S100 proteins in the pathogenesis and diagnosis of inflammatory bowel disease

Crohn’s disease and ulcerative colitis (the inflammatory bowel diseases) are two well characterized conditions featuring inflammation of the gastrointestinal tract. Gut inflammation may be detected, assessed and measured by a variety of methods but their utility varies extensively. Over the past decade, calprotectin, belonging to a family of S100 proteins, has been shown to be a reliable marker of gut inflammation that corresponds to neutrophil migration. In addition, other members of the S100 family have important roles in inflammation and may also be useful markers of gut inflammation. Furthermore, these proteins may have functional roles in gut defense or in the pathogenesis of inflammatory bowel disease.     

胶囊状全消化道介入诊查装置的三维磁定位

为了对微型诊查胶囊进入人体消化道后的三维位置进行测量,提出了不可见状态下的非接触式永磁定位新方法.具体做法是:根据等效磁荷的原理,建立永磁体空间磁场与空间方位的简化定位模型;根据定位模型确定具体的定位方案;并对磁传感器的输出数据进行差分处理,消除了静态和准静态环境磁场干扰.实验证明定位模型能满足精度要求,定位方案正确可行,此定位法可投入实际应用.     

消化道微型诊疗装置磁定位系统的软件设计

为实现对消化道微型诊疗装置在人体内的实时定位与跟踪,使用可视化工具包(VTK)在VC++.Net平台下设计了可应用于消化道微型诊疗装置的定位跟踪软件.该软件采用多线程处理技术,在实时检测电子胶囊内磁标记物的空间磁场信息基础上,利用非线性最优化算法求解出电子胶囊位置和姿态信息,最后将定位结果以二维和三维的形式实时显示并存档.实验结果表明:该程序在基于磁通传感器阵列的硬件平台下,能够稳定的实现磁传感器阵列的数据采集,对非线性最优化磁定位算法进行实时处理,以及空间定位结果的二维、三维显示和数据保存三项任务的流水线并行处理和数据回放等功能,每次传感器阵列数据采集时间小于2 s,定位算法时间小于600 ms.该软件可实时处理定位信息的采集、处理运算及结果显示,能满足消化道内微型装置实时跟踪定位的需要.     

Primary hepatic neuroendocrine carcinoma

Primary neuroendocrine carcinoma of the liver is a rare tumour, probably arising from scattered neuroendocrine cells of the bile duct. We present the case of a 72-year-old male who experienced gradual weight loss and diarrhoea. Given the fact that he had stayed in the Dominican Republic, a parasitic disease was initially suspected. However, this was not confirmed. Further examination showed tumour infiltration of the liver. Fine needle aspiration cytology of the tumour site was performed. The diagnostic procedure revealed neuroendocrine carcinoma. The tumour cells expressed the following neuroendocrine markers (chromogranin, synaptophysin, CD56 and NSE) as well as the epithelial marker AE1-AE3. The tumour was considered metastasis of the primary tumour located in the gastrointestinal tract. A thorough clinical examination was performed including gastroscopy, colonoscopy, In-111 Octreoscan scintigraphy, computed tomography and magnetic resonance imaging. These methods revealed metastases in the vertebrae, pelvis, long bones and skull. No other tumour sites were found in the lungs, gastrointestinal tract or pancreas. The patient became increasingly cachexic and later died. An autopsy showed massive multicentric tumour infiltration of the liver. Histological examination revealed well differentiated neuroendocrine carcinoma which transformed into intermediate and small cells. The autopsy found no tumour sites in the gastrointestinal tract, lungs or pancreas. The results were suggestive of primary neuroendocrine carcinoma of the liver. Keywords: neuroendocrine carcinoma - liver - primary tumour.     

