Evaluation of antenatal umbilical coiling index at 16-21 weeks of gestation as a predictor of trisomy 21 and other chromosomal defects.

OBJECTIVES: To determine whether there is an association between sonographically assessed hyper- or hypocoiling of the umbilical cord and the presence of trisomy 21, to provide reference values for the antenatal umbilical coiling index (aUCI) at a gestational age of 16-21 weeks and to determine whether these measurements are reliable and reproducible. METHODS: This was a prospective study of 737 pregnancies in which the aUCI was measured between 16 and 21 weeks of gestation by ultrasound at the time of amniocentesis. The aUCI was calculated as the reciprocal value of the mean length of one complete coil in centimeters. We created reference curves and studied the relationship with trisomy 21 and other chromosomal defects. In 30 pregnancies we studied the intra- and interobserver variation in measurements using Bland-Altman plots with associated 95% limits of agreement and intraclass correlation coefficients. RESULTS: aUCI was found to be non-linearly related to gestational age at 16-21 weeks and reference curves were created for the mean aUCI and the 2.3(rd) , 10(th) , 90(th) and 97.7(th) percentiles. There was no significant difference in aUCI values between the reference group (n = 714) and cases with trisomy 21 (n = 16) or other aneuploidies (n = 7) (one-way ANOVA, P = 0.716). There was good intra- and interobserver agreement in aUCI measurements. CONCLUSIONS: The aUCI can be measured reliably and varies according to gestational age at 16-21 weeks. The aUCI was not significantly associated with trisomy 21 or other chromosomal defects.

No beneficial effect of intrathecal methylprednisolone acetate in postherpetic neuralgia patients.

BACKGROUND: High efficacy of intrathecal methylprednisolone acetate (MPA) with lidocaine has been reported in a large patient group suffering from intractable postherpetic neuralgia (PHN). Because the treatment effect was never independently confirmed and there are ongoing safety concerns, intrathecal MPA did not become standard care for intractable PHN. We report the results of a replication trial assessing pain relief and spinal cytokine/chemokine levels in PHN patients. METHODS: The number of patients to be included was determined using sequential analysis to limit patient exposure to the invasive experimental treatment. Patients were randomized to the treatment group receiving MPA 60 mg + lidocaine 60 mg or control group receiving lidocaine 60 mg only. Four injections at 7-day intervals were administered after cerebrospinal fluid (CSF) collection to measure cytokine/chemokine levels. Visual analogue scores for pain and the square allodynic area were collected during follow-up, with the primary end point set at 8 weeks follow-up. RESULTS: In total, 10 patients were included, of whom six were randomized to the treatment group. All six MPA-treated patients experienced a pain increase at 8 weeks, versus one of four patients in the control group. The square allodynic area increased in four of six MPA-treated patients versus one of four control patients. CSF interleukin-8 levels remained stable in the control group, but increased significantly after the first intrathecal MPA injection. The trial was stopped because of safety concerns and futility. CONCLUSION: Considering the absence of clinical benefits and the potential risks of the treatment, intrathecal administration of MPA is not recommended.

Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality.

BACKGROUND: The impact of nationwide centralization of pancreaticoduodenectomy (PD) on mortality is largely unknown. The aim of this study was to analyse changes in hospital volumes and in-hospital mortality after PD in the Netherlands between 2004 and 2009. METHODS: Nationwide data on International Classification of Diseases, ninth revision (ICD-9) code 5-526 (PD, including Whipple), patient age, sex and mortality were retrieved from the independent nationwide KiwaPrismant registry. Based on established cut-off points of annually performed PDs, hospitals were categorized as very low (fewer than 5), low (5-10), medium (11-19) or high (at least 20) volume. A subgroup analysis based on a cut-off age of 70 years was also performed. RESULTS: Some 2155 PDs were included. The number of hospitals performing PD decreased from 48 in 2004 to 30 in 2009 (P = 0·011). In these specific years, the proportion of patients undergoing PD in a medium- or high-volume centre increased from 52·9 to 91·2 per cent (P < 0·001). Nationwide mortality rates after PD decreased from 9·8 to 5·1 per cent (P = 0·044). The mortality rate during the 6-year period was 14·7, 9·8, 6·3 and 3·3 per cent in very low-, low-, medium- and high-volume hospitals respectively (P < 0·001). The difference in mortality between medium- and high-volume centres was statistically significant (P = 0·004). The volume-outcome relationship was not influenced by age (P = 0·467). The mortality rate after PD in patients aged at least 70 years was 10·4 per cent compared with 4·4 per cent in younger patients (P < 0·001). CONCLUSION: With nationwide centralization of PD, the in-hospital mortality rate after this procedure decreased. Further centralization of PD is likely to decrease mortality further, especially in the elderly.

