Portal vein thrombosis in cirrhosis with variceal hemorrhage

Organized thrombus in the main trunk of the portal vein was encountered in 85 (6.5%) of 1300 patients with cirrhosis and variceal hemorrhage who underwent direct portacaval shunt (PCS). The thrombus was successfully removed with restoration of portal blood flow in all patients by phlebothrombectomy and balloon catheter extraction. Of the 85 patients, 65 were among 400 unselected patients who underwent emergency PCS (16%), and 20 were among 900 selected patients who underwent elective PCS (2%). All patients were closely followed for at least 5 years. Patients with portal vein thrombosis (PVT) had more advanced liver disease than those without PVT, reflected preoperatively in significantly higher (P < 0.01) incidences of ascites (75%), severe muscle wasting (52%), varices of very large size (94%), the hyperdynamic state (94%), severe hypersplenism with a platelet count of less than 50,000/mm3 (92%), and placement in Child's class C (52%). Side-to-side PCS reduced the portal vein-inferior vena cava pressure gradient to a mean of 23 mm saline solution in patients with PVT, similar to the marked pressure reduction obtained in patients without PVT. PCS promptly stopped variceal bleeding in all patients in the emergency PCS group. Permanent prevention of recurrent variceal bleeding was successful in 95% of patients with PVT and more than 99% of patients without PVT. Survival rates were similar in patients with and without PVT. In patients with PVT, survival rates at 30 days and 1, 5, 10, and 15 years following emergency PCS were 69%, 66%, 65%, 55%, and 51%, respectively, and following elective PCS were 95%, 90%, 70%, 65%, and 60%, respectively. Quality of life was similar in patients with and without PVT. Long-term PCS patency was demonstrated yearly in 93% of patients in the group with PVT and in 99.7% of patients without PVT. Other similarities after 5 years between patients with and without PVT, respectively, were the incidences of recurrent encephalopathy (9% vs. 8%), alcohol abstinence (61% vs. 64%), improved liver function (68% vs. 62% to 75%), and return to work (52% vs. 56% to 64%). It was concluded that in patients with cirrhosis and variceal hemorrhage it is almost always possible to remove portal vein thrombus by means of phlebothrombectomy and then perform a direct PCS with results similar to those achieved in the absence of PVT.     

Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding

BACKGROUND: Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS: Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS: Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS: As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.     

Circadian occurrence of variceal bleeding in patients with liver cirrhosis

Several clinical events have a rhythmicity over the 24 h period. We assessed the presence of periodic rhythm in the occurrence of haematemesis in patients with liver cirrhosis under different daylight regimens, namely during standard time and during daylight savings. Over a 48 month period there were 212 consecutive admissions of 118 cirrhotics with variceal bleeding. Complete data were available for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60 (33.1%) started with melaena. One hundred and two (56%) episodes occurred during daylight savings and 79 (44%) occurred during standard time. The cosinor test showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45 h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple component rhythmometry. The time peaks of onset of variceal haemorrhage did not change significantly during standard time and daylight savings. Patients with more than one haematemesis episode significantly bled over the same time interval. The present study confirms that over the 24 h period variceal bleeding in cirrhotic patients occurs with a predictable rhythmicity that does not seem to be under the control of the light-dark cycle. The finding of a chronorisk for variceal haemorrhage addresses specific questions for pathophysiological studies as well as for new treatment strategies.     

Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding. A prospective randomized study

BACKGROUND/AIMS: Long-term endoscopic injection sclerotherapy of oesophageal varices prevents rebleeding in patients with cirrhosis surviving an acute variceal bleeding episode. However, this treatment is associated with a substantial complication rate. Endoscopic band ligation is a newly developed technique in an attempt to provide a safer alternative. The aim of this study was to compare the efficacy and safety of injection sclerotherapy versus variceal ligation in the management of patients with cirrhosis after variceal haemorrhage. METHODS: Seventy-seven patients with cirrhosis who proved to have oesophageal variceal bleeding were studied. After initial control of haemorrhage by sclerotherapy, 40 of the patients were randomly assigned to sclerotherapy and 37 to ligation. Both procedures were performed under midazolam sedation at intervals of 7-14 days until all varices in the distal oesophagus were eradicated or were too small to receive further treatment. RESULTS: The eradication of varices required a lower mean number of sessions with ligation (3.7 +/- 1.9) than with sclerotherapy (5.8 +/- 2.7, p = 0.002). The mean duration of follow-up was similar in both groups (15.6 months +/- 7.3 and 15 +/- 7.4, respectively). The proportion of patients remaining free from recurrent bleeding against time was significantly higher in the ligation group as compared to the sclerotherapy group (chi 2 = 3.86, p = 0.05). Only 13 patients (35%) developed complications in the ligation group as compared to 24 (60%, p = 0.05) in the sclerotherapy group. The mortality rate was similar in both groups (20% and 21%, respectively). CONCLUSIONS: Variceal ligation is better than sclerotherapy in the long-term management of patients with cirrhosis after variceal haemorrhage which was initially controlled with sclerotherapy.     

