Tumour progression or pseudoprogression? A review of post-treatment radiological appearances of glioblastoma.

Glioblastoma (GBM) is a common brain tumour in adults, which, despite multimodality treatment, has a poor median survival. Efficacy of therapy is assessed by clinical examination and magnetic resonance imaging (MRI) features. There is now a recognised subset of treated patients with imaging features that indicate "progressive disease" according to Macdonald's criteria, but subsequently, show stabilisation or resolution without a change in treatment. In these cases of "pseudoprogression", it is believed that non-tumoural causes lead to increased contrast enhancement and conventional MRI is inadequate in distinguishing this from true tumour progression. Incorrect diagnosis is important, as failure to identify pseudoprogression could lead to an inappropriate change of effective therapy. The purpose of this review is to outline the current research into radiological assessment with MRI and molecular imaging of post-treatment GBMs, specifically the differentiation between pseudoprogression and tumour progression.

Stomach position in prediction of survival in left-sided congenital diaphragmatic hernia with or without fetoscopic endoluminal tracheal occlusion.

OBJECTIVE: To investigate the value of fetal stomach position in predicting postnatal outcome in left-sided congenital diaphragmatic hernia (CDH) with and without fetoscopic endoluminal tracheal occlusion (FETO). METHODS: This was a retrospective review of CDH cases that were expectantly managed or treated with FETO, assessed from May 2008 to October 2013, in which we graded, on a scale of 1-4, stomach position on the four-chamber view of the heart with respect to thoracic structures. Logistic regression analysis was used to investigate the effect of management center (Paris, Brussels, Barcelona, Milan), stomach grading, observed-to-expected lung area-to-head circumference ratio (O/E-LHR), gestational age at delivery, birth weight in expectantly managed CDH, gestational ages at FETO and at removal and period of tracheal occlusion, on postnatal survival in CDH cases treated with FETO. RESULTS: We identified 67 expectantly managed CDH cases and 47 CDH cases that were treated with FETO. In expectantly managed CDH, stomach position and O/E-LHR predicted postnatal survival independently. In CDH treated with FETO, stomach position and gestational age at delivery predicted postnatal survival independently. CONCLUSION: In left-sided CDH with or without FETO, stomach position is predictive of postnatal survival.

[Congenital diaphragmatic hernia: antenatal care]. / Hernie congénitale du diaphragme : prise en charge anténatale.

The prenatal evaluation of the postnatal prognosis of fetuses displaying congenital diaphragmatic hernia (CDH) has improved over the past five years. Although the accuracy of these outcome predictions remains a matter of debate, it seems important that all teams in charge of those fetuses use the same prognostic factors in order to be able to improve and compare their practice. Prediction will be based on Lung over Head Ratio (LHR) between 22 and 28 weeks or the LHR observed/expected whatever the gestational age, (the measurement of which relies on very strict criteria), the position of the liver and lung volumes measured by MRI. These factors allow the identification of a group of fetuses likely to have a poor outcome. In the group with LHR less than 1 or LHR o/e less than 25% and where the liver is in the thorax, survival is less than 20%. In utero treatment could be offered to these fetuses. A balloon can be placed in the trachea, under the vocal cords, by foetoscopy between 28 and 30 weeks of pregnancy. The balloon is retrieved at 34 weeks. The preliminary results show that survival in this group increases from 20% to up to 50%. The morbidity does not seem to be increased but is currently under evaluation.

Intestinal myofibroblasts: targets for stem cell therapy.

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA(+)) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA(+) subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).

Mesenchymal cells of the intestinal lamina propria.

The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow-derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ascribed solely to subepithelial myofibroblasts. We review the functional anatomy of intestinal mesenchymal cells and describe what is known about their origin in the embryo and their replacement in adults. As part of their putative role in intestinal mucosal morphogenesis, we consider the intestinal stem cell niche. Lastly, we review emerging information about myofibroblasts as nonprofessional immune cells that may be important as an alarm system for the gut and as a participant in peripheral immune tolerance.

Prenatal diagnosis and evaluation of defect length in esophageal atresia using direct and indirect (tracheal print) signs.

The prenatal diagnosis of esophageal atresia is challenging. The length of the defect of the esophageal atretic portion is one of the parameters affecting outcome and prenatal evaluation of this length has not, to our knowledge, been described previously. We report on seven fetuses assessed prospectively which were suspected to have esophageal atresia. Targeted ultrasound examination of both fetal cervical and thoracic structures was performed in each case in order to assess prenatally the atretic portion. The length of the defect was assessed both directly, by visualizing the interruption of the hyperechoic lines representing the walls of the esophagus in a mid-sagittal view (n = 4), and indirectly, by means of the 'tracheal print' (n = 5). Both methods were used in three cases. Prenatal results were compared with postnatal or postmortem findings. The prenatal diagnosis of esophageal atresia was made correctly in six of the seven cases and in all of these there was concordance between prenatal and postnatal estimates of the esophageal defect lengths. Direct or indirect sonographic assessment of the esophagus in cases of suspected prenatal esophageal atresia improves the specificity of its diagnosis and aids prenatal evaluation.

Intestinal mesenchymal cells.

The non-white blood cell mesenchymal elements of the intestinal lamina propria are the myofibroblasts, fibroblasts, pericytes, stromal stem cells, muscularis mucosae, and the smooth muscle of the villus core associated with the lymphatic lacteal. We review the functional anatomy of these mesenchymal cells, what is known about their origin in the embryo and their replacement in adults, their putative role in intestinal mucosal morphogenesis, and the intestinal stem cell niche, and we consider new information about myofibroblasts as nonprofessional immune cells. Although our knowledge of the function of mesenchymal cells in intestinal disease is rudimentary, we briefly consider here their roles in cancer and intestinal inflammation.

Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex.

OBJECTIVES: To determine the prevalence of specific cerebral lesions of tuberous sclerosis complex (TSC) and neurological outcome in cases diagnosed prenatally with cardiac rhabdomyomas. METHODS: We reviewed all fetuses diagnosed prenatally with cardiac rhabdomyomas which had undergone detailed ultrasound evaluation and cerebral magnetic resonance imaging (MRI) and which were recorded in the database of a single institution covering the period January 1992 to December 2005. RESULTS: Fifty-one fetuses were included in the study. MRI was performed at a mean +/- SD gestational age of 30 +/- 3 gestational weeks and showed specific lesions of TSC in 49% of cases. Termination of pregnancy was chosen by the parents in 26 cases. Neurological development was studied in 20 cases, follow-up lasting 4.8 +/- 2.9 years. Neurodevelopmental events occurred during the follow-up period in 45% of cases. Neurological complications occurred in 67% of patients who had cerebral lesions at MRI and in 33% of patients with normal MRI results. There was no significant difference between the two groups of patients (P = 0.2). CONCLUSION: In fetuses with cardiac rhabdomyomas detailed ultrasound examination and third-trimester cerebral MRI are able to diagnose most TSC cerebral lesions, but fail to determine neurological outcome.

Keyhole sign: how specific is it for the diagnosis of posterior urethral valves?

