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.     

Three-dimensional view of the vascular structure of the lower esophagus in clinical portal hypertension

The venous anatomy of the lower esophagus and upper stomach was studied in nine patients with portal hypertension and in five without, following infusion of a silicon rubber compound into vessels of the excised organs within whole tissues made transparent with methyl salicylate. Four venous channels were identified in normal tissues: intraepithelial, subepithelial superficial, deep submucosal and adventitial veins. In portal hypertensive patients, giant esophageal varices formed 2 to 3 cm above the esophagogastric junction fused with numerous superficial and deep submucosal veins. Gastric varices were present in the submucosa where the left gastric venous branch penetrated the gastric wall 2 cm below the esophagogastric junction. The lower esophageal varices were classified into two types of vascular structure: palisading type in five and bar type in four. The palisading type had dilated intraepithelial channels and numerous small superficial collateral veins extending in a longitudinal arrangement. The bar type had triply dilated subepithelial superficial veins and deep submucosal veins which eroded the epithelium, and the gastric varices were present in the latter type. Our study provides evidence of the three-dimensional vascular structure of the lower esophageal varices without the necessity for tissue dissection.     

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.     

Angioarchitecture of the lower esophagus in portal hypertension

In order to clarify the angioarchitecture of the palisade zone in the lower esophagus for portal hypertensive cases, we examined the thirty untreated autopsy cases of portal hypertension. At autopsy, barium added gelatin was injected from gastric coronary vein of the gastric wall and we observed them histologically and histometrically. 1) In portal hypertension, the palisade zone has increasing veins running in the submucosa, which veins belonged originally to the lamina propria. 2) A difference in angioarchitecture is present between the palisade and truncal zones. 3) The palisade zone in esophageal varices was classified into two types of angioarchitecture by Hashizume. Our 30 cases were composed of 22 cases with palisading type and of 8 those with bar type. The later showed well developed varices.     

Gastric adenocarcinoma of fundic gland type: Five cases treated with endoscopic resection

Recently,a new disease entity termed gastric adenocarcinoma of fundic gland type(GA-FG) was proposed.We treated five cases of GA-FG with endoscopic submucosal dissection.All tumors were small and located in the upper third of the stomach.Four tumors were macroscopically identified as 0-IIa and one was identified as 0-Ⅱb.Narrow-band imaging with magnifying endoscopy showed an irregular microvascular pattern in 2 cases and a regular microvascular pattern in the remainder.All tumors arose from the deep layer of the lamina propria mucosae and showed submucosal invasion.Lymphatic invasion was seen only in one case,while no venous invasion was recognized.All tumors were positive for pepsinogen-Ⅰ and MUC6 by immunohistochemistry.None showed p53 overexpression,and the labeling index of Ki-67 was low in all cases.All cases have been free from recurrence or metastasis.Herein,we discussed the clinicopathological features of GA-FG in comparison with past reports.     

Experimental chronic gastric ulcer due to ischemia in rats

Ligation of the left gastric and right gastroepiploic arteries and veins resulted in chronic gastric ulcer formation in the rat. Linear mucosal corpus hemorrhages appeared within 8 hr of ligation. By 2 days large corpus hemorrhagic erosions were present. A single, large ulcer involving nearly the entire corpus was present at 3–5 days. In the ulcerated area the mucosa and muscularis mucosae were destroyed, thick granulation tissue filled the submucosa and the muscularis propria was severely damaged. Progressive healing occurred thereafter and 75% of the ulcers healed completely grossly in 2–8 weeks. Histologic studies showed that healing and mucosal regeneration occurred by the outgrowth of a layer of cells from the adjacent intact epithelium extending over the surface of the ulcer. Invaginations from this covering layer of cells formed a glandular mucosa composed of mucous cells. Later parietal and chief cells appeared, and eventually (6 months) a normal corpus-type mucosa covered the entire corpus. With time smooth-muscle fibers appeared in the outer half of the dense submucosal granulation tissue and eventually a normal muscularis mucosae, submucosa, and muscularis propria were present (6–12 months). These studies show that: (1) ischemia can give rise to chronic gastric ulcer, and (2) all elements of the gastric wall, including the mucosa, the muscularis mucosae, and the muscularis propria can fully regenerate.Supported by Veterans Administration Project Number 3324-02 and NIAMDD Peptic Ulcer Center Grant 17328     

