The three-dimensional microstructure of intramural lymphatics in the canine large intestine

The three-dimensional microstructure of the intramural lymphatics of canine large intestine was clarified micrographically. After direct injection of India ink into the colon wall, we prepared 2<3cm fullthickness transparent specimens of the opened colon wall and transparent sections. Lymph vessels were distinguished from blood vessels by intraarterial injection of cinnabar ink. A stereomicroscope was used for observation, and stereograms were reproduced. Lymph vessel networks were present in the shallow and deep layers of the lamina propria mucosae and the deep layer of the submucosa. The lymph vessel networks in the lamina propria mucosae were present immediately beneath the blood capillary networks. The thickest lymph vessels and the densest network appeared in the submucosa. From the submucosa, some of the lymph vessels existed immediately to merge into the collecting trunks and other lymph vessels which compose a minor pathway existed along lymph vessels in the muscular layer and finally merged into the collecting trunks in the subserosa.     

Morphology of lymphatics in the canine large intestine

The finer distribution of lymphatics in the large intestine of adult dogs was morphologically examined by puncture injection of colored dyes, intra-arterial injection of silver nitrate mixed with India ink, and electron microscopy. In the lamina propria there was a double-layer of lymphatic channels - a shallow network (near the mucosal surface) and a deep compartment (just above the muscularis mucosae). Sparse lymph capillaries also extended vertically paralleling intestinal glands. Some lymphatics penetrated into the submucosa where they demonstrated prominent valves and formed collecting lymphatic trunks alongside blood vessels.     

Pathology of fundic varices of the stomach and rupture

BACKGROUND AND AIM: Gastric varices, the rupture of which can be a fatal complication of portal hypertension, have not been well documented histopathologically. While cardiac varices develop in continuity with esophageal varices, fundic varices develop independently, having characteristic pathophysiology. Elucidation of the angioarchitecture of fundic varices will facilitate future improvement of treatment. METHODS: Twelve stomachs with fundic varices, either resected or autopsied, were examined by injecting a barium-gelatin solution into the vein that was forming varices, soft X-rayed for the study of the vessel course, and then the stomach made into transparent preparations for stereoscopic study. Five fundic varices with a recognizable rupture site were studied histologically. RESULTS: Fundic varices could be classified into two types: Type I, single vein forming the supplying vessel, varix and draining vessel without changing caliber (eight cases) or plural veins supplying the varix (one case) and; Type II, many branching vessels existing beside the main supplying and draining vessels (three cases). Fundic varices exist in the submucosa with no enlarged vein in the lamina propria, and rupture occurs through the portion of the varix that protrudes into the stomach lumen penetrating the muscularis mucosae and lamina propria. CONCLUSIONS: Fundic varices form with the supplying vessel, mostly singular, and the draining vessel is frequently a gastrorenal collateral. Fundic varices form in the submucosa, unlike esophageal varices, and perforate through the overlying muscularis mucosae and lamina propria.     

Lymph and blood capillaries of the human gastric mucosa. A morphologic basis for metastasis in early gastric carcinoma

The distribution of lymph and blood capillaries has been studied by light and transmission electron microscopy in 16 endoscopic and surgical specimens of human gastric mucosa and submucosa. Four specimens were completely normal, seven showed mild gastritis, and five showed severe gastritis. On light microscopy, no definite distinction could be made between small mucosal lymph and blood capillaries. The distinction was achieved only by transmission electron microscopy where lymph capillaries could be identified by the presence of anchoring filaments and the demonstration of open gaps and overlapping endothelial cell processes, as well as by the absence of a basement membrane and "fenestrations" typical of the endothelial cells of blood capillaries. Although large lymph vessels were observed in the submucosa, lymph capillaries were found only in the deep lamina propria adjacent to and within the muscularis mucosae. The upper and middle levels of the lamina propria of the gastric mucosa contained no lymph capillaries. The entire mucosa showed a rich supply of blood capillaries, many of which were adjacent to the basal lamina of gastric glands and the surface epithelium. These morphologic findings correlate with clinicopathologic observations on early gastric cancer. The particularly low incidence of lymph node metastases in the subtype of early gastric cancer that remains confined to the mucosa may be explained by the rarity of lymph capillaries in the mucosa. The high percentage of blood-borne metastases in recurrent early gastric cancer may be related to the rich vascularity of gastric mucosa.     

