Tadashi Iwao

Echo‐Doppler measurements of portal vein and superior mesenteric artery blood flow in humans: Inter‐ and intra‐observer short‐term reproducibility

The reproducibility of echo‐Doppler measurements of portal vein and superior mesenteric artery blood flow has not been extensively studied. In the present study, two groups of subjects were examined to test inter‐ and intra‐observer reproducibility. Each study population consisted of 15 non‐portal hypertensive and 15 portal hypertensive subjects. With a standardized technique, the cross‐sectional area and velocity of blood flow in the portal vein and superior mesenteric artery were recorded in triplicate by skilled operators. The flow volume of each vessel was calculated by multiplying the cross‐sectional area by the velocity of blood flow. The measurements were performed in a blind fashion over a 60 min period. The reproducibility of measurements was assessed by calculation of intraclass correlation coefficients and coefficients of variation. The intra‐observer intraclass correlation coefficient was 0.77 for portal vein blood flow and 0.84 for superior mesenteric artery blood flow, suggesting good reproducibility. The intra‐observer coefficient of variation was 11 and 9%, respectively. In contrast, the interobserver intraclass correlation coefficient was calculated to be 0.49 for portal blood vein blood flow and 0.57 for superior mesenteric artery blood flow, indicating fair reproducibility. In addition, the interobserver coefficients of variation were calculted to be 20 and 18%, respectively. These data suggest that intra‐observer reproducibility in echo‐Doppler measurements of portal vein and superior mesenteric artery blood flow is acceptable but inter‐observer reproducibility is not. Examination by a single operator, rather than multiple operators, is therefore advisable. Even when measurements are performed by a single investigator an approximate variance of 10% in the measurement in a single subject should be expected.

LIGATION PLUS LOW-VOLUME SCLEROTHERAPY FOR HIGH-RISK ESOPHAGEAL VARICES : COMPARISONS WITH LIGATION THERAPY OR SCLEROTHERAPY ALONE

Abstract: Endoscopic variceal ligation therapy (EVL) seems to be a more effective and safer method than endoscopic injection variceal sclerotherapy (EVS) for treating bleeding esophageal varices. However, EVL may entail a higher recurrence rate than EVS. The aim of this study was to examine whether EVL combined with low-dose EVS reduced the recurrence rate compared to treatment with EVL alone and reduced the complication rate compared to treatment with EVS alone. In this prospective study, 59 patients with cirrhosis and high-risk (F2 or F3, red color sign ++ or +++) esophageal varices were enrolled. They were randomly assigned to an EVS group (n = 18), an EVL group (n = 20), and a combination EVL plus low-dose EVS group (n = 21). After the eradication of varices, follow-up endoscopic examinations were carried out for 24 months to determine the recurrence of varices. Complications, e.g., severe dysphagia, fever, renal dysfunction and pleuritis were also evaluated. The recurrence-free rate was significantly lower in the EVL group (60% at 24 months) than in either the EVS group (90%, P < 0.05) or the combination group (88%, P < 0.05). However, no significant difference was found between the EVS group and the combination group. The complication rate was significantly higher in the EVS group (50%) than in either the EVL group (5%, P < 0.01) or the combination group (10%, P < 0.01). The combination therapy seems to be useful to improve the benefits achieved with EVL alone and to reduce the harmful effects induced by EVS alone. EVL plus low-volume EVS is advisable in the treatment of high-risk esophageal varices.

Portal-hypertensive gastropathy develops less in patients with cirrhosis and fundal varices

BACKGROUND/AIMS The aim of this prospective study was to examine the association of portal-hypertensive gastropathy and fundal varices in patients with cirrhosis. METHODS We carried out an endoscopic observation in 476 patients with cirrhosis (study 1), including 62 patients undergoing endoscopic obliteration of esophageal varices (study 2). In study 1, patients were classified into five subgroups: no esophagofundal varices (n=119), small esophagofundal varices (n=127), dominant esophageal varices (n=177), dominant fundal varices (n=27), and large esophagofundal varices (n=26). The severity of liver dysfunction was assessed by Pugh-Child classification: class A (n=222), class B (n=200), and class C (n=54). In study 2, two groups, poorly developed fundal varices (n=50) and well developed fundal (n=12), were distinguished and the follow-up endoscopic examinations were performed on the basis of 3-month intervals for 2 years. In each study, the severity of portal-hypertensive gastropathy was scored: 0 (absent), 1 (mild), 2 (severe), and 3 (bleeding). RESULTS Study 1: One-way ANOVA showed that both variceal pattern and Pugh-Child class significantly influenced portal-hypertensive gastropathy score. However, two-way ANOVA indicated that variceal pattern was the only significant variable. Portal-hypertensive gastropathy score was significantly higher in patients with dominant esophageal varices than in either patients with no esophagofundal varices or patients with small esophagofundal varices. In contrast, portal-hypertensive gastropathy score in patients with dominant fundal varices was similar to that in patients with no esophagofundal varices and was significantly lower compared with that in patients with dominant esophageal varices. Furthermore, portal-hypertensive gastropathy score was significantly lower in patients with large esophagofundal varices than in patients with dominant esophageal varices. Study 2: After the obliteration of esophageal varices, portal-hypertensive gastropathy score in patients with poorly developed fundal varices became significantly higher at 3-, 6-, 9-months while it was not modified in patients with well developed fundal varices during the follow-up period. Furthermore, the integrated incremental change in portal-hypertensive gastropathy score during the first 1-year follow-up period was significantly lower in patients with well developed fundal varices than in patients with poorly developed fundal varices. CONCLUSIONS These results indicate that both spontaneous and obliteration-induced portal-hypertensive gastropathy lesions develop less in patients with cirrhosis and fundal varices.

Portal‐hypertensive gastropathy

In the present article we describe updated information concerning the clinical feature of portal‐hypertensive gastropathy (PHG), which is characterized by mucosal and submucosal vascular dilatation without inflammation. Although this lesion represents non‐variceal bleeding, there is a wide variation of its prevalence. Portal pressure and some humoral factors may play important roles in its pathogenesis. Gastric acid secretory activity is reduced, whereas the gastric mucosal barrier is impaired. With regard to gastric mucosal haemodynamics, whether ‘overflow’ (i.e. active congestion) or ‘stasis’ (i.e. passive congestion) cause gastric mucosal hyperaemia is not known. A severe lesion is a potential source of bleeding, while mild lesions are of little clinical significance and endoscopic variceal obliteration aggravates PHG in some patients. In the treatment of PHG, pharmacological (e.g. propranolol), surgical (e.g. portosystemic shunt) and radiological (e.g. transjugular intrahepatic portosystemic shunt) procedures may be useful in preventing bleeding from PHG.

Effect of posture-induced blood volume expansion on systemic and regional hemodynamics in patients with cirrhosis

BACKGROUND/AIMS This study aimed to investigate the effects of posture-induced blood volume expansion on systemic and regional hemodynamics in patients with cirrhosis. METHODS The mean arterial pressure, cardiac index, peripheral vascular resistance index, and flow volume index of the superior mesenteric artery (SMA) and femoral artery (FA) were measured in 10 patients with cirrhosis and portal hypertension and 10 controls after they had been standing for 2 h. Plasma atrial natriuretic peptide, plasma renin activity, and plasma glucagon levels were also determined. These measurements were repeated after 30 min and 60 min when the patients were recumbent. RESULTS In the upright posture, systemic hemodynamics, FA blood flow index, plasma atrial natriuretic peptide level, and plasma renin activity level were similar in patients and controls. However, SMA blood flow index and plasma glucagon level were significantly higher in patients than in controls. On the assumption of the supine position, cardiac index and plasma atrial natriuretic peptide level significantly increased in the two groups, but the changes were greater in patients than in controls. Mean arterial pressure remained unchanged. The reduction in peripheral vascular resistance index was therefore greater in patients in controls. SMA and FA blood flow index increased significantly in the two groups, but the changes were greater in patients than in controls. Furthermore, SMA blood flow fraction (SMA blood flow index/cardiac index) was steady in controls, whereas it increased significantly in patients. In contrast, FA blood flow fraction (FA blood flow index/cardiac index) remained unchanged in the two groups. In patients, the change in peripheral vascular resistance index was correlated inversely with that of SMA blood flow index, but not with that of FA blood flow index. Plasma renin activity level dropped significantly, but the decline was similar in the two groups. Plasma glucagon level was not modified in either group. CONCLUSIONS In patients with cirrhosis, splanchnic vasodilation appears to be present, even in the upright position, and further abnormal vasodilation occurs on recumbency-induced blood volume expansion. This abnormal shear-stress phenomenon observed in the splanchnic circulation seems to be mediated by a local vasodilator rather than a general vasodilator.