Oral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial.

To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies (sporadic inclusion body myositis excluded) we performed a multicenter, double-blind randomised controlled clinical trial with 18 months follow-up. Sixty-two patients were randomised into 28-day cycles of oral high-dose dexamethasone or daily high-dose prednisolone. Primary outcome measures included (1) seven point composite score of six clinically relevant outcomes and (2) (time-to) remission and (time-to) relapse. No difference between both treatment groups on the composite score was found. Side-effects occurred significantly less frequently in the dexamethasone group. Median time to relapse was 60 (2.9) weeks in the prednisolone and 44 (4.7) weeks in the dexamethasone group (log-rank test p=0.03). In conclusion, pulsed high-dose oral dexamethasone is not superior to daily prednisolone as first-line treatment of idiopathic inflammatory myopathies, but is a good alternative by causing substantially fewer side-effects.

Two-protein signature of novel serological markers apolipoprotein-A2 and serum amyloid alpha predicts prognosis in patients with metastatic renal cell cancer and improves the currently used prognostic survival models.

BACKGROUND: In metastatic renal cell cancer (mRCC), the Memorial Sloan-Kettering Cancer Center (MSKCC) risk model is widely used for clinical trial design and patient management. To improve prognostication, we applied proteomics to identify novel serological proteins associated with overall survival (OS). PATIENTS AND METHODS: Sera from 114 mRCC patients were screened by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). Identified proteins were related to OS. Three proteins were subsequently validated with enzyme-linked immunosorbent assays and immunoturbidimetry. Prognostic models were statistically bootstrapped to correct for overestimation. RESULTS: SELDI-TOF MS detected 10 proteins associated with OS. Of these, apolipoprotein A2 (ApoA2), serum amyloid alpha (SAA) and transthyretin were validated for their association with OS (P = 5.5 x 10(-9), P = 1.1 x 10(-7) and P = 0.0004, respectively). Combining ApoA2 and SAA yielded a prognostic two-protein signature [Akaike's Information Criteria (AIC) = 732, P = 5.2 x 10(-7)]. Including previously identified prognostic factors, multivariable Cox regression analysis revealed ApoA2, SAA, lactate dehydrogenase, performance status and number of metastasis sites as independent factors for survival. Using these five factors, categorization of patients into three risk groups generated a novel protein-based model predicting patient prognosis (AIC = 713, P = 4.3 x 10(-11)) more robustly than the MSKCC model (AIC = 729, P = 1.3 x 10(-7)). Applying this protein-based model instead of the MSKCC model would have changed the risk group in 38% of the patients. CONCLUSIONS: Proteomics and subsequent validation yielded two novel prognostic markers and survival models which improved prediction of OS in mRCC patients over commonly used risk models. Implementation of these models has the potential to improve current risk stratification, although prospective validation will still be necessary.

Inter- and intra-observer agreement of intrapartum ST analysis of the fetal electrocardiogram in women monitored by STAN.