Primary prophylaxis of variceal bleeding in cirrhosis: a cost-effectiveness analysis

BACKGROUND & AIMS: Prophylaxis against the first variceal bleeding has been proposed to reduce morbidity and mortality in cirrhotic patients. No previous information is available regarding the cost-effectiveness of prophylaxis. The aim of this study was to compare the cost-effectiveness of variceal bleeding prophylaxis with propranolol, sclerotherapy, and shunt surgery in cirrhotic patients stratified by bleeding risk. METHODS: A hypothetical cohort was stratified according to bleeding risk. The natural history of cirrhosis with esophageal varices was simulated using a Markov model. Transitional probabilities extracted from published studies and costs were obtained from our institution's billing department. Sensitivity analyses were performed for important variables. RESULTS: Propranolol results in cost savings ranging between $450 and $14,600 over a 5-year period. The extent of cost savings depended on the individual patient's bleeding risk. In addition, propranolol increased the quality-adjusted life expectancy by 0.1-0.4 years. Sclerotherapy was significantly less cost-effective than propranolol and had no advantage on quality of life. Shunt surgery was effective therapy for prevention of bleeding but decreased life expectancy and quality of life in some risk groups and was not cost-effective. CONCLUSIONS: Propranolol is the only cost-effective form of prophylactic therapy for preventing initial variceal bleeding in cirrhosis regardless of bleeding risk.     

Pharmacoangiography in experimental tumours. Evaluation of vasoactive drugs

Pharmacoangiography with four vasoactive drugs was performed in experimental renal and hepatic tumours in rats in order to compare their ability to demonstrate tumour vascularity. Three vasoconstrictors, angiotensin, norepinephrine and vasopressin, and one vasodilator, tolazoline, were tested, vasoconstrictors giving most diagnostic information and the difference in effect among these sometimes being small and probably dose-related. This diagnostic effect is based upon the primitive character of tumour vessels, being unable to react upon a vasoactive stimulus. Angiotensin turned out to be the superior drug which corresponds to clinical experiences of this drug.     

Therapy of acute variceal hemorrhage and spontaneous bacterial peritonitis in liver cirrhosis

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.     

Effects of endoscopic variceal ligation on oxygen transport and the arterial lactate levels in patients with cirrhosis

OBJECTIVE: Despite the increased cardiac output and oxygen delivery, an impaired oxygen uptake has been noted in patients with cirrhosis. We recently observed that endoscopic variceal ligation decreased the cardiac output due to a reduction in the cardiac preload. It is thus possible that a variceal ligation decreases the oxygen delivery and thereby negatively influences tissue oxygenation in patients receiving such treatment. We thus investigated the effects of variceal ligation on oxygen delivery, oxygen uptake, and the arterial lactate levels. METHODS: There were 22 patients with compensated cirrhosis and risky esophageal varices (Child's class A:B=13:9). Twelve patients underwent an endoscopic variceal ligation and 10 patients received gastroscopy as a control. The cardiac function, blood gas status, oxygen delivery, and arterial lactate concentration were also assessed before and after variceal ligation. The oxygen uptake was calculated by the Fick equation. RESULTS: Following variceal ligation, there was an immediate decrease in the cardiac output and oxygen delivery. The reduction in oxygen delivery was associated with a slight but significant increase in the arterial lactate concentration. The decreased oxygen delivery was also associated with a concomitant decrease in the oxygen uptake. In the control subjects, gastroscopy did not alter the systemic hemodynamics, arterial oxygen status, or arterial lactate levels. CONCLUSION: We found a significant decrease in the oxygen delivery in patients undergoing an endoscopic variceal ligation. Such deteriorated tissue oxygenation may be serious especially in patients with a low oxygen transport ability such as in patients with variceal hemorrhage with anemia. However, the clinical significance of these changes remains unclear and further studies are therefore warranted.     

Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis

BACKGROUND: There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS: Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.     

Postural changes in plasma renin activity and responses to vasoactive drugs in a case of Shy-Drager syndrome

A male aged 47 years with gross autonomic insufficiency as part of the Shy-Drager syndrome is described. He did not sweat normally when warmed, and his circulatory responses to mental arithmetic, the Valsalva manoeuvre, and head-up tilt were abnormal indicating severe sympathetic failure. During head-up tilt there was a rise in plasma renin activity and plasma aldosterone. It is argued that plasma renin activity is not dependent on sympathetic nervous activity and may be mediated by renal baroreceptors. These rises may help sustain the blood pressure in such patients during repeated head-up tilts. Infusions of L-noradrenaline and angiotension produced greater hypertension, and injections of isoprenaline greater hypotension than in controls. Although it is difficult to exclude the possibility that one factor in this may be hypersensitivity of receptors in blood vessel walls, the principal factor is likely to be the absence of those baroreflexes of which the efferent pathways are in the sympathetic nervous system.     