A Gastrointestinal Endoscopic Study on Secondary Amyloidosis Complicating Rheumatoid Arthritis

Abstract: Biopsy specimens endoscopically obtained from the stomach, duodenum, sigmoid colon and rectum of 58 patients with rheumotoid arthritis (RA) were examined for amyloid deposition by light microscopy. Six cases (10.3%) were diagnosed as being amyloidosis. In cases with more than moderate amyloid deposition, amyloid was most notable in the lamina propria mucosae. In cases with slight amyloid deposition, amyloid was seen in the blood vessel walls of the lamina muscularis mucosae and tela submucosa. On the whole, amyloid deposition was most marked in the duodenum. Endoscopically, whitish, irregular, partially nodular thickening of mucosa was characteristic in the sites with severe amyloid deposition. A fine granular appearance was observed in the sites with moderate amyloid deposition. No particular abnormal findings were noticed in the sites with slight amyloid deposition. Erosions, redness and a tendency for easy mucosal bleeding appeared frequently in the sites with more than moderate amyloid deposition. The endoscopic abnormal findings were most remarkable in the duodenum, and mildest in the recto-sigmoid colon. It was suggested that these abnormal findings were correlated with the degree of amyloid deposition especially in the lamina propria mucosae. All the amyloidosis cases were in advanced anatomical stages of RA. The degree of anemia was more severe, and total protein, albumin and total cholesterol values were lower in the amyloidosis cases than in non-amyloidosis cases. It is clear that when endoscopic examinations of RA patients are done to rule out amyloidosis, a biopsy should be taken from a depth including the submucosa even if the endoscopic finding is normal.     

人结直肠黏膜层淋巴管微细分布及超微结构

目的观察人结直肠正常肠壁黏膜层内淋巴管的形态及结构特点,为探讨结直肠癌淋巴道转移的途经提供形态学依据。 方法人结直肠蜡块标本连续切片,通过免疫组化两步法,以鼠抗人D2-40单克隆抗体及鼠抗CD34单克隆抗体为一抗分别标记,光镜下观察抗体标记情况。黏膜层超薄切片电镜下观察淋巴管微观结构。 结果D2-40单克隆抗体免疫组化染色后,在黏膜层,棕黄色显色分布于黏膜固有层与黏膜肌层之间及黏膜肌层内,少量,管壁薄、管腔小,管壁不完整。与CD34染色无重叠。电镜下见黏膜层内少量淋巴管管壁很薄,仅由一层内皮细胞构成,无孔窗,无周细胞,基膜不连续或缺如,内皮细胞间形成端端、重叠或插入连接,管壁外连有锚丝。 结论正常人结直肠黏膜层内有淋巴管存在,存在于固有层与黏膜肌层之间及黏膜肌层内,与黏膜下层淋巴管可能存在通道相联,具备淋巴道转移的解剖学基础。     

Light microscopy of the lymphatics of the human atrial wall and lymphatic drainage of supraventricular pacemakers

After injection of Indian ink stained 2% gelatine in 42 human hearts the lymph drainage of the regions of supraventricular cardiac pacemakers and the patterns of the lymphatic vascular bed in the atrial wall were studied. From the sites of the pacemakers the lymph is drained into the tracheobronchial nodes in 100%. Only two of those regions are drained through additional pathways, namely the SAN region into the anterior mediastinal node situated at the azygos vein and the coronary sinus area into the anterior mediastinal lateropericardiac nodes. In the cleared specimens as microscopically the epicardial lymph vessels produce polygonal superficial network; oblique anastomoses of that network run into the deeper layers of subepicardial tissue where they join with deep irregular lymphatic network. Deep subepicardial lymph vessels are often accompanied by veins and nerves. The course of most of myocardial lymph vessels follows the position of muscle cells. In the connective septa these vessels join to form larger trunks and open into the subepicardial vessels.     

