Microcystic elongated and fragmented (MELF) pattern of invasion: Molecular features and prognostic significance in the PORTEC-1 and -2 trials.

OBJECTIVE: Microcystic, elongated fragmented (MELF) pattern of myometrial invasion is a distinct histologic feature occasionally seen in low-grade endometrial carcinomas (EC). The prognostic relevance of MELF invasion was uncertain due to conflicting data, and it had not yet appropriately been studied in the context of the molecular EC classification. We aimed to determine the relation of MELF invasion with clinicopathological and molecular characteristics, and define its prognostic relevance in early-stage low/intermediate risk EC. METHODS: Single whole tumor slides of 979 (85.8%) out of 1141 (high)intermediate-risk EC of women who participated in the PORTEC-1/-2 trials were available for review. Clinicopathological and molecular features were compared between MELF invasion positive and negative cases. Time-to-event analyses were done by Kaplan-Meier method, log-rank tests and Cox' proportional hazards models. RESULTS: MELF invasion was found in 128 (13.1%) cases, and associated with grade 1-2 histology, deep myometrial invasion and substantial lymph-vascular space invasion (LVSI). 85.6% of MELF invasion positive tumors were no-specific-molecular-profile (NSMP) EC. NSMP EC with MELF invasion were CTNNB1 wild type in 92.2% and KRAS mutated in 24.4% of cases. Risk of recurrence was lower for MELF invasion positive as compared to MELF invasion negative cases (4.9% vs. 12.7%, p = 0.026). However, MELF invasion had no independent impact on risk of recurrence (HR 0.65, p = 0.30) after correction for clinicopathological and molecular factors. CONCLUSIONS: MELF invasion has no independent impact on risk of recurrence in early-stage EC, and is frequently observed in low-grade NSMP tumors. Routine assessment of MELF invasion has no clinical implications and is not recommended.

EAN guideline on palliative care of people with severe, progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. METHODS: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score > 6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. RESULTS: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. CONCLUSIONS: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis.

BACKGROUND AND PURPOSE: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. METHODS: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. RESULTS: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre-specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre-specified topics, 227 (40%) on additional topics (16 guideline-pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient-important outcomes and of taxing issues. CONCLUSIONS: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient-important outcomes.

Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy.

BACKGROUND: PORTEC-2 was a randomised trial for women with high-intermediate risk (HIR) endometrial cancer, comparing pelvic external beam radiotherapy (EBRT) with vaginal brachytherapy (VBT). We evaluated long-term outcomes combined with the results of pathology review and molecular analysis. METHODS: 427 women with HIR endometrial cancer were randomised between 2002-2006 to VBT or EBRT. Primary endpoint was vaginal recurrence (VR). Pathology review was done in 97.4%, combined with molecular analysis. RESULTS: Median follow-up was 116 months; 10-year VR was 3.4% versus 2.4% for VBT vs. EBRT (p = 0.55). Ten-year pelvic recurrence (PR) was more frequent in the VBT group (6.3% vs. 0.9%, p = 0.004), mostly combined with distant metastases (DM). Ten-year isolated PR was 2.5% vs. 0.5%, p = 0.10, and DM 10.4 vs. 8.9% (p = 0.45). Overall survival for VBT vs. EBRT was 69.5% vs. 67.6% at 10 years (p = 0.72). L1CAM and p53-mutant expression and substantial lymph-vascular space invasion were risk factors for PR and DM. EBRT reduced PR in cases with these risk factors. CONCLUSION: Long-term results of the PORTEC-2 trial confirm VBT as standard adjuvant treatment for HIR endometrial cancer. Molecular risk assessment has the potential to guide adjuvant therapy. EBRT provided better pelvic control in patients with unfavourable risk factors.

Dynamics of patient reported quality of life and symptoms in the acute phase of online adaptive external beam radiation therapy for locally advanced cervical cancer.

OBJECTIVE: For locally advanced cervical cancer patients, treated with External Beam Radiotherapy (EBRT), Quality of Life (QoL) questionnaires arefrequently used to evaluate treatment-related symptoms and functioning scales. Currently, it is unknown how those evolve during the radiation treatment course. In this prospective study we report on weekly-captured patient-reported QoL and symptoms during image-guided adaptive radiotherapy (IGART) of cervical cancer patients. MATERIAL AND METHODS: Between January 2012 and September 2016, all locally advanced cervical cancer patients treated with IGART and brachytherapy with or without chemotherapy or hyperthermia, were eligible. QoL was assessed at baseline; weekly during the first five weeks of treatment; 1week, 1 and 3months after treatment, using the EORTC QLQ-C30 and the QLQ-CX24 questionnaires. Comparisons were made with an age-matched norm population. RESULTS: Among the 138 (70%) responders, most symptoms showed a moderate-to-large increase, reaching a maximum at the end of treatment, or first week after treatment with return to baseline value at 3months after treatment. While most symptoms gradually increased during the first five weeks, diarrhea and bowel cramps already markedly increased within the first three weeks to reach a plateau at the 5th week of treatment. Global health and functioning were temporarily decreased and returned to a plateau at baseline level 3months after treatment, except for cognitive functioning. CONCLUSION: A profound impact on QoL was observed during the radiation treatment course, temporarily affecting functioning. The maximum impaired was reached at the end of EBRT.

A nurse-led sexual rehabilitation intervention after radiotherapy for gynecological cancer.

PURPOSE: Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. METHODS: Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). RESULTS: Twenty participants were 26-71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. CONCLUSIONS: According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial.

Dosimetric impact of bone marrow sparing for robustly optimized IMPT for locally advanced cervical cancer.

BACKGROUND AND PURPOSE: To investigate the trade-off between bone marrow sparing (BMS) and dose to organs at risk (OARs) for intensity modulated proton therapy (IMPT) for women with locally advanced cervical cancer (LACC). MATERIALS AND METHODS: Twenty LACC patients were retrospectively included. IMPT plans were created for each patient using automated treatment planning. These plans progressively reduced bone marrow mean doses by steps of 1 GyRBE, while constraining target coverage and conformality. The relation between bone marrow dose and bladder, small bowel, rectum, and sigmoid doses was evaluated. RESULTS: A total of 140 IMPT plans were created. Plans without BMS had an average [range] bone marrow mean dose of 17.3 [14.7-21.6] GyRBE , which reduced to 12.0 [10.0-14.0] GyRBE with maximum BMS. The mean OAR dose [range] increased modestly for 1 GyRBE BMS: 0.2 [0.0 - 0.6] GyRBE for bladder, 0.3 [-0.2 - 0.7] GyRBE for rectum, 0.4 [0.1 - 0.8] GyRBE for small bowel, and 0.2 [-0.2 - 0.4] GyRBE for sigmoid. Moreover, for maximum BMS, mean OAR doses [range] escalated by 3.3 [0.1 - 6.7] GyRBE for bladder, 5.8 [1.8 - 12.4] GyRBE for rectum, 3.9 [1.6 - 5.9] GyRBE for small bowel, and 2.7 [0.6 - 5.9] GyRBE for sigmoid. CONCLUSION: Achieving 1 GyRBE BMS for IMPT is feasible for LACC patients with limited dosimetric impact on other OARs. While further bone marrow dose reduction is possible for some patients, it may increase OAR doses substantially for others. Hence, we recommend a personalized approach when introducing BMS into clinical IMPT treatment planning to carefully assess individual patient benefits and risks.

Benefit of replacing the Sigma-60 by the Sigma-Eye applicator. A Monte Carlo-based uncertainty analysis.

BACKGROUND AND PURPOSE: To investigate the clinical benefit of replacing the BSD-2000 Sigma-60 with the Sigma-Eye applicator, taking into account effects of uncertainties in tissue and water bolus parameters. PATIENTS AND METHODS: For 20 patients, specific absorption rate (SAR) and temperature distributions were calculated and optimized, based on computed tomography (CT) scans in treatment position. The impact of uncertainties on predicted distributions was studied using a Monte Carlo uncertainty assessment. RESULTS: Replacing the Sigma-60 by the Sigma-Eye applicator resulted in a higher SAR in the tumor [on average a decrease of the hotspot tumor quotient (HTQ) by 24%; p < 0.001], and higher temperatures (T90: +0.4°C, p < 0.001; T50: +0.6°C, p < 0.001) using literature values and SAR optimization. When temperature optimization (T90) was used, a larger average increase was found (T90: +0.7°C, p < 0.001; T50: +0.8°C, p < 0.001). When taking into account uncertainties, a decrease of 23% in median HTQ (p < 0.001) and an increase in T50 and T90 of 0.4°C (p < 0.001) could be demonstrated. CONCLUSION: Based on this uncertainty analysis, significant and clinically relevant improvements in HTQ and tumor temperature were achieved when replacing the Sigma-60 by the Sigma-Eye applicator.

Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.

BACKGROUND: After surgery for intermediate-risk endometrial carcinoma, the vagina is the most frequent site of recurrence. This study established whether vaginal brachytherapy (VBT) is as effective as pelvic external beam radiotherapy (EBRT) in prevention of vaginal recurrence, with fewer adverse effects and improved quality of life. METHODS: In this open-label, non-inferiority, randomised trial undertaken in 19 Dutch radiation oncology centres, 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were randomly assigned by a computer-generated, biased coin minimisation procedure to pelvic EBRT (46 Gy in 23 fractions; n=214) or VBT (21 Gy high-dose rate in three fractions, or 30 Gy low-dose rate; n=213). All investigators were masked to the assignment of treatment group. The primary endpoint was vaginal recurrence. The predefined non-inferiority margin was an absolute difference of 6% in vaginal recurrence. Analysis was by intention to treat, with competing risk methods. The study is registered, number ISRCTN16228756. FINDINGS: At median follow-up of 45 months (range 18-78), three vaginal recurrences had been diagnosed after VBT and four after EBRT. Estimated 5-year rates of vaginal recurrence were 1.8% (95% CI 0.6-5.9) for VBT and 1.6% (0.5-4.9) for EBRT (hazard ratio [HR] 0.78, 95% CI 0.17-3.49; p=0.74). 5-year rates of locoregional relapse (vaginal or pelvic recurrence, or both) were 5.1% (2.8-9.6) for VBT and 2.1% (0.8-5.8) for EBRT (HR 2.08, 0.71-6.09; p=0.17). 1.5% (0.5-4.5) versus 0.5% (0.1-3.4) of patients presented with isolated pelvic recurrence (HR 3.10, 0.32-29.9; p=0.30), and rates of distant metastases were similar (8.3% [5.1-13.4] vs 5.7% [3.3-9.9]; HR 1.32, 0.63-2.74; p=0.46). We recorded no differences in overall (84.8% [95% CI 79.3-90.3] vs 79.6% [71.2-88.0]; HR 1.17, 0.69-1.98; p=0.57) or disease-free survival (82.7% [76.9-88.6] vs 78.1% [69.7-86.5]; HR 1.09, 0.66-1.78; p=0.74). Rates of acute grade 1-2 gastrointestinal toxicity were significantly lower in the VBT group than in the EBRT group at completion of radiotherapy (12.6% [27/215] vs 53.8% [112/208]). INTERPRETATION: VBT is effective in ensuring vaginal control, with fewer gastrointestinal toxic effects than with EBRT. VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk. FUNDING: Dutch Cancer Society.

Brachytherapy quality assurance in the PORTEC-4a trial for molecular-integrated risk profile guided adjuvant treatment of endometrial cancer.

OBJECTIVE: The PORTEC-4a trial investigates molecular-integrated risk profile guided adjuvant treatment for endometrial cancer. The quality assurance programme included a dummy run for vaginal brachytherapy prior to site activation, and annual quality assurance to verify protocol adherence. Aims of this study were to evaluate vaginal brachytherapy quality and protocol adherence. METHODS: For the dummy run, institutes were invited to create a brachytherapy plan on a provided CT-scan with the applicator in situ. For annual quality assurance, institutes provided data of one randomly selected brachytherapy case. A brachytherapy panel reviewed and scored the brachytherapy plans according to a checklist. RESULTS: At the dummy run, 15 out of 21 (71.4%) institutes needed adjustments of delineation or planning. After adjustments, the mean dose at the vaginal apex (protocol: 100%; 7 Gy) decreased from 100.7% to 99.9% and range and standard deviation (SD) narrowed from 83.6-135.1 to 96.4-101.4 and 8.8 to 1.1, respectively. At annual quality assurance, 22 out of 27 (81.5%) cases had no or minor and 5 out of 27 (18.5%) major deviations. Most deviations were related to delineation, mean dose at the vaginal apex (98.0%, 74.7-114.2, SD 7.6) or reference volume length. CONCLUSIONS: Most feedback during the brachytherapy quality assurance procedure of the PORTEC-4a trial was related to delineation, dose at the vaginal apex and the reference volume length. Annual quality assurance is essential to promote protocol compliance, ensuring high quality vaginal brachytherapy in all participating institutes.

Reirradiation combined with hyperthermia in breast cancer recurrences: overview of experience in Erasmus MC.

For superficial hyperthermia a custom-built multi-applicator multi-amplifier superficial hyperthermia system operating at 433 MHz is utilised. Up to 6 Lucite Cone applicators can be used simultaneously to treat an area of 600 cm2. Temperatures are measured continuously with fibre optic multi-sensor probes. For patients with non-standard clinical problems, hyperthermia treatment planning is used to support decision making with regard to treatment strategy. In 74% of our patients with recurrent breast cancer treated with a reirradiation scheme of 8 fractions of 4 Gy in 4 weeks, combined with 4 or 8 hyperthermia treatments, a complete response is achieved, approximately twice as high as the CR rate following the same reirradation alone. The CR rate in tumours smaller than 30 mm is 80-90%, for larger tumours it is 65%. Hyperthermia appears beneficial for patients with microscopic residual tumour as well. To achieve high CR rates it is important to heat the whole radiotherapy field, and to use an adequate heating technique.

Changes in abdominal muscle thickness measured by ultrasound are not associated with recovery in athletes with longstanding groin pain associated with resisted hip adduction.

STUDY DESIGN: Longitudinal single-cohort study. BACKGROUND: Athletes with longstanding groin pain associated with resisted hip adduction have been shown to have abnormal activation of the transversus abdominis (TA). Therefore, exercises targeting the TA to help stabilize the lumbopelvic area are generally used in the rehabilitation of these athletes. OBJECTIVES: To investigate if (1) changes in abdominal muscle resting thickness and changes in relative thickness during lower extremity tasks after 14 weeks of intervention are related to changes in clinical status and (2) the changes in abdominal muscle resting/relative thickness are significant postintervention. METHODS: In 21 athletes with longstanding groin pain associated with resisted hip adduction, ultrasound imaging of the abdominal musculature on the right side was performed at rest, during the active straight-leg raise (left and right), and during bilateral isometric hip adduction. Athletes then followed a 14-week rehabilitation protocol. Clinical outcome measured by self-reported sports restriction and change in abdominal muscle resting and relative thickness during lower extremity tasks were evaluated. RESULTS: There was an overall significant decrease in self-reported sports restriction after intervention for this group of athletes. Apart from a significant negative correlation for changes in TA resting thickness, no significant association between changes in abdominal muscle thickness and change in self-reported sports restriction were found. Postintervention, TA resting thickness was significantly increased but relative thickness during the lower extremity tasks was found not to be statistically different for all muscles, except for a decreased relative thickness of obliquus externus abdominus (OE) during the active straight-leg raise for the left lower extremity. CONCLUSION: There was no association between changes in abdominal muscle resting thickness and relative thickness during lower extremity tasks, and change in self-reported sports restriction after a period of physical therapy in athletes with longstanding groin pain associated with resisted hip adduction. Although this study was designed as a single-cohort longitudinal study, the data suggest that the intervention described can change TA resting thickness. The intervention did not influence abdominal muscle relative thickness during lower extremity tasks.

The Effect of the Time Interval Between Radiation and Hyperthermia on Clinical Outcome in 400 Locally Advanced Cervical Carcinoma Patients.

Background: Addition of deep hyperthermia to radiotherapy results in improved local control (LC) and overall survival compared to radiotherapy alone in cervical carcinoma patients. Based on preclinical data, the time interval between radiotherapy, and hyperthermia is expected to influence treatment outcome. Clinical studies addressing the effect of time interval are sparse. The repercussions for clinical applications are substantial, as the time between radiotherapy and hyperthermia should be kept as short as possible. In this study, we therefore investigated the effect of the time interval between radiotherapy and hyperthermia on treatment outcome. Methods: We analyzed all primary cervical carcinoma patients treated between 1996 and 2016 with thermoradiotherapy at our institute. Data on patients, tumors and treatments were collected, including the thermal dose parameters TRISE and CEM43T90. Follow-up data on tumor status and survival as well as late toxicity were collected. Data was analyzed using Cox proportional hazards analysis and Kaplan Meier analysis. Results: 400 patients were included. Kaplan Meier and univariate Cox analysis showed no effect of the time interval (range 30-230 min) on any clinical outcome measure. Besides known prognostic factors, thermal dose parameters TRISE and CEM43T90 had a significant effect on LC. In multivariate analysis, the thermal dose parameter TRISE (HR 0.649; 95% CI 0.501-0.840) and the use of image guided brachytherapy (HR 0.432; 95% CI 0.214-0.972), but not the time interval, were significant predictors of LC and disease specific survival. Conclusions: The time interval between radiotherapy and hyperthermia, up to 4 h, has no effect on clinical outcome. These results are re-ensuring for our current practice of delivering hyperthermia within maximal 4 h after radiotherapy.

Diagnostics in athletes with long-standing groin pain.

Chronic adductor dysfunction, osteitis pubis and abdominal wall deficiency are mentioned as pathologies explaining long-standing groin pain (LGP) in athletes. The main objective of this study was to evaluate the validity of diagnostic tests used to identify these pathologies in athletic OKE. Additionally, starting points for intervention were searched for. A systematic literature search was performed to retrieve all relevant diagnostic studies and studies describing risk factors. The methodological quality of the identified studies was evaluated. Seventeen studies provided an insight into pathologies; eight provided relevant information for intervention. Adduction provocation tests are moderately valid for osteitis pubis. A pelvic belt might provide some insight into the role of the pubic symphysis during adduction provocation. Palpation can be used for provocation of adductors and symphysis. Roentgen, bone scan and herniography show poor validity. Bilateral abdominal abnormalities on ultrasound appear to be a valid marker for LGP. Magnetic resonance imaging (MRI) can visualize edema and other abnormalities, although the relation to groin pain is not unambiguous. The methodological quality of the studies ranged from poor to good. MRI and ultrasound should be the primary diagnostic tools after clinical examination.

What is the optimal number of library plans in ART for locally advanced cervical cancer?

PURPOSE: Library-of-plans ART is used to manage daily anatomy changes in locally advanced cervical cancer. In our institute, the library contains 2 VMAT plans for patients with large cervix-uterus motion. Increasing this number could be beneficial for tissue sparing, but is burdensome while the dosimetric gain is yet unclear. This study's aim is to determine the optimal number of plans at an individual patient level. MATERIAL AND METHODS: Data of 14 treated patients were analyzed. Plan libraries were created containing 1-4 VMAT plans. Pre-treatment extent of uterus motion was defined by the 99th percentile of the Hausdorff distance (HD99). For dosimetric evaluations, OARs were contoured in daily CBCT scans, plan selection was simulated, and the V45Gy and V40Gy parameters were recorded. RESULTS: Moderate to strong correlations were found between HD99 and the volume of spared OARs. All patients benefitted from adding a 2nd plan, as is the clinical practice. For patients with a HD99 between 30 and 50mm, a 3-plan library reduced the composite V40Gy with 11-21ml compared to a 2-plan library. CONCLUSION: Patients with large uterus motion (HD99>30mm) would benefit from an extension of the plan library to 3. HD99 is an easy-to-implement criteria to select those patients pre-treatment.

Effect of CT-based treatment planning on portal field size and outcome in radiation treatment of localized prostate cancer.

The portal field sizes of 361 consecutive patients treated with curative radiotherapy for localized prostate cancer were measured. The introduction of CT-based information resulted in a significant increase of field sizes, leading to an almost doubling of the treated volume, some increase in late rectal toxicity, but also in local control.

The Dutch Uniform Multicenter Registration system for genetic disorders and malformation syndromes.

In medical genetics, several systems are used to classify and code genetic disorders for the purpose of automated registration. In the Netherlands, a genetic diagnosis code system has been developed that links a unique four-digit code to a principal description and all current synonyms. The main goal of this coding system is to enable nationwide uniformity of coding, without losing access to information stored in the past, identified by the ICD/BPA code (the International Classification of Diseases as adapted by the British Paediatric Association) and/or the MIM code (McKusick's classification in Mendelian Inheritance in Man). To this effect, the Dutch diagnosis code is cross-referenced with the 2 pre-existing classification systems. Developments in medical genetics make regular updates of all coding systems necessary. In the Netherlands, new diagnosis codes are assigned centrally to preserve uniformity and distributed periodically to all 8 clinical genetic centers. Diagnosis codes are assigned in numerical order of inclusion, enabling quick and easy updates. It is possible to include subclassifications of disorders according to pattern of inheritance, gene location, and gene mutations and to cover all disorders and disorder subtypes which are not clearly distinguished by the 2 pre-existing classification systems. The architecture of the coding system is suitable for international use. It offers a practical solution for clinical geneticists in need of a coding system suitable for clinical use. The use of the diagnosis code will also facilitate reliable comparison of data and nationwide genetic epidemiological studies.

Understanding peripartum pelvic pain. Implications of a patient survey.

STUDY DESIGN: An analysis was made of the self-reported medical histories of patients with peripartum pelvic pain. OBJECTIVES: To compile an inventory of the disabilities of patients with peripartum pelvic pain, analyze factors associated with the risk for development of the disease, and to formulate a hypothesis on pathogenesis and specific preventive and therapeutic measures. SUMMARY OF BACKGROUND DATA: Pregnancy is an important risk factor for development of chronic low back pain. Understanding the pathogenesis of pelvic and low back pain during pregnancy and delivery could be useful in understanding and managing nonspecific low back pain. METHODS: By means of a questionnaire, background data were collected among patients of the Dutch Association for Patients With Pelvic Complaints in Relation to Symphysiolysis. Results were compared with the general population. Subgroups were compared with each other. RESULTS: Peripartum pelvic pain seriously interferes with many activities of daily living such us standing, walking, sitting, and all other activities in which the pelvis is involved. Most patients experience a relapse around menstruation and during a subsequent pregnancy. Occurrence of peripartum pelvic pain was associated with twin pregnancy, first pregnancy, higher age at first pregnancy, larger weight of the baby, forceps or vacuum extraction, fundus expression, and a flexed position of the woman during childbirth; a negative association was observed with cesarean section. CONCLUSIONS: It is hypothesized that peripartum pelvic pain is caused by strain of ligaments in the pelvis and lower spine resulting from a combination of damage to ligaments (recently or in the past), hormonal effects, muscle weakness, and the weight of the fetus.

The function of the long dorsal sacroiliac ligament: its implication for understanding low back pain.

