The value of post-operative chemotherapy after chemoradiotherapy in patients with high-risk locally advanced rectal cancer-results from the RAPIDO trial.

BACKGROUND: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial. PATIENTS AND METHODS: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression. RESULTS: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT ≥75% versus pCT-/-). However, all 95% confidence intervals included 1. CONCLUSIONS: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.

Blended online learning for oncologists to improve skills in shared decision making about palliative chemotherapy: a pre-posttest evaluation.

PURPOSE: To improve shared decision making (SDM) with advanced cancer patients, communication skills training for oncologists is needed. The purpose was to examine the effects of a blended online learning (i.e. e-learning and online training session) for oncologists about SDM in palliative oncological care and to compare this blended format with a more extensive, fully in-person face-to-face training format. METHODS: A one-group pre-posttest design was adopted. Before (T0) and after (T2) training, participants conducted simulated consultations (SPAs) and surveys; after the e-learning (T1), an additional survey was filled out. The primary outcome was observed SDM (OPTION12 and 4SDM). Secondary outcomes included observed SDM per stage, SPA duration and decision made as well as oncologists' self-reported knowledge, clinical behavioural intentions, satisfaction with the communication and evaluation of the training. Additionally, outcomes of the blended learning were compared with those of the face-to-face training cohort. Analyses were conducted in SPSS by linear mixed models. RESULTS: Oncologists (n = 17) showed significantly higher SDM scores after the blended online learning. The individual stages of SDM and the number of times the decision was postponed as well as oncologists' beliefs about capabilities, knowledge and satisfaction increased after the blended learning. Consultation duration was unchanged. The training was evaluated as satisfactory. When compared with the face-to-face training, the blended learning effects were smaller. CONCLUSION: Blended online SDM training for oncologists was effective. However, the effects were smaller compared to face-to-face training. The availability of different training formats provides opportunities for tailoring training to the wishes and needs of learners.

Brain lesions in a patient with rectal cancer: mind your step.

Cerebral toxoplasmosis is a potentially fatal infection most commonly seen in immunocompromised patients. We present a patient on long-term immunosuppressive therapy after kidney transplantation and a recent history of oligometastatic rectal cancer, with cerebral lesions as a result of toxoplasmosis. Heightened awareness of the occurrence of opportunistic infections in patients with cancer who are taking immunosuppressive drugs is needed among clinicians.

Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group.

BACKGROUND: Hand-foot syndrome (HFS) is a common side-effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with previously untreated mCRC and planned treatment with fluoropyrimidine monochemotherapy were randomized 1 : 1 to receive either capecitabine (1250 mg/m2 orally for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice daily on days 1-14) or S-1 (30 mg/m2 orally twice daily on days 1-14) in 3-weekly cycles, with bevacizumab optional in both groups. The primary endpoint was the incidence of any grade HFS, as assessed by both physicians and patients (diaries). Secondary endpoints included grade 3 HFS, other toxicities, relative dose intensity, progression-free survival, response rate and overall survival. RESULTS: A total of 161 patients were randomized in 27 centres. The incidence of any grade HFS as assessed by physicians was 73% in the capecitabine group (n = 80) and 45% in the S-1 group (n = 80) [odds ratio (95% confidence interval) 0.31 (0.16-0.60), P = 0.0005]. The incidence of grade 3 HFS was 21% and 4% (P = 0.003), respectively. Patient-assessed any grade HFS was 84% and 58%, respectively (P = 0.004). Grade 3 anorexia was more common in the S-1 group (3% versus 13%, P = 0.03). Median relative dose intensity was 88% in the capecitabine group and 95% in the S-1 group (P = 0.026). There were no statistically significant differences in median progression-free survival, response rate and overall survival rates. CONCLUSION: Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01918852.

Plain articaine or prilocaine for spinal anaesthesia in day-case knee arthroscopy: a double-blind randomized trial.

