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食道・胃静脈瘤

著者: 中村真一 東京女子医科大学 消化器内科

監修: 上村直実 国立国際医療研究センター 国府台病院

著者校正済:2021/09/22
現在監修レビュー中
参考ガイドライン:
  1. 小原勝敏、豊永純、國分茂博.食道・胃静脈瘤内視鏡治療ガイドライン.日本消化器内視鏡学会卒後教育委員会責任編集.消化器内視鏡ガイドライン 第3版.東京:医学書院,2006,p.215-233.
  1. 中村真一、小原勝敏、吉田智治.食道・胃静脈瘤に対する治療.消化器内視鏡ハンドブック.日本消化器内視鏡学会監修、日本消化器内視鏡学会卒後教育委員会責任編集.東京:日本メディカルセンター,2012,p.199-210.
  1. 日本門脈圧亢進症学会編:門脈圧亢進症取扱い規約 第3版.東京:金原出版,2013.
  1. 日本消化器病学会・日本肝臓学会編:肝硬変診療ガイドライン2020 改訂第3版.東京:南江堂,2020.
  1. 日本門脈圧亢進症学会編:門脈圧亢進症診療マニュアル.東京:南江堂、2015.
  1. 小原勝敏、近森文夫監、入澤篤志、於保和彦、中村真一編:改訂第4版 食道・胃静脈瘤.東京:日本メディカルセンター、2021
  1. Portal Hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 65:310-335.2017.PMID:27786365.
患者向け説明資料

概要・推奨   

  1. 食道静脈瘤出血に対して、内視鏡治療が有効である。特にEVLの有用性が認められる(推奨度1)。
  1. 食道静脈瘤に対する内視鏡治療として、EVLが推奨されている(推奨度2)。
  1. 食道静脈瘤に対する粘膜線維化治療(地固め療法)にアルゴンプラズマ凝固法は有効である(推奨度2)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご 契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に はご契約が必要となり ます。閲覧にはご契約が 必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
中村真一 : 特に申告事項無し[2021年]
監修:上村直実 : 未申告[2021年]

改訂のポイント:
  1. 肝硬変診療ガイドラインが改訂されたため、最新版を紹介した。
  1. 最近の専門書を紹介した。
  1. 胃静脈瘤の内視鏡所見について修正を行った。
  1. 食道・胃静脈瘤内視鏡所見記載基準の表記について追加した。
  1. Histoacrylについて説明を追加した。
  1. 所属の変更に伴い修正した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 食道・胃静脈瘤とは、食道あるいは胃噴門部周囲の粘膜下層の静脈が拡張蛇行し、瘤状に隆起した連続血管走行として肉眼的に認められるものである。
  1. 門脈圧亢進症により代償的に自然に形成された、門脈系から大循環系への側副血行路である。多くは慢性肝疾患に伴ってみられる。繰り返し治療を行っても消失しないもの、治療後早期に再発するものを難治症例とする。
  1. 超音波内視鏡検査、CT angiographyで門脈血行動態を把握する。
 
門脈圧亢進症に伴う側副血行路

門脈圧亢進症に伴って形成される側副血行路を示している。食道静脈瘤は奇静脈系短絡路、胃静脈瘤は腎静脈系短絡路において形成される。

 
  1. 門脈圧亢進症を来す疾患はすべて原因となり得る。逆に食道・胃静脈瘤を認めれば、門脈圧亢進状態を疑うことができる。
問診・診察のポイント  
  1. 一般に無症状である。静脈瘤出血により吐下血、貧血を認める以外は基礎疾患(主に慢性肝疾患)による症状のみである。

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文献 

著者: Arun J Sanyal, Robert J Fontana, Adrian M Di Bisceglie, James E Everhart, Michael C Doherty, Gregory T Everson, John A Donovan, Peter F Malet, Savant Mehta, Muhammad Y Sheikh, Andrea E Reid, Marc G Ghany, David R Gretch, Halt-C Trial Group
雑誌名: Gastrointest Endosc. 2006 Dec;64(6):855-64. doi: 10.1016/j.gie.2006.03.007.
Abstract/Text BACKGROUND: The factors predictive of the presence or the absence of esophageal varices in hepatitis C virus (HCV) and advanced fibrosis have not been defined.
OBJECTIVES: To define the prevalence of esophageal varices and the factors that are positively and negatively with such varices in hepatitis C and advanced fibrosis.
DESIGN: A prospective study of esophageal varices and associated risk factors in subjects with hepatitis C and advanced fibrosis.
SETTING: Prerandomization data from the HALT-C (hepatitis C long-term antiviral treatment against cirrhosis) clinical trial.
PATIENTS AND INTERVENTION: Subjects with bridging fibrosis or cirrhosis, who were virologic nonresponders to treatment with pegylated interferon alpha 2a and ribavirin, underwent endoscopy.
RESULTS: Sixteen percent of subjects with bridging fibrosis (95/598) and 39% of subjects with cirrhosis (164/418) had varices (P < .0001); 2% of subjects with bridging fibrosis (13/598) and 11% of those with cirrhosis (48/418) had medium or large varices. Subjects with bridging fibrosis and varices had a significantly lower platelet count and higher bilirubin and international normalized ratio (INR) compared with those without varices, suggesting that the biopsy may have underestimated the severity of fibrosis. A platelet count >150,000/mm(3) was associated with a negative predictive value of 99% for esophageal varices. By logistic regression modeling, African American race and female sex were protective, whereas a lower platelet count and higher bilirubin and INR predicted varices (c statistic, 0.758).
CONCLUSIONS: The risk of having varices increases with decreasing platelet counts, increasing bilirubin, and INR. The probability of having medium or large varices at platelet counts >150,000/mm(3) is negligible in this population.

