Mobile right heart thrombus with minimal pulmonary embolism. A case report

The generalisation of the use of transthoracic echocardiography in the investigation of pulmonary embolism leads to the diagnosis of mobile right heart thrombus in about 5% of cases. A review of the literature shows that this association is mainly observed in clinically severe pulmonary embolism. The presence of a mobile right heart thrombus is associated with a poor prognosis and emergency treatment is based on thrombolytic therapy or surgical embolectomy. In minimal or infraclinical pulmonary embolism, the finding of a mobile right heart thrombus is rare and there is no consensus about its treatment. The authors report the case of a 61 year old man admitted to hospital for bilateral deep vein thrombosis with no symptoms of pulmonary embolism in whom investigations revealed a mobile right heart thrombus with minimal pulmonary embolism. The outcome was favourable with progressive resolution of the right heart thrombus with oral anticoagulation after three weeks of heparin therapy.     

4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT

Objective:

To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability () using an in-house developed dose model.

Methods:

Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain for each plan.

Results:

The average variation observed in mean dose to the target volumes were −0.76% ± 0.36% for the 20-fraction treatment and −0.26% ± 0.68% and −1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in was −1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was −2.80% ± 1.68% and −4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min⁻¹ for the single-fraction treatments, the drop in was reduced by approximately 1.5%.

Conclusion:

The effect of interplay on is negligible for conventionally fractionated treatments, whereas considerable drop in is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect.

Advances in knowledge:

A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on .Respiration-induced organ motion represents a serious challenge regarding the accuracy of dose delivery in radiotherapy (RT) and its impact on clinical outcome. Lung tumours are the most common tumours affected by respiration-induced motion, and local failure (approximately 70% of the cases) is considered as a major cause of tumour-related deaths. Studies have highlighted the importance of dose escalation for improving local control in non-small-cell lung cancers (NSCLC).^1,2Since intensity-modulated RT (IMRT) has the potential to deliver higher doses with fewer normal tissue complications,³ IMRT is often used nowadays to treat lung tumours. Moreover, hypofractionated treatments have been shown to result in better clinical outcomes for medically inoperable early-stage lung tumours.^4–7 Better targeting accuracy coupled with superior normal tissue sparing and higher dose conformality, especially with smaller treatment fields used in stereotactic treatments, allows clinicians to prescribe extremely high doses in very few fractions (approximately three). With the advent of image-guided RT, this type of treatment is becoming increasingly common for lung RT. In conventional treatments where the fluence is uniform at the central portion of the fields, respiration-induced tumour motion causes dose blurring at the edges of the target volume, which can be accounted for by a sufficient planning target volume (PTV) margin. However, in multileaf collimator (MLC)-based IMRT delivery where the fluence is non-uniform across the fields, the interplay between respiration-induced tumour motion and the movement of MLC leaves can result in undesired motion artefacts in dose delivery.^8,9 Consequently, motion management or correction techniques such as tumour tracking or gating have been suggested for treating moving tumours with IMRT.^10–13 It should also be noted that lung tumours have one of the steepest dose–response curves (γ₅₀ = 3.9),¹⁴ which means that a small change in dose results in a relatively large change in tumour control probability (TCP). Although motion management techniques are currently available, it may not be possible to use such techniques for each patient either owing to time or resource constraints. Thus, it is important to understand and quantify the effect of tumour motion in IMRT treatments, that is, the interplay effect, in the absence of tumour tracking or gating. By quantifying, we mean not only in terms of absorbed dose, a purely physical quantity, but more importantly in terms of changes in the probability of local tumour control.Several studies have investigated the effect of respiration-induced tumour motion on IMRT treatments.^9,15–20 Jiang et al¹⁵ have investigated the effect of interplay for three different modes of IMRT delivery (step-and-shoot with 10 and 20 intensity levels, sliding window) using a 0.6-cm³ farmer chamber positioned at the centre of the artificial tumour in a moving phantom. They found that the mean dose to the moving tumour for all the fields varies from <2% to 3%, but it could be as high as 30% for a single field. They have also shown that the variation in dose is insensitive to the mode of delivery and the dose differences due to interplay decrease as the number of treatment fractions becomes large (approximately 30). This has been previously emphasized by Bortfeld et al⁹ who showed by statistical analysis that the mean dose to a moving tumour is insensitive to the delivery technique, and the standard deviation (SD) in dose for a 30-fraction treatment is generally <1% of the mean dose. However, the conclusion derived from point-dose measurements by Jiang et al does not provide a complete picture of the interplay effect to the overall tumour volume. Using two-dimensional (2D) film measurements, Berbeco et al²¹ have shown that the SD of the dose to a pixel inside the target volume can be as high as 2–4% for single-fraction treatments, which corresponds to stereotactic radiosurgery, although the effect is reduced to 0.4–0.7% with 30 fractions. According to their measurements, the maximum dose in the target varies <1%, while the minimum dose varies up to approximately 6%. This indicates that there could be considerable underdosage of the target volume even for treatments with large number of fractions and the effect of interplay is significant for hypofractionated treatments. In a recent study by Zhao et al²² in a three-fraction treatment, the results showed that the clinical target volume (CTV) could be considerably underdosed owing to the interplay effect in a Cyberknife® treatment (Accuray Inc., Sunnyvale, CA). Furthermore, Seco et al²³ have emphasized that reduced dose errors owing to the interplay effect in many-fraction treatments will not apply to hypofractionated treatments. Nevertheless, the effect of tumour motion and MLC leaves remains a concern for hypofractionated treatments, and this has been emphasized by American Association of Physicists in Medicine report 91.²⁴Although there are numerous studies addressing the issues of interplay effects in terms of dose variation in the tumour, studies quantifying the clinical significance of these dose variations are much rarer. Use of TCP as a metric would provide a more valuable insight into the true significance of the interplay effect. As mentioned by Niemierko,²⁵ it would be interesting to know the clinical significance of “x” amount of dose error and “y” amount of geometric error rather than mere variation in the dose. Duan et al¹⁸ have performed a TCP analysis using a moving phantom and found the TCP changes to be 2.3% and 4.3% for five- and single-fraction treatments. However, the volume of the target used in their study is fixed (4.5-cm diameter sphere). TCP values could significantly differ with the volume of the target even for the same prescribed dose with a uniform clonogen density in the CTV, which is the case in this study. Moreover, the TCP values provided were not calculated from a large number of simulations, which raises concern over its applicability for a population of patients.     