BACKGROUND: Both prilocaine and articaine are short-acting local anaesthetics suited for spinal anaesthesia for day-case knee arthroscopy. Articaine is thought to have a faster onset and shorter duration of action than prilocaine, although no comparative study has been published in the anaesthetic literature. METHODS: In this prospective randomized double-blind study, spinal anaesthesia was performed in 72 ASA I-II patients undergoing knee arthroscopy with 50 mg of either plain prilocaine or plain articaine. The primary outcome variable was duration of motor block. Secondary outcomes were onset of sensory and motor blocks, maximum spread of the sensory block, time to spontaneous voiding, and side-effects. RESULTS: Time to full motor function recovery was shorter after articaine than prilocaine [mean (SD) 140 (33) vs 184 (46) min, respectively, P<0.001]. Time to spontaneous voiding was shorter after articaine than prilocaine [mean (SD) 184 (39) vs 227 (45) min, respectively, P<0.001]. One patient in the articaine group reported mild transient neurological symptoms (TNS) limited to the first postoperative day, but there were no significant differences in adverse effects between the groups. CONCLUSIONS: Spinal anaesthesia with plain articaine 50 mg resulted in a faster recovery of motor function and earlier spontaneous voiding compared with plain prilocaine 50 mg. Surgical anaesthesia was not different. The incidence of TNS was low.

Encapsulating peritoneal sclerosis in patients on peritoneal dialysis.

Encapsulating peritoneal sclerosis (EPS) is an uncommon but one of the most serious complications in patients on long-term peritoneal dialysis. EPS is characterised by a diffuse thickening and/or sclerosis of the peritoneal membrane which leads to a decreased ultrafiltration and ultimately to bowel obstruction. We present four cases of EPS and discuss the clinical manifestations, multifactorial aetiology, diagnosis, treatment, prognosis, and prevention. We end with a proposal for the development of an EPS prevention guideline.

Cyclosporine short infusion and C2 monitoring in haematopoietic stem cell transplant recipients.

Blood concentrations of cyclosporine A (CsA) >or=800 microg/l measured 2 h post-dosing, the C2 concentration, is necessary to obtain a maximal pharmacological effect and correlates well with transplant-related complications such as transplant rejection and toxicity. In an open crossover study CsA blood levels were measured during 24 h to generate a pharmacokinetic profile on days 1, 8 and 15 after starting CsA infusion in 21 haematopoietic allogeneic stem cell transplant recipients who were receiving intravenously CsA 3 mg/kg/day either by continuous infusion or by 2 h infusion given every 12 h. C2 levels after the 2 h infusion correlated better than C1 or C3 levels with the area under the concentration-time curve from 0 to 4 h (r2=0.62). C2 levels >or=800 microg/l were also achieved for 20 out of 24 (83%) of cases after the 2 h infusion of CsA without any increase of CsA-related toxicity but for only three of the 23 patients (13%) after continuous infusion. Therefore, we recommend CsA infusions in 2 h during transplant and perform C2 monitoring to obtain therapeutic C2 levels >or=800 microg/l.

Cognitive deterioration and electrical status epilepticus during slow sleep.

The results of long-term follow-up of 10 children with global or specific cognitive deterioration and, on the electroencephalogram, electrical status epilepticus during sleep (ESES) are described. They were referred because of cognitive deterioration and underwent repeated neurological and neuropsychological examinations and all-night electroencephalography. A previous cognitive level was known or could be estimated in all. Seven children had a continuous spikes and waves during sleep (CSWS) syndrome, with global cognitive deterioration in four and more specific cognitive decline in three, and another three children had Landau-Kleffner syndrome (LKS). Of the last three, two children never had seizures, while the other had localization-related epilepsy. No children experienced aggravation of clinical seizures. However, therapy was disappointing. Cognitive dysfunction did not respond to valproate and/or benzodiazepines in 9 of the 10 children. A frontal epileptic focus was found in 5 of 7 children with CSWS, and a left temporal focus in 2 of 3 children with LKS. The ESES persisted in CSWS for 5-9 years and in LKS for 1-5 years, and disappeared at puberty. Good cognitive recovery after disappearance of ESES occurred in only one child, and partial recovery in four. An unfavorable prognosis of cognitive deterioration seems to be related to long-duration ESES and/or early onset epileptic activity. The authors are of the opinion that cognitive deterioration in children, with or without manifest epileptic seizures, should mandate electroencephalographic investigation during sleep.