STUDY DESIGN: In embalmed human bodies the tension of the long dorsal sacroiliac ligament was measured during incremental loading of anatomical structures that are biomechanically relevant. OBJECTIVES: To assess the function of the long dorsal sacroiliac ligament. SUMMARY OF BACKGROUND DATA: In many patients with aspecific low back pain or peripartum pelvic pain, pain is experienced in the region in which the long dorsal sacroiliac ligament is located. It is not well known that the ligament can be easily palpated in the area directly caudal to the posterior superior iliac spine. Data on the functional and clinical importance of this ligament are lacking. METHODS: A dissection study was performed on the sacral and lumbar regions. The tension of the long dorsal sacroiliac ligament (n = 12) was tested under loading. Tension was measured with a buckle transducer. Several structures, including the erector spinae muscle, the posterior layer of the thoracolumbar fascia, the sarcotuberous ligament, and the sacrum, were incrementally loaded (with forces of 0-50 newtons). The sacrum was loaded in two directions, causing nutation (ventral rotation of the sacrum relative to the iliac bones) and counternutation (the reverse). RESULTS: Forced nutation in the sacroiliac joints diminished the tension and forced counternutation increased the tension. Tension in the long dorsal sacroiliac ligament increased during loading of the ipsilateral sacrotuberous ligament and erector spinae muscle. The tension decreased during traction to the gluteus maximus muscle. Tension also decreased during traction to the ipsilateral and contralateral posterior layer of the thoracolumbar fascia in a direction simulating contraction of the latissimus dorsi muscle. CONCLUSIONS: The long dorsal sacroiliac ligament has close anatomical relations with the erector spinae muscle, the posterior layer of the thoracolumbar fascia, and a specific part of the sacrotuberous ligament (tuberoiliac ligament). Functionally, it is an important link between legs, spine, and arms. The ligament is tensed when the sacroiliac joints are counternutated and slackened when nutated. The reverse holds for the sacrotuberous ligament. Slackening of the long dorsal sacroiliac ligament can be counterbalanced by both the sacrotuberous ligament and the erector muscle. Pain localized within the boundaries of the long ligament could indicate among other things a spinal condition with sustained counternutation of the sacroiliac joints. In diagnosing patients with aspecific low back pain or peripartum pelvic pain, the long dorsal sacroiliac ligament should not be neglected. Even in cases of arthrodesis of the sacroiliac joints, tension in the long ligament can still be altered by different structures.

Reliability and validity of the active straight leg raise test in posterior pelvic pain since pregnancy.

STUDY DESIGN: A cross-sectional analysis was performed in a group of women meeting strict criteria for posterior pelvic pain since pregnancy (PPPP). The scores on the Active Straight Leg Raise Test (ASLR test) were compared with the scores of healthy controls. OBJECTIVES: To develop a new diagnostic instrument for use in patients with PPPP. The objectives of the present study were to assess the validity and reliability of the ASLR test. SUMMARY OF BACKGROUND DATA: Various diagnostic tools are used to diagnose PPPP, but there is still a need for simple tests with high reliability, sensitivity, and specificity. METHODS: Reliability of the ASLR test was assessed in a group of 50 women with lumbopelvic pain of various etiologies and various degrees of severity. Sensitivity was assessed in 200 patients with PPPP and specificity in 50 healthy women. Sensitivity and specificity of the ASLR test were compared with the posterior pelvic pain provocation test (PPPP test). RESULTS: The test-retest reliability measured with Pearson's correlation coefficient between the two ASLR scores 1 week apart was 0.87. The intraclass correlation coefficient (ICC) was 0.83. Pearson's correlation coefficient between the scores of the patient and the scores of a blinded assessor was 0.78; the ICC was 0.77. In the patient group, the ASLR score ranged from 0-10; in the control group it ranged from 0-2. The best balance between specificity and sensitivity was found when scores 1-10 are designated as positive and zero as negative. With this cut-off point sensitivity of the test was 0.87 and specificity was 0.94. The sensitivity of the ASLR test is higher than the sensitivity of the PPPP test; an advantage of the ASLR test is the simplicity of measuring the score. CONCLUSION: The ASLR test is a suitable diagnostic instrument to discriminate between patients who are disabled by PPPP and healthy subjects. The test is easy to perform; reliability, sensitivity, and specificity are high. It seems that the integrity of the function to transfer loads between the lumbosacral spine and legs is tested by the ASLR test.