OBJECTIVE: The objective of this study was to quantify inter- and intra-observer agreement on classification of the intrapartum cardiotocogram (CTG) and decision to intervene following STAN guidelines. DESIGN: A prospective, observational study. SETTING: Obstetrics Department of a tertiary referral hospital. POPULATION: STAN recordings of 73 women after 36 weeks of gestation with a high-risk pregnancy, induced or oxytocin-augmented labour, meconium-stained amniotic fluid or epidural analgesia. METHODS: Six observers classified 73 STAN recordings and decided if and when they would suggest an intervention. Proportions of specific agreement (Ps) and kappa values (Kappa) were calculated. MAIN OUTCOME MEASURES: Agreement upon classification of the intrapartum CTG and decision to perform an intervention. RESULTS: Agreement for classification of a normal and a (pre)terminal CTG was good (Ps range 0.50-0.84), but poor for the intermediary and abnormal CTG (Ps range 0.34-0.56). Agreement on the decision to intervene was higher, especially on the decision to perform 'no intervention' (Ps range 0.76-0.94). Overall inter-observer agreement on the decision to intervene was considered moderate in five of six observer combinations according to the kappa (Kappa range 0.42-0.73). Intra-observer agreement for CTG classification and decision to intervene was moderate (Kappa range 0.52-0.67 and 0.61-0.75). CONCLUSIONS: Inter-observer agreement on classification of the intrapartum CTG is poor, but addition of information regarding fetal electrocardiogram, especially in case of intermediary or abnormal CTG traces, results in a more standardised decision to intervene.

Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis.

Radioembolization with yttrium-90 microspheres ((90)Y-RE), either glass- or resin-based, is increasingly applied in patients with unresectable liver malignancies. Clinical results are promising but overall response and survival are not yet known. Therefore a meta-analysis on tumor response and survival in patients who underwent (90)Y-RE was conducted. Based on an extensive literature search, six groups were formed. Determinants were cancer type, microsphere type, chemotherapy protocol used, and stage (deployment in first-line or as salvage therapy). For colorectal liver metastases (mCRC), in a salvage setting, response was 79% for (90)Y-RE combined with 5-fluorouracil/leucovorin (5-FU/LV), and 79% when combined with 5-FU/LV/oxaliplatin or 5-FU/LV/irinotecan, and in a first-line setting 91% and 91%, respectively. For hepatocellular carcinoma (HCC), response was 89% for resin microspheres and 78% for glass microspheres. No statistical method is available to assess median survival based on data presented in the literature. In mCRC, (90)Y-RE delivers high response rates, especially if used neoadjuvant to chemotherapy. In HCC, (90)Y-RE with resin microspheres is significantly more effective than (90)Y-RE with glass microspheres. The impact on survival will become known only when the results of phase III studies are published.

Sonographic longitudinal cervical length measurements in nulliparous women at term: prediction of spontaneous onset of labor.

OBJECTIVE: The aim of this study was to predict spontaneous onset of labor by serial transvaginal ultrasound measurement of cervical length (CL) in a homogeneous population of nulliparous women at term. METHODS: 162 nulliparous women with singleton fetuses in cephalic presentation were examined at weekly intervals from 36 weeks' gestation to delivery. CL was measured by transvaginal ultrasound in the supine and upright positions. RESULTS: There was a significant decrease in CL in the last 12 days prior to delivery. However, this decrease was small with substantial variation between individuals. Women with spontaneous onset of labor could be divided into three different groups: those with unchanged CL before delivery; those with a fall in CL in the last 2 weeks prior to delivery; and those with a gradual change in CL starting before the last 2 weeks prior to delivery. A single CL measurement below 30 mm between 37 and 38 weeks of gestation predicted spontaneous onset of labor before 41 weeks' gestation with a sensitivity of 46%, specificity of 78%, positive predictive value (PPV) of 82%, negative predictive value (NPV) of 40% in the supine position; and sensitivity of 53%, specificity of 72%, PPV of 81%, NPV of 40% in the upright position. CONCLUSION: Between 37 and 38 weeks' gestation, spontaneous onset of labor before 41 weeks can be predicted by a CL measurement, but with low sensitivity and NPV. Inter-individual variations in CL and in CL changes are large, which hampers the value of single and repeated CL measurements for the prediction of spontaneous onset of labor at term.

[Less ventilator-associated pneumonia after oral decontamination with chlorhexidine; a randomised trial]. / Minder beademingspneumonieën door orale decontaminatie met chloorhexidine; gerandomiseerde trial.

OBJECTIVE: To determine the effect of oral decontamination with either chlorhexidine (CHX, 2%) or the combination chlorhexidine-colistin (CHX-COL, 2%-2%) on the frequency and the time to onset of ventilator-associated pneumonia in Intensive Care patients. DESIGN: Double blind, placebo-controlled, multicentre, randomised trial. METHODS: Consecutive ICU patients needing at least 48 h of mechanical ventilation were enrolled in a randomized trial with 3 arms: CHX, CHX-COL, and placebo (PLAC). The trial medication was administered in the oral cavity every 6 h. Oropharyngeal swabs were obtained daily and analysed quantitatively for Gram-positive and Gram-negative microorganisms. Endotracheal colonisation was monitored twice weekly. Ventilator-associated pneumonia was diagnosed on the basis of a combination of clinical, radiological and microbiological criteria. RESULTS: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX-COL. Baseline characteristics in the three groups were comparable. The daily risk of ventilator-associated pneumonia was reduced in both treatment groups compared to PLAC: 65% (HR= 0.352; 95% CI: 0.160-0.791; p = 0.012) for CHX and 55% (HR= 0.454; 95%/ CI: 0.224-0.925; p = 0.030) for CHX-COL. CHX-COL provided a significant reduction in oropharyngeal colonisation with both Gram-negative and Gram-positive microorganisms, whereas CHX significantly affected only colonisation with Gram-positive microorganisms. There were no differences in the duration of mechanical ventilation, ICU-stay or ICU-survival. CONCLUSION: Oral decontamination of the oropharyngeal cavity with chlorhexidine or the combination chlorhexidine-colistin reduced the incidence and the time to onset ofventilator-associated pneumonia.

New algorithm for treatment allocation reduced selection bias and loss of power in small trials.

OBJECTIVE: In clinical trials, patients become available for treatment sequentially. Especially in trials with a small number of patients, loss of power may become an important issue, if treatments are not allocated equally or if prognostic factors differ between the treatment groups. We present a new algorithm for sequential allocation of two treatments in small clinical trials, which is concerned with the reduction of both selection bias and imbalance. STUDY DESIGN AND SETTING: With the algorithm, an element of chance is added to the treatment as allocated by minimization. The amount of chance depends on the actual amount of imbalance of treatment allocations of the patients already enrolled. The sensitivity to imbalance may be tuned. We performed trial simulations with different numbers of patients and prognostic factors, in which we quantified loss of power and selection bias. RESULTS: With our method, selection bias is smaller than with minimization, and loss of power is lower than with pure randomization or treatment allocation according to a biased coin principle. CONCLUSION: Our method combines the conflicting aims of reduction of bias by predictability and reduction of loss of power, as a result of imbalance. The method may be of use in small trials.

Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naïve adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).

BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naïve adults were randomized to either twice-daily nelfinavir and stavudine and once-daily didanosine (regimen A) or simplified once-daily dosed antiretroviral regimens consisting of nevirapine, didanosine, and lamivudine (regimen B) or saquinavir, ritonavir, didanosine, and lamivudine (regimen C). RESULTS: At 48 weeks of therapy, the proportion of patients with a blood plasma HIV-1 RNA concentration (pVL) <50 copies/mL by intention-to treat analysis was 42.3%, 50.0%, and 56.5% for regimens A (n = 26), B (n = 22), and C (n = 23), respectively. The time to a pVL <50 copies/mL for the first time was significantly shorter in regimen C, and there was significantly more progression to CDC events in regimen B. These differences are possibly due to differences in baseline characteristics. Adverse events were lowest for regimen C; more signs associated with mitochondrial toxicity occurred in regimen A. Increase in CD4 count was comparable between arms. CONCLUSION: No statistically significant difference in efficacy was found between the two investigated once-daily dosed treatment regimens (B and C) and the reference (A). Regimen C possibly had a better virological response and less toxicity than regimens A and B.

Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery.