Gastric mucosal blood flow after smoking in healthy human beings assessed by laser Doppler flowmetry

We measured regional gastric mucosal blood flow by laser Doppler flowmetry before and after control (n = 8) or cigarette smoking (n = 8) in healthy human beings. The control group showed no change in both antrum (from 1.15 +/- 0.32 to 1.20 +/- 0.39 V, NS) and corpus gastric mucosal blood flow (from 1.15 +/- 0.32 to 1.12 +/- 0.28 V, NS). In contrast, cigarette smoking caused a significant reduction in gastric mucosal blood flow in the antrum (from 1.08 +/- 0.31 to 0.71 +/- 0.22 V, p < 0.01) and in the corpus (from 0.99 +/- 0.26 to 0.66 +/- 0.24 V, p < 0.01). The magnitude of reduction in gastric mucosal blood flow was similar between the antrum and the corpus (-34% +/- 11% versus -33% +/- 15%, NS). We conclude that cigarette smoking induces a significant reduction in gastric mucosal blood flow and that no heterogeneous response occurs in regional gastric mucosa. In addition, the laser Doppler flowmeter appears to be a sensitive method to assess rapid change in gastric mucosal blood flow in human beings.

Effect of vasopressin on esophageal varices blood flow in patients with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow

BACKGROUND/AIMS Vasopressin reduces portal pressure which may be due to decreased portal inflow. However, it remains unclear whether vasopressin is able to selectively reduce esophageal varices blood flow. The aim of this study was to address this question. METHODS Fifteen patients with cirrhosis and esophageal varices were included in this prospective study. Portal vein and superior mesenteric artery flow velocity were measured with a percutaneous echo-Doppler. Esophageal varices flow velocity was measured using a transesophageal echo-Doppler technique. Mean arterial pressure and heart rate were also recorded. These measurements were performed at baseline condition and 15 min after observer blind drug administration. In this study, two groups, six patients receiving placebo and nine patients receiving 0.3 U/min of vasopressin, were randomized according to the coded number. RESULTS Placebo administration had no effect on systemic and splanchnic circulation. In contrast, vasopressin administration increased mean arterial pressure (p < 0.05) associated with a bradycardia (p < 0.01). In splanchnic circulation, vasopressin decreased portal vein (-32 +/- 3%, p < 0.01), superior mesenteric artery (-30 +/- 2%, p < 0.01), and esophageal varices flow velocity (-48 +/- 5%, p < 0.01). When the magnitude of these reductions was compared, ANOVA showed a significant difference (p < 0.01). Furthermore, the reduction in esophageal varices flow velocity was significantly higher than that in portal vein flow velocity (p < 0.01) and that in superior mesenteric artery flow velocity (p < 0.01). CONCLUSIONS These data support the view that vasopressin is able to selectively reduce esophageal varices blood flow. This effect, in addition to its well-established portal pressure reducing action, may play a role in its therapeutic efficacy in the treatment of variceal bleeding.

