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Endosonography as a predictive tool for first oesophagogastric variceal bleeding
Arab Journal of Gastroenterology 11 (2010) 149–152
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Endosonography as a predictive tool for first oesophagogastric variceal bleeding Hussein Hassan Okasha a,*, Fardous Ramadan b, Mohamed El-Saadany b, Moammar Al-Rabat b, Mazen Ibrahim Naga a, Ahmed El-Badri a, Ayman Fouda a, Ahmed Murad Hashem a a b
Internal Medicine and Gastroenterology Department, Cairo University, Cairo, Egypt Internal Medicine Department, Mansoura University, Mansoura, Egypt
a r t i c l e
i n f o
Article history: Received 13 February 2010 Accepted 12 July 2010
Keywords: Endosonography Liver cirrhosis Variceal bleeding
a b s t r a c t Background and study aims: Endosonography (EUS) is a useful tool for evaluating the fine details of the vascular structures at the gastroesophageal junction. The aim of this study is to evaluate the value of extraluminal gastroesophageal vascular collaterals as predictors for first variceal bleeding. Patients and methods: Fifty cirrhotic patients with no history of previous upper gastrointestinal (GI) bleeding were recruited into this prospective cohort study. All patients were subjected to upper endoscopy and EUS for assessing the number and size of extramural vascular collaterals and perforating vessels. All patients were followed up for 24 ± 7.5 months for upper gastrointestinal bleeding. Results: Eighteen out of 50 patients (36%) had at least one attack of upper GI bleeding during the follow up period. All patients had one or more types of extraluminal venous collaterals. The presence of gastric varices (p = 0.02), perigastric collaterals (p = 0.03) and perforators (p = 0.02) were independent risk factors for first variceal bleeding. The presence of 3 or more paraoesophageal collaterals and the presence of perforators were significantly higher in bleeders when compared to non-bleeders (p = 0.034). Perigastric and paragastric collateral sizes were significantly larger in bleeders than in non-bleeders (p = 0.019 and 0.038, respectively). Perigastric and paragastric collaterals of size more than or equal to 2 mm and 6.20 mm, respectively were associated with significantly increased risk of first variceal bleeding. Conclusion: EUS may be a promising tool for predicting first variceal bleeding in cirrhotic patients. Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction At least 80–90% of cirrhotic patients develop varices during their life time as evidenced during follow up endoscopic assessment. About 30–40% of patients with oesophagogastric varices develop upper gastrointestinal (GI) bleeding and the mortality rate from the first attack of variceal haemorrhage remains high (20– 35%) [1]. Preventing first variceal haemorrhage offers the chance of reducing mortality, morbidity and associated health care costs [2]. Endosonography (EUS) has emerged as an accurate, non-invasive means of providing data in patients with portal hypertension. Dilated venous abnormalities outside the gut lumen, which cannot be diagnosed by endoscopy are readily visible by EUS. The technique is also useful in the prediction of the risk of variceal recurrence and, thus, in the prediction of the risk of rebleeding after endoscopic therapy which cannot be reliably predicted using * Corresponding author. Address: Internal Medicine and Gastroenterology, Cairo University, 1007 Kornish El-Nil, El-Malek El-Saleh, Cairo, Egypt. Tel.: +20 10 1000502; fax: +20 23 3366605. E-mail addresses: [email protected], [email protected] (H.H. Okasha).
endoscopy alone [3–6]. Thus, EUS may give a promising chance for the detection of predictors of upper gastrointestinal bleeding and thus justifying primary prophylaxis for patients with liver cirrhosis and oesophagogastric varices. The aim of this study was to evaluate the relationship between extraluminal vascular collaterals and first variceal bleeding and to highlight predictors of variceal bleeding. Patients and methods This study was approved by the local ethics committee. It is a prospective cohort study that was conducted on 50 patients having liver cirrhosis with oesophageal and/or gastric varices as documented by upper endoscopy with no history of upper gastrointestinal bleeding. All patients were subjected to full clinical assessment after taking their consent. Complete blood count, liver function tests, kidney function tests, hepatitis C virus (HCV) antibody and hepatitis B (HBV) surface were done. Child Pugh’s score and grade were estimated. Abdominal ultrasonography, oesophagogastroduodenoscopy (EGD) and EUS were done electively. Patients with portal vein thrombosis or hepatocellular carcinoma were excluded from our work.
1687-1979/$ - see front matter Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2010.07.011
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H.H. Okasha et al. / Arab Journal of Gastroenterology 11 (2010) 149–152
adventitial veins with luminal GEV were classified as perforating veins (Fig. 2). EUS was carried out by an independent endoscopist, who was blinded to the patients’ clinical data as well as to the results of the other examinations, especially EGD. Patients were observed for upper GI bleeding for a follow up period of 24 ± 7.5 months. According to the occurrence of upper GI bleeding the patients were subdivided into bleeders and nonbleeders. Bleeding patients were admitted to the hospital where urgent EGD was done once haemodynamic stability was achieved. Actively spurting varices were seen during endoscopy in 12 patients while in the other 6 patients blood was seen in the stomach with no other sources of upper GI bleeding. Cyanoacrylate injection and band ligation were used to control variceal bleeding. Four patients died during the follow up period, two patients died of hepatic encephalopathy and two patients died of hepatorenal syndrome. Fig. 1. Large isolated serpentine gastric varices.
Data management and statistical analysis According to the endoscopic picture, varices were classified into oesophageal and gastric varices which were further subdivided into isolated gastric varices and gastric extensions (Fig. 1). For the diagnosis of oesophageal varices, EGD was used as the gold standard. All patients were subjected to EUS examination using a radial scanning video echoendoscope; Olympus GF-UM-200 (Tokyo, Japan). During the echoendoscopic examination, the presence of oesophageal and gastric varices, extraluminal vascular collateral vessels and perforating collateral veins were determined. Since EUS proved to be more sensitive in detecting gastric varices compared with EGD, EUS was used as the gold standard for the diagnosis of gastric varices [7]. The extraluminal collateral vessels outside the oesophagus were classified as perioesophageal collateral veins (peri-ECV) if they were in direct contact with the muscularis propria (4th layer), or as paraoesophageal collateral veins (para-ECV) if they were located away from the muscularis propria layer [5]. Peri-ECVs were also classified as none, small (maximal diameter < 2 mm) or large (maximal diameter P 2 mm). Para-ECVs were classified as none, small (maximal diameter < 5 mm) or large (maximal diameter P 5 mm). Dilated veins outside the gastric wall were classified in a similar way as peri- and paragastric collateral veins (peri-GCV and para-GCV) according to their relationship with the muscularis propria. Venous channels joining extraluminal
The chi-square (v2) was used to find the association between row and column variables of qualitative data. Student t-test was used to compare the means of two groups. The One-Way ANOVA procedure produces a one-way analysis of variance for a quantitative dependent variable by a single factor (independent) variable. Correlation between the variables was done using Pearson correlation for parametric data. Logistic regression was used to predict the presence or absence of a characteristic outcome based on the values of a set of predictor variables. Results No statistical significant difference was found between the bleeding and the non-bleeding groups regarding Child-Pugh classification, while ascites and splenomegaly were present in the bleeding group more than in the non-bleeding group (Table 1). Concerning the aetiology of liver cirrhosis, we found that hepatitis C was more common than hepatitis B (80% versus 20% respectively). Oesophageal varices were present in all patients. While bleeding patients had more advanced grade of oesophageal varices, yet, this difference was not statistically significant. Gastric varices were significantly more in the bleeders and it is an independent risk for variceal bleeding (p-value = 0.02). Concerning the mean diameter of vascular collaterals, we found no significant difference between perioesophageal and paraoesophageal mean diameters in both groups, while perigastric and paragastric venous diameters were significantly larger in bleeders than in non-bleeders (Table 2). The presence of three or more paraoesophageal venous collaterals was significantly higher in bleeders compared to non-bleeders, this
Table 1 Clinical and laboratory data of studied patients. Number (%)
HBV HCV Child A B C Ascites Spleen Fig. 2. A perforating vein located in the region of the fundus by colour EUS.
*
p-Value
Odd’s ratio
8 (25) 24 (75)
0.621 0.621
– –
8 (25) 16 (50) 8 (25) 8 (25) 20 (62.5)
0.151
2.22 (0.79–6.22)
0.041* 0.035*
2.66 (1.01–7.0) 1.60 (1.09–2.33)
Bleeders (n = 18)
Non-bleeders (n = 32)
2 (11.1) 16 (88.9) – 8 (44.4) 10 (55.6) 12 (66.7) 18 (100)
Statistically significant (p < 0.05).
151
H.H. Okasha et al. / Arab Journal of Gastroenterology 11 (2010) 149–152 Table 2 Diameter of various gastroesophageal collateral venous channels in the bleeding versus the non-bleeding group. Diameter (mm)
Perioesophageal Paraoesophageal Perigastric Paragastric *
Mean ± SD
p-Value
Bleeders (n = 18)
Non-bleeders (n = 32)
3.06 ± 0.45 5.60 ± 1.72 6.21 ± 3.37 8.12 ± 4.21
2.69 ± 0.69 4.83 ± 1.23 2.92 ± 2.97 4.83 ± 3.19
Spleen Ascites Child C Grade 1 varices Grade 2 varices Grade 3 varices Grade 4 varices Gastric varices Perioesophageal varices Paraoesophageal varices Perigastric varices Paragastric varices Perforators
0.165 0.211 0.019* 0.038*
Statistically significant (p < 0.05).
Table 3 Value of number of gastroesophageal collateral venous channels in the bleeder versus the non-bleeder groups. Number of patients with P3 vascular collaterals
Perioesophageal Paraoesophageal Perigastric Paragastric *
Table 6 Binary logistic regression analysis of predictors of first variceal bleeding.
Bleeders (n = 18)
Non-bleeders (n = 32)
Number
%
Number
%
10 10 10 10
55.6 55.6 55.6 55.6
14 4 6 6
43.8 12.5 18.8 18.8
*
Score
Df
Significance
3.698 2.425 1.010 1.383 0.269 2.122 1.916 5.455 1.257 0.321 4.714 2.163 5.455
1 1 1 1 1 1 1 1 1 1 1 1 1
0.054 0.119 0.315 0.240 0.604 0.145 0.166 0.020* 0.262 0.571 0.030* 0.141 0.020*
Statistically significant (p < 0.05).
pValue
esophageal, paraoesophageal and paragastric collaterals was not statistically significant (Table 5). Regression analysis of combined clinical, endoscopic and endosonographic parameters for cirrhotic patients during the follow up period demonstrated that gastric varices, perigastric collaterals and perforators are independent predictors of first variceal bleeding (Table 6).
0.688 0.034* 0.163 0.154
Statistically significant (p < 0.05).
was not the case in perioesophageal, perigastric and paragastric veins (Table 3). Table 4 shows the significance and risk value of various gastroesophageal collateral venous channels as detected by EUS when their diameter exceeded the median size. Perigastric venous size > 4.45 mm in diameter was significantly higher in the bleeders versus the non-bleeders with a more than triple fold-increased ratio for bleeders. Paragastric venous size > 6.2 mm in diameter was significantly higher in the bleeder group versus the non-bleeder group with a more than double fold-increased ratio for bleeding, however, the perioesophageal and paraoesophageal median sizes did not reach statistical significance (Table 4). The presence of perforator veins was associated with a significant risk for bleeding. Table 5 shows the significance and risk value of various gastroesophageal collateral venous channels as detected by EUS when their diameters exceed the size proposed by Irisawa et al. [8]. Perigastric venous size P 2 mm in diameter was significantly higher in the bleeder group, while the difference in perio-
Discussion Despite the advent of effective drugs and endoscopic therapy for variceal bleeding, about a quarter of deaths occur very early after bleeding. This highlights the importance of primary prophylaxis to prevent first variceal haemorrhage in patients with liver cirrhosis [9,10]. Several prognostic indices based on clinical and endoscopic parameters have been developed to predict the risk of bleeding; however, their degree of accuracy is unsatisfactory [11]. Several studies have focused on EUS in studying portal haemodynamics and gastroesophageal collaterals because it is less invasive and provides high-resolution images of collaterals surrounding the lower oesophagus and the upper stomach [4–6,12]. For verifying the risk of first variceal bleeding in cirrhotic patients, many studies have been conducted over the years. Plevris et al. [13] found that serum bilirubin and platelet count were of significant value in predicting variceal bleeding. However, Kleber
Table 4 Significance of various gastroesophageal collateral venous channels. Bleeders (n = 18)
Perioesophageal (median > 3.3 mm) Paraoesophageal (median > 5.2 mm) Perigastric (median > 4.45 mm) Paragastric (median > 6.2 mm) Perforator *
Non-bleeders (n = 32)
Number
%
Number
%
10 10 12 14 10
55.6 55.6 75 77.8 55.6
10 14 6 12 4
31.3 43.8 21.4 37.5 12.5
p-Value
Odd’s ratio
0.397 0.688 0.014* 0.05* 0.048*
1.77 (0.7–4.51) 1.27 (0.56–2.84) 3.5* (1.18–10.3) 2.07 (1.00–4.27) 4.44* (1.07–18.42)
Statistically significant (p < 0.05).
Table 5 Significance of various gastroesophageal collateral venous channels when their diameter exceeded the size proposed by Irisawa et al. Bleeders (n = 18)
Perioesophageal P 2 mm Paraoesophageal P 5 mm Perigastric P 2 mm Paragastric P 5 mm *
Statistically significant (p < 0.05).
Non-bleeders (n = 32)
Number
%
Number
%
18 10 18 14
100 55.6 100 77.8
26 14 18 16
81.3 43.8 57.1 50
p-Value
Odd’s ratio
0.280 0.688 0.049* 0.229
1.23 (0.97–1.55) 1.270 (0.56–82.84) 1.750* (1.112–2.755) 1.556 (0.852–2.839)
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H.H. Okasha et al. / Arab Journal of Gastroenterology 11 (2010) 149–152
et al. [14] stated that platelet count was not significant in predicting variceal bleeding which is similar to our results. They also found that the presence of gastric varices in association with oesophageal varices raised the risk of bleeding by three times. Our study supports this fact, where the incidence of gastric varices was more significant in bleeders than in non-bleeders. This is also in agreement with Faigel et al. [7] where the incidence of gastric varices in bleeders was significantly higher. In our study, we tested the hypothesis that the use of EUS could improve the accuracy of prediction of first variceal haemorrhage by studying the periand paraoesophagogastric collaterals. Many studies used endoscopic ultrasound to assess the recurrence of oesophagogastric collaterals [15–18]. We found that perigastric and paragastric collateral size were significantly larger in bleeders than in nonbleeders. Perigastric variceal collaterals of size P 2 mm showed high risk for bleeding in cirrhotic patients and when the collateral size is > 4.45 mm (median size), the risk value of bleeding increased much more than three and a half times. The size of paragastric variceal collaterals was not significantly different in both groups when their sizes are P5 mm, however, a size of >6.2 mm (median size) was associated with a double fold increased risk ratio of bleeding. Sato et al. [19], demonstrated that perforating veins were mostly afferent veins to oesophageal varices, this may explain the high risk value of perforating veins as predictor of first variceal bleeding. In our study, we found that perforators were significantly present in bleeder group than in non-bleeders. Irisawa et al. [20] reported that the perforating veins were detected more in patients with bleeding recurrent varices than in patients with non-recurrent varices, however this is not in concordance with Awadein et al. [21] who demonstrated no relationship between perforating veins and variceal bleeding. Although perioesophageal and paraoesophageal collaterals had larger diameters in bleeders when compared to non-bleeders, yet it did not reach a statistical significance. This is in agreement with Awadein et al. [21], who found the mean diameters of the different extramural collateral veins were greater in those patients with prior variceal bleeding than in those without, yet this difference did not reach statistical significance probably due to the rather small sample size as they proposed. In our study, the detection of 3 or more paraoesophageal collaterals was associated with the risk of bleeding and this is in agreement with Dhiman et al. [15] who found that paraoesophageal collaterals’ number and size were significantly associated with variceal bleeding. In our work, binary logistic regression analysis revealed that perigastric collateral vessels and perforators in addition to the presence of gastric varices were the only independent risk factors for first variceal bleeding. We recommend more prospective studies on large number of patients with longer follow up periods for more evaluation of extraluminal varices as predictors of variceal bleeding. Also, for more evaluation of the cutoff point of variceal sizes, we recommend studying larger number of patients to verify the value of this cutoff point that might justify prophylactic interventional therapies for non-bleeding varices of cirrhotic patients.
Conflicts of interest The authors declared that there was no conflict of interest. References [1] Jensen DM. Endoscopic screening for varices in cirrhosis: Findings, implications and outcomes. Gastroenterology 2002;122(6):1620–30. [2] Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 1997;92(7):1081–91. [3] Sgouros SN, Bergele C, Avgerinos A. Endoscopic ultrasonography in the diagnosis and management of portal hypertension. Where are we next? Dig Liver Dis 2006;38(5):289–95. [4] Kassem AM, Salama ZA, Zakaria MS, Hassaballah M, Hunter MS. Endosonography and Doppler endosonography of the azygos vein following sclerotherapy of oesophageal varices. Digestion 1998;59(Suppl. 3):339. [5] Salama ZA, Hassaballah M, Kassem AM, Zakaria MS, Hunter MS. The role of endosonography in prediction of variceal bleeding. Endoscopy 2000;32(Suppl. 1):E57. [6] Kassem AM, Salama ZA, Zakaria MS, Hassaballah M, Hunter MS. Endoscopic ultrasonographic study of the azygos vein before and after obliteration of esophagogastric varices by injection sclerotherapy. Endoscopy 2000;32:630–4. [7] Faigel DO, Rosen HR, Sasaki A, et al. EUS in cirrhotic patients with and without prior variceal hemorrhage in comparison with noncirrhotic control subjects. Gastrointest Endosc 2000;52(4):455–62. [8] Irisawa A, Obara K, Sato Y, et al. EUS analysis of collateral veins inside and outside the esophageal wall in portal hypertension. Gastrointest Endosc 1999;50(3):374–80. [9] Nidegger D, Ragot S, Berthelemy P, et al. Cirrhosis and bleeding: the need for very early management. J Hepatol 2003;39(4):509–14. [10] Lay CS, Tsai YT, Lee FY, et al. Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis. J Gastroenterol Hepatol 2006;21(2):413–9. [11] De Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis 2001;5(3):645–63. [12] Kakutani H, Hino S, Ikeda K, et al. Prediction of recurrence of esophageal varices – special reference to a role for endoscopic ultrasonography. Hepatol Res 2005;33(4):259–66. [13] Plevris JN, Dhariwal A, Elton RA, et al. The platelet count as a predictor of variceal hemorrhage in primary biliary cirrhosis. Am J Gastroenterol 1995;90(6):959–61. [14] Kleber G, Sauerbruch T, Ansari H, et al. Prediction of variceal hemorrhage in cirrhosis: a prospective follow-up study. Gastroenterology 1991;100(5 Pt 1):1332–7. [15] Dhiman RK, Choudhuri G, Saraswat VA, et al. Role of paraoesophageal collaterals and perforating veins on outcome of endoscopic sclerotherapy for esophageal varices: an endosonographic study. Gut 1996;38(5):759–64. [16] Leung VK, Sung JJ, Ahuja AT, et al. Large paraesophageal varices on endosonography predict recurrence of esophageal varices and rebleeding. Gastroenterology 1997;112(6):1811–6. [17] Konishi Y, Nakamura T, Kida H, et al. Catheter US probe EUS evaluation of gastric cardia and perigastric vascular structures to predict esophageal variceal recurrence. Gastrointest Endosc 2002;55(2):197–203. [18] Irisawa A, Obara K, Bhutani MS, et al. Role of para-esophageal collateral veins in patients with portal hypertension based on the results of endoscopic ultrasonography and liver scintigraphy analysis. J Gastroenterol Hepatol 2003;18(3):309–14. [19] Sato T, Yamazaki K, Toyota J, et al. Perforating veins in recurrent esophageal varices evaluated by endoscopic color Doppler ultrasonography with a galactose-based contrast agent. J Gastroenterol 2004;39(5):422–8. [20] Irisawa A, Saito A, Obara K, et al. Endoscopic recurrence of esophageal varices is associated with the specific EUS abnormalities: Severe periesophageal collateral veins and large perforating veins. Gastrointest Endosc 2001;53(1):77–84. [21] Awadein M, Okasha H, El Gendy D, et al. Diagnosis of gastroesophageal varices and portal venous collaterals in cirrhotic patients. Egypt J Internal Med 2005;17(2):297–305.
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Endosonography as a predictive tool for first oesophagogastric variceal bleeding Hussein Hassan Okasha a,*, Fardous Ramadan b, Mohamed El-Saadany b, Moammar Al-Rabat b, Mazen Ibrahim Naga a, Ahmed El-Badri a, Ayman Fouda a, Ahmed Murad Hashem a a b
Internal Medicine and Gastroenterology Department, Cairo University, Cairo, Egypt Internal Medicine Department, Mansoura University, Mansoura, Egypt
a r t i c l e
i n f o
Article history: Received 13 February 2010 Accepted 12 July 2010
Keywords: Endosonography Liver cirrhosis Variceal bleeding
a b s t r a c t Background and study aims: Endosonography (EUS) is a useful tool for evaluating the fine details of the vascular structures at the gastroesophageal junction. The aim of this study is to evaluate the value of extraluminal gastroesophageal vascular collaterals as predictors for first variceal bleeding. Patients and methods: Fifty cirrhotic patients with no history of previous upper gastrointestinal (GI) bleeding were recruited into this prospective cohort study. All patients were subjected to upper endoscopy and EUS for assessing the number and size of extramural vascular collaterals and perforating vessels. All patients were followed up for 24 ± 7.5 months for upper gastrointestinal bleeding. Results: Eighteen out of 50 patients (36%) had at least one attack of upper GI bleeding during the follow up period. All patients had one or more types of extraluminal venous collaterals. The presence of gastric varices (p = 0.02), perigastric collaterals (p = 0.03) and perforators (p = 0.02) were independent risk factors for first variceal bleeding. The presence of 3 or more paraoesophageal collaterals and the presence of perforators were significantly higher in bleeders when compared to non-bleeders (p = 0.034). Perigastric and paragastric collateral sizes were significantly larger in bleeders than in non-bleeders (p = 0.019 and 0.038, respectively). Perigastric and paragastric collaterals of size more than or equal to 2 mm and 6.20 mm, respectively were associated with significantly increased risk of first variceal bleeding. Conclusion: EUS may be a promising tool for predicting first variceal bleeding in cirrhotic patients. Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction At least 80–90% of cirrhotic patients develop varices during their life time as evidenced during follow up endoscopic assessment. About 30–40% of patients with oesophagogastric varices develop upper gastrointestinal (GI) bleeding and the mortality rate from the first attack of variceal haemorrhage remains high (20– 35%) [1]. Preventing first variceal haemorrhage offers the chance of reducing mortality, morbidity and associated health care costs [2]. Endosonography (EUS) has emerged as an accurate, non-invasive means of providing data in patients with portal hypertension. Dilated venous abnormalities outside the gut lumen, which cannot be diagnosed by endoscopy are readily visible by EUS. The technique is also useful in the prediction of the risk of variceal recurrence and, thus, in the prediction of the risk of rebleeding after endoscopic therapy which cannot be reliably predicted using * Corresponding author. Address: Internal Medicine and Gastroenterology, Cairo University, 1007 Kornish El-Nil, El-Malek El-Saleh, Cairo, Egypt. Tel.: +20 10 1000502; fax: +20 23 3366605. E-mail addresses: [email protected], [email protected] (H.H. Okasha).
endoscopy alone [3–6]. Thus, EUS may give a promising chance for the detection of predictors of upper gastrointestinal bleeding and thus justifying primary prophylaxis for patients with liver cirrhosis and oesophagogastric varices. The aim of this study was to evaluate the relationship between extraluminal vascular collaterals and first variceal bleeding and to highlight predictors of variceal bleeding. Patients and methods This study was approved by the local ethics committee. It is a prospective cohort study that was conducted on 50 patients having liver cirrhosis with oesophageal and/or gastric varices as documented by upper endoscopy with no history of upper gastrointestinal bleeding. All patients were subjected to full clinical assessment after taking their consent. Complete blood count, liver function tests, kidney function tests, hepatitis C virus (HCV) antibody and hepatitis B (HBV) surface were done. Child Pugh’s score and grade were estimated. Abdominal ultrasonography, oesophagogastroduodenoscopy (EGD) and EUS were done electively. Patients with portal vein thrombosis or hepatocellular carcinoma were excluded from our work.
1687-1979/$ - see front matter Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2010.07.011
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H.H. Okasha et al. / Arab Journal of Gastroenterology 11 (2010) 149–152
adventitial veins with luminal GEV were classified as perforating veins (Fig. 2). EUS was carried out by an independent endoscopist, who was blinded to the patients’ clinical data as well as to the results of the other examinations, especially EGD. Patients were observed for upper GI bleeding for a follow up period of 24 ± 7.5 months. According to the occurrence of upper GI bleeding the patients were subdivided into bleeders and nonbleeders. Bleeding patients were admitted to the hospital where urgent EGD was done once haemodynamic stability was achieved. Actively spurting varices were seen during endoscopy in 12 patients while in the other 6 patients blood was seen in the stomach with no other sources of upper GI bleeding. Cyanoacrylate injection and band ligation were used to control variceal bleeding. Four patients died during the follow up period, two patients died of hepatic encephalopathy and two patients died of hepatorenal syndrome. Fig. 1. Large isolated serpentine gastric varices.
Data management and statistical analysis According to the endoscopic picture, varices were classified into oesophageal and gastric varices which were further subdivided into isolated gastric varices and gastric extensions (Fig. 1). For the diagnosis of oesophageal varices, EGD was used as the gold standard. All patients were subjected to EUS examination using a radial scanning video echoendoscope; Olympus GF-UM-200 (Tokyo, Japan). During the echoendoscopic examination, the presence of oesophageal and gastric varices, extraluminal vascular collateral vessels and perforating collateral veins were determined. Since EUS proved to be more sensitive in detecting gastric varices compared with EGD, EUS was used as the gold standard for the diagnosis of gastric varices [7]. The extraluminal collateral vessels outside the oesophagus were classified as perioesophageal collateral veins (peri-ECV) if they were in direct contact with the muscularis propria (4th layer), or as paraoesophageal collateral veins (para-ECV) if they were located away from the muscularis propria layer [5]. Peri-ECVs were also classified as none, small (maximal diameter < 2 mm) or large (maximal diameter P 2 mm). Para-ECVs were classified as none, small (maximal diameter < 5 mm) or large (maximal diameter P 5 mm). Dilated veins outside the gastric wall were classified in a similar way as peri- and paragastric collateral veins (peri-GCV and para-GCV) according to their relationship with the muscularis propria. Venous channels joining extraluminal
The chi-square (v2) was used to find the association between row and column variables of qualitative data. Student t-test was used to compare the means of two groups. The One-Way ANOVA procedure produces a one-way analysis of variance for a quantitative dependent variable by a single factor (independent) variable. Correlation between the variables was done using Pearson correlation for parametric data. Logistic regression was used to predict the presence or absence of a characteristic outcome based on the values of a set of predictor variables. Results No statistical significant difference was found between the bleeding and the non-bleeding groups regarding Child-Pugh classification, while ascites and splenomegaly were present in the bleeding group more than in the non-bleeding group (Table 1). Concerning the aetiology of liver cirrhosis, we found that hepatitis C was more common than hepatitis B (80% versus 20% respectively). Oesophageal varices were present in all patients. While bleeding patients had more advanced grade of oesophageal varices, yet, this difference was not statistically significant. Gastric varices were significantly more in the bleeders and it is an independent risk for variceal bleeding (p-value = 0.02). Concerning the mean diameter of vascular collaterals, we found no significant difference between perioesophageal and paraoesophageal mean diameters in both groups, while perigastric and paragastric venous diameters were significantly larger in bleeders than in non-bleeders (Table 2). The presence of three or more paraoesophageal venous collaterals was significantly higher in bleeders compared to non-bleeders, this
Table 1 Clinical and laboratory data of studied patients. Number (%)
HBV HCV Child A B C Ascites Spleen Fig. 2. A perforating vein located in the region of the fundus by colour EUS.
*
p-Value
Odd’s ratio
8 (25) 24 (75)
0.621 0.621
– –
8 (25) 16 (50) 8 (25) 8 (25) 20 (62.5)
0.151
2.22 (0.79–6.22)
0.041* 0.035*
2.66 (1.01–7.0) 1.60 (1.09–2.33)
Bleeders (n = 18)
Non-bleeders (n = 32)
2 (11.1) 16 (88.9) – 8 (44.4) 10 (55.6) 12 (66.7) 18 (100)
Statistically significant (p < 0.05).
151
H.H. Okasha et al. / Arab Journal of Gastroenterology 11 (2010) 149–152 Table 2 Diameter of various gastroesophageal collateral venous channels in the bleeding versus the non-bleeding group. Diameter (mm)
Perioesophageal Paraoesophageal Perigastric Paragastric *
Mean ± SD
p-Value
Bleeders (n = 18)
Non-bleeders (n = 32)
3.06 ± 0.45 5.60 ± 1.72 6.21 ± 3.37 8.12 ± 4.21
2.69 ± 0.69 4.83 ± 1.23 2.92 ± 2.97 4.83 ± 3.19
Spleen Ascites Child C Grade 1 varices Grade 2 varices Grade 3 varices Grade 4 varices Gastric varices Perioesophageal varices Paraoesophageal varices Perigastric varices Paragastric varices Perforators
0.165 0.211 0.019* 0.038*
Statistically significant (p < 0.05).
Table 3 Value of number of gastroesophageal collateral venous channels in the bleeder versus the non-bleeder groups. Number of patients with P3 vascular collaterals
Perioesophageal Paraoesophageal Perigastric Paragastric *
Table 6 Binary logistic regression analysis of predictors of first variceal bleeding.
Bleeders (n = 18)
Non-bleeders (n = 32)
Number
%
Number
%
10 10 10 10
55.6 55.6 55.6 55.6
14 4 6 6
43.8 12.5 18.8 18.8
*
Score
Df
Significance
3.698 2.425 1.010 1.383 0.269 2.122 1.916 5.455 1.257 0.321 4.714 2.163 5.455
1 1 1 1 1 1 1 1 1 1 1 1 1
0.054 0.119 0.315 0.240 0.604 0.145 0.166 0.020* 0.262 0.571 0.030* 0.141 0.020*
Statistically significant (p < 0.05).
pValue
esophageal, paraoesophageal and paragastric collaterals was not statistically significant (Table 5). Regression analysis of combined clinical, endoscopic and endosonographic parameters for cirrhotic patients during the follow up period demonstrated that gastric varices, perigastric collaterals and perforators are independent predictors of first variceal bleeding (Table 6).
0.688 0.034* 0.163 0.154
Statistically significant (p < 0.05).
was not the case in perioesophageal, perigastric and paragastric veins (Table 3). Table 4 shows the significance and risk value of various gastroesophageal collateral venous channels as detected by EUS when their diameter exceeded the median size. Perigastric venous size > 4.45 mm in diameter was significantly higher in the bleeders versus the non-bleeders with a more than triple fold-increased ratio for bleeders. Paragastric venous size > 6.2 mm in diameter was significantly higher in the bleeder group versus the non-bleeder group with a more than double fold-increased ratio for bleeding, however, the perioesophageal and paraoesophageal median sizes did not reach statistical significance (Table 4). The presence of perforator veins was associated with a significant risk for bleeding. Table 5 shows the significance and risk value of various gastroesophageal collateral venous channels as detected by EUS when their diameters exceed the size proposed by Irisawa et al. [8]. Perigastric venous size P 2 mm in diameter was significantly higher in the bleeder group, while the difference in perio-
Discussion Despite the advent of effective drugs and endoscopic therapy for variceal bleeding, about a quarter of deaths occur very early after bleeding. This highlights the importance of primary prophylaxis to prevent first variceal haemorrhage in patients with liver cirrhosis [9,10]. Several prognostic indices based on clinical and endoscopic parameters have been developed to predict the risk of bleeding; however, their degree of accuracy is unsatisfactory [11]. Several studies have focused on EUS in studying portal haemodynamics and gastroesophageal collaterals because it is less invasive and provides high-resolution images of collaterals surrounding the lower oesophagus and the upper stomach [4–6,12]. For verifying the risk of first variceal bleeding in cirrhotic patients, many studies have been conducted over the years. Plevris et al. [13] found that serum bilirubin and platelet count were of significant value in predicting variceal bleeding. However, Kleber
Table 4 Significance of various gastroesophageal collateral venous channels. Bleeders (n = 18)
Perioesophageal (median > 3.3 mm) Paraoesophageal (median > 5.2 mm) Perigastric (median > 4.45 mm) Paragastric (median > 6.2 mm) Perforator *
Non-bleeders (n = 32)
Number
%
Number
%
10 10 12 14 10
55.6 55.6 75 77.8 55.6
10 14 6 12 4
31.3 43.8 21.4 37.5 12.5
p-Value
Odd’s ratio
0.397 0.688 0.014* 0.05* 0.048*
1.77 (0.7–4.51) 1.27 (0.56–2.84) 3.5* (1.18–10.3) 2.07 (1.00–4.27) 4.44* (1.07–18.42)
Statistically significant (p < 0.05).
Table 5 Significance of various gastroesophageal collateral venous channels when their diameter exceeded the size proposed by Irisawa et al. Bleeders (n = 18)
Perioesophageal P 2 mm Paraoesophageal P 5 mm Perigastric P 2 mm Paragastric P 5 mm *
Statistically significant (p < 0.05).
Non-bleeders (n = 32)
Number
%
Number
%
18 10 18 14
100 55.6 100 77.8
26 14 18 16
81.3 43.8 57.1 50
p-Value
Odd’s ratio
0.280 0.688 0.049* 0.229
1.23 (0.97–1.55) 1.270 (0.56–82.84) 1.750* (1.112–2.755) 1.556 (0.852–2.839)
152
H.H. Okasha et al. / Arab Journal of Gastroenterology 11 (2010) 149–152
et al. [14] stated that platelet count was not significant in predicting variceal bleeding which is similar to our results. They also found that the presence of gastric varices in association with oesophageal varices raised the risk of bleeding by three times. Our study supports this fact, where the incidence of gastric varices was more significant in bleeders than in non-bleeders. This is also in agreement with Faigel et al. [7] where the incidence of gastric varices in bleeders was significantly higher. In our study, we tested the hypothesis that the use of EUS could improve the accuracy of prediction of first variceal haemorrhage by studying the periand paraoesophagogastric collaterals. Many studies used endoscopic ultrasound to assess the recurrence of oesophagogastric collaterals [15–18]. We found that perigastric and paragastric collateral size were significantly larger in bleeders than in nonbleeders. Perigastric variceal collaterals of size P 2 mm showed high risk for bleeding in cirrhotic patients and when the collateral size is > 4.45 mm (median size), the risk value of bleeding increased much more than three and a half times. The size of paragastric variceal collaterals was not significantly different in both groups when their sizes are P5 mm, however, a size of >6.2 mm (median size) was associated with a double fold increased risk ratio of bleeding. Sato et al. [19], demonstrated that perforating veins were mostly afferent veins to oesophageal varices, this may explain the high risk value of perforating veins as predictor of first variceal bleeding. In our study, we found that perforators were significantly present in bleeder group than in non-bleeders. Irisawa et al. [20] reported that the perforating veins were detected more in patients with bleeding recurrent varices than in patients with non-recurrent varices, however this is not in concordance with Awadein et al. [21] who demonstrated no relationship between perforating veins and variceal bleeding. Although perioesophageal and paraoesophageal collaterals had larger diameters in bleeders when compared to non-bleeders, yet it did not reach a statistical significance. This is in agreement with Awadein et al. [21], who found the mean diameters of the different extramural collateral veins were greater in those patients with prior variceal bleeding than in those without, yet this difference did not reach statistical significance probably due to the rather small sample size as they proposed. In our study, the detection of 3 or more paraoesophageal collaterals was associated with the risk of bleeding and this is in agreement with Dhiman et al. [15] who found that paraoesophageal collaterals’ number and size were significantly associated with variceal bleeding. In our work, binary logistic regression analysis revealed that perigastric collateral vessels and perforators in addition to the presence of gastric varices were the only independent risk factors for first variceal bleeding. We recommend more prospective studies on large number of patients with longer follow up periods for more evaluation of extraluminal varices as predictors of variceal bleeding. Also, for more evaluation of the cutoff point of variceal sizes, we recommend studying larger number of patients to verify the value of this cutoff point that might justify prophylactic interventional therapies for non-bleeding varices of cirrhotic patients.
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