BACKGROUND: Neurological deficit after repair of a thoracic or thoracoabdominal aortic aneurysm (TAA/TAAA) remains a devastating complication. The aim of our study was to investigate the clinical value of biochemical markers [S-100B, neurone-specific enolase (NSE) and lactate dehydrogenase (LD)], evoked potentials and their combinations for identifying adverse neurological outcome after TAA/TAAA surgery. METHODS: From 69 patients, cerebrospinal fluid and blood samples for biochemical analysis were drawn after the induction of anaesthesia, during the cross-clamp period, 5 min, 2, 4, 6, 8, and 19 h, respectively, after reperfusion. In addition, continuous perioperative recording of motor-evoked potentials after transcranial electrical stimulation (tcMEP) and somatosensory-evoked potentials was carried out. Furthermore, neurological examinations were performed. RESULTS: In patients with a defined decrease in lower extremity tcMEP during the cross-clamp period, we found that combinations of the serum concentrations of S-100B and tcMEP ratios at 4, 6, and 8 h after reperfusion had a positive and negative predictive value of 100% in predicting adverse neurological outcome after TAA/TAAA surgery. Furthermore, combinations of the serum concentrations of S-100B and NSE or LD at 19 h after reperfusion had both a positive and negative predictive value of 100% in identifying patients with adverse outcome after TAA/TAAA repair. CONCLUSIONS: TcMEP monitoring during TAA/TAAA surgery seems to be an effective but not completely sufficient guide in our protective multi-modality strategy. Combinations of the serum concentrations of S-100B and tcMEP ratios during the early reperfusion period might be associated with adverse neurological complications. Furthermore, biochemical markers could detect central nervous system injury on the first postoperative day and may have prognostic value.

Quality of life: patients and doctors don't always agree: a meta-analysis.

OBJECTIVE: In addition to traditional clinical markers, quality-of-life assessment can be helpful to estimate the well-being of patients. Discrepancies in perception of well-being between physicians and patients may interfere with the effectiveness of treatment. A systematic review and meta-analysis were performed to explore the (dis-)agreement in quality-of-life assessments between patients and physicians. STUDY DESIGN AND SETTING: Data on the proportion agreement of paired observations were collected from Medline, Embase, Psychlit, and Social Abstracts. RESULTS: Of the 1,316 articles found, six met the selection criteria, four studied the proportion agreement between children and physicians, and all six the proportion agreement between parents and physicians. None examined the magnitude of over- or underestimation by physicians. The agreement was lower in the more subjective domains (0.54-0.77) in comparison to the more objective domains (0.79-0.94). CONCLUSION: Quality-of-life assessment should be integrated in clinical practice. During long-term treatment the perception of the patients' well-being by physicians and patients themselves can easily diverge from each other, resulting in misunderstandings about the treatment and its usefulness in relation to perceived quality of life, and may even become the base for noncompliance.

Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group.

BACKGROUND: We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. METHODS: In 565 patients, we analyzed general results and looked for the potential prognostic variables of age, sex, delay, clinical and pathologic T and N stage, site (332 parotid, 76 submandibular, 129 oral cavity, 28 pharynx/larynx), pain, facial weakness, clinical and pathologic skin involvement, histologic type (WHO 1972 classification), treatment, resection margins, spill, perineural and vascular invasion, number of neck nodes, and extranodal disease. The median follow-up period was 74 months; it was 99 months for patients who were alive on the last follow-up. RESULTS: The rates of local control, regional control, distant metastasis-free and overall survival after 10 years were, respectively, 78%, 87%, 67%, and 50%. In multivariable analysis, local control was predicted by clinical T-stage, bone invasion, site, resection margin, and treatment. Regional control depended on N stage, facial nerve paralysis, and treatment. The relative risk with surgery alone, compared to surgery plus postoperative radiotherapy, was 9.7 for local recurrence and 2.3 for regional recurrence. Distant metastases were independently correlated with T and N stage, sex, perineural invasion, histologic type, and clinical skin involvement. Overall survival depended on age, sex, T and pN stage, site, skin and bone invasion. CONCLUSIONS: Several prognostic factors for locoregional control, distant metastases, and overall survival were found. Postoperative radiotherapy was found to improve locoregional control.

Surgical treatment of traumatic fractures of the thoracic and lumbar spine: a systematic review of the literature on techniques, complications, and outcome.

STUDY DESIGN: A systematic review of the literature, pertaining surgical treatment of traumatic thoracic and lumbar spine fractures, was performed. OBJECTIVES: To provide information on surgical techniques for traumatic spine fracture management, their respective performance and complication rates, based on previously published information. SUMMARY OF BACKGROUND DATA: The treatment of traumatic fractures of the thoracic and lumbar spine remains controversial. There is insufficient evidence in the literature to choose between the various surgical options. In absence of conclusive studies, a systematic review can be an alternative to obtain more convincing information. METHODS: Full-text papers from 1970 until 2001 were included if strict inclusion criteria were met. Five surgical subgroups were recognized: posterior short-segment (PS), posterior long-segment (PL), reports on both posterior short- and long-segment (PSL), anterior (A), and anterior combined with posterior (AP) techniques. Clearly defined and generally accepted parameters were scored and subsequently analyzed. The preoperative injury severity of the surgical groups was compared. The neurologic, radiologic, and functional outcome and complications of all groups were assessed. RESULTS: A total of 132 papers, the majority being retrospective case-series, were included representing 5,748 patients. The preoperative injury severity revealed an inequality between the subgroups. Partial neurologic deficits had the potential to resolve irrespective of treatment choice. None of the five techniques used was able to maintain the corrected kyphosis angle. The functional outcome after surgery seems to be better than generally believed. Complications are relatively rare. CONCLUSIONS: In general, surgical treatment of traumatic spine fractures is safe and effective. Surgical techniques can only be compared using randomized controlled trials.

A prospective quality of life study in patients with locally advanced prostate cancer, treated with radiotherapy with or without regional or interstitial hyperthermia.

INTRODUCTION: The aim of this prospective study was to describe quality of life (QoL) in patients with locally advanced prostate carcinoma treated with conventional radiotherapy and to evaluate the influence of adding regional or interstitial hyperthermia. MATERIALS AND METHODS: All patients were irradiated using a CT-planned conventional three field technique, administering 70 Gy to prostate and vesicles. In two different phase I studies, hyperthermia was added to the radiotherapy. Twelve patients were treated with one interstitial hyperthermia treatment, lasting 60 min. Fourteen patients have been treated with five regional hyperthermia treatments, lasting 75 min each. In both hyperthermia studies, the body, bladder and rectum temperatures remained below safety limits. Patients treated with radiotherapy alone (n = 58) or combined with regional (n = 8) or interstitial hyperthermia (n = 12) completed the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (C30 + 3), the EORTC prostate cancer module (PR25) and the Rand 36 health survey before treatment and 1 and 6 months after completion of treatment. Analysis of Variance (ANOVA) for repeated measurements has been performed to describe the data. RESULTS: All patient groups were comparable concerning patient characteristics. No significant interaction or difference in QoL has been noticed between the two hyperthermia patient groups and the patient group without hyperthermia. Therefore, all groups were analysed together (n = 78) to detect QoL changes in time. A deterioration of QoL has been measured from baseline to 1 month after treatment. Fatigue, pain, urinary symptoms, bowel symptoms and financial difficulties increased significantly. Social, physical and role functioning worsened significantly. No differences in QoL were measured 6 months after treatment compared to the baseline measurement, except for a decrease in sexual activity. CONCLUSIONS: After radiotherapy with or without hyperthermia only a temporary deterioration of QoL occurs, concerning social, psychological and disease related symptoms. Additional hyperthermia does not seem to decrease QoL.

Eye shielding during total body irradiation for bone marrow transplantation in children transplanted for a hematological disorder: risks and benefits.