肝硬化患者脾肝体积比与食管胃底静脉曲张的关系

目的探讨脾肝体积比在预测静脉曲张程度中的价值。方法对51例确诊的肝硬化患者进行胃镜和增强CT检查,将食管胃底静脉曲张程度分级并计算患者的脾肝体积比;比较这两个指标的相关性和各级静脉曲张患者的脾肝体积比。结果食管胃底静脉曲张的分级与脾肝体积比相关性明显(t=0.693,P<0.001)。各级食管胃底静脉曲张之间的脾肝体积比差异均有统计学意义。结论肝硬化患者随着脾肝体积比值的升高,静脉曲张程度加重,脾肝体积比可以作为无创性检测手段判断静脉曲张程度,为进一步的工作打下了一定的基础。     

Successful endoscopic therapy of superficial esophageal cancer on varices in a patient with alcoholic liver cirrhosis

A case of successful endoscopic therapy of superficial esophageal cancer on varices in a patient with alcoholic liver cirrhosis is reported. A slightly depressed superficial cancer (type 0‐IIc) occupied half the inner surface of the middle esophagus. Endoscopic ultrasonography revealed esophageal varices and periesophageal collaterals, but no perforating veins connecting the varices and collaterals were observed where the cancer was located. The esophageal cancer could not be detected even with a 20 MHz microprobe. The tortuous esophageal varices in the lower esophagus were endoscopically ligated to reduce blood flow just below the cancer and 10 mL polidocanol solution was endoscopically injected to induce sclerosis of the varices. After these procedures, the mucosal cancer was endoscopically resected without any severe complications and residual cancer was eliminated by cauterization using a heater probe. Histopathological examination revealed that poorly differentiated squamous cell carcinoma invaded into the lamina propria mucosae but not into the vessels or the lymphatic system. Three years after treatment, the patient showed no signs of local recurrence of cancer. It is considered that the endoscopic techniques used in this patient constitute a valuable and minimally invasive treatment for superficial esophageal cancer on varices.     

Effect of early bosentan administration on the development of esophageal varices in cirrhotic rats: experimental study in Wistar rats

Background  This study was conducted to investigate the effect of chronic bosentan administration on the development of esophageal varices in carbon tetrachloride-induced cirrhosis in rats. Methods  For the development of liver cirrhosis and esophageal varices, 60 rats underwent ligation of the left adrenal vein, followed by phenobarbital and carbon tetrachloride administration. Two weeks after the beginning of carbon tetrachloride administration, rats were separated into two groups. In group I, comprising 30 rats, bosentan was continuously administered throughout the study, whereas in group II, also 30 rats, placebo instead of bosentan was continuously administered. Hemodynamic studies and morphometric analysis of the lower esophagus were performed after complete induction of cirrhosis. The total number of veins counted in the submucosa, the number of submucosal veins/mm² of submucosa, the total submucosal area occupied by vessels, the mean cross-sectional vessel area, the relative submucosal area (percentage) occupied by vessels, and the area of the single most-dilated submucosal vein were studied. Results  Bosentan induced a significant (P < 0.05) decrease in portal pressure, while morphometric analysis revealed a significant reduction (P < 0.05) of all parameters studied in bosentan-treated rats, except in the total and relative number of submucosal veins. Conclusions  Bosentan administration seemed to significantly attenuate dilation of submucosal veins in the lower esophagus of cirrhotic rats. This effect was mainly attributed to a decrease in the portal pressure induced by chronic bosentan administration.     