PMID 17140886  Gastrointest Endosc. 2006 Dec;64(6):855-64. doi: 10.101・・・
著者: Shinichi Nakamura, Hiroyuki Konishi, Maiko Kishino, Satoru Yatsuji, Katsutoshi Tokushige, Etsuko Hashimoto, Keiko Shiratori
雑誌名: Hepatol Res. 2008 Jun;38(6):572-9. doi: 10.1111/j.1872-034X.2008.00318.x. Epub 2008 Mar 4.
Abstract/Text 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.

PMID 18328071  Hepatol Res. 2008 Jun;38(6):572-9. doi: 10.1111/j.1872-・・・
著者: H Imazu, T Matsui, R Noguchi, K Asada, Y Miyamoto, M Kawata, M Nakayama, N Matsuo, M Matsumura, H Fukui
雑誌名: Endoscopy. 2000 Oct;32(10):766-72. doi: 10.1055/s-2000-7706.
Abstract/Text BACKGROUND AND STUDY AIMS: Endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) are used worldwide as the treatment for esophageal varices. We evaluated portal hemodynamics using magnetic resonance angiography (MRA) in these two forms of treatment.
PATIENTS AND METHODS: The study was carried out in 50 cirrhotic patients. MRA was performed to identify the hepatofugal supply vein selectively for esophageal varices. Those who showed a positive MR angiogram for the supply vein were randomly allocated to one of two groups, using the sealed envelope method, and underwent either EIS or EVL. On the other hand, those with a negative angiogram received only EVL. EIS was done to embolize esophageal varices as well as their feeders by intravariceal injection of sclerosant under fluoroscopic guidance.
RESULTS: A positive MR angiogram of the hepatofugal left gastric vein as the supply vein was observed in 41 patients. Nine patients showed negative MRA results. Among those with positive angiograms, the rate of eradication of the left gastric vein was higher in the EIS-treated group than in the EVL treated group (50% vs. 8.6%). After either treatment, the recurrence-free rate for high risk esophageal varices was higher in patients with complete eradication of the left gastric vein than in those without (88% vs. 35%). In patients with negative angiogram results, who only underwent EVL, high risk esophageal varices did not reappear over a long period.
CONCLUSION: MRA is useful for evaluating portal hemodynamics. With the aim of avoiding recurrence of esophageal varices, EIS was suitable for patients who had a hepatofugal supply vein for the varices because recurrence could be prevented by embolization of the supply vein. EVL may be expected to be efficacious in patients where no image of a hepatofugal supply vein is found on MRA.

PMID 11068835  Endoscopy. 2000 Oct;32(10):766-72. doi: 10.1055/s-2000-・・・
著者: Toru Ishikawa, Takashi Ushiki, Ken-ichi Mizuno, Tadayuki Togashi, Kouji Watanabe, Kei-ichi Seki, Hironobu Ohta, Toshiaki Yoshida, Keiko Takeda, Tomoteru Kamimura
雑誌名: World J Gastroenterol. 2005 Dec 21;11(47):7515-9.
Abstract/Text AIM: To evaluate the efficacy of CT-maximum intensity projection (CT-MIP) in the detection of gastric varices and their inflowing and outflowing vessels in patients with gastric varices scheduled to undergo balloon-occluded retrograde transvenous obliteration (B-RTO).
METHODS: Sixteen patients with endoscopically confirmed gastric varices were included in this study. All patients were evaluated with CT-MIP using three-dimensional reconstructions, before and after B-RTO.
RESULTS: CT-MIP clearly depicted gastric varices in 16 patients (100%), the left gastric vein in 6 (32.5%), the posterior gastric vein in 12 (75.0%), the short gastric veins in 13 (81.3%), gastrorenal shunts in 16 (100%), the hemiazygos vein (HAZV) in 4 (25.0%), the pericardiophrenic vein (PCPV) in 9 (56.3%), and the left inferior phrenic vein in 9 patients (56.3%). Although flow direction itself cannot be determined from CT-MIP, this modality provided clear images of the inflowing and the outflowing vessels. Moreover, in one patient, short gastric veins were not seen on conventional angiographic portography images of the spleen, but were clearly revealed on CT-MIP.
CONCLUSION: We suggest that CT-MIP should be considered as a routine method for detecting and diagnosing collateral veins in patients with gastric varices scheduled for B-RTO. Furthermore, CT-MIP is more useful than endoscopy in verifying the early therapeutic effects of B-RTO.

PMID 16437726  World J Gastroenterol. 2005 Dec 21;11(47):7515-9.
著者: Guadalupe Garcia-Tsao, Arun J Sanyal, Norman D Grace, William Carey, Practice Guidelines Committee of the American Association for the Study of Liver Diseases, Practice Parameters Committee of the American College of Gastroenterology
雑誌名: Hepatology. 2007 Sep;46(3):922-38. doi: 10.1002/hep.21907.
Abstract/Text
PMID 17879356  Hepatology. 2007 Sep;46(3):922-38. doi: 10.1002/hep.219・・・
著者: Rosario Gonzalez, Javier Zamora, Judith Gomez-Camarero, Luis-Miguel Molinero, Rafael Bañares, Agustín Albillos
雑誌名: Ann Intern Med. 2008 Jul 15;149(2):109-22.
Abstract/Text BACKGROUND: Combining endoscopic therapy and beta-blockers may improve outcomes in patients with cirrhosis and bleeding esophageal varices.
PURPOSE: To assess whether a combination of endoscopic and drug therapy prevents overall and variceal rebleeding and improves survival better than either therapy alone.
DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and conference proceedings through 30 December 2007.
STUDY SELECTION: Randomized trials comparing endoscopic plus beta-blocker therapy with either therapy alone, without language restrictions.
DATA EXTRACTION: Two reviewers independently extracted data on interventions and the primary study outcomes of overall rebleeding and mortality. Metaregression and stratified analysis were used to explore heterogeneity.
DATA SYNTHESIS: 23 trials (1860 patients) met inclusion criteria. Combination therapy reduced overall rebleeding more than endoscopic therapy alone (pooled relative risk, 0.68 [95% CI, 0.52 to 0.89]; I(2) = 61%) or beta-blocker therapy alone (pooled relative risk, 0.71 [CI, 0.59 to 0.86]; I(2) = 0%). Combination therapy also reduced variceal rebleeding and variceal recurrence. Reduction in mortality from combination therapy did not statistically significantly differ from that from endoscopic (Peto odds ratio, 0.78 [CI, 0.58 to 1.07) or drug therapy (Peto odds ratio, 0.70 [CI, 0.46 to 1.06]). Effects were independent of the endoscopic procedure (injection sclerotherapy or banding). No trial-level variable associated with the effect was identified through metaregression or stratified analysis.
LIMITATION: Statistically significant heterogeneity in trial quality and evidence for selective reporting and publication bias were found.
CONCLUSION: A combination of endoscopic and drug therapy reduces overall and variceal rebleeding in cirrhosis more than either therapy alone.

PMID 18626050  Ann Intern Med. 2008 Jul 15;149(2):109-22.
著者: G H Lo, K H Lai, J S Cheng, J H Hwu, C F Chang, S M Chen, H T Chiang
雑誌名: Hepatology. 1995 Aug;22(2):466-71.
Abstract/Text We conducted a prospective, randomized trial comparing sclerotherapy and ligation in 120 patients with acute bleeding of esophageal varices. All the patients were cirrhotic, 59 received sclerotherapy, and 61 received ligation. Treatment was repeated regularly until the varices were obliterated. The mean follow-up period was 295 +/- 120 days and 310 +/- 105 days for the sclerotherapy and ligation groups, respectively. The control of active bleeding was 12/15 (80%) in the sclerotherapy group and 18/19 (94%) in the ligation group (P = .23). The numbers of treatment sessions required to achieve variceal obliteration were 6.5 +/- 1.2 in the sclerotherapy group and 3.8 +/- 0.4 in the ligation group (P < .001). Recurrent bleeding from the gastrointestinal tract was 51% in the sclerotherapy group compared with 33% in the ligation group (P < .05). Recurrent bleeding from esophageal varices was 36% in the sclerotherapy group and 11% in the ligation group (P < .01). However, bleeding from ectopic varices and congestive gastropathy was less common in the sclerotherapy group (7%) than in the ligation group (18%) (P = .05). Significant complications were encountered in 19% of the sclerotherapy group and in 3.3% of the ligation group (P < .01). Comparison of Kaplan-Meier estimates of time to death of both groups showed a significantly lower mortality in the ligation group (P = .011). Both sclerotherapy and ligation can effectively arrest active bleeding from esophageal varices. However, ligation is more effective than sclerotherapy in decreasing the risk of rebleeding from esophageal varices with fewer complications. Ligation can also achieve obliteration of esophageal varices more rapidly than sclerotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 7635414  Hepatology. 1995 Aug;22(2):466-71.
著者: M C Hou, H C Lin, B I Kuo, C H Chen, F Y Lee, S D Lee
雑誌名: Hepatology. 1995 Jun;21(6):1517-22.
Abstract/Text To determine the efficacy of endoscopic variceal sclerotherapy (EVS) and ligation (EVL) in the management of esophageal variceal bleeding, 134 cirrhotic patients were randomized to receive either treatment. The clinical and endoscopic characteristics were similar in both groups. Active bleeding was controlled with ligation (20 of 20) as efficiently as with sclerotherapy (14 of 16). Elective sclerotherapy consumed less time than ligation (7.9 +/- 1.8 minutes vs. 11.5 +/- 2.7 minutes, P < .001), but there was no difference between emergent sclerotherapy (14.5 +/- 5.8 minutes) and ligation (14.9 +/- 4.1 minutes). Ligation reduced one grade of variceal size more quickly than sclerotherapy (1.1 +/- 0.4 vs. 2.0 +/- 1.7 session, P < .001). The rebleeding rate was lower with ligation (13 of 67 vs. 28 of 67, P < .01). Esophageal ulcer was the most common source of rebleeding. Recurrence of varices appears more probable with ligation (P = .079). The complication rate was higher with sclerotherapy (15 of 67 vs. 3 of 67, P < .01), with esophageal stricture being the most common cause. Survival rate was the same in both groups even after stratifying patients into good and poor hepatic reserve groups. Hepatic failure was the major cause of death, followed by exsanguination. In summary, EVL was superior to EVS regarding rebleeding and complications but not in other aspects such as time consumption in elective treatment and recurrence of varices. Substantial results for long-term follow-up are required before conclusion of the treatment of choice.

PMID 7768494  Hepatology. 1995 Jun;21(6):1517-22.
著者: D Baroncini, G L Milandri, D Borioni, A Piemontese, V Cennamo, P Billi, P P Dal Monte, N D'Imperio
雑誌名: Endoscopy. 1997 May;29(4):235-40.
Abstract/Text BACKGROUND AND STUDY AIMS: Endoscopic ligation (EVL) and endoscopic variceal sclerotherapy (EVS) are known to be equally effective in eradicating bleeding esophageal varices in patients with hepatic cirrhosis, but the long-term safety and efficacy of the two techniques have not been clearly established. The aim of this study was to determine the relative frequency of rebleeding, recurrence of varices, and survival after treatment with the two techniques during a relatively long follow-up period.
PATIENTS AND METHODS: A total of 111 patients without bleeding at the index endoscopy were randomly assigned to either EVL (n = 57) or EVS (n = 54). After eradication of the varices, the patients received endoscopic examinations every three months and for each episode of rebleeding.
RESULTS: The mean follow-up periods were 534 +/- 42 days in the EVS group and 496 +/- 40 days in the EVL group. The two techniques were equally effective in eradicating varices (93% in EVL group and 92.5% in EVS group). The mean number of sessions required to obtain eradication was slightly lower (mean +/- SE) in the EVL group (3.5 +/- 0.1 vs. 4.0 +/- 0.1, P = 0.004), while the time required for eradication was longer (33.8 +/- 2.1 vs. 27.3 +/- 1.4, P = 0.01). The comparison of the Kaplan-Meier estimates of survival and time to first rebleeding did not show any statistically significant differences between the two groups. The rate of complications was significantly higher in the EVS group than in the EVL group (31% vs. 11%, P = 0.001), while the rate of recurrent varices during follow-up was higher in the EVL group (30% vs. 13%, P = 0.03).
CONCLUSIONS: While the two techniques are equally effective, ligation treatment shows greater advantages in the short-term follow-up, but is associated with more frequent recurrence of varices in the longer term. These two aspects should be considered for evaluation in the cost-benefit ratio and quality of life analysis. All patients should have frequent endoscopic evaluations (every three or four months) throughout the first year of follow-up.

PMID 9255524  Endoscopy. 1997 May;29(4):235-40.
著者: S K Sarin, G S Lamba, M Kumar, A Misra, N S Murthy
雑誌名: N Engl J Med. 1999 Apr 1;340(13):988-93. doi: 10.1056/NEJM199904013401302.
Abstract/Text BACKGROUND AND METHODS: We compared propranolol therapy and endoscopic ligation for the primary prevention of bleeding from esophageal varices. This prospective, controlled trial included consecutive eligible patients who had large varices (>5 mm in diameter) that were at high risk for bleeding. The patients were assigned to either propranolol therapy, at a dose sufficient to decrease the base-line heart rate by 25 percent, or variceal ligation, to be performed weekly until the varices were obliterated or so reduced in size that it was not possible to continue treatment.
RESULTS: Of the 89 patients, 82 of whom had cirrhosis of the liver, 44 received propranolol and 45 underwent variceal ligation. The mean (+/-SD) duration of follow-up in each group was 14+/-9 and 13+/-10 months, respectively. The mean time required to achieve an adequate reduction in the heart rate was 2.5+/-1.7 days; the mean number of sessions needed to complete variceal ligation was 3.2+/-1.1. After 18 months, the actuarial probability of bleeding was 43 percent in the propranolol group and 15 percent in the ligation group (P=0.04). Twelve patients in the propranolol group and four in the ligation group had bleeding. Three of the four in the ligation group had bleeding before their varices had been obliterated. Nine patients in the ligation group had recurrent varices, a mean of 3.7 months after the initial treatment. Five patients in each group died; bleeding from the varices was the cause of death of four patients in the propranolol group and of three in the ligation group. There were no serious complications of variceal ligation; in the propranolol group, treatment was stopped in two patients because of side effects.
CONCLUSIONS: In patients with high-risk esophageal varices, endoscopic ligation of the varices is safe and more effective than propranolol for the primary prevention of variceal bleeding.

PMID 10099140  N Engl J Med. 1999 Apr 1;340(13):988-93. doi: 10.1056/N・・・
著者: P Svoboda, I Kantorová, J Ochmann, L Kozumplík, J Marsová
雑誌名: Surg Endosc. 1999 Jun;13(6):580-4.
Abstract/Text BACKGROUND: Endoscopic ligation (EVL) and endoscopic sclerotherapy (EIS) are both effective in the treatment of bleeding esophageal varices, but the efficacy of the two techniques in the prophylaxis of first variceal bleeding has not been investigated. The aim of this study was to investigate the frequency of first variceal bleeding, the recurrence of varices, and survival after treatment with the two techniques, as compared to a nontreated control group.
METHODS: A total of 157 patients with liver cirrhosis and advanced esophageal varices with no previous history of upper gastrointestinal bleeding were randomly assigned to either an EIS group (n = 55), an EVL group (n = 52), or a nontreated control group (n = 50). After the eradication of esophageal varices in the EIS and in EVL groups and in all control patients, the endoscopic examination was performed at 3-month intervals.
RESULTS: There were no significant differences between EIS and EVL in the eradication rate of esophageal varices (85% in the EIS group versus 81% in the EVL group). The mean number of sessions required to obtain eradication was lower in the EVL group than in the EIS group (4.8 +/- 1.8 versus 6.2 +/- 2.0; p = 0.0003), but the recurrence of esophageal varices was higher in the EVL group (31% versus 11%; p = 0.01). Total mortality was significantly lower in the EIS patients than in the controls (20% versus 38%; p = 0.04). It was also lower, but not significantly, in the EVL patients than in the controls (23% versus 38%; p = 0.10). A significant decrease in variceal bleeding was observed both in sclerotherapy cases (20%) and controls (54%; p = 0.0005) and in ligation cases and controls (29%; p = 0.01). No significant difference in bleeding episodes was observed between the sclerotherapy and ligation cases (p = 0.29). No serious complications were observed either in the EIS or EVL groups.
CONCLUSIONS: EIS and EVL are similarly effective in the prevention of first variceal bleeding. The choice between EIS and EVL depends on the skill of the endoscopic unit. For highly experienced surgeons facing no complications, sclerotherapy seems to be preferable; for all others, it is technically easier to perform ligation.

PMID 10347295  Surg Endosc. 1999 Jun;13(6):580-4.
著者: S Nakamura, A Mitsunaga, Y Murata, S Suzuki, N Hayashi
雑誌名: Endoscopy. 2001 Mar;33(3):210-5. doi: 10.1055/s-2001-12804.
Abstract/Text BACKGROUND AND STUDY AIMS: Esophageal varices are treated by endoscopic ligation with or without sclerotherapy. Here we used argon plasma coagulation (APC) to promote mucosal fibrosis and compared the efficacy of ligation plus APC with ligation alone in the treatment of esophageal varices.
PATIENTS AND METHODS: Our prospective study included 30 patients with esophageal varices randomly assigned to receive APC after ligation (combined group) and 30 patients assigned to receive ligation only (ligation group). Endoscopic ligation was performed until the varix shrank to F1 without red color sign or smaller. This was followed by induction of fibrosis of the distal esophageal mucosa using APC in the combined group. APC was performed using an argon gas at a flow rate of 1.5-2 l/min and a high frequency arc output of 50-60 W. Treatment outcome and complications were compared between the two groups.
RESULTS: The mean follow-up time was 18.5+/-6.8 and 15.8+/-7.7 months (+/- SD) for the combined and ligation groups, respectively. The number of treatment sessions was slightly lower in the ligation group (2.9+/-0.6 vs. 2.5+/-0.6, P<0.05). The number of ligation bands used was not different between the two groups (13.4+/-3.1 vs. 14.9+/-2.4). The cumulative recurrence-free rate at 24 months after treatment in the combined group was significantly higher than in the ligation group (74.2% vs. 49.6%, P < 0.05). A significantly higher incidence of pyrexia was encountered in the combined group (P <0.05), but the incidences of other complications were similar in both groups.
CONCLUSION: Our results indicate that endoscopic ligation of esophageal varices combined with APC is superior to ligation alone. Since APC is theoretically well suited for mucosal fibrosis therapy, it can be used for the complete elimination of esophageal varices and for fibrosis of the distal esophageal mucosa.

PMID 11293751  Endoscopy. 2001 Mar;33(3):210-5. doi: 10.1055/s-2001-12・・・
著者: K Furukawa, Y Aoyagi, T Harada, H Enomoto
雑誌名: Hepatol Res. 2002 Jul;23(3):220-225.
Abstract/Text BACKGROUND AND STUDY AIM: esophageal variceal ligation (EVL) has been spread widely as a simple and effective method for treating esophageal varices. However, in view of the unacceptably high rate of recurrence associated with this technique, the availability of other supplemental consolidation therapies has been earnestly desired. Under these circumstances, attempts such as endoscopic injection sclerotherapy (EIS) have been made for this particular therapeutic purpose. In the current study, we tested the clinical usefulness and safety of the argon plasma coagulation technique (APC). PATIENTS AND METHODS: 11 patients with imminent signs of esophageal varix rupture in our hospital were subjects in the present study. Before APC was performed, these patients underwent EVL with consequent improvement of esophageal varices from F3 (largest sized varices) to disappear or F1 (straight). RESULTS: the patients were followed up for a mean post-treatment period of 637.4 (SD +/-56.5) days, and no obvious recurrence of varices in the so-called critical area was noted. In addition, no serious complications were observed. CONCLUSION: our current clinical study has demonstrated that APC may be an effective prevention consolidation therapy after EVL without serious complications.

PMID 12076718  Hepatol Res. 2002 Jul;23(3):220-225.
著者: Livio Cipolletta, Maria Antonia Bianco, Gianluca Rotondano, Riccardo Marmo, Costantino Meucci, Roberto Piscopo
雑誌名: Gastrointest Endosc. 2002 Oct;56(4):467-71. doi: 10.1067/mge.2002.127409.
Abstract/Text BACKGROUND: Endoscopic variceal ligation is an established procedure for eradication of esophageal varices. However, varices frequently recur after endoscopic variceal ligation. Argon plasma coagulation has been used as supplemental treatment for eradication of varices and for prevention of variceal recurrence in small uncontrolled series. The aim of this study was to determine whether argon plasma coagulation is effective in reducing variceal recurrence after endoscopic variceal ligation.
METHODS: Thirty patients with cirrhosis, a history of acute esophageal variceal bleeding, and eradication of varices by endoscopic variceal ligation were randomized to argon plasma coagulation (16 patients) or observation (14 patients). The 2 groups were similar with respect to all background variables including age, Child-Pugh score, presence of gastric varices, and degree of portal hypertensive gastropathy. In the argon plasma coagulation group, the entire esophageal mucosa 4 to 5 cm proximal to the esophagogastric junction was thermocoagulated circumferentially with argon plasma coagulation in 1 to 3 sessions performed at weekly intervals. Endoscopy was performed every 3 months to check for recurrence of varices in both groups.
RESULTS: During the course of the study, no serious complication was noted. After argon plasma coagulation, transient fever occurred in 13 patients and 8 complained of dysphagia or retrosternal pain/discomfort. Mean follow-up for all patients was 16 months (range 9-28 months). No recurrence of varices or variceal hemorrhage was observed in the argon plasma coagulation group, whereas varices recurred in 42.8% (6/14) of the patients in the control group (p < 0.04) and bleeding recurred in 7.2% (1/14).
CONCLUSIONS: Argon plasma coagulation of the distal esophageal mucosa after eradication of esophageal varices by endoscopic variceal ligation is safe and effective for reducing the rate of variceal recurrence.

