Preoperative imaging in patients undergoing trachelectomy for cervical cancer: Validation of a combined T2- and diffusion-weighted endovaginal MRI technique at 3.0 T

Aim

The aim of this study is to validate high-resolution endovaginal T2- and diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved cervical canal) against histology in patients undergoing trachelectomy.

Patients/interventions

55 consecutive patients 25–44 years with cervical cancer being considered for trachelectomy were prospectively assessed with endovaginal T2-W and diffusion-weighted MRI. Two independent observers blinded to histology recorded maximum tumour dimension, volume and distance from the superior aspect of the tumour to the internal os. Following trachelectomy, pathologist-outlined tumour sections were photographed with a set scale and similar measurements were recorded.

Results

Fifteen of 45 patients subsequently treated with fertility-sparing surgery had residual tumour (median histological volume: 0.28 cm³, IQR = 0.14–1.06 cm³). Sensitivity, specificity, positive and negative predictive values for detecting tumour: Observer1: 86.7%, 80.0%, 68.4%, and 92.3%, respectively; Observer2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and volume correlated between observers (r = 0.96, 0.84, respectively, p < 0.0001). Size correlated between each observer and histology (observer 1 r = 0.91, p < 0.0001; observer 2 r = 0.93, p < 0.0001), volume did not (observer 1: r = 0.08, p = 0.6; observer 2: r = 0.21, p = 0.16); however, differences between observer measurements and histology were not significant (size p = 0.09, volume p = 0.15). Differences between MRI and histology estimates of endocervical canal length were not significant (p = 0.1 both observers).

Conclusion

In subcentimetre cervical cancers, endovaginal MRI correlates with pathology and is invaluable in assessing patients for fertility-sparing surgery.     

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

ABSTRACT: BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant familyspecific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27- q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.     

EBV+ diffuse large B-cell lymphoma arising within atrial myxoma. An example of a distinct primary cardiac EBV+ DLBCL of immunocompetent patients

Cardiac myxoma and diffuse large B-cell lymphoma are uncommon tumors, yet four composite tumors have been reported since 2009. We are reporting on the fifth case providing detailed immunohistochemical and FISH analyses. The lymphoma was present as superficially located nests of large cells with patchy necrosis in the background of a typical atrial myxoma. It displayed features of DLBCL with non-germinal center phenotype, expressed EBER, LMP1, EBNA2 and shared the following features with the previously reported cases: B-cell lineage, high-grade cytology, high proliferation rate, EBV infection in latency type 3 with one tested case and an excellent outcome. The lymphomas arising within myxoma may follow a pathogenic pathway driven by EBV, whose transformation potential is unleashed in the cytokine-rich milieu of a myxoma, presumably accentuating age-related decline of adaptive immunity known as immune senescence. DLBCL arising within atrial myxoma grouped together with EBV+ DLBCL associated with valve prosthesis and with an atrial thrombus differs in the immunocompetent patients from primary cardiac DLBCL, not otherwise specified, in clinical presentation, pathological features and a course of the disease. Distinction between these groups may have important therapeutic consequences.     

Augmented Reality Based Navigation for Computer Assisted Hip Resurfacing: A Proof of Concept Study

Implantation accuracy has a great impact on the outcomes of hip resurfacing such as recovery of hip function. Computer assisted orthopedic surgery has demonstrated clear advantages for the patients, with improved placement accuracy and fewer outliers, but the intrusiveness, cost, and added complexity have limited its widespread adoption. To provide seamless computer assistance with improved immersion and a more natural surgical workflow, we propose an augmented-reality (AR) based navigation system for hip resurfacing. The operative femur is registered by processing depth information from the surgical site with a commercial depth camera. By coupling depth data with robotic assistance, obstacles that may obstruct the femur can be tracked and avoided automatically to reduce the chance of disruption to the surgical workflow. Using the registration result and the pre-operative plan, intra-operative surgical guidance is provided through a commercial AR headset so that the user can perform the operation without additional physical guides. To assess the accuracy of the navigation system, experiments of guide hole drilling were performed on femur phantoms. The position and orientation of the drilled holes were compared with the pre-operative plan, and the mean errors were found to be approximately 2 mm and 2°, results which are in line with commercial computer assisted orthopedic systems today.     

Real-time PCR for single-cell genotyping in sickle cell and thalassemia syndromes as a rapid, accurate, reliable, and widely applicable protocol for preimplantation genetic diagnosis

Sickle-cell and beta-thalassemia syndromes are priority genetic diseases for prevention programs involving population screening with the option of prenatal diagnosis for carrier couples. Preimplantation genetic diagnosis (PGD) represents a specialized alternative to prenatal diagnosis and is most appropriately used for couples with an unsuccessful reproductive history and/or undergoing assisted reproduction. However, clinical application of PGD has been hindered by difficulties in reliably transferring molecular diagnostic protocols to the single-cell level. We standardized and validated a protocol involving first-round multiplex PCR, amplifying the region of the beta-globin gene containing most of the common disease mutations world-wide and two unlinked microsatellite markers (GABRB3 and D13S314), followed by: 1) analysis of beta-globin genotypes with real-time PCR and 2) microsatellite sizing to exclude chance contamination. The protocol was standardized on 100 single lymphocytes from a beta-thalassemia heterozygote, including 15 artificially contaminated samples, the latter demonstrated through microsatellite analysis. PCR failure and allele drop-out (ADO) were observed in one (uncontaminated) sample each (1.2%). A pilot study in six clinical PGD cycles with five different beta-globin genotype interactions achieved results (in 5-6 hr) in 46 out of 50 single blastomeres (92%), all concordant with results from an established PGD method applied simultaneously; microsatellite analysis detected only parental alleles, excluding contamination. Beta-globin genotypes were also confirmed in two blastomeres through prenatal diagnosis (twin pregnancy), and in 11 out of 12 spare embryos, revealing one incident of ADO. Overall, the protocol proved to be sensitive, accurate, reliable, rapid, and applicable for many genotype interactions, with internal monitoring of contamination, thus fulfilling all requirements for clinical PGD application.     