Can optimal acid suppression prevent rebleeding in peptic ulcer patients with a non-bleeding visible vessel: a preliminary report of a randomized comparative study

BACKGROUND/AIMS: The hypothesis that profound acid suppression might prevent clot lysis and thus benefit patients with a non-bleeding visible vessel has not been confirmed. Omeprazole can suppress gastric acid remarkably and may be beneficial for patients with peptic ulcer bleeding. METHODOLOGY: Fifty-two patients with a non-bleeding visible vessel at the ulcer base were enrolled and randomized into four groups (N = 13 in each group). In the cimetidine group, the patients received cimetidine 300 mg i.v. bolus followed by 300 mg i.v. every 6 hr during hospitalization. In the heater probe thermocoagulation + cimetidine group, the patients received heater probe thermocoagulation and cimetidine 300 mg i.v. bolus followed by 300 mg i.v. every 6 h during hospitalization. In the omeprazole q.d. group, the patients received omeprazole 40 mg i.v. bolus followed by 40 mg i.v. daily for two days. In the omeprazole q 12 h group, the patients received omeprazole 40 mg i.v. bolus followed by 40 mg i.v. every 12 h for two days. A 24 hr intragastric pH was recorded for every case. RESULTS: The mean 24 hr intragastric pH were higher in the omeprazole q.d. (mean 5.8) and the omeprazole q 12 h groups (mean 6.4) than in the cimetidine (mean 4.3) and the heater probe thermocoagulation + cimetidine groups (mean 4.9) (p < 0.05). Rebleeding occurred in 5, 2, 2 and 2 patients in the cimetidine, heater probe thermocoagulation + cimetidine, omeprazole q.d., and omeprazole q 12 h groups, respectively (p > 0.05). Volume of blood transfusion and number of days in hospital were not statistically different among the four groups. CONCLUSIONS: Omeprazole can remarkably suppress gastric acid when it is compared to that of the H2 receptor blocker. Patients with a non-bleeding visible vessel using omeprazole do not exhibit a decrease in the rebleeding rate as compared with those patients using cimetidine.     

Endoscopic variceal ligation in prophylaxis of first variceal bleeding in cirrhotic patients with high-risk esophageal varices

To determine the efficacy of endoscopic variceal ligation (EVL) in prophylaxis on the rate of first esophageal variceal bleeding, we conducted a prospective, randomized trial in 126 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. Life-table curves showed that prophylactic EVL significantly diminished the rate of variceal hemorrhage (12/62 [19%] vs. 38/64 [60%]; P = .0001) and overall mortality (17/62 [28%] vs. 37/64 [58%]; P = .0011). The 2-year cumulative bleeding rate was 19% (12/ 62) in the EVL group and 60% (38/64) in the control group. The 2-year cumulative mortality rate was 28% (17/62) in the EVL group and 58% (37/64) in the control group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed significantly lower mortality in the ligation group (P = .001). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. The lower risk in the EVL group was attributed to a rapid reduction of variceal size. Prophylactic EVL was more efficient in preventing first bleeding in patients with good condition (Child A) than in those with decompensated disease (Child B and C). We conclude that prophylactic EVL can decrease the incidence of first variceal bleeding and death over a period of 2 years in cirrhotic patients with high-risk esophageal varices.     

Maintenance antipsychotic drugs do prevent relapse: A reply to Tobias and MacDonald.

Responds to L. L. Tobias and M. L. MacDonald's (see record 1994-03715-001) questioning of the assumption that long-term administration of antipsychotic drugs prevents relapse in chronic psychotics. Tobias and MacDonald asserted that the conclusions of studies maintaining this assumption were not warranted because of methodological flaws in the research. The present authors argue that some of these criticisms are incorrect, while others are valid. The effects of these methodological sources of error, however, would have operated in the direction of increasing variability and thus decreasing the chances of finding a significant difference between the drug and placebo group. In fact there are 25 controlled studies, essentially all of which find that any antipsychotic drug prevents relapse. A total of 377 out of 1,884 patients on drugs relapsed (20%) in comparison to 705 out of 1,346 patients on placebo (52%). It is concluded that Tobias and MacDonald's evidence for the value of maintenance medicine was misstated and misleading. The present authors emphasize this conclusion in light of the widespread use of maintenance medicine with chronic schizophrenics. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurodevelopmental consequences of early exposure to phencyclidine and related drugs

In the early development of the central nervous system, stimulation of N-methyl-D-aspartate (NMDA) receptors may be critical for neuronal cell survival and differentiation, as well as the establishment of neural networks resulting from "experience-dependent plasticity." The trophic influence of NMDA receptor stimulation may be present only during a certain critical period of development. There are, therefore, major concerns associated with the administration of noncompetitive NMDA receptor antagonists (such as MK-801 [dizocilpine]) as neuroprotective and anticonvulsant agents to pregnant women, neonates, infants, and young children. Several studies showing disruptive effects of noncompetitive NMDA receptor antagonists on normal neurobehavioral development are reviewed in this article. This research has important public health implications because phencyclidine (PCP), a noncompetitive NMDA receptor antagonist, is a frequently-abused drug that may disrupt brain development in utero when abused by pregnant women. The article also reviews studies of neonatal blockade of the NMDA receptor complex in animals; studies that may lead to useful models of human neