Bouveret's syndrome: presentation of two cases with review of the literature and development of a surgical treatment strategy

BACKGROUND Bouveret's syndrome causes gastric outlet obstruction when a gallstone is impacted in the duodenum or stomach via a bilioenteric fistula. It is a rare condition that causes significant morbidity and mortality and often occurs in the elderly with significant comorbidities. Individual diagnostic and treatment strategies are required for optimal management and outcome. The purpose of this paper is to develop a surgical strategy for optimized individual treatment of Bouveret's syndrome based on the available literature and motivated by our own experience. CASE PRESENTATION Two cases of Bouveret's syndrome are presented with individual management and restrictive surgical approaches tailored to the condition of the patients and intraoperative findings. CONCLUSIONS Improved diagnostics and restrictive individual surgical approaches have shown to lower the mortality rates of Bouveret's syndrome. For optimized outcome of the individual patient: The medical and perioperative management and time of surgery are tailored to the condition of the patient. CT-scan is most often required to secure the diagnosis. The surgical approach includes enterolithotomy alone or in combination with simultaneous or subsequent cholecystectomy and fistula repair. Lower overall morbidity and mortality are in favor of restrictive surgical approaches. The surgical strategy is adapted to the intraoperative findings and to the risk for secondary complications vs. the age and comorbidities of the patient.

Summer Temperature Trend Over the Past Two Millennia Using Air Content in Himalayan Ice

Two Himalayan ice cores display a factor-two decreasing trend of air content over the past two millennia, in contrast to the relatively stable values in Greenland and Antarctica ice cores over the same period. Because the air content can be related with the relative frequency and intensity of melt phenomena, its variations along the Himalayan ice cores provide an indication of summer temperature trend. Our reconstruction point toward an unprecedented warming trend in the 20th century but does not depict the usual trends associated with "Medieval Warm Period" (MWP), or "Little Ice Age" (LIA).

Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.

BACKGROUND Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. FINDINGS Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. INTERPRETATION This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. FUNDING Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.

Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.

Fully Automatic CT Segmentation for Computer-Assisted Pre-operative Planning of Hip Arthroscopy

Extraction of both pelvic and femoral surface models of a hip joint from CT data for computer-assisted pre-operative planning of hip arthroscopy is addressed. We present a method for a fully automatic image segmentation of a hip joint. Our method works by combining fast random forest (RF) regression based landmark detection, atlas-based segmentation, with articulated statistical shape model (aSSM) based hip joint reconstruction. The two fundamental contributions of our method are: (1) An improved fast Gaussian transform (IFGT) is used within the RF regression framework for a fast and accurate landmark detection, which then allows for a fully automatic initialization of the atlas-based segmentation; and (2) aSSM based fitting is used to preserve hip joint structure and to avoid penetration between the pelvic and femoral models. Validation on 30 hip CT images show that our method achieves high performance in segmenting pelvis, left proximal femur, and right proximal femur surfaces with an average accuracy of 0.59 mm, 0.62 mm, and 0.58 mm, respectively.

3D Intervertebral Disc Localization and Segmentation from MR Images by Data-Driven Regression and Classification

In this paper we propose a new fully-automatic method for localizing and segmenting 3D intervertebral discs from MR images, where the two problems are solved in a unified data-driven regression and classification framework. We estimate the output (image displacements for localization, or fg/bg labels for segmentation) of image points by exploiting both training data and geometric constraints simultaneously. The problem is formulated in a unified objective function which is then solved globally and efficiently. We validate our method on MR images of 25 patients. Taking manually labeled data as the ground truth, our method achieves a mean localization error of 1.3 mm, a mean Dice metric of 87%, and a mean surface distance of 1.3 mm. Our method can be applied to other localization and segmentation tasks.

FACTS: Fully Automatic CT Segmentation of a Hip Joint

Extraction of surface models of a hip joint from CT data is a pre-requisite step for computer assisted diagnosis and planning (CADP) of periacetabular osteotomy (PAO). Most of existing CADP systems are based on manual segmentation, which is time-consuming and hard to achieve reproducible results. In this paper, we present a Fully Automatic CT Segmentation (FACTS) approach to simultaneously extract both pelvic and femoral models. Our approach works by combining fast random forest (RF) regression based landmark detection, multi-atlas based segmentation, with articulated statistical shape model (aSSM) based fitting. The two fundamental contributions of our approach are: (1) an improved fast Gaussian transform (IFGT) is used within the RF regression framework for a fast and accurate landmark detection, which then allows for a fully automatic initialization of the multi-atlas based segmentation; and (2) aSSM based fitting is used to preserve hip joint structure and to avoid penetration between the pelvic and femoral models. Taking manual segmentation as the ground truth, we evaluated the present approach on 30 hip CT images (60 hips) with a 6-fold cross validation. When the present approach was compared to manual segmentation, a mean segmentation accuracy of 0.40, 0.36, and 0.36 mm was found for the pelvis, the left proximal femur, and the right proximal femur, respectively. When the models derived from both segmentations were used to compute the PAO diagnosis parameters, a difference of 2.0 ± 1.5°, 2.1 ± 1.6°, and 3.5 ± 2.3% were found for anteversion, inclination, and acetabular coverage, respectively. The achieved accuracy is regarded as clinically accurate enough for our target applications.