Pathomorphology of esophageal and gastric varices

In this article, the gross pathology of varices and supplying veins are described comparing esophageal varices and varices of the cardia and fundus of the stomach. The angioarchitecture of the lower esophagus is such that normally very thin parallel veins in the lamina propria mucosae in the palisade zone become enlarged in portal hypertension and join the few larger submucosal veins to form esophageal varices. Enlarged parallel veins come to pile up and join the submucosal veins at an acute angle, rendering this area vulnerable to rupture. Most ruptures occur in this critical area. The basic differences between esophageal and gastric varices are the layers in which the varicose veins form: the lamina propria mucosae and submucosa in the esophageal varices and the submucosa in gastric varices. While cardiac veins and varices are continuous with esophageal varices, fundic varices develop independently as part of a splenogastrorenal shunt that runs through the stomach wall, having rare communications with other veins. The fundic varix is so large in caliber that when it ruptures, the muscularis mucosae and lamina propria are penetrated with massive bleeding. The treatment of varices calls for complete thrombosis of all varicose veins, and merits and demerits of available treatment modalities are discussed based on autopsies from the pathologic point of view. Because of the large size, the management of fundic varices is difficult, and the new technique called balloon-occluded retrograde transvenous obliteration for occluding fundic varices is discussed.     

Some recent, or claiming to be recent, data on the superficial lymphatic circulation of the limbs

Superficial collecting lymphatics of the limbs are present in much greater number than deep collecting vessels. There is practically no connexion between both networks. Although lymphatics are abundant distally, they tend to fuse toward the root of the limb. At certain "critical" points along their course, local aggression of the vessels may cause lymphedema. In the lower extremity, at the knee and thigh levels, the "critical" area takes the form of a narrow strip of adipose tissue along the path of the great saphenous vein. In the groin, danger is localized at the inferior superficial inguinal nodes, where the superficial collecting lymph vessels merge. In the upper limb, superficial lymphatics converge towards the base of the axilla, where they form three or four trunks that perforate the clavipectoral fascia, each penetrating through its own orifice. Draining lymphatics may approach the axillary space independently. Unfortunately, the inferior axillary nodes wherein they converge also drain the breast, as can be demonstrated by injecting different coloring materials concurrently in both areas. Excision of nodes draining the mammary gland unavoidably jeopardize superficial lymphatic drainage of the upper extremity.     

The Vascular Architecture of the Different Forms of Small Intestinal Villi in the Rat (Rattus norvegicus)

The vascular anatomy of the intestinal villi in the rat was studied by injection with Indian ink and silicone rubber. The vascular pattern in finger- leaf- and tongue-shaped villi is the same. One central arteriole divides into two marginal vessels, giving rise to a capillary net, which in turn collects into two para-axial venues. In ridge-shaped villi there are multiple arterioles and venules. It appears that finger-shaped villi turn into leaf-shaped villi by lateral upgrowth of the lamina propria, and that ridge-shaped villi are also formed by upgrowth of the lamina propria between adjacent leaf-shaped villi.     

Correlation of rectum-associated lymph nodules with the development of experimentally induced acute colonic inflammation in rats