This is a retrospective analysis of 188 children who underwent total body irradiation (TBI) in one or two fractions before bone marrow transplantation (BMT) for a hematological disorder. While 139 children had eye shielding during TBI to decrease cataract formation, 49 did not. The blocks used for shielding caused cylindrical areas of decreased dose intensity in the brain. The aim of the study was to determine if there was an increased risk of relapse in the eyes or in the CNS after shielding of the eyes. The probability and severity of cataract formation with and without shielding were also evaluated. None of the 49 children without shielding had a relapse in their eyes or in the CNS after BMT. Of the children with shielding, none had a relapse in the eyes but two of the 139 (1.4%) had a CNS relapse. The incidence of cataracts without shielding was 90% (19 of 21 evaluable patients), while with shielding it was 31% (20 of 64). Severe cataracts were present in eight of 21 (38%) patients without and two of 64 (3%) patients with shielding. The probability of staying cataract free for at least five years was 0.77 with and 0.33 without shielding, at 8 years it was 0.53 and 0.24 respectively. The relative risk of developing a cataract without shielding vs shielding was three (95% CI=1.5; 5.9). It appears that the incidence of relapse in the eyes and CNS is not increased when the eyes are shielded during TBI. Shielding increased the latency time of cataract formation and decreased the severity of cataracts.

Acute toxicity of concurrent adjuvant radiotherapy and chemotherapy (CMF or AC) in breast cancer patients. a prospective, comparative, non-randomised study.

The concurrent administration of adjuvant chemotherapy and radiotherapy in breast cancer treatment might lead to an increased incidence of side-effects. In this prospective, non-randomised, comparative study, the acute toxicity of radiotherapy alone (RT) and radiotherapy concurrent with doxorubicin-cyclophosphamide (AC/RT) and radiotherapy concurrent with cyclophosphamide-methotrexate-5-fluorouracil (CMF/RT) was compared. We used the common toxicity criteria (CTC) to score the level of acute toxicity before, during and 6 months after the completion of the period of irradiation. The number of hospital admissions, as well as the compliance of chemotherapy, were noted. We observed that patients treated with AC/RT and CMF/RT had significant higher incidences of (high-grade) skin-toxicity, oesophagitis, dyspnoea, malaise, anorexia, nausea and hospital admission compared with those treated with RT only. The target-volume of radiotherapy was the main predictor of (high-grade) acute skin toxicity and oesophagitis. AC/RT was associated with significant more (high-grade) skin toxicity than CMF/RT. The dose of chemotherapy was reduced to less than 85% of the planned dose in 11% of patients, 17% of patients treated with concurrent chemotherapy and radiotherapy needed admission to hospital. From the results of our study, we conclude that the concurrent administration of adjuvant chemotherapy and radiotherapy leads to an unacceptably high level of acute toxicity.

[Sequential analysis in clinical and epidemiological research]. / Sequentiële analysen in klinisch en epidemiologisch onderzoek.

In clinical trials and epidemiological studies, interim analyses are usually performed for ethical or economical reasons, although efficiency aspects can also be a reason. The analysis is referred to as group-sequential analysis or continuous-sequential analysis, dependent on the number of interim analyses performed. Repeated testing of cumulative data requires an adjustment to the significance level or type I error alpha of a statistical test. On average a (group-)sequential analysis of a clinical or epidemiological study requires less patients than the analysis of a fixed-sample study.

Proliferative capacity in head and neck cancer.

BACKGROUND: Shortening of overall treatment time (accelerated radiotherapy) appears to result in an increase of the efficacy of irradiation. In this study, we compared the proliferative capacity between tumors originating in different sites of the head and neck region. Tumors with a large proliferating capacity might, theoretically, benefit most from accelerated radiotherapy. MATERIAL AND METHODS: BrdUrd was administered intravenously in patients with head and neck carcinomas. Tumor samples were analyzed with flow cytometry. T and N stages were assessed in accordance with the TNM classification system (UICC 1987). RESULTS: No significant differences in proliferation parameters were observed with respect to site of origin of head and neck tumors. For T3/T4 tumors, DNA ploidy is an important tumor characteristic: G1- and S-phase fractions, labeling index, and tumor doubling time Tpot differences were statistically significant; the aneuploid tumors showed the largest proliferative potential. CONCLUSIONS: (1) In general, no significant differences in proliferation parameters were observed with respect to site of origin. (2) Aneuploid head and neck tumors have a higher proliferative capacity than diploid ones, they might benefit most from accelerated irradiation.