食管胃底静脉曲张血供与侧支的研究

目的通过多层螺旋CT(multi—detecter row computed tomography，MDCT)了解食管胃底静脉曲张及与之相关的侧支循环，为食管胃底静脉曲张破裂出血治疗方案的选择和预后的判断提供客观依据。方法选择51例临床证实的肝硬化门静脉高压患者，其中胃镜显示食管静脉曲张51例，伴胃底静脉曲张31例。对所有患者进行MDCT血管成像，重点观察食管胃底静脉曲张及相关侧支循环。结果MDCT血管成像能清晰地显示肝硬化门体侧支血管，并显示所有食管静脉曲张。MDCT显示胃底静脉曲张32例(62．7％)，与胃镜检查结果(31／51，60．8％)比较，两者具有高度一致性，Kappa值为0．876。食管曲张静脉几乎全部由胃左静脉供血，30例(58．8％)单纯由胃左静脉前支供血，21例(41．2％)伴有食管旁静脉；24例(75％)胃底曲张静脉为单纯胃左静脉供血，3例(9．4％)由胃短(胃后)静脉供血，5例(15．6％)为胃短(胃后)和胃左静脉双重供血，双重供血者因胃底静脉曲张和食管静脉曲张常相互交通，所以这些病例胃短(胃后)静脉也同时参与食管静脉曲张的形成。结论MDCT能较清晰地显示食管胃底静脉曲张侧支循环。食管静脉曲张主要由胃左静脉供血，大部分由前支经贲门进入曲张静脉，部分伴有食管旁静脉。胃底静脉曲张大部分由胃左静脉供血，但小部分则由胃短系统供血。     

Collateral vessels around the esophageal wall in patients with portal hypertension: comparison of EUS imaging and microscopic findings at autopsy

BACKGROUND: In patients with portal hypertension, EUS reveals the presence of collateral vessels within and outside the esophageal wall such as esophageal varices, periesophageal collateral veins (peri-ECVs), paraesophageal collateral veins (para-ECVs), and perforating veins. This study retrospectively compared radial EUS images of these collateral vessels with histopathologic findings. METHODS: Four patients with esophageal varices treated by endoscopic injection sclerotherapy were studied. EUS was performed to evaluate the effects of endoscopic injection sclerotherapy. After endoscopic injection sclerotherapy, the segment of the esophagus from the esophagogastric junction to a point 5 cm proximal to junction was imaged with a 20-MHz radial scanning catheter US probe. Esophageal collateral veins outside the esophageal wall were identified as peri-ECVs (veins lateral to muscularis propria or within adventitia) and para-ECVs (veins lateral and separate from muscularis propria) along with perforating veins (veins connecting extramural collateral veins to submucosal varices). At autopsy, the esophagus with surrounding tissue was removed and cross-sectioned at 1-cm intervals from the esophagogastric junction to a point 5 cm proximal to the junction. Radial EUS images were correlated with histopathologic findings. RESULTS: Radial EUS after endoscopic injection sclerotherapy demonstrated peri-ECVs and perforating veins in all cases and para-ECVs in 3 cases. Based on histopathologic findings, veins associated with the esophageal wall were divided into 3 groups: those adjacent to the muscularis propria, veins separated from the wall without contact with the muscularis propria, and veins perforating the muscularis propria. All 3 groups of veins were observed in all cases. These 3 types of veins identified by histopathologic examination corresponded, respectively, to the peri-ECVs, para-ECVs, and perforating veins observed by EUS. CONCLUSION: Collateral esophageal veins demonstrated by radial EUS in patients with portal hypertension correspond to collateral veins identified histopathologically. In patients with portal hypertension, EUS is useful for assessment of vascular anatomy around the esophageal wall.     

Sclerotherapy of esophageal varices: an endoscopic and portographic study

A prospective series of 26 patients with portal hypertension and recent bleeding from esophageal varices was investigated with percutaneous transhepatic selective portography (PTP). PTP was performed immediately prior to and, in 23 patients, just after the initial endoscopic injection sclerotherapy (ST) session to study the acute effects of ST on the mediastinal portal-systemic collaterals. Late follow-up PTP was performed after a median of 8 months in 21 of 26 patients considered endoscopically to be free from esophageal varices after a median of 6 ST sessions. Five patients rebled from esophageal or gastric varices during the follow-up period of 15 months, but there were no fatalities due to variceal hemorrhage. In all patients, the initial PTP showed portal-systemic mediastinal collaterals. Immediately after ST, it was not possible to opacify esophageal varices at all (10 patients) or only partially (7 patients). Five patients died prior to late follow-up PTP. Endoscopic judgment of complete eradication of esophageal varices after repeated ST was in agreement with the late PTP results in 18 of 21 patients. In one patient, PTP showed residual esophageal varices subsequently confirmed by endoscopy. The results were uncertain in two patients for technical reasons. This study supports the opinion that submucosal esophageal varicose veins, as visualized by PTP, can be efficiently eradicated by serial ST, leaving the other mediastinal collaterals unaffected.     

RARE GASTRIC CALCIFYING FIBROUS PSEUDOTUMOR REMOVED BY ENDOSCOPIC SUBMUCOSAL DISSECTION

We report a case of a calcifying fibrous pseudotumor of the stomach that we resected using endoscopic submucosal dissection (ESD). A 61‐year‐old male with a gastric submucosal tumor was admitted to our hospital for treatment. By upper gastrointestinal tract endoscopy, a smooth‐surfaced submucosal tumor measuring 2 cm in diameter was observed in the anterior wall of the middle body of the stomach. By endoscopic ultrasonography, a mass was observed in the stomach submucosa; the mass had a well‐defined boundary. Internally, the mass was heterogeneous and hypoechoic; high spots were scattered throughout the mass. Continuity between the mass and the muscularis mucosae and muscularis propria was not observed. Strongly suspecting that this mass was a gastrointestinal stromal tumor arising from the stomach, we resected the mass by ESD for total biopsy. Histopathologically, the mass consisted of proliferation of eosinophilic collagen fibers with plasma cell infiltration and lymphoid follicle proliferation. Calcification was also observed in some parts of the mass. Thus, the mass was identified as calcifying fibrous pseudotumor. Calcifying fibrous pseudotumor of the stomach is extremely rare and its histogenesis remains unclear; however, its morphology became distinct by comparing endoscopic/radiological and histopathological findings.     

A case of gastrointestinal stromal tumor of the stomach arising from the muscularis mucosae]

A 75-year-old man, in whom upper gastrointestinal endoscopy revealed a submucosal tumor in the greater curvature of the gastric angle, was hospitalized for further investigations. Since the tumor was shown to be located in the submucosal layer by endoscopic ultrasonography, we performed endoscopic mucosal resection. Pathological studies of the resected specimen revealed a gastrointestinal stromal tumor of the stomach. It was also formed that the tumor was connected not to muscularis propria, but to the muscularis mucosae. There has been no previous report about a case of gastrointestinal stromal tumor of the stomach arising from the muscularis mucosae in Japan.     

Acute gastric hemorrhage secondary to wandering spleen

Summary A patient presenting with acute life-threatening upper gastrointestinal hemorrhage caused by a wandering spleen is reported. Emergency laparotomy revealed profuse gastric bleeding, large engorged varicose veins in the gastric wall, and a normal liver parenchyma. Gastroscopy after arrest of the hemorrhage showed varicose veins in the fundus without esophageal varices. Angiography revealed an ectopic spleen, occlusion of the splenic vein, and large venous collaterals in the gastric fundus. Elective splenectomy was performed. Wandering spleen as a cause of left-sided portal hypertension, also referred to as segmental splenic hypertension, is discussed.     

Ultrastructure of endocrine-like cells in lamina propria of human gastric mucosa.

Endocrine cells of gastric and gut mucosa are commonly thought to be present only within mucosal glands. In a previous report, we described argyrophilic cells in the lamina propria in 40% of surgical gastric specimens, using light microscopy. All these patients had chronic gastritis. Argyrophilia, however, is a non-specific reaction which could occur in other than endocrine cells. The present study was undertaken to describe the ultrastructure of argyrophil cells in the lamina propria. In five patients with chronic gastritis, endoscopic biopsies were taken from the fundic, intermediate, and pyloric areas of the stomach. Single and/or clustered argyophil cells were seen by light microscopy in the lamina propria of the intermediate and pyloric areas. On electron-microscopy, these cells had the following characteristics of endocrine-like cells: they were characterised by numerous electron dense granules in the cytoplasm, 100-300 nm in diameter; the cytoplasm contained poorly-developed rough endoplasmic reticulum and well-developed smooth endoplasmic reticulum with occasional vesicles. Immunostaining gave negative results for various gastrointestinal hormones. These ultrastructural characteristics of lamina propria cells are similar to endocrine cells of the APUD series. We conclude that endocrine-like cells occur in the lamina propria of the human stomach in the presence of chronic gastritis.     