Methods for imaging the structure and function of living tissues and cells: 1. Optical coherence tomography

This is the first in a series of review articles which aim to present a concise and systematic overview of the principles, limitations, advantages, and uses of some of the more important recently developed techniques capable of imaging living histology. Optical coherence tomography (OCT) is now an established optical biopsy method, imaging 2-3 mm into opaque tissue. It is analogous to optical 'ultrasound' but has an outstanding resolution, being capable of imaging single cells in the intact animal via a surface, intravascular or endoscopic approach. Both two-dimensional (2D) and three-dimensional (3D) image datasets can be acquired and studied over time (4D imaging) in the live animal or human subject without the need to remove tissue or perform any tissue processing or staining. It has been used in ophthalmology, gastrointestinal tract (GI) studies, gynaecological tract investigation, and endovascular imaging, to name but a few areas. A degree of differential tissue contrast information can also be gleaned, since different tissue components give different OCT reflectivity signals such that adipose, muscle, collagen, and elastic components may all be resolved without staining. Continuing developments include faster data acquisition for real-time recording and Doppler OCT for more functional imaging.     

A portable method for assessing gastrointestinal motility by simultaneously measuring transit time and contraction frequency

To portably monitor the motility of the total GI tract, a method for assessing GI motility by simultaneously measuring transit time and contraction frequency is put forward. The portable monitoring system is composed of a swallowable telemetric capsule, a portable recorder, magnetizing coils deposited in vitro, and workstation for data processing. The transit time and contraction frequency of the GI tract are deduced by analysing the variation of the position and orientation angles of a telemetric capsule in time domain and frequency domain. AC electromagnetic localization method is used to determine the position and orientation of the telemetric capsule in vivo. In the paper, the localization model based on a quasi-static magnetic field, the method of monitoring GI motility and the set-up of the monitoring system are detailed. Then from static and dynamic experiments, the performances of the system including the accuracy and dynamic response are evaluated. Finally, the electromagnetic safety of the system is verified by simulating electromagnetic radiation to the human body.     

Cystatin C in the human pancreas and gut: An immunohistochemical study of normal and neoplastic tissues

Summary The occurrence of immunoreactive cystatin C (CC) in normal and neoplastic cells of the human pancreas and gut was investigated using an indirect streptavidin-biotin method on formaldehyde-fixed and paraffin-embedded tissues. Virtually all pancreatic islet cells and many neuroendocrine cells throughout the gastrointestinal tract showed strong CC immunoreactivity and a granular cytoplasmic staining pattern. All 14 endocrine pancreatic tumours (insulinomas, glucagonomas, gastrinomas and non-producing tumours), as well as 16 of 17 gut carcinoid tumours, were also strongly CC immunoreactive. In addition, non-endocrine epithelial cells of pancreatic ducts and the gastrointestinal mucosa and 20 of the 24 adenocarcinomas from these sites showed weak CC immunoreactivity. Thus, CC cannot be used as a reliable immunohistochemical marker for endocrine gastro-entero-pancreatic tumours despite the fact that the protein is strongly expressed in a majority of such tumours.     

Hardware-software co-design of portable functional gastrointestinal stimulator system

In the recent years, functional electrical stimulation has been applied to restore impaired motility in the gastrointestinal tract. Unlike other methods of electrical stimulation of the gut, microprocessor-controlled, sequential electrical stimulation has been shown to induce peristalsis and enhance emptying in acute canine gastric and colonic models. This study aims at completing the development of a portable microprocessor-based functional stimulator system consisting of a microelectronic stimulator, patient-specific computer-based real-time software and a programming interfacing device. The ultimate goals of the design are to ensure that (1) the portable stimulator can be efficiently utilized in chronic animal experiments; and (2) the device can be further miniaturized into an implantable version. The designed portable stimulator generates four channel sequential bipolar rectangular pulse trains with programmable parameters within the stimulation requirements obtained from a previously developed computer model. Real-time simulation of colonic peristalsis and a case-specific stimulation model were implemented using patient-specific computer-based software. A chronic canine case study confirmed the feasibility of this microprocessor-controlled stimulation method for future clinical applications in humans.     