Relationships between epilepsy-related factors and memory impairment.

OBJECTIVES: In this study, we will explore the effect of epilepsy-related factors such as: 'type of epilepsy, 'site and side of focus localisation' and 'age at onset', as well as four seizure-related factors: 'years with continuing seizures', 'seizure type' and 'seizure frequency', and the treatment factor 'adverse effects of the medication', on memory impairment. Additionally, we explored whether these epilepsy factors are related to different aspects of memory, i.e. short-term recall vs long-term recall, learning, and verbal memory vs non-verbal memory. MATERIAL AND METHODS: A total of 252 patients with epilepsy and subjective memory complaints were consecutively included from the three epilepsy centres in the Netherlands. To assess memory functions the Wechsler Memory Scale-Revised (WMS-r), and the Dutch version of the California Verbal Learning Test for verbal list learning, was administered. RESULTS: A multivariate analysis of variance (MANOVA) did not show statistically significant effects of the epilepsy factors on memory for the total study sample. For the patients with a unilateral epileptogenic focus in the temporal lobes, MANOVA showed statistically significant effects of lateralisation, with most impairment for patients with left temporal lobe epilepsy and, independently, seizure frequency and 'years with seizures'. CONCLUSION: We may conclude that epilepsy-related dysfunctions in the temporal lobe are the dominant risk factor for developing memory problems, specifically verbal memory problems (verbal learning and problems consolidating verbal information), with more severe impairments with continuing seizures and when seizure frequency is high.

Long-term effects of temporal lobectomy on intelligence.

OBJECTIVE: To characterize the long-term effects of anterior temporal resection on intelligence. METHODS: Twenty-eight left temporal lobectomy (LTL) and 43 right temporal lobectomy (RTL) patients were followed at standard time points for at least 6 years after surgery. RESULTS: The average gain 6 years after operation was 3.6 Verbal IQ (VIQ) points and 10.3 Performance IQ (PIQ) points in LTL patients and 2.9 VIQ points and 7.7 PIQ points in RTL patients. A seizure-free outcome did not influence the increase in IQ, nor was the extent of resection related to IQ scores at the 6-year follow-up. Patients with exclusively mesial temporal sclerosis did not perform as well as patients with other pathologies, both before and after surgery. Major predictors of improved performance at 6 years were initial higher level of performance and lower age at surgery. Much of the observed improvement may be related to retest effects. CONCLUSIONS: The effects of epilepsy surgery on intelligence in the long term are limited. The largest gain in VIQ is seen from 2 to 6 years after surgery.

Lateralization of auditory rhythm length in temporal lobe lesions.

In the visual modality, short rhythmic stimuli have been proven to be better processed (sequentially) by the left hemisphere, while longer rhythms appear to be better (holistically) processed by the right hemisphere. This study was set up to see if the same holds in the auditory modality. The rhythm task as originally designed by Seashore was computerized and is part of the Fepsy Neuropsychological battery. This task was performed by 85 patients with intractable temporal lobe epilepsy (left TLE = 32; right TLE = 53) enrolled in the Dutch Collaborative Epilepsy Surgery Program. They performed the task before and 6 months after surgery. The task consists of 30 pairs of rhythmic patterns in 3 series of 10 items. The series contains patterns of 5, 6, or 7 notes. The purpose is to indicate whether the two patterns are the same or different. Reaction times are also measured. If the hypothesis is true, the short-item sequence will be better processed by patients with right temporal lobe epilepsy (nonimpaired left temporal lobe), the longer sequence will be better processed by the left temporal epilepsy group (nonimpaired right temporal lobe). No overall laterality effect on rhythm perception could be found and no difference was found between both test moments. IQ did not correlate with rhythm performance. However, there was an interaction effect of laterality and rhythm length on performance and reaction time. This effect can be explained by the increase after the operation of the score of the left focus group and a decrease in the right focus group on the longer rhythms. This effect was somewhat less strong in the reaction times: a clear tendency for faster reaction times after surgery in the left and longer reaction times in the right focus group. The effect could not be explained for by the difference in extent of resection in either temporal lobe. This study showed that memory for and discrimination of auditory rhythm is dependent on which hemisphere is used in processing. The effect could be demonstrated for the right hemisphere, which uses a holistic processing of stimuli, which outperforms the left in rhythms consisting of a long sequence. In left temporal resections an improvement occurs on the longer rhythms and in right temporal resections the performance on the longest rhythms decreases.