Biosynthesis and assembly of platelet GPIIb-IIIa in human megakaryocytes: evidence that assembly between pro-GPIIb and GPIIIa is a prerequisite for expression of the complex on the cell surface

The platelet membrane glycoproteins GPIIb and GPIIIa form a calcium- dependent heterodimer that functions as a receptor for adhesive proteins on stimulated platelets. In this study, we have investigated the kinetics of the assembly reaction that result in GPIIb-IIIa dimerization. Pulse-chase experiments analysis performed on human megakaryocytes obtained from liquid cultures of chronic myelogenous leukemic patients with antibodies specific for GPIIIa or GPIIb demonstrated the existence of a pro-GPIIb-GPIIIa complex and of a large pool (60%) of unassociated GPIIIa; nearly all the GPIIb and the pro- GPIIb molecules were found associated with GPIIIa. This free GPIIIa was not exposed on the cell surface. Pulse-chase experiments on a subclone of the human megakaryocytic cell line LAMA-84 revealed that the cells from this subclone produced only the pro-GPIIb, which was neither processed into mature GPIIb nor expressed on the cell surface. The expression of GPIIIa in PMA treated cells resulted in the production of the mature GPIIb form and the expression of the GPIIb-IIIa complex on the cell surface. These results indicate that assembly between the early forms of pro-GPIIb and GPIIIa is an obligatory step for the maturation of the heterodimer and its expression on the cell surface.     

Bacteriophage T4 polynucleotide kinase triggers degradation of mRNAs

The bacteriophage T4-encoded RegB endoribonuclease is produced during the early stage of phage development and targets mostly (but not exclusively) the Shine-Dalgarno sequences of early genes. In this work, we show that the degradation of RegB-cleaved mRNAs depends on a functional T4 polynucleotide kinase/phosphatase (PNK). The 5'-OH produced by RegB cleavage is phosphorylated by the kinase activity of PNK. This modification allows host RNases G and E, with activity that is strongly stimulated by 5'-monophosphate termini, to attack mRNAs from the 5'-end, causing their destabilization. The PNK-dependent pathway of degradation becomes effective 5 min postinfection, consistent with our finding that several minutes are required for PNK to accumulate after infection. Our work emphasizes the importance of the nature of the 5' terminus for mRNA stability and depicts a pathway of mRNA degradation with 5'- to 3'-polarity in cells devoid of 5'-3' exonucleases. It also ascribes a role for T4 PNK during normal phage development.     

Gynaecological cancers in pregnancy

Cervical and ovarian cancers are the most common gynaecological cancers diagnosed during pregnancy. In early-stage cervical cancer during the first and at the beginning of the second trimester, the two main considerations for management of the patient are the tumour size (and stage) and nodal staging. MRI and laparoscopic lymphadenectomy are useful for clinicians planning a potentially conservative approach. The management of patients with locally advanced cervical disease is controversial and should be discussed on a case-by-case basis according to the tumour size, radiological findings, the term of pregnancy, and the patient's wishes. Different histological types of malignant ovarian diseases arise during pregnancy and their management depends on the diagnosis (histological subtypes, tumour differentiation, and nodal status), the tumour stage, and the trimester of the pregnancy. In patients with peritoneal spread or high-risk early-stage disease, neoadjuvant chemotherapy with pregnancy preservation could be appropriate.     

Pharmacokinetics and biodistribution of technetium 99m labelled standard heparin and a low molecular weight heparin (enoxaparin) after intravenous injection in normal volunteers

For a better understanding of low molecular weight heparin pharmacokinetics, 99m technetium labelled heparin and enoxaparin were injected intravenously to four normal volunteers, after approval by the Ethics Committee and preliminary animals studies. In vitro and in vivo, the labelled products proved to be stable and identical to the non-labelled drugs. Radioactivity curves in blood, organs and urines were similar for both products. Anti Xa plasma half-life was 3 times longer for enoxaparin than for heparin. Anti IIa plasma half-lives were similar. However, radioactivity persisted much longer than biological activities for both products. After chromatography, most of the radioactivity was bound to AT III, where an anti Xa activity peak was also detected. The anti Xa activity peak seen after adding AT III to plasma was much higher with heparin than with enoxaparin. In urine, biological activities, measured with AT III supplementation, were higher with enoxaparin than with heparin. These results suggest that phenomena other than biodistribution are responsible for the differences in pharmacokinetics observed between these two products. The two most likely explanations are differences in metabolism and/or a release of an endogenous factor.     

Long-term results of hysteroscopic myomectomy in 235 patients

OBJECTIVE: To assess the efficacy of transcervical resection of submucous fibroids according to type and size. MATERIALS AND METHODS: Retrospective follow-up of 235 women with submucous fibroids at outpatient hysteroscopy who underwent a hysteroscopic transcervical resection. The main indications were the abnormal uterine bleeding and fertility problems. Thirty-seven percent of patients had an associated endometrial ablation and 32% had a polyp resection. Fifty-one percent of women were menopausal. In cases of incomplete resection a repeat procedure was offered. RESULTS: Intra-operative complications were rare (2.6%) and there was no major complication. Eighty-four percent of cases were followed-up. The median follow-up was 40 months (range 18-66 months). The procedure was classed as a success in 94.4% of patients. Among the cases that were classed as a failure, four patients had a repeated hysteroscopic procedure, three patients had a subsequent hysterectomy and four patients presented with abnormal uterine bleeding at follow-up. CONCLUSION: The hysteroscopic transcervical resection of submucous fibroids is a safe and highly effective long-term therapy for carefully selected women presenting with abnormal uterine bleeding and fertility problems. It produces satisfactory long-term results with few complications.     

Spontaneous uterine artery rupture during pregnancy in a woman with sickle cell disease: a case report

BACKGROUND: Spontaneous rupture of uterine vessels during pregnancy is rare and usually involves uteroovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic collapse due to hemoperitoneum. An atypical case of subacute uterine artery rupture at 27 weeks of gestation occurred in a woman with sickle cell disease. CASE: A 28-year-old, nulliparous woman with sickle cell disease was admitted at 27 weeks of gestation for sharp abdominal pain radiating to the right flank. The first diagnosis included acute renal colic and a sickling vasoocclusive crisis. One week after admission the patient experienced paroxysmal, diffuse abdominal pain associated with acute fetal distress requiring an emergency cesarean section. Laparotomy revealed an 800-mL hemoperitoneum. Active bleeding from a ruptured uterine artery was observed and successfully treated by selective suture. CONCLUSION: Spontaneous rupture of the uterine artery during pregnancy may present as a 2-step process.     

Sentinel node biopsy in cervical cancer: state-of-the-art in 2007

In cervical cancer, lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy warranting the lymphadenectomy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of solid cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and recently in breast cancer. In cervical cancer, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results and clinical implications of sentinel node procedure in cervical cancer.