PMID 12297759  Gastrointest Endosc. 2002 Oct;56(4):467-71. doi: 10.106・・・
著者: Mikiya Kitamoto, Michio Imamura, Koji Kamada, Hiroshi Aikata, Yoshiiku Kawakami, Akiko Matsumoto, Yoshika Kurihara, Hirotaka Kono, Hiroo Shirakawa, Toshio Nakanishi, Katsuhide Ito, Kazuaki Chayama
雑誌名: AJR Am J Roentgenol. 2002 May;178(5):1167-74. doi: 10.2214/ajr.178.5.1781167.
Abstract/Text OBJECTIVE: This study was performed to evaluate the clinical efficacy, feasibility, and complications of balloon-occluded retrograde transvenous obliteration for patients with hemorrhage from gastric fundal varices.
SUBJECTS AND METHODS: Between December 1994 and February 2001, 24 consecutive patients with hemorrhage from gastric fundal varices were enrolled in this study. Balloon-occluded retrograde transvenous obliteration consisted of injecting 5% ethanolamine oleate iopamidol through the outflow vessels during balloon occlusion. The treatment was performed during acute bleeding in 11 patients and electively in 13 patients. Among those patients with acute bleeding, six were treated for temporary hemostasis with balloon tamponade, and five were treated endoscopically.
RESULTS: Cannulation into the outflow vessels was performed in 23 patients, but the balloon catheter could not be inserted in one patient who had inferior phrenic vein outflow. Complete success was obtained in 88% (21/24) of patients, and partial success was obtained in two patients. In nine of 11 patients with acute bleeding, complete success was achieved. Rebleeding from gastric varices was not observed in patients treated with complete success, whereas two patients treated partially rebled within 1 week of the treatment (rate of rebleeding, 9%). Eradication of gastric varices was obtained in all patients (n = 19) who were examined by endoscopy 3 months after the treatment. Eight patients experienced worsening of esophageal varices. These patients were treated endoscopically because of findings that suggested a risk of hemorrhage. The overall mortality rate was 4% (1/24). No damage to the kidney was observed, although 11 patients had macrohematuria.
CONCLUSION: Balloon-occluded retrograde transvenous obliteration followed by any hemostatic procedure might be effective for both prophylaxis of rebleeding and eradication of gastric fundal varices, even in urgent cases.

PMID 11959725  AJR Am J Roentgenol. 2002 May;178(5):1167-74. doi: 10.2・・・
著者: Teruhisa Ninoi, Norifumi Nishida, Toshio Kaminou, Yukimasa Sakai, Toshiaki Kitayama, Masao Hamuro, Ryusaku Yamada, Kenji Nakamura, Tetsuo Arakawa, Yuichi Inoue
雑誌名: AJR Am J Roentgenol. 2005 Apr;184(4):1340-6. doi: 10.2214/ajr.184.4.01841340.
Abstract/Text OBJECTIVE: Our aim was to evaluate the long-term clinical results after balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices with spontaneous gastrorenal shunt.
MATERIALS AND METHODS: A total of 78 patients with cirrhosis and with gastric varices, successfully treated by B-RTO, were enrolled in this study. Recurrence and bleeding of gastric varices and worsening of esophageal varices were endoscopically evaluated. Univariate and multivariate analyses were used to assess the prognostic factors for worsening of esophageal varices and survival.
RESULTS: Recurrence of gastric varices was found in two patients; the 5-year recurrence rate was 2.7%. Bleeding of gastric varices occurred in only one patient after B-RTO; the 5-year bleeding rate was 1.5%. Worsening of esophageal varices was observed in 29 patients, and the worsening rates at 1, 3, and 5 years were 27%, 58%, and 66%, respectively. These esophageal varices were endoscopically treated to prevent rupture. Multivariate analysis showed the presence of esophageal varices before B-RTO was a prognostic factor for worsening (relative risk, 4.956). At a median follow-up of 700 days (range, 137-2,339 days), the survival rates at 1, 3, and 5 years were 93%, 76%, and 54%, respectively. The prognostic factors associated with survival were presence of hepatocellular carcinoma (relative risk, 24.342) and the Child-Pugh classification (relative risk, 5.780).
CONCLUSION: B-RTO is an effective method for gastric varices with gastrorenal shunt and provides lower recurrence and bleeding rates. We believe that B-RTO can become a standard treatment for gastric varices with gastrorenal shunt, although treatment of worsened esophageal varices may be necessary after B-RTO.

PMID 15788621  AJR Am J Roentgenol. 2005 Apr;184(4):1340-6. doi: 10.22・・・
著者: Shinichi Nakamura, Nobuyuki Torii, Satoru Yatsuji, Hiroyuki Konishi, Maiko Kishino, Makiko Taniai, Katsutoshi Tokushige, Etsuko Hashimoto, Keiko Shiratori
雑誌名: Hepatol Res. 2008 Apr;38(4):340-7. doi: 10.1111/j.1872-034X.2007.00282.x. Epub 2007 Nov 16.
Abstract/Text 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.

PMID 18021226  Hepatol Res. 2008 Apr;38(4):340-7. doi: 10.1111/j.1872-・・・
著者: G H Lo, K H Lai, J S Cheng, M H Chen, H T Chiang
雑誌名: Hepatology. 2001 May;33(5):1060-4. doi: 10.1053/jhep.2001.24116.
Abstract/Text Gastric variceal bleeding is a catastrophic event. Both cyanoacrylate injection and banding ligation have been proven to be effective in the management of bleeding gastric varices. This study was performed to compare the efficacy and complications of both the modalities. Cirrhotic patients with a history of gastric variceal bleeding were randomized to 2 groups. The group receiving endoscopic obturation (group A) comprised 31 patients and the group receiving band ligation (group B) comprised 29 patients. Butyl cyanoacrylate and pneumatic-driven ligator were applied, respectively. Treatment was repeated regularly until obliteration of gastric varices. Active bleeding occurred in 15 patients in group A and 11 patients in group B. Initial hemostatic rate (defined as no bleeding for 72 hours after treatment) was 87% in group A and 45% in group B (P = .03). The sessions required to achieve variceal obliteration and obliteration rates were similar in both the groups. However, rebleeding rates were significantly higher in group B (54%) than group A (31%) (P = .0005). Treatment-induced ulcer bleeding occurred in 2 patients (7%) in group A and 8 patients (28%) in group B (P = .03). The amount of blood transfusions required were also higher in group B than group A (4.2 +/- 1.3 vs. 2.6 +/- 0.9 units, respectively) (P < .01). Nine patients of group A and 14 patients of group B died (P = .05). In conclusion, endoscopic obturation using cyanoacrylate proved more effective and safer than band ligation in the management of bleeding gastric varices.

