Pathogenesis of varices in schistosomal portal hypertension

Patients with schistosomiasis and portal hypertension have significantly lower levels of hydroxyproline in their saphenous veins and anterior rectus sheaths than do individuals without schistosomal hepatic fibrosis. The stomach of patients with schistosomal portal hypertension demonstrates an increased number of lymphatics by lymphangiography. The disrupted lymph node architecture in these patients could be partially responsible for dilation, tortuosity, and retrograde lymph flow in the gastric lymphatics. These histological and lymphangiographic findings could be attributed to the effect of venous and lymphatic hypertension. A postmortem histological examination of the esophagus of patients with decompensated schistosomal portal hypertension revealed edema of the entire esophageal wall with lymphatic dilation and tortuosity. Based upon these data, we suggest that the varices that develop in patients with schistosomal portal hypertension occur as a consequence of an increased portal venous pressure together with acquired lymphangectasia as well as an intrinsic weakness of the walls of the portosystemic venous channels.     

Metoclopramide inhibits development of esophageal varices in rat model

We examined the preventive effect of metoclopramide on the development of esophageal varices in a rat model. Thirty rats were divided into three groups: metoclopramide (7.5 mg/kg twice a day, intraperitoneally), control group I (saline 2 ml/kg twice a day, intraperitoneally), and control group II (incised lower esophageal sphincter and metoclopramide 7.5 mg/kg twice a day, intraperitoneally). On the 14th postoperative day, lower esophageal sphincter pressure in the metoclopramide group (8.6±1.4 cm H₂O) increased more than in the control groups (5.4±0.5, 5.0±0.5 cm H₂O, P<0.01). Development of small collateral vessels from the spleen to the retroperitoneum was evident only in the metoclopramide group, as seen on the portography (P<0.01). Histologically, the variceal area of the horizontal cross section of the esophagus in the metoclopramide group (0.62±0.26 mm ²)was significantly smaller than in the controls (2.67±0.95, 2.78±0.82 mm ²),determined using an image processor-analyzer for photographing histological specimens (P<0.01). We also investigated the effect of metoclopramide on smooth muscle cells in the rat portal vein, using isometric-tension recording. Metoclopramide relaxed the smooth muscle precontracted with norepinephrine, in a concentration-dependent manner. Thus, metoclopramide inhibits the development of esophageal varices in this rat model due to both an increase in resistance of the lower esophagus and to development of small collaterals.     

Long-term follow up of esophageal varices after balloon-occluded retrograde transvenous obliteration for gastric varices.

Aim: Because the procedure of balloon-occluded retrograde transvenous obliteration (B-RTO) causes extensive thrombosis of the major shunt that connects the spleen and gastric/renal venous systems, an increase in portal pressure is unavoidable. The aim of the present study was to assess the long-term outcome of B-RTO, including changes in esophageal varices. Methods: B-RTO was conducted in 22 patients with gastric varices, who were divided according to the severity of esophageal varices at baseline; there were no esophageal varices (n = 7), F(1) varices (n = 11), and F(2) varices (n = 4). The outcome measures included the development/worsening of esophageal varices after B-RTO and survival rates. Results: The cumulative bleeding-free probability for all 22 patients at 3 years after B-RTO was 100%. The overall 3-year survival was 94.4%. Seven patients who had no esophageal varices prior to B-RTO did not develop any after the procedure. Seven (63.6%) of the 11 patients with stage F(1) esophageal varices prior to B-RTO showed no changes in the varices after B-RTO, while two patients progressed to F(2) varices and two developed F(3) varices. The cumulative treatment-free probability of the esophageal varices at 24 months after B-RTO was 100% for patients without esophageal varices at baseline, 80.8% for patients with pre-existing F(1) varices, and 75% for those with pre-existing F(2) varices. Conclusion: Although the B-RTO procedure is considered useful for the treatment of gastric varices, changes in hemodynamics due to obliteration of this major shunt must be taken into account and observed closely.     

Use of the Six-Shooter Ligation Device in the Management of Bleeding Esophageal Varices: A Developing-Country Experience

Endoscopic variceal ligation has emerged as a superior alternative to endoscopic injection sclerotherapy, however, the single-shot mechanism of the generally used Stiegman–Goff ligator made the procedure tedious and time-consuming and required overtube placement, associated with discomfort and potentially life-threatening complications. In this study we describe our experience with the Saeed Six-Shooter (multiple-ligation device). Fifty consecutive patients with variceal bleeding were prospectively studied. After initial endoscopic ligation, subsequent sessions were every 2 weeks. Study outcomes were: the ability to control active bleeding, the frequencies of rebleeding, the number of treatment sessions and time required for irradication, the percentage eradication of varices, complications, and mortality. Active bleeding was controlled in all eight (100%) patients. Four (8%) patients rebled, three from esophageal varices, and one from portal hypertensive gastropathy. Esophageal varices were eradicated in 47 (94%) patients (3.1 ± 1.3 sessions). Time needed till eradication was 6.2 ± 1.9 weeks. Chest pain was reported in two (4%), low, grade pyrexia in two (4%), and pneumonia in one (2%) patient. There were three deaths, none due to exsanguination. The Six-Shooter is a safe and efficient device for the endoscopic ligation of esophageal varices which has overcome the limitations of the single-shot ligator: (1) Visualization is better (the endoscopic tunnel vision and internal light reflection from the stainless-steel banding cylinder of the single-shot device are avoided); and (2) the use of an overtube is no longer necessary and serious complications can be avoided.     

Rectal varices in extrahepatic portal hypertension

Abstract Rectal varices, as distinct from haemorrhoids, occur due to high pressure in the inferior mesenteric venous system in patients with portal hypertension. The exact prevalence of rectal varices in extrahepatic portal hypertension is unknown. To determine this, 116 patients with extrahepatic portal hypertension were studied for the presence of rectal varices. These lesions were found in 103 (88.8%) patients. Bleeding from rectal varices occurred in 14.6% of patients. Massive bleeding requiring hospitalization and blood transfusion was not encountered. It is concluded that rectal varices are common in extrahepatic portal hypertension. Bleeding from them is uncommon, and often mild and self-limiting. The available literature is reviewed and the importance of recognizing the condition stressed.     

Ileal varices associated with recurrent bleeding in a patient with liver cirrhosis

We report a rare case of massive and recurrent bleeding from ileal varices in a patient with hepatitis C virus-positive liver cirrhosis. A 66-year old woman, who had undergone laparotomy and blood transfusion 36 years before (because of an extrauterine pregnancy) and endoscopic sclerotherapy for esophageal varices 1 year previously, was admitted to our hospital with loss of bright red blood per rectum. The bleeding was massive and recurrent, and frequent blood transfusions were required. Endoscopic studies failed to find the bleeding site. In the venous phase of selective superior mesenteric angiography, mesenteric varices in the lower part of the abdominal cavity were observed. Laparotomy was performed to control the repeated bleeding which had lasted for more than 1 month. Varices communicating with the right ovarian vein were found on the ileal wall and segmental resection of the ileum was performed. Histological examination demonstrated a massive varicose vein and several dilated veins in the submucosa. The patient's postoperative course was favorable, with no hemorrhagic events during a follow-up of more than 6 months after surgery. Ileal varices should be considered in the diagnosis of a patient who presents with lower gastrointestinal bleeding and portal hypertension. (Received: July 9, 1998; accepted: Oct. 23, 1998)     

Prevalence of esophagogastric varices in patients with non-alcoholic steatohepatitis.