胎儿胃肠道胃泌素细胞与生长抑素细胞的免疫组织化学研究

本文用PAP免疫组织比学法和间接免疫荧光组织化学法,对60例8～38周胎儿胃肠粘膜中胃泌素细胞(G细胞)和生长抑素细胞(D细胞)的发生进行了研究。这两种细胞最早出现于8～9周胎儿十二指肠上皮中,但在固有膜及肌层未观察到。12周后,D细胞出现在胎儿胃肠全长粘膜,G细胞则只见于胃窦及小肠粘膜。本文还对各时期胎儿胃肠粘膜中D细胞和G细胞的分布、数量,以及二者比例变化等进行了观察。胃窦中G细胞与D细胞一样,基底部伸出突起,可能具有旁分泌功能。除胃底腺外,其余部位的D细胞和G细胞多为开放型细胞。本文对这两种细胞在胎儿胃肠发育中的可能功能进行了讨论,并与成人胃窦和十二指肠上部粘膜中G、D细胞的比例进行了对比观察。     

磁场方式的内窥镜体内三维定位与追踪方法研究

本研究以磁场方式来测定内窥镜探头在人体内的三维位置及姿态角。根据三个互相正交的圆环线圈在其周围空间任意点产生的三维磁感应强度表达式 ,以及附着于内窥镜探头上的三个相互正交的磁场传感器在该磁场空间任意点以任意姿态感应磁场时所获得信号的表达式 ,建立以空间位置 (x ,y ,z) ,姿态角 (a ,b ,c)为未知数的六元非线性方程组。使用具有全局收敛特性的牛顿 拉夫森算法求解非线性方程组 ,由磁场传感器所获得的测量数据计算出对应的一组位置和姿态 (x ,y ,z ,a ,b,c) ,从而实现内窥镜探头的三维定位和跟踪     

The gastrointestinal tract stem cell niche

The gastrointestinal epithelium is unique in that cell proliferation, differentiation, and apoptosis occur in an orderly fashion along the crypt-villus axis. The intestinal crypt is mainly a proliferative compartment, is monoclonal and is maintained by stem cells. The villus represents the differentiated compartment, and is polyclonal as it receives cells from multiple crypts. In the small intestine, cell migration begins near the base of the crypt, and cells migrate from here emerging onto the villi. The basal crypt cells at position 5 are candidate stem cells. As the function of stem cells is to maintain the integrity of the intestinal epithelium, it must self-renew, proliferate, and differentiate within a protective niche. This niche is made up of proliferating and differentiating epithelial cells and surrounding mesenchymal cells. These mesenchymal cells promote the epithelial-mesenchymal crosstalk required to maintain the niche. A stochastic model of cell division has been proposed to explain how a single common ancestral stem cell exists from which all stem cells in a niche are descended. Our group has argued that these crypts then clonally expand by crypt fission, forming two daughters’ crypts, and that this is the mechanism by which mutated stem cells or even cancer stem cell clones expand in the colon and in the entire gastrointestinal tract. Until recently, the differentiation potential of stem cells into adult tissues has been thought to be limited to cell lineages in the organ from which they were derived. Bone marrow cells are rare among adult stem cells regarding their abundance and role in the continuous, lifelong, physiological replenishment of circulating cells. In human and mice experiments, we have shown that bone marrow can contribute to the regeneration of intestinal myofibroblasts and thereby after epithelium following damage, through replacing the cells, which maintain the stem cells niche. Little is known about the markers characterizing the stem and transit amplifying populations of the gastrointestinal tract, although musashi-1 and hairy and enhancer of split homolog-1 have been proposed. As the mammalian gastrointestinal tract develops from the embryonic gut, it is made up of an endodermally-derived epithelium surrounded by cells of mesoderm origin. Cell signaling between these two tissue layers plays a critical role in coordinating patterning and organogenesis of the gut and its derivatives. Many lines of evidence have revealed that Wnt signaling is the most dominant force in controlling cell proliferation, differentiation, and apoptosis along the crypt-villus axis. We have found Wnt messenger RNAs expression in intestinal subepithelial myofibroblasts and frizzled messenger RNAs expression in both myofibroblasts and crypt epithelium. Moreover, there are many other factors, for example, bone morphogenetic protein, homeobox, forkhead, hedgehog, homeodomain, and platelet-derived growth factor that are also important to stem cell signaling in the gastrointestinal tract.     