Localization and Segmentation of 3D Intervertebral Discs in MR Images by Data Driven Estimation

This paper addresses the problem of fully-automatic localization and segmentation of 3D intervertebral discs (IVDs) from MR images. Our method contains two steps, where we first localize the center of each IVD, and then segment IVDs by classifying image pixels around each disc center as foreground (disc) or background. The disc localization is done by estimating the image displacements from a set of randomly sampled 3D image patches to the disc center. The image displacements are estimated by jointly optimizing the training and test displacement values in a data-driven way, where we take into consideration both the training data and the geometric constraint on the test image. After the disc centers are localized, we segment the discs by classifying image pixels around disc centers as background or foreground. The classification is done in a similar data-driven approach as we used for localization, but in this segmentation case we are aiming to estimate the foreground/background probability of each pixel instead of the image displacements. In addition, an extra neighborhood smooth constraint is introduced to enforce the local smoothness of the label field. Our method is validated on 3D T2-weighted turbo spin echo MR images of 35 patients from two different studies. Experiments show that compared to state of the art, our method achieves better or comparable results. Specifically, we achieve for localization a mean error of 1.6-2.0 mm, and for segmentation a mean Dice metric of 85%-88% and a mean surface distance of 1.3-1.4 mm.

Evaluation and Comparison of Anatomical Landmark Detection Methods for Cephalometric X-Ray Images: A Grand Challenge

Cephalometric analysis is an essential clinical and research tool in orthodontics for the orthodontic analysis and treatment planning. This paper presents the evaluation of the methods submitted to the Automatic Cephalometric X-Ray Landmark Detection Challenge, held at the IEEE International Symposium on Biomedical Imaging 2014 with an on-site competition. The challenge was set to explore and compare automatic landmark detection methods in application to cephalometric X-ray images. Methods were evaluated on a common database including cephalograms of 300 patients aged six to 60 years, collected from the Dental Department, Tri-Service General Hospital, Taiwan, and manually marked anatomical landmarks as the ground truth data, generated by two experienced medical doctors. Quantitative evaluation was performed to compare the results of a representative selection of current methods submitted to the challenge. Experimental results show that three methods are able to achieve detection rates greater than 80% using the 4 mm precision range, but only one method achieves a detection rate greater than 70% using the 2 mm precision range, which is the acceptable precision range in clinical practice. The study provides insights into the performance of different landmark detection approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques.

Fully Automatic Segmentation of Hip CT Images

Automatic segmentation of the hip joint with pelvis and proximal femur surfaces from CT images is essential for orthopedic diagnosis and surgery. It remains challenging due to the narrowness of hip joint space, where the adjacent surfaces of acetabulum and femoral head are hardly distinguished from each other. This chapter presents a fully automatic method to segment pelvic and proximal femoral surfaces from hip CT images. A coarse-to-fine strategy was proposed to combine multi-atlas segmentation with graph-based surface detection. The multi-atlas segmentation step seeks to coarsely extract the entire hip joint region. It uses automatically detected anatomical landmarks to initialize and select the atlas and accelerate the segmentation. The graph based surface detection is to refine the coarsely segmented hip joint region. It aims at completely and efficiently separate the adjacent surfaces of the acetabulum and the femoral head while preserving the hip joint structure. The proposed strategy was evaluated on 30 hip CT images and provided an average accuracy of 0.55, 0.54, and 0.50 mm for segmenting the pelvis, the left and right proximal femurs, respectively.

Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and associate with increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes mellitus and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (p=2.4*10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. SNPs at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in average UACR per minor allele was 21% for HS6ST1 and 13% for RAB38/CTSC (p=6.3*10(-7) and 5.8*10(-7), respectively). Experiments using streptozotocin-treated diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout vs. control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared to controls. The loci identified here confirm known and highlight novel pathways influencing albuminuria.

MASCG: Multi-Atlas Segmentation Constrained Graph method for accurate segmentation of hip CT images

This paper addresses the issue of fully automatic segmentation of a hip CT image with the goal to preserve the joint structure for clinical applications in hip disease diagnosis and treatment. For this purpose, we propose a Multi-Atlas Segmentation Constrained Graph (MASCG) method. The MASCG method uses multi-atlas based mesh fusion results to initialize a bone sheetness based multi-label graph cut for an accurate hip CT segmentation which has the inherent advantage of automatic separation of the pelvic region from the bilateral proximal femoral regions. We then introduce a graph cut constrained graph search algorithm to further improve the segmentation accuracy around the bilateral hip joint regions. Taking manual segmentation as the ground truth, we evaluated the present approach on 30 hip CT images (60 hips) with a 15-fold cross validation. When the present approach was compared to manual segmentation, an average surface distance error of 0.30 mm, 0.29 mm, and 0.30 mm was found for the pelvis, the left proximal femur, and the right proximal femur, respectively. A further look at the bilateral hip joint regions demonstrated an average surface distance error of 0.16 mm, 0.21 mm and 0.20 mm for the acetabulum, the left femoral head, and the right femoral head, respectively.