The A-B neuropsychological assessment schedule (ABNAS): the relationship between patient-perceived drug related cognitive impairment and results of neuropsychological tests.

Our intention was to evaluate the relationships between the A-B neuropsychological assessment schedule (ABNAS) as a measure of patient-perceived cognitive effects of antiepileptic drugs (AEDs) and the results of neuropsychological tests. The measure was developed specifically to assess patient-perceived cognitive effects of AED treatment. Evidence of its reliability and validity has been previously documented. In this study 96 patients were included using stratified inclusion-criteria to guarantee variability of performance: 55 patients were included from a 'low risk condition' with respect to possible cognitive effect (i.e. monotherapy carbamazepine within a dose range of 600-1200 mg/day) and 41 patients were included from a 'high risk condition' (i.e. polytherapy of three or two AEDs including either phenytoin, phenobarbitone or a benzodiazepine; treatment with topiramate with a titration speed using 50 mg or higher increments per week and within the first 6 months of treatment). All patients were prospectively assessed using the ABNAS and five neuropsychological tests (all part of the FePsy test system) with proven sensitivity of cognitive effects of antiepileptics: three tasks using reaction-time to measure speed ('simple (visual) reaction-time measurement', 'the binary choice reaction test' and 'the computerized visual searching task'); one test measuring motor speed ('the finger tapping task'); and a memory test ('recognition of words'). The three reaction-time tasks and the finger tapping test were significantly correlated with the ABNAS-score with correlations ranging from 0.22 to 0.35. The highest correlation was with 'simple (visual) reaction-time measurement' (0.35). Discriminant analysis showed that with the neuropsychological tests 61.5% of the patients were correctly identified as having high/low ABNAS-scores. The ABNAS underestimated impairment in 17.8% of the patients ( = low ABNAS-score but impairment on the neuropsychological tests). The present study contributes to the already existing evidence of validity of the ABNAS as a screening instrument for clinical practice as the relationship between the ABNAS-score and results of neuropsychological tests can help to identify who is at risk and needs further referral for neuropsychological assessment. Moreover the correlation between ABNAS-score and those neuropsychological tests that are sensitive for drug-effects may provide a sensitive instrument in early drug-development phases while keeping the burden on financial and time resources to a minimum.

Memory Complaints in Medically Refractory Epilepsy: Relationship to Epilepsy-Related Factors.

This study reports the results of a multicenter study on memory complaints in 252 patients with epilepsy who presented with subjective complaints about memory problems in daily life. Memory complaints were measured with a standardized memory questionnaire (GKLE). The main purpose was to analyze the type of memory complaints and to examine the relationship between subjective complaints and several epilepsy-related factors. These include seizure type, lateralization and location of the focus, etiology, duration, age at onset, and antiepileptic medication. As expected patients experienced significantly more memory complaints. In particular, patients of older age and higher intelligence level complained more about their memory functioning. Although the clinical significance is marginal, neuroticism showed a significant relationship to the total complaint score. The total amount of subjective complaints is not related to the localization or lateralization of the epileptic disturbances. Patients with a longer duration of epilepsy complained significantly more about memory problems, especially about retrieving information from memory. All other epilepsy-related factors showed no relationship to memory complaints.