BACKGROUND AND AIMS: The mechanisms of inflammation in ulcerative colitis occurring initially in the rectum and then extending throughout the colon are still unknown. The aim of this study is to investigate the correlation of rectum-associated lymph nodules (RALN) and the development of a dextran sulfate sodium-induced experimentally acute colonic inflammation in rats. METHODS: We immunohistochemically analyzed the lymph nodules in the rectal region of rats using monoclonal antibodies to specific markers. RESULTS: Rectum-associated lymph nodules resembled the Peyer's patches, where CD4+, CD8+ lymphocytes and Mar 1+ macrophages were observed. After the administration of dextran-sulfate sodium (DSS), RALN showed hypertrophy with an increase in the number of CD4+, CD8+, and interleukin (IL)-2R+ lymphocytes in the periphery, as well as Mar 1+ macrophages in the entire region. Concurrently, platelet/endothelin cell adhesion molecule-1 (PECAM-1+) blood vessels, including high-endothelial venules (HEV), were increased in number in the interfollicular areas. Furthermore, a number of small lymph nodules varying in size were observed in the upper region of the rectum. Some of them were initially confined to the lamina propria mucosae, and became large enough to extend deeper into the tela submucosa. These DSS-induced lymph nodules contained large numbers of CD4+ lymphocytes, IL-2R+ lymphocytes, and Mar 1+ macrophages. CONCLUSIONS: The pathological changes of ulcerative colitis were well correlated with the development of both RALN and DSS-induced lymph nodules. The immunological reaction that occurred in DSS-induced lymph nodules is significantly associated with the expansion of colitis from the lower region of rectum to the upper region of rectum and colon.     

A pedunculated polyp-shaped small-bowel lymphangioma causing gastrointestinal bleeding and treated by double-balloon enteroscopy

We report a rare case of a small-bowel lymphangioma causing massive gastrointestinal (GI) bleeding that we successfully diagnosed and treated using double-balloon enteroscopy (DBE). An 81-year-old woman suffering from repeated GI bleeding of unknown origin underwent a capsule endoscopy at a previous hospital. She was suspected of having bleeding from the jejunum, and was referred to our department for diagnosis and treatment. An oral DBE revealed a 20 mm × 10 mm, regularly surfaced, white to yellowish, elongated, pedunculated jejunal polyp with small erosions at 10 cm distal to the ligament of Treiz. Since no other source of bleeding was identified by endoscopy in the deep jejunum, an endoscopic polypectomy (EP) was performed for this lesion. A subsequent histopathological examination of the resected polyp showed clusters of lymphatic vessels with marked cystic dilatation in the submucosa and the deep layer of the lamina propria mucosae. These characteristics are consistent with the typical features of small-bowel lymphangioma with erosions. Although clipping hemostasis was performed during EP, re-bleeding occurred. Finally, a complete hemostasis was achieved by performing an additional argon plasma coagulation.     

Changes in distribution of three isoforms of nitric oxide synthase in ulcerative colitis

BACKGROUND: Nitric oxide (NO) has an important role both in normal physiology and pathological events of the colon. Our aim was to study possible changes of the three nitric oxide synthases in ulcerative colitis (UC). METHODS: Tissue samples from normal colon and least and moderately affected regions of ulcerative colitis colon were obtained at surgery and immunostained for NOS-1, NOS-2, NOS-3, and GAP-43, a marker of nerve fibers. Quantitative analysis of NOS-1 immunoreactivity was performed on the circular muscle layer. RESULTS: NOS-1-immunoreactive fibers in the muscularis mucosae disappeared in least affected and moderately affected UC colon. Quantitative analysis of NOS-1-immunoreactive nerve fibers in the circular muscle showed no differences between normal and diseased colon. NOS-2 immunoreactivity appeared apically in the epithelial cells. In normal colon some specimens showed immunoreactivity in lower parts of crypts. NOS-2 immunoreactivity increased according to the severity of UC. NOS-3 immunoreactivity was exclusively localized in the vascular endothelium. The difference in NOS-3 staining intensity between the lamina propria and submucosa observed in normal tissue disappeared in moderately affected UC colon. The number of NOS-3-immunoreactive vascular profiles increased in the lamina propria of UC colon. CONCLUSIONS: All three NOS isoforms show specific changes in UC colon.     

Matrix Composition in Opossum Esophagus

The esophagus of mammalian species is organized into mucosa, connective tissue, and muscle, but little is known about the matrix of these layers. We studied by immunohistochemistry the distribution of collagens, fibronectin, versican, and elastin in the smooth muscle segment of the American opossum. Cryosections were exposed to specific antibodies and fluorescent-stained using conjugates of rhodamine or isothiocyanate. Staining was scored by two observers. We found that collagen I was prominent in the submucosa and in the muscular septa; collagen III formed fibrillar meshes in the lamina propria and the submucosa but was virtually absent from the epithelial and muscular layers; collagen IV was restricted to the base of the epithelium; collagen V, in contrast to collagen III, was prominent in epithelium and muscularis mucosae and sparse in muscular septa and submucosa. Fibronectin distribution followed collagen III; it formed layers in lamina propria and submucosa and strands in muscle septa and between individual muscle cells. Versican distribution followed collagen V; it was prominent in large muscle septa and formed thick sheets at the boundaries of submucosa/circular muscle and of circular/longitudinal muscle. We also determined the tissue contents of protein, hexuronic acid, and fibronectin. The mucosal layers exceeded the muscular layers in their content of hexuronic acid and fibronectin but not protein. We conclude that individual layers of the smooth muscle esophagus each have their own characteristic matrix. Lamina propria and submucosa are similar with regard to fiber orientation but lamina propria contains relatively more collagen III (small fibril) and submucosa comparatively more collagen I (large fibril). Nonfibrillar collagen V and versican are particularly prominent specifically on the boundaries between contracting muscle tissue and connective tissue framework.     

Microvasculature of the esophagus and gastroesophageal junction: Lesson learned from submucosal endoscopy

Advanced therapeutic endoscopy,in particular endoscopic mucosal resection,endoscopic submucosal dissection,per-oral endoscopic myotomy,submucosal endoscopic tumor resection opened a new era where direct esophageal visualization is possible.Combining these information with advanced diagnostic endoscopy,the esophagus is organized,from the luminal side to outside,into five layers(epithelium,lamina propria with lamina muscularis mucosa,submucosa,muscle layer,adventitia).A specific vascular system belonging to each layer is thus visible: Mucosa with the intra papillary capillary loop in the epithelium and the sub-epithelial capillary network in the lamina propria and,at the lower esophageal sphincter(LES) level with the palisade vessels; submucosa with the drainage vessels and the spindle veins at LES level; muscle layer with the perforating vessels; periesophageal veins in adventitia.These structures are particularly important to define endoscopic landmark for the gastro-esophageal junction,helpful in performing submucosal therapeutic endoscopy.     

Long-term outcome after endoscopic mucosal resection in patients with esophageal squamous cell carcinoma invading the muscularis mucosae or deeper

BACKGROUND: Endoscopic mucosal resection is recommended for squamous cell carcinoma of the esophagus confined to the lamina propria. However, endoscopic mucosal resection is often performed in patients with tumors that invade the muscularis mucosa or upper submucosa to minimize surgical invasiveness, despite the increased risk of lymph node metastasis. This study prospectively evaluated long-term outcome in such patients. METHODS: Twenty-six consecutive patients with squamous cell esophageal carcinoma invading the muscularis mucosa or submucosa who underwent endoscopic mucosal resection from June 1992 through March 2000 (extended endoscopic mucosal resection group) were studied. As control group, 44 consecutive patients with esophageal carcinoma invading the muscularis mucosae or upper third of the submucosa and no preoperative evidence of lymph node metastasis who underwent esophagectomy during the same period (surgical resection group) were studied. RESULTS: Overall survival rates at 5 years in the extended endoscopic mucosal resection group and surgical resection group were, respectively, 77.4% and 84.5%. There was no significant difference between survival distributions. Cause-specific survival rates at 5 years in extended endoscopic mucosal resection and surgical resection groups were, respectively, 95.0% and 93.5%. Survival curves for the groups were similar. CONCLUSION: Although patients were not randomized to extended endoscopic mucosal resection or surgical resection in this study, the results suggest that endoscopic mucosal resection may be safe and effective for management of squamous cell esophageal carcinoma invading the muscularis mucosae or upper submucosa.     