OBJECTIVES: Posterior urethral valves (PUV) are the most common cause of renal impairment in boys during early childhood. Although antenatal suspicion of this pathology has become quite common in recent years, prenatal diagnosis remains challenging. The aim of this study was to evaluate the predictive value of different ultrasound criteria currently used to diagnose PUV. METHODS: We reviewed the antenatal and postnatal files of 54 male patients referred to our center from 2000 to 2006 after detection of fetal bilateral hydronephrosis. The following ultrasound criteria were evaluated in relation to the postnatal diagnosis of PUV: amniotic fluid volume, bladder wall thickness, bladder dilatation and the presence of the 'keyhole sign'. RESULTS: Forty-two fetuses (77.8%) were suspected to have PUV on prenatal examination. Out of these, 29 (69.0%) had PUV confirmed postnatally. The sensitivity and specificity of the antenatal diagnosis of PUV were 94% and 43%, respectively. Increased bladder wall thickness and bladder dilatation were highly associated with the diagnosis of PUV (P < 0.001). However, a thick-walled bladder was observed in 39.1% and a dilated bladder in 47.8% of the infants with a postnatal diagnosis other than PUV. The presence of the keyhole sign was not found to predict a diagnosis of PUV (P = 0.27). CONCLUSION: In this series the use of classical prenatal ultrasound signs to diagnose PUV showed high sensitivity but low specificity. The best diagnostic indicators were increased bladder wall thickness and dilatation of the bladder. The keyhole sign was not found to be a reliable predictor of PUV.

Early second-trimester diagnosis of intracranial teratoma.

Congenital brain tumors are rare and, whether diagnosed prenatally or postnatally, the most frequent type is teratoma. Prenatal diagnosis relies on sonography and magnetic resonance imaging, and is usually achieved during the second or third trimester. We report a case of an intracranial tumor diagnosed in the early second trimester. The diagnosis had been suspected at first-trimester routine sonography, which showed a compressive intracranial mass with mild vascularization. Because of the poor prognosis, termination of pregnancy was discussed with the parents and was carried out at 14 weeks of gestation. Postmortem examination provided a diagnosis of right frontal immature teratoma.

Prenatal diagnosis of dumbbell neuroblastoma.

A neuroblastoma that develops in the sympathetic nodes can infiltrate the intervertebral foramina and invade the spinal canal, leading to spinal cord and nerve root compression and neurological impairment. Dumbbell neuroblastomas are now considered to be unresectable tumors and preoperative chemotherapy is recommended. We report the prenatal diagnosis of a dumbbell neuroblastoma successfully managed through premature delivery followed by immediate chemotherapy. We suggest that delivering prematurely in such cases is only of benefit if chemotherapy can be administered under favorable conditions. Chemotherapy should proceed immediately after delivery in order to reduce the size of the tumoral mass and its effects on the spine.

Twins discordant for fetal skeletal abnormalities: a natural confrontation between the two siblings.

BACKGROUND: Skeletal abnormalities encompass a heterogeneous group of disorders characterized by anomalies of cartilage as well as bone growth and development. Some are lethal and express early during fetal life, making them amenable to prenatal diagnosis. The increasing use of routine ultrasonography (US) during pregnancy permits a reliable primary evaluation of the fetal skeleton. However, when a skeletal dysplasia is suspected, it is more difficult to establish a specific diagnosis. Moreover, detailed ultrasonographic evaluation of the whole fetal skeleton may be limited in some circumstances, especially during the third trimester due to the fetal position and in the case of multiple pregnancies. METHODS: Retrospective study of twin pregnancies complicated with skeletal abnormalities. RESULTS: 6 twin pregnancies were reviewed. The prenatal diagnosis was correctly made in 66.66% (4/6) with the primary use of combined 2D and 3D-US. 3D-HCT permits to improve the simultaneous assessment of both fetuses, and is of greater value than US in 16.66% (1/6). CONCLUSION: The combined use of 2D or 3D-US with 3D-HCT permits the best imaging evaluation.

HETEs enhance IL-1-mediated COX-2 expression via augmentation of message stability in human colonic myofibroblasts.

Proinflammatory cytokines and eicosanoids are central players in intestinal inflammation. IL-1, a key cytokine associated with intestinal mucosal inflammation, induces COX-2 expression in human colonic myofibroblasts (CMF) and increased prostaglandin E(2) secretion is associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). We have previously demonstrated that IL-1alpha-induced cyclooxygenase-2 (COX-2) expression is the result of NF-kappaB- and ERK-mediated transcription, as well as COX-2 message stabilization, which depends on p38, MAPKAPK-2 (MK-2) and human antigen R (HuR) RNA binding protein activation. Lipoxygenase (LOX)-derived hydroxyeicosatetraenoic acids (HETEs) are elevated in IBD and colonic adenomas and "cross talk" has been observed between the COX and LOX pathways. Since COX-2 expression is primarily in CMFs in colonic adenomas, we examined the impact of LOX metabolites, particularly HETEs, on IL-1alpha-induced COX-2 expression in human CMFs. Although 5(S)-, 12(R)-, and 15(S)-HETEs alone had little to no effect on COX-2 expression, they enhanced IL-1-mediated COX-2 expression 3.6 +/- 0.5-fold. Studies utilizing heterogeneous nuclear RNA amplification and 5,6-dichloro-beta-d-ribofuranosylbenzimidazole treatment were undertaken to measure COX-2 transcription and message stabilization, respectively. We found that HETEs enhanced IL-1-induced COX-2 mRNA levels in CMF as the result of increased p38, MK-2, and HuR activity, increasing message stability greater than that observed with IL-1 alone. Thus HETEs can act synergistically with IL-1alpha to induce COX-2 expression in human CMFs. HETEs may play a role in both colonic inflammation and in increasing the risk of CRC in IBD independently and via induction of COX-2-mediated prostaglandin secretion.

Prospective randomized trial of laparoscopic gastrojejunostomy versus duodenal stenting for malignant gastric outflow obstruction.

BACKGROUND: We prospectively compared laparoscopic gastrojejunostomy with duodenal stenting as a means of palliating malignant gastric outflow obstruction. METHODS: A total of 27 patients with malignant gastric outflow obstruction were randomized to either laparoscopic gastrojejunostomy (LGJ) or duodenal stenting (DS) over a 3-year period. RESULTS: Thirteen patients underwent successful LGJ and 10 had successful DS. Eight patients had complications after LGJ, but none had complications after DS. Patients who underwent LGJ had a significant increase in visual analog pain score at day 1 (p = 0.05), and also had a longer hospital stay compared to those who underwent DS (11.4 vs. 5.2 days, p = 0.02). After DS, patients experienced an improvement in physical health at 1 month as measured using the Short Form-36 (SF-36) questionnaire (p < 0.01). There was no change following LGJ. CONCLUSION: Duodenal stenting is a safe means of palliating malignant gastric outflow obstruction. It offers significant advantages for patients compared with minimal-access surgery.

Class II MHC-expressing myofibroblasts play a role in the immunopathogenesis associated with staphylococcal enterotoxins.

Food poisoning due to staphylococcal enterotoxins (SEs) affects hundreds of thousands of people each year. Little is known about how SEs initiate immune responses and cause pathogenesis. Here, we demonstrate that cultured human intestinal myofibroblasts (IMFs) bind SEs in an MHC class II-dependent fashion. IMFs respond to SE exposure with increased secretion of IL-6, IL-8, and TNF-alpha. A significant proliferative T cell response was observed when MHC class II-expressing IMFs were pulsed with SEA and cocultured with human CD4(+) T cells. In conclusion, our findings support the hypothesis that IMFs may play an important role in pathology associated with staphlococcocal enterotoxigenic disease.

Intestinal myofibroblasts and immune tolerance.

Stromal cells, such as myofibroblasts and fibroblasts, represent a significant fraction of MHC class II-positive cells in the normal human colonic lamina propria, suggesting they may play an important role in CD4(+) T cell regulation in a tolerogenic environment. The aim of this study was to examine whether human colonic myofibroblasts (CMFs) phenotypically and functionally resemble conventional antigen-presenting cells (APCs). Our results support the hypothesis that intestinal myofibroblasts are a novel, nonprofessional APC phenotype important in modulating mucosal T cell responses. Given their strategic location, we propose that intestinal myofibroblasts play a critical role in mediating tolerance to luminal antigens.