PMID 11343232  Hepatology. 2001 May;33(5):1060-4. doi: 10.1053/jhep.20・・・
著者: Eun Jung Kang, Soung Won Jeong, Jae Young Jang, Joo Young Cho, Sae Hwan Lee, Hyun Gun Kim, Sang Gyune Kim, Young Seok Kim, Young Koog Cheon, Young Deok Cho, Hong Soo Kim, Boo Sung Kim
雑誌名: World J Gastroenterol. 2011 Mar 21;17(11):1494-500. doi: 10.3748/wjg.v17.i11.1494.
Abstract/Text AIM: To evaluate the long-term efficacy and safety of endoscopic obliteration with Histoacryl(®) for treatment of gastric variceal bleeding and prophylaxis.
METHODS: Between January 1994 and March 2010 at SoonChunHyang University Hospital, a total of 127 patients with gastric varices received Histoacryl(®) injections endoscopically. One hundred patients underwent endoscopic Histoacryl(®) injections because of variceal bleeding, the other 27 patients received such injections as a prophylactic procedure.
RESULTS: According to Sarin classification, 56 patients were GOV1, 61 patients were GOV2 and 10 patients were IGV. Most of the varices were large (F2 or F3, 111 patients). The average volume of Histoacryl(®) per each session was 1.7 ± 1.3 cc and mean number of sessions was 1.3 ± 0.6. (1 session-98 patients, 2 sessions-25 patients, ≥ 3 sessions-4 patients). Twenty-seven patients with high risk of bleeding (large or fundal or RCS+ or Child C) received Histoacryl(®) injection as a primary prophylactic procedure. In these patients, hepatitis B virus was the major etiology of cirrhosis, 25 patients showed GOV1 or 2 (92.6%) and F2 or F3 accounted for 88.9% (n = 24). The rate of initial hemostasis was 98.4% and recurrent bleeding within one year occurred in 18.1% of patients. Successful hemostasis during episodes of rebleeding was achieved in 73.9% of cases. Median survival was 50 mo (95% CI 30.5-69.5). Major complications occurred in 4 patients (3.1%). The rebleeding rate in patients with hepatocellular carcinoma or GOV2 was higher than in those with other conditions. None of the 27 subjects who were treated prophylactically experienced treatment-related complications. Cumulative survival rates of the 127 patients at 6 mo, 1, 3, and 5 years were 92.1%, 84.2%, 64.2%, and 45.3%, respectively. The 6 mo cumulative survival rate of the 27 patients treated prophylactically was 75%.
CONCLUSION: Histoacryl(®) injection therapy is an effective treatment for gastric varices and also an effective prophylactic treatment of gastric varices which carry high risk of bleeding.

PMID 21472110  World J Gastroenterol. 2011 Mar 21;17(11):1494-500. doi・・・
著者: Gin-Ho Lo, Chih-Wen Lin, Daw-Shyong Perng, Chi-Yang Chang, Ching-Tai Lee, Chuan-Yuan Hsu, Huay-Min Wang, Hui-Chen Lin
雑誌名: Scand J Gastroenterol. 2013 Oct;48(10):1198-204. doi: 10.3109/00365521.2013.832792.
Abstract/Text BACKGROUND. Esophageal varices extending along lesser curvature side of stomach is classified as GOV1. The optimal therapy for GOV1 bleeding is still undetermined. METHODS. One hundred and sixty-two patients diagnosed as acute hemorrhage from GOV1 were enrolled. At endoscopists' discretion, 118 patients received glue injection (Glue group) and 44 patients received ligation to arrest bleeding [endoscopic variceal ligation (EVL) group]. This study aimed to compare hemostasis, rebleeding, complications and mortality within 42 days. RESULTS. Both groups were comparable in baseline data. In 109 patients (92%) in the Glue group and 36 patients (82%) in the EVL group (p = 0.07) 48-h hemostasis was achieved . Hemostasis of active bleeding was achieved in 49 of 55 patients (89%) in the Glue group and 24 of 28 patients (85%) in the EVL group (p = 0.70). Treatment failure was noted in 14% of the Glue group and 23% in the EVL group (p = 0.22). Eight patients in the Glue group and four patients in the EVL group rebled between 5 and 42 days (p = 0.73). A total of 48 and 19 adverse events occurred in the Glue and EVL groups, respectively (p = 0.85). Six patients in the Glue group and seven patients in the EVL group encountered posttreatment gastric ulcer bleeding (p = 0.04). Seventeen patients (14%) in the Glue group and 10 (23%) patients in the EVL group died within 42 days (p < 0.001). CONCLUSIONS. Banding ligation was similar to glue injection in achieving successful hemostasis of acute bleeding from GOV1. However, a higher incidence of posttreatment ulcer bleeding and mortality may be associated with banding ligation.