Aim: In non-alcoholic steatohepatitis (NASH), fibrosis begins around the central veins, as also happens with alcoholic liver disease, so the symptoms of portal hypertension may be due to central vein occlusion. The aim of this study was to define the prevalence of esophagogastric varices and the clinical outcome after endoscopic treatment in NASH patients with severe fibrosis. Methods: The subjects were 72 patients with clinicopathologically confirmed NASH who had bridging fibrosis (F3) or cirrhosis (F4) determined by the examination of liver biopsy specimens, and who underwent upper gastrointestinal endoscopy. The prevalence and pattern of endoscopically detected varices at the time of liver biopsy were evaluated. The results of NASH patients (n = 11) with endoscopically treated esophageal varices were compared to those with alcoholic (n = 67) and hepatitis C virus-associated cirrhosis (n = 152). Results: Esophagogastric varices were detected in 34 out of the 72 (47.2%) patients; esophageal varices in 25 (34.7%) and gastric varices in nine (12.5%), while six of these patients had variceal bleeding. In NASH patients, the cumulative recurrence-free probability at 24 months after endoscopic treatment was 63.6%, the bleeding-free probability was 90.9%, and the 5-year survival was 100%. Only one out 11 patients died of liver failure at 70 months after treatment. Conclusion: About half of NASH patients with severe fibrosis had esophagogastric varices. The clinical status and course of the varices do not necessarily improve after endoscopic treatment. NASH patients with esophagogastric varices need to be followed up carefully, like patients with other chronic liver diseases.     

Evaluation of magnetic resonance angiography in detection of gastric varices

We evaluated the detection of gastric varices, inflowing blood vessels to gastric varices, and outflowing blood vessels from gastric varices via magnetic resonance (MR) angiography in 31 patients with gastric varices. Twenty-four patients had F₂ type varices and 7 had F₃ type, classified according to the Japanese Research Society for Portal Hypertension. Seventeen patients had cardiofornical varices, and 14 had fundal varices. All patients were examined with an MR system operating at 1.5 T. MR angiography was performed using the two-dimensional time-of-flight method. With MR angiography, the imaging of gastric varices was clearly delineated in 28 of the 31 patients (90.3%). From the images of MR angiography, flow direction itself cannot be determined. The outflowing blood vessels of gastric varices were reported to be the gastro-renal shunt and the subphrenic vein, and angiographic findings have shown the inflowing blood vessels to be the left gastric vein (LGV), the short gastric vein (SGV), and the posterior gastric vein (PGV). In 25 of the 31 patients (80.7%), the outflowing blood vessels from gastric varices were detected (gastro-renal shunt in 24; subphrenic vein in 1). MR angiography provided clear images of the inflowing blood vessels to gastric varices in 18 of the 31 patients (58.1%). These inflowing vessels were categorized as SGV in 7 patients, LGV in 5, LGV and SGV in 4, and LGV and PGV in 2. We suggest that MR angiography be used as a routine method for detecting and diagnosing collateral veins in patients with gastric varices. Received: September 2, 1998/Accepted: December 18, 1998     

Treatment of bleeding stomal varices by balloon-occluded retrograde transvenous obliteration

Although stomal varices are a rare complication, bleeding stomal varices often need to be treated owing to symptoms of hypovolemic shock, recurrence of stomal bleeding, or deterioration in the quality of life. Various treatment strategies for the management of bleeding stomal varices have thus far been reported. We report the case of a 60-year-old woman with refractory recurrent bleeding from varices in a sigmoid stoma, along with nonalcoholic steatohepatitis and marked splenomegaly. A physical examination revealed that the skin was discolored and bluish around the circumference of the sigmoid stoma. The venous phase of a celiac arteriogram revealed an afferent vein from the splenic vein and another from the inferior mesenteric vein, and veins draining into the left superficial epigastric vein. A balloon-occluded retrograde transvenous obliteration (BRTO) procedure was performed. The skin around the stoma, initially discolored bluish, improved markedly. After 10 months of follow-up, the patient has remained well without further episodes of stomal bleeding. To our knowledge, this is the first case of recurrent hemorrhage from stomal varices that was successfully treated by BRTO in a patient with portal hypertension.     

Oesophageal varices: assessment of the risk of bleeding and mortality

Patients with oesophageal varices run a high risk of bleeding and even death, however rates of bleeding and mortality vary greatly. Indeed, a number of patients with varices never bleed. Prophylactic therapy is effective, but can be associated with side-effects. It remains to be determined which patients are at high risk of bleeding and require treatment. In addition, since non-response to medical therapy has been reported to occur in 20-40% of patients, the effect of a given prophylactic drug, or combinations of drugs, needs to be tested. A review is given of available methods of assessment. The Hepatic Venous Pressure Gradient, and measurements of the variceal pressure, are two proven methods, and the latter has the advantages of being non-invasive and having value in presinusoidal portal hypertension.     

Frequency of gastropathy and gastric varices in children with extrahepatic portal venous obstruction treated with sclerotherapy

BACKGROUND: There are limited reports of the effect of endoscopic sclerotherapy (EST) on portal hypertensive gastropathy (PHG) and gastric varices (GV) in children with extrahepatic portal venous obstruction (EHPVO). We have studied the prevalence of PHG and GV in children with EHPVO and assessed the effect of EST on them on long-term follow-up. METHODS: From January 1992 to June 2002, consecutive children presenting with variceal bleeding due to EHPVO were included in this study. All children underwent EST at presentation and at 2-3 week intervals thereafter. During each session of endoscopy, gastric mucosa and fundus of the stomach was screened carefully to detect PHG and GV. Gastric varices were classified as gastroesophageal (GOV) and isolated gastric varices (IGV). RESULTS: In total, 274 cases of EHPVO were managed during the study period. The mean age was 7.4 +/- 3.5 years with a male to female ratio of 2.3:1. Of these 274 cases, 186 completed the EST program (study population), 60 were lost to follow-up, five died and 23 underwent surgery. At presentation (n = 274) 27% cases had PHG (3.6% severe) and 68.6% had GV (GOV 66.8%, IGV 1.8%). Following EST (n = 186) there was a significant (P < 0.001) decrease in GOV (45% from 64%) but an increase in IGV (14% from 1%) and PHG (51.6% from 24.7%).There was also a significant increase in severe PHG (15.6% from 3.2%, P < 0.05). On follow-up (mean follow-up 38 +/- 30 months) 19% children with IGV bled while none with PHG bled. CONCLUSIONS: Portal hypertensive gastropathy and gastric varices are quite common in children with EHPVO. Following EST, there is a chance of developing isolated gastric varices.     

30岁以下人群食管胃静脉曲张患者临床特点分析

目的 分析总结30岁以下食管胃静脉曲张(GOV)患者的临床特点。方法 2015年1月～2020年12月解放军总医院第一医学中心消化内科医学部收治的61例30岁以下GOV患者,提取、分析和总结其临床资料。结果 在61例GOV患者中,肝硬化门静脉高压症27例(44.3%),其中隐源性肝硬化占40.7%,乙型肝炎肝硬化占33.3%,和非肝硬化性门静脉高压(NCPH)34例(55.7%),其中以门静脉海绵样变占61.8%;基于内镜下静脉曲张LDRf分型,在位置方面主要以Le/g型多见(77.1%),在直径方面,D1.0占41.0%,在出血风险方面,Rf1分级占77.1%;针对GOV治疗,以二级预防治疗为主(85.7%),多采用组织胶或硬化剂注射或套扎联合治疗(66.1%);NCPH患者GOV再出血比例为11.8%,显著低于肝硬化组的29.6%(P<0.01)。结论 30岁以下人群GOV患者以NCPH居多,其中以各种原因引起的门脉海绵样变最多见。NCPH患者并发GOV经内镜治疗后再出血发生率显著低于肝硬化患者。     

三种内镜下治疗方法对胃底静脉曲张的疗效

目的 探讨3种内镜下治疗方法对胃底静脉曲张的疗效。方法 将40例胃底静脉曲张患者分为3组进行内镜下治疗，分别为胃底静脉曲张结扎术组(11例)、静脉内注射组织粘合剂组(15例)以及静脉内注射鱼肝油酸钠和凝血酶组(14例)。术后随访6个月，了解其有效率、胃底静脉曲张消失率、再出血率、不良反应发生率以及成本-效益比。结果 3组患者6个月的有效率分别为100．0％、100．0％、72．7％；胃底静脉曲张消失率分别为25．0％、30．8％、0；再出血率分别为27．3％、20．0％、28．6％。结论 胃底静脉曲张结扎术和静脉内注射组织粘合剂的疗效优于静脉内注射鱼肝油酸钠和凝血酶，胃底静脉曲张结扎术的成本-效益比最好。     

硬化剂在肝硬化食管静脉曲张破裂出血防治中的优化应用

约50%的肝硬化患者初诊时即存在食管胃静脉曲张,尤以食管静脉曲张(EV)常见,且EV的发生率随肝脏疾病严重程度增加而增高(Child-Pugh A 43%、Child-Pugh B 71%、Child-Pugh C 76%)[1]。<5 mm的EV以每年10%的速度进展为大的EV,小EV的年出血率为5%,而大EV可达15%,EV出血后6周内死亡率高达20%[2-4]。急性EV破裂出血停止后再次出血率和死亡率较高,未进行二级预防的EV患者1~2年内再次出血率高达60%,死亡率高达33%[5]。因此EV破裂出血的防治非常重要,内镜干预在EV破裂出血的防治中起重要作用,包括内镜下静脉曲张套扎术(EVL)、内镜下硬化剂注射治疗(EIS)、自膨式金属支架等[5-6]。本文就EIS在EV破裂出血的防治作用做一述评。     

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis

Sarcoidosis is a multi‐systemic disease of unknown etiology that results in the development of non‐caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow‐up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.     

The value of the endoscopic therapies in the treatment of rectal varices: a retrospective comparison between injection sclerotherapy and band ligation.

This study consisted of 15 patients who had undergone endoscopic injection sclerotherapy (EIS) or endoscopic variceal ligation (EVL) for rectal varices. Ten of fifteen patients had histories of anal bleeding, and colonoscopy revealed signs of the risk of variceal rupture in the other five patients. EIS was perfomed in six of the fifteen patients, and the other nine patients underwent EVL. EIS was performed weekly from 2 to 4 times (mean, 3.0), and the total amount of sclerosant ranged from 3.2 to 5.8ml (mean, 4.9ml). After EIS, colonoscopy revealed shrinkage of the rectal varices in all six patients with no complications. EVL was performed weekly from 1 to 3 times (mean, 2.2), and bands were placed on the varices at 2-12 sites (mean, 8.0). After EVL, colonoscopy revealed both ulcers and shrinkage of the varices in the rectum in all nine patients. Eight of the nine experienced no operative complications. However, in the other case, colonoscopy revealed bleeding from ulcers after EVL. The average follow-up period after EIS or EVL was 30 months. The overall non-recurrence rate of rectal varices was 11 of 15 (73.3%); this includes five of the six patients (83.3%) receiving EIS and six of the nine who received EVL (66.7%). The non-recurrence rate was no difference between EIS group and EVL group statistically (P=0.57) by reason of small number of cases. In conclusion, EIS is some superior to EVL with regard to long-term effectiveness, complications on rectal varices.     

Prognosis in patients with cirrhosis and mild portal hypertension

Objective. Sixty to 70% of upper gastrointestinal bleeding episodes in patients with cirrhosis are caused by oesophageal varices. Prophylaxis is indicated in patients with varices and a hepatic venous pressure gradient (HVPG) above 12 mmHg. The study of the natural history of patients with lower HVPG has been sparse. In this study, long-term survival and the risk of complications in mild portal hypertension were analysed. Material and methods. Sixty-one patients with cirrhosis and HVPG below 10 mmHg were included in the study. Data were collected from medical files and National Patient Registries. Variceal bleeding, hepatic encephalopathy and death related to cirrhosis were registered. Thirty-nine patients were graded as Child class A, 19 as class B and 3 as class C. Median survival time was 11 years. Results. Twenty-eight patients (46%) developed one or more complications: variceal bleeding in 10 (16%) and hepatic encephalopathy in 18 patients (30%). Twenty-three patients (38%) died from complications of cirrhosis. Two patients (3%) died from variceal bleeding, another two (3%) from gastrointestinal bleeding of unidentified source. Survival rate was significantly decreased compared with that in the background population. Conclusions. The frequency of complications in patients with mild portal hypertension is considerable, and guidelines for follow-up or medical prophylaxis are warranted. The risk of bleeding from oesophageal varices is low and bleeding-related deaths rare.