Multiple esophagogastric granular cell tumors

Multiple granular cell tumors of the esophagus and the stomach found in a 53-year-old man are reported. One lesion was detected within the lower thoracic esophagus and seven lesions were detected in the stomach. The esophageal tumor was resected endoscopically, and gastrectomy was performed for the multiple gastric lesions. Histologically, the tumors consisted of spindle or polyhedral cells and the cytoplasm contained punctated eosinophilic granules with positive immunohistochemical staining for S-100 protein. The tumors were mainly located in the submucosal layer. Some tumor cells were seen in the mucosae propria and the muscularis propria. The tumor cells were only slightly positive for p53- and Ki-67-immunohistochemical stainings. Based on these findings, we diagnosed the granular cell tumors as benign. Granular cell tumor is comparatively rare in clinical practice, but a few such tumors have been seen in the digestive tract. A few cases of multiple esophagogastric granular cell tumors have also been reported in the literature.     

EFFECT OF ENDOSCOPIC VARICEAL LIGATION FOR ESOPHAGEAL VARICES: VASCULAR STRUCTURE IMAGES BY MINIATURE ULTRASOUND PROBE

Background: The effect of eradication of esophageal varices on the collateral veins beside the esophagogastric junction in portal hypertensive patients remains unclear. Methods: The intramural and extramural vascular structures of the cardia and lower esophagus of 35 patients with portal hypertension were examined by endoscopic ultrasonography (EUS) before and after treatment of esophageal varices with endoscopic variceal ligation (EVL), in which ligations were repeatedly performed until complete obliteration of the varices. The vascular structures were classified into the gastric, palisade/perforating (p/p), and truncal zones, and were quantitatively evaluated. Results: No esophageal varices remained in the p/p nor in the truncal zones after EVL. EVL significantly reduced the total cross‐sectional area (CSA) of the submucosal vessels and number of perforating veins in the gastric zone (P < 0.01, P < 0.01), and the total CSA of the peri‐esophageal collateral veins (peri‐ECV) and number of perforating veins in the p/p zone (P < 0.001, P < 0.001). Furthermore, the total CSA of the peri‐ECV was larger among patients with perforating veins in the p/p zone than among those without, both before and after EVL. Conclusions: EVL obliterated esophageal varices, and indirectly influenced the intramural and extramural vascularities in the region of the esophagogastric junction, which may contribute to prevention of variceal recurrence.     

内镜超声在消化道黏膜下肿瘤诊断与治疗中的价值

目的 评价内镜超声在消化道黏膜下肿瘤的诊断及治疗中的价值.方法 对内镜检查中怀疑黏膜下肿瘤者进行内镜超声检查,根据黏膜下肿瘤的起源层次及性质决定治疗方案,内镜治疗包括内镜下黏膜切除术、黏膜剥离-肿瘤摘除术、高频电切术及硬化治疗.结果 73例良性间质瘤起源于黏膜肌层,7例直肠类癌位于黏膜固有层;脂肪瘤13例、异位胰腺17例、胃底静脉曲张5例、囊肿6例起源于黏膜下层;95例良性间质瘤及21例恶性间质瘤起源于固有肌层,1例类癌侵及固有肌层.61例源于黏膜肌层及8例源于固有肌层的良性间质瘤、8例脂肪瘤、8例异位胰腺及7例类癌经内镜切除,4例囊肿行内镜下穿刺治疗;33例源于固有肌层的良性间质瘤、18例恶性间质瘤、2例脂肪瘤、2例异位胰腺及1例类癌经手术切除.病理符合率为97.97%.结论 超声内镜能够对消化道黏膜下肿瘤进行起源和定性诊断,对黏膜下肿瘤治疗方案的选择具有重要的指导意义.     

Endoscopic Resection of Gastric Plasmacytoma

Gastric plasmacytoma is a rare form of extramedullary plasmacytoma. It is usually diagnosed with a barium meal or endoscopy for various gastrointestinal symptoms. Most gastric plasmacytomas are treated by surgical resection, even when they are confined to gastric mucosal lamina propria or submucosa, that is, in the early stages. We present here a case of gastric plasmacytoma showing an endoscopic feature of submucosal tumor approximately 2.5 cm in diameter, found through an X‐ray study in a mass screening. Endoscopic ultrasonography revealed a hypoechoic tumor located in the submucosal layer, and the tumor appeared to be safely excised by routineendoscopic resection. In order to obtain histlogical diagnosis, we resected the tumor, which was diagnosed as a plasmacytoma. The patient did not shown any sign of local and/or generalized recurrence during follow up for 2.5 years. We have not found a successful case of endoscopic resection of gastric plasmacytoma reported previously.