human skills that depend on automatic sensory control in which predictive feed-forward mechanisms integrate somatosensory and visual signals with sensory-motor memory systems. Memory representations of physical and task-relevant properties of the object play a pivotal role. Anticipatory strategies are crucial when purposeful actions arise from learned relationships between afferent patterns and efferent commands. The development of even elementary precision grip skills is a protracted process not concluded until early adolescence. Not surprisingly, the neural control of manual actions engages most central nervous system areas known to be involved in motor control.