Endovaginal magnetic resonance imaging of stage 1A/1B cervical cancer with A T2- and diffusion-weighted magnetic resonance technique: effect of lesion size and previous cone biopsy on tumor detectability

Objective.

To evaluate the effects of previous cone biopsy and lesion size on detectability of stage 1a/1b cervical cancer using endovaginal T2- and diffusion-weighted magnetic resonance imaging.

Methods.

One hundred and thirteen patients with cervical tumor were imaged using an endovaginal coil with T2-weighted (T2-W) and diffusion-weighted single-shot echo-planar sequences; 85 managed surgically (58 with prior cone biopsy/LLETZ) were evaluated. T2-W images and ADC maps viewed simultaneously were scored positive or negative for tumor and compared with histology at surgery. MRI tumor volumes, maximum radiological and histological dimensions were recorded. ROC analysis determined the MRI volume with optimal sensitivity/specificity for identifying tumor in those without and with prior cone biopsy/LLETZ and the maximum histological dimension for correctly identifying tumor with MRI. Mean apparent diffusion coefficients (ADCs) from tumor and adjacent normal epithelium were compared.

Results.

Sensitivity and specificity for detecting tumor in those without (100%; 100% respectively) and with (80%; 78.9% respectively) prior cone biopsy/LLETZ were significantly different (p < 0.001). Following cone biopsy/LLETZ, MRI tumor volume of 83 mm³ detected tumor with 80% sensitivity, 94.7% specificity; a 5.3 mm maximal histological dimension was detected on MRI with 100% sensitivity, 100% specificity. Tumor ADCs were significantly lower (p < 0.001) than paired normal epithelial tissue (median, 988 × 10⁻⁶ mm²/s vs. 1564 × 10⁻⁶ mm²/s) but neither tumor nor epithelial ADCs differed significantly between patients with or without prior cone biopsy/LLETZ (p = 0.48 and 0.15, respectively).

Conclusions.

Endovaginal MRI with T2- and diffusion-weighted sequences has significantly lower sensitivity and specificity for tumor detection following cone biopsy/LLETZ.     

Full genome screen for Alzheimer disease: Stage II analysis*

We performed a two‐stage genome screen to search for novel risk factors for late‐onset Alzheimer disease (AD). The first stage involved genotyping 292 affected sibling pairs using 237 markers spaced at approximately 20 cM intervals throughout the genome. In the second stage, we genotyped 451 affected sibling pairs (ASPs) with an additional 91 markers, in the 16 regions where the multipoint LOD score was greater than 1 in stage I. Ten regions maintained LOD scores in excess of 1 in stage II, on chromosomes 1 (peak B), 5, 6, 9 (peaks A and B), 10, 12, 19, 21, and X. Our strongest evidence for linkage was on chromosome 10, where we obtained a peak multipoint LOD score (MLS) of 3.9. The linked region on chromosome 10 spans approximately 44 cM from D10S1426 (59 cM) to D10S2327 (103 cM). To narrow this region, we tested for linkage disequilibrium with several of the stage II microsatellite markers. Of the seven markers we tested in family‐based and case control samples, the only nominally positive association we found was with the 167 bp allele of marker D10S1217 (chi‐square = 7.11, P = 0.045, df = 1). © 2002 Wiley‐Liss, Inc.     

Reproductive risks of cocaine

Cocaine use during pregnancy in the USA has increased dramaticallyin the past decade, and has resulted in an associated increasein a variety of maternal and perinatal complications. However,a number of confounding factors make it difficult to determinethe direct impact of perinatal cocaine use on maternal and fetaloutcome. Many substance-abusing women use multiple drugs whilepregnant, receive inadequate prenatal care and are predisposedto other health problems that impact on perinatal outcome. Asa result of the rapid clearance of cocaine and limitations ofavailable screening methods, the identification of individualusers can be difficult. Furthermore, the determination of accurateprevalence rates of cocaine use during pregnancy has been frustratedby sampling bias. Cocaine has profound systemic and cardiovasculareffects in both the mother and the fetus, and as a rsult a numberof complications (i.e. fetal malformations, preterm labour,placental abruption) have been attributed to perinatal cocaineexposure. In addition, maternal cocaine use has been associatedwith a number of neonatal abnormalities, including cardio-pulmonaryeffects, somatic changes and neuro-behavioural sequelae. Itis estimated that US $500 million dollars in additional healthexpenditure resulted from increased neonatal hospital costsand longer lengths of stay for cocaine-exposed neonates. Thisarticle reviews the reproductive risks associated with prenatalcocaine use. The pharmacology and physiology of cocaine in relationto pregnancy is discussed, and the impact of this substanceon the growth and development of the fetus and infant is reviewed.