On the use of EPID-based implanted marker tracking for 4D radiotherapy

Four-dimensional (4D) radiotherapy delivery to dynamically moving tumors requires a real-time signal of the tumor position as a function of time so that the radiation beam can continuously track the tumor during the respiration cycle. The aim of this study was to develop and evaluate an electronic portal imaging device (EPID)-based marker-tracking system that can be used for real-time tumor targeting, or 4D radiotherapy. Three gold cylinders, 3 mm in length and 1 mm in diameter, were implanted in a dynamic lung phantom. The phantom range of motion was 4 cm with a 3-s "breathing" period. EPID image acquisition parameters were modified, allowing image acquisition in 0.1 s. Images of the stationary and moving phantom were acquired. Software was developed to segment automatically the marker positions from the EPID images. Images acquired in 0.1 s displayed higher noise and a lower signal-noise ratio than those obtained using regular (> 1 s) acquisition settings. However, the markers were still clearly visible on the 0.1-s images. The motion of the phantom blurred the images of the markers and further reduced the signal-noise ratio, though they could still be successfully segmented from the images in 10-30 ms of computation time. The positions of gold markers placed in the lung phantom were detected successfully, even for phantom velocities substantially higher than those observed for typical lung tumors. This study shows that using EPID-based marker tracking for 4D radiotherapy is feasible, however, changes in linear accelerator technology and EPID-based image acquisition as well as patient studies are required before this method can be implemented clinically.     

Perivascular epithelioid cell tumor in the duodenum: challenge in differential diagnosis

Defined as a family of scarce mesenchymal neoplasm which distinctively co-express melanocytic markers and muscle markers, perivascular epithelioid cell tumors (PEComas) have been reported almost everybody site. Perivascular epithelioid cell tumors-not otherwise specified (PEComas-NOS) arising in the gastrointestinal (GI) tract are still restricted into sporadic case reports. Herein we present a case of GI PEComas-NOS which occurs in the duodenum of a 27-year-old male. Our initial diagnosis tended to gastrointestinal stromal tumor or smooth muscle tumor till the correct diagnosis of perivascular epithelioid cell tumor (PEComa) was established by postoperative pathological examination. We also make a literature review of GI PEComas-NOS and highlight the challenge it brings to the differential diagnosis.     

胚胎及新生大鼠胃肠道IAPP免疫反应细胞的个体发生

用免疫组织化学ＰＡＰ法研究了胚胎及新生大鼠肠道ＩＡＰＰ免疫反应细胞的个体发生。结果表明，胚胎１４及１５ｄ，大鼠胃肠道未见ＩＡＰＰ－ＩＲ细胞，胚胎１７ｄ，ＩＡＰＰ－ＩＲ细胞很少，分散在未分化完全的肠上皮细胞间，胚胎１９ｄ，在胃和小肠可见到ＩＡＰＰ－ＩＲ细胞，以十二肠较多。胚胎２１ｄ及新生大鼠，ＩＡＰＰ－ＩＲ细胞分布于胃肠道各段，仍以十二指肠多见。它们主要位于上皮细胞间，偶见于小肠绒毛中轴的结缔组织中     

Cloning of rat betacellulin and characterization of its expression in the gastrointestinal tract

Betacellulin (BTC) is relatively a more recently discovered member of the EGF family of growth factors. As a prelude to its expression and functional studies in rat models of gut damage/repair, we have cloned rat BTC and examined its expression in the gastrointestinal tract. Rat BTC was found to be nearly identical to mouse betacellulin. A single 3 kb mRNA species was detected by Northern blotting, and ribonuclease protection analysis showed that its expression was ubiquitous but low in abundance throughout the gut. BTC mRNA and protein were found expressed in the gastric surface and upper pit epithelium as well as in some cells of gastric glands. In the jejunum, BTC mRNA and protein were localised to the crypt epithelium and in villous goblet cells. In the colon, BTC mRNA and protein were found produced in crypt and surface epithelium as well as in goblet cells. Taken together, the wide spread expression in the gut epithelium and in mucous cells in particular suggests an important and unique role for BTC in the gastrointestinal tract.     