Arterial oxygen desaturation during non-sedated diagnostic upper gastrointestinal endoscopy

We studied oxygen saturation (SaO2) using a pulse oximeter in 120 patients undergoing non-sedated diagnostic upper gastrointestinal endoscopy. The baseline SaO2 was 98.3 +/- 1.0%. During the procedure, absence of oxygen desaturation (SaO2 > or = 95%) was found in 56%, mild oxygen desaturation (95% > SaO2 > or = 90%) in 35%, and severe oxygen desaturation (SaO2 < 90%) in 9%. Age (p = 0.56), gender (p = 0.47), smoking (p = 0.35), hemoglobin level (p = 0.52), body mass index (p = 0.27), or total endoscopy time (p = 0.72) was not related to the degree of oxygen desaturation. These results suggest that oxygen desaturation is frequently observed during non-sedated diagnostic upper gastrointestinal endoscopy although severe oxygen desaturation, which may induce rare but serious cardiopulmonary events, is not common. Furthermore, we cannot predict in which patients desaturation will occur. We therefore recommend continuous monitoring of arterial oxygenation in all patients during the procedure.

Gastric red spots in patients with cirrhosis: Subclinical condition of gastric mucosal hemorrhage?

SummaryThe present study was intended to assess the incidence and the nature of gastric red spots (GRS) in patients with liver cirrhosis. Endoscopically, GRS was more frequently observed in patients with cirrhosis (n = 146) than those without cirrhosis (n = 103) (43.2% vs. 4.8%; P< 0.001). There was no relationship between the incidence of GRS and the severity of cirrhosis or the size of varices. Portal venous pressure was higher in cirrhotics with GRS (n=21) than those without GRS (n=25) (33.7±6.0 mmHg vs. 28.2±4.8 mmHg; P<0.001). Morphometric analysis using the biopsied specimens was made in 16 cirrhotics with GRS, 12 cirrhotics without GRS, and 15 non-cirrhotics. The capillary bed occupation ratio (vascular area/mucosal area) was higher in cirrhotics with GRS (9.3±4.0%) than those without GRS 84.1 ±1.1%) or the non-cirrhotics (3.4±9.8%) (P< 0.005, P< 0.005), while there was no significant differences in the number of capillaries per unit area. Infiltrating inflammatory cell count was similar among the three groups. Extravascular red blood cell count per unit area was higher in cirrhotics with GRS (29.7±31.4) than those without GRS (5.4±5.1) or non-cirrhotics (5.4±6.3) (P< 0.05, P< 0.01). Furthermore, extravasation of red blood cells through defective portion of the endothelium and interposition of red blood cells in interepithelial spaces were observed electron microscopically in cirrhotics with GRS. These results indicate that (a) the nature of GRS in cirrhotics is preexistential capillary ectasia with intramucosal hemorrhage which is caused by high portal pressure and (b) the GRS in cirrhotics might be a subclinical condition of gastric mucosal hemorrhage.

Portal pressure after prophylactic sclerotherapy in patients with high-risk varices

Portal hemodynamics and transhepatic portal venographic findings were studied before and after prophylactic sclerotherapy (mean duration = 40 +/- 14 days) in 16 patients with high-risk esophageal varices. Portal pressure, evaluated by the portal venous pressure gradient, increased by a mean of 21% in eight patients (50%) and decreased by a mean of 20% in eight patients (50%) with no statistically significant change overall. The two groups were further analyzed separately to identify the mechanism of the change in portal pressure. Intrahepatic vascular resistance did not change significantly in either group. However, the prevalence of extravariceal portosystemic shunts was greater in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 25%, p < 0.05). Further, the enlargement of extravariceal portosystemic shunts was more marked in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 0%, p < 0.01). In addition, liver function, assessed by intrinsic clearance, was not modified in the two groups. We conclude that prophylactic sclerotherapy increases or decreases portal pressure without modifying liver function. Although the mechanism of these portal pressure changes is not clear, intrahepatic vascular resistance does not play an important role and the presence of extravariceal portosystemic shunts may prevent further increases in portal pressure.