PMID 24047398  Scand J Gastroenterol. 2013 Oct;48(10):1198-204. doi: 1・・・
著者: A Irisawa, K Obara, Y Sato, A Saito, F Takiguchi, H Shishido, H Sakamoto, R Kasukawa
雑誌名: Gastrointest Endosc. 1999 Sep;50(3):374-80. doi: 10.1053/ge.1999.v50.97777.
Abstract/Text BACKGROUND: The relation between esophageal varices and venous collaterals outside the esophageal wall in patients with portal hypertension remains unclear. We investigated this relationship with endoscopy and endoscopic ultrasound (US).
METHODS: Twenty-two patients with untreated varices were examined. The collaterals were studied with a 20 MHz US catheter probe. Collaterals were divided into two groups: (1) periesophageal collateral veins adjacent to the muscularis externa of the esophagus and (2) paraesophageal collateral veins external to the esophageal wall but without contact with the muscularis externa. Periesophageal and paraesophageal collateral veins were scored as mild or severe according to stage of development.
RESULTS: Varix form as defined endoscopically was significantly larger in the severe periesophageal collateral veins group than in the mild periesophageal collateral veins group (p < 0. 01). In contrast, varix form did not differ significantly between the mild and severe paraesophageal collateral veins groups. Perforating veins were detected in the distal esophagus in 18 of 22 patients (81.8%) by means of US. The prevalence of perforating veins increased in relation to varix form. Two types of perforating veins were found on the basis of connection with periesophageal and paraesophageal collateral veins. The frequency with which perforating veins were connected to periesophageal collateral veins was 81.8%; the frequency of connection to paraesophageal collateral veins was 27.3%.
CONCLUSION: Periesophageal collateral veins play a more important role in the formation of esophageal varices than do paraesophageal collateral veins.

PMID 10462659  Gastrointest Endosc. 1999 Sep;50(3):374-80. doi: 10.105・・・
著者: S Hino, H Kakutani, K Ikeda, H Yasue, Y Kitamura, K Sumiyama, Y Uchiyama, A Kuramochi, K Matsuda, H Arakawa, K Hachiya, M Kawamura, K Masuda, H Suzuki
雑誌名: Endoscopy. 2001 Oct;33(10):869-72. doi: 10.1055/s-2001-17339.
Abstract/Text BACKGROUND AND STUDY AIMS: The time to recurrence of esophageal varices may vary greatly between patients even after the same endoscopic therapy. To clarify the factors which contribute to recurrence after endoscopic treatment, the hemodynamics and morphology of the left gastric vein (LGV) were investigated using color Doppler endoscopic ultrasonography (EUS).
PATIENTS AND METHODS: A total of 31 patients with high-risk esophageal varices underwent color Doppler-EUS before receiving endoscopic variceal ligation and endoscopic injection sclerotherapy combined therapy. Endoscopic examination was performed every 3 months after the treatment to evaluate recurrence of varices.
RESULTS: A total of 18 patients responded to the therapy, while 13 patients did not respond, and had recurrence within 12 months. The hepatofugal flow velocity in the LGV trunk was significantly lower in the responders (9.9 vs. 13.9 cm/sec; P = 0.02). The branch pattern of the LGV was categorized into three groups: anterior branch dominant, posterior branch dominant, and no-dominant type. The incidence of the anterior branch dominant type was significantly less in responders (17 vs. 70 %; P = 0.01). There was no significant difference in the LGV trunk diameter and the size of the paraesophageal vein between the two groups.
CONCLUSION: Risk factors for recurrence can be analyzed in detail using color Doppler-EUS. Further investigation using color Doppler-EUS may enable us to select the optimal way to treat esophageal varices to prevent recurrence.

PMID 11571684  Endoscopy. 2001 Oct;33(10):869-72. doi: 10.1055/s-2001-・・・
著者: Goro Shibukawa, Atsushi Irisawa, Ayako Saito, Atsushi Takahashi, Hiroshi Sato, Tadayuki Takagi, Go Yamamoto, Takuto Hikichi, Hitoshi Oyama, Naoto Sato, Takashi Sugino, Toshimitsu Suzuki, Katsutoshi Obara, Yukio Sato
雑誌名: Hepatogastroenterology. 2004 May-Jun;51(57):744-7.
Abstract/Text BACKGROUND/AIMS: The perforating veins as a lateral blood supply route for esophageal varices in lower esophagus are associated with the recurrence of esophageal varices after sclerotherapy, but not vessels at the esophagogastric junction as an ascending blood supply route. To date, however, frequency of association perforating veins alone with variceal recurrence has not been investigated. To clarify the influence of perforating veins alone on variceal recurrence after endoscopic injection sclerotherapy, we studied the prevalence of variceal recurrence in patients with perforating veins detected by endoscopic ultrasonography after treatment.
METHODOLOGY: Forty-two patients who underwent injection sclerotherapy and received endoscopic ultrasonography after treatment to evaluate the effect on the collaterals around the esophagus, were studied. Subjects were classified in four groups according to endosonographic findings as follows: group A: perforating veins (+) and vessels at esophagogastric junction (+), group B: perforating veins (+) and vessels at esophagogastric junction (-), group C: perforating veins (-) and vessels at esophagogastric junction (+), group D: perforating veins (-) and vessels at esophagogastric junction (-).
RESULTS: Variceal recurrence was observed in 60% (6/10) of patients in group A, 64.3% (9/14) of patients in group B, 33.3% (1/3) of patients in group C, 0% (0/15) of patients in group D, respectively. The prevalence of variceal recurrence was compared between the 4 groups. No significant difference between group A or C and B was noted, and there was a significant difference between group A or B and D.
CONCLUSIONS: These results suggested that perforating veins are highly associated with variceal recurrence after sclerotherapy even if perforating veins are independent.

PMID 15143906  Hepatogastroenterology. 2004 May-Jun;51(57):744-7.

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