Small intestinal angiosarcoma leading to perforation and acute abdomen: a case report and review of the literature

A 76-year-old man presented to the emergency room with abdominal pain and fatigue. The patient had a history of gastrointestinal bleeding. An abdominal computed tomographic scan showed collections of free air in the abdomen with obstruction of the distal small intestine and multiple masses in the liver. Laparotomy revealed a widespread malignant neoplasm in the abdomen, with multiple tumor nodules in the ileal wall, mesentery, and liver. The ileal wall was perforated within the area of one of the tumors. Pathologic examination of the lesion showed a neoplasm composed of solid sheets of spindle and undifferentiated cells, forming interlacing delicate vascular channels with atypical endothelial cells. The tumor cells were positive for the endothelial marker CD31, whereas reactivity for a broad panel of epithelial and other endothelial markers was negative. This case demonstrates that although angiosarcomas of the gastrointestinal tract are rare, they should be considered in cases of intestinal perforation or severe bleeding, especially in the elderly. A broad panel of immunochemical markers might be necessary to establish the pathologic diagnosis.     

Modality-integrated magnetic catheter tracking for x-ray vascular interventions

A novel setup for the integration of a magnetic tracking system (MTS) into a catheter laboratory environment by attaching the field generator of the MTS to the C-arm of the x-ray system was investigated. The metal interference of the x-ray system with the MTS then becomes static and can be calibrated. The registration of a tracked catheter to 2D live x-ray images with high and well-defined accuracy is thus possible for arbitrary C-arm positions. Interference with imaging by blocking the field of view is avoided. Real-time registration methods to maintain the registration of the catheter also to static 2D or 3D images (roadmaps), regardless of the C-arm rotation during catheter tracking, were investigated. Residual registration errors of the tracked catheter with respect to the static roadmaps (2D and 3D) were reduced by using the vessel geometry and shape information. The algorithms potentially allow for motion correction (e.g. due to respiration). Using the shape-based correction algorithms the average registration accuracies to static roadmaps for different C-arm angulations and catheter positions were determined to be 3.3-4.2 mm. The magnetic registration of the C-arm was furthermore allowed to compute the imaging geometry (position of the C-arm) and to produce virtual angiographic preview images before contrast injection and x-ray dose application. Thus, optimal projection geometries and collimator settings for the target region can be chosen in an 'off line' fashion. The proposed MTS-supported navigation setup on both 3D (static) and 2D (live and static) roadmaps merges the high resolution and real-time feedback of 2D x-ray images with the navigation support from 3D static images.     

Real-time 3D surface-image-guided beam setup in radiotherapy of breast cancer

We describe an approach for external beam radiotherapy of breast cancer that utilizes the three-dimensional (3D) surface information of the breast. The surface data of the breast are obtained from a 3D optical camera that is rigidly mounted on the ceiling of the treatment vault. This 3D camera utilizes light in the visible range therefore it introduces no ionization radiation to the patient. In addition to the surface topographical information of the treated area, the camera also captures gray-scale information that is overlaid on the 3D surface image. This allows us to visualize the skin markers and automatically determine the isocenter position and the beam angles in the breast tangential fields. The field sizes and shapes of the tangential, supraclavicular, and internal mammary gland fields can all be determined according to the 3D surface image of the target. A least-squares method is first introduced for the tangential-field setup that is useful for compensation of the target shape changes. The entire process of capturing the 3D surface data and subsequent calculation of beam parameters typically requires less than 1 min. Our tests on phantom experiments and patient images have achieved the accuracy of 1 mm in shift and 0.5 degrees in rotation. Importantly, the target shape and position changes in each treatment session can both be corrected through this real-time image-guided system.