小肠移植中急性抗体介导排斥反应的病理学

目的:观察重度急性抗体介导排斥反应(antibody-mediated rejection,AMR)的病理形态学改变,回顾分析相关文献,为小肠移植急性AMR的诊断总结经验.方法:切除的失功能移植肠经10%中性福尔马林固定,石蜡包埋,4?m切片并行HE染色.详细观察移植物中肠壁各层及肠系膜内组织中主要的病理形态学改变,分级评价急性排斥反应及血管病变,并进行C4d免疫组织化学染色.结果:移植物内各级血管广泛受累,包括肠壁及肠系膜内各级血管.受累血管的改变以肠壁浆膜下层内的小血管及动静脉的滋养血管最为显著,主要表现为小血管壁的纤维素性坏死和/或血管内血栓形成,受累血管周围组织中性粒细胞浸润,红细胞漏出,组织水肿,部分病变血管周围伴有纤维素性坏死.免疫组织化学染色可见病变血管内膜C4d沉积.小肠黏膜固有层内血管显著扩张伴淤血,偶见血栓形成,肠黏膜隐窝上皮细胞正常,未见急性排斥反应.结论:血管壁的纤维素性坏死及血管内血栓形成是重度急性AMR的主要病理学改变.病变可以广泛累及移植物内各级血管;小肠黏膜内血管的病变可能不代表最严重的病变;临床早期确诊AMR的发生不能单纯依赖小肠黏膜活检.     

Palisading longitudinal esophagus vessels at esophago-gastric junction

BACKGROUND/AIMS: Endoscopically, as a marker of the EGJ (Esophago-gastric Junction), the most distal end of the palisading longitudinal esophagus vessels (PLEVs) is useful. The aim of this study is to clarify the origin of PLEVs. METHODOLOGY: The present study included 10 patients who underwent esophagectomy and proximal gastrectomy. Vascular injection of radiopaque medium was performed for fresh resected specimens. Subsequently, specimens were opened longitudinally, pinned on a corkboard, and fixed overnight in 4% buffered formaldehyde. Injected vessels were simultaneously examined macroscopically, radiographically, and histopathologically. The injection medium consisted of liquid barium (providing radiopacity), 3% agarose gel (1g/100 mL H2O, providing stability) and carmin (providing macroscopical visibility with red color). Five cases were performed via veins and the other 5 cases via arteries. RESULTS: All vein-injected and longitudinally-opened specimens showed PLEVs around EGJ. Red color stained thin vessels were superficially recognized at almost the same density of vascularity as radiopraphically examined vessels. Macroscopic and radiographic images were easily superimposed concoding PLEVs and EGJ. On the other hand, there are no cases demonstrating PLEVs by artery-injected images. Histopathologically, PLEVs were apparent in the lamina propria mucosae just above muscularis mucosae. PLEVs penetrate obliquely from oral to distal in the submucosa at EGJ. PLEVs were positive for CD31 but negative for D2-40. CONCLUSIONS: PLEVs are the stream of superficial veins, not arteries.     

氩气刀结合黏膜下注射治疗结肠息肉的安全性研究

目的探讨氩气刀结合黏膜下注射治疗结肠息肉的安全性。方法取健康肉猪的新鲜乙状结肠30份,每份均设立实验组（黏膜下注射后氩气烧灼）和对照组（直接氩气烧灼）,烧灼后病理组织学观察猪结肠壁各层损伤情况并行组间对比分析。另选择10例结肠广基息肉患者（息肉直径1～2cm,厚度在3mm以内）,均分成观察组（黏膜下注射后氩气烧灼）和对照组（直接氩气烧灼）,烧灼后超声内镜观察人结肠壁各层损伤情况。结果病理组织学观察显示,对照组损伤猪结肠固有肌层5份、黏膜下层25份（上1／34份、中1／312份、下1／39份）,实验组损伤猪结肠黏膜下层26份（上1／322份、中1／34份）、黏膜肌层4份,2组差异有统计学意义（P〈0．01）。超声内镜观察显示：对照组人结肠黏膜层与黏膜下层融合、层次不清,局部黏膜下层与固有肌层边缘毛糙、不规则;观察组人结肠1、2层边缘稍毛糙模糊,其余各层层次界限清晰。结论黏膜下注射对氩气刀烧灼损伤具有保护作用,可减少结肠息肉患者氩气刀治疗发生穿孔的概率。