Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome.     

Proton and phosphorus magnetic resonance spectroscopy of the healthy human breast at 7 T

In vivo water‐ and fat‐suppressed ¹H magnetic resonance spectroscopy (MRS) and ³¹P magnetic resonance adiabatic multi‐echo spectroscopic imaging were performed at 7 T in duplicate in healthy fibroglandular breast tissue of a group of eight volunteers. The transverse relaxation times of ³¹P metabolites were determined, and the reproducibility of ¹H and ³¹P MRS was investigated. The transverse relaxation times for phosphoethanolamine (PE) and phosphocholine (PC) were fitted bi‐exponentially, with an added short T₂ component of 20 ms for adenosine monophosphate, resulting in values of 199 ± 8 and 239 ± 14 ms, respectively. The transverse relaxation time for glycerophosphocholine (GPC) was also fitted bi‐exponentially, with an added short T₂ component of 20 ms for glycerophosphatidylethanolamine, which resonates at a similar frequency, resulting in a value of 177 ± 6 ms. Transverse relaxation times for inorganic phosphate, γ‐ATP and glycerophosphatidylcholine mobile phospholipid were fitted mono‐exponentially, resulting in values of 180 ± 4, 19 ± 3 and 20 ± 4 ms, respectively. Coefficients of variation for the duplicate determinations of ¹H total choline (tChol) and the ³¹P metabolites were calculated for the group of volunteers. The reproducibility of inorganic phosphate, the sum of phosphomonoesters and the sum of phosphodiesters with ³¹P MRS imaging was superior to the reproducibility of ¹H MRS for tChol. ¹H and ³¹P data were combined to calculate estimates of the absolute concentrations of PC, GPC and PE in healthy fibroglandular tissue, resulting in upper limits of 0.1, 0.1 and 0.2 mmol/kg of tissue, respectively.     

Neurological symptoms in children with intussusception

Aim:  The classical combination of abdominal pain, vomiting, rectal blood loss and a palpable abdominal mass is only present in a minority of children with intussusception. Neurological signs and symptoms have been described, but are not a well understood phenomenon. We performed a retrospective study to ascertain the frequency and nature of these symptoms and to describe the characteristics of the patients presenting in this atypical way.
Methods:  The records of 58 children presenting with intussusception from 2003 to 2008 were reviewed for abdominal and neurological signs and symptoms, duration of symptoms and effectiveness of treatment.
Results:  In 10 out of 58 patients (17%), one or more neurological symptoms were recorded at presentation, with lethargy being the most frequent, followed by hypotonia and fluctuating consciousness. The patients with neurological abnormalities were significantly younger and presented with a shorter duration of symptoms. Therapy was more invasive, although not statistically significant, in this patient category.
Conclusion:  Intussusception should be considered in the differential diagnosis in young children presenting with lethargy, hypotonia and/or sudden alterations of consciousness even in the absence of the classical symptoms of intussusception.     

Maternal thyroid function during gestation is related to breech presentation at term

Objective To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. Design Prospective follow‐up study during three trimesters of gestation. Patients A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (≥37 weeks) delivery. Measurements Maternal thyroid parameters [TSH, free T4 (FT4) and auto‐antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term. Results At term, 58 women (5·5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0·007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH ≥ 2·5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4·8% in the women with TSH < 2·50 mIU/l (P = 0·006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (≥2·5 mIU/l) at 36 weeks gestation (O.R.: 2·23, 95% CI: 1·14–4·39), but not at 12 and 24 weeks gestation. Conclusions Women with TSH levels above 2·5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

Forced expression of the interferon regulatory factor 2 oncoprotein causes polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cells

The IFN regulatory factor-2 (IRF-2) oncoprotein controls the cell cycle-dependent expression of histone H4 genes during S phase and may function as a component of an E2F-independent mechanism to regulate cell growth. To investigate the role of IRF-2 in control of cell proliferation, we have constructed a stable FDC-P1 cell line (F2) in which expression of IRF-2 is doxycycline (DOX)-inducible, and a control cell line (F0). Both the F2 and F0 cell lines were synchronized in the G1 phase by isoleucine deprivation, and IRF-2 was induced by DOX on release of cells from the cell cycle block. Flow cytometric analyses indicated that forced expression of IRF-2 has limited effects on cell cycle progression before the first mitosis. However, continued cell growth in the presence of elevated IRF-2 levels results in polyploidy (>4n) or genomic disintegration (<2n) and cell death. Western blot analyses revealed that the levels of the cell cycle regulatory proteins cyclin B1 and the cyclin-dependent kinase (CDK)-inhibitory protein p27 are selectively increased. These changes occur concomitant with a significant elevation in the levels of the FAS-L protein, which is the ligand of the FAS (Apo1/CD95) receptor. We also found a subtle change in the ratio of the apoptosis-promoting Bax protein and the antiapoptotic Bcl-2 protein. Hence, IRF-2 induces a cell death response involving the Fas/FasL apoptotic pathway in FDC-P1 cells. Our data suggest that the IRF-2 oncoprotein regulates a critical cell cycle checkpoint that controls progression through G2 and mitosis in FDC-P1 hematopoietic progenitor cells.     

Comment on ‘Predicting recurrence in axillary node negative breast cancer patients’, by Rosner and Lane

on behalf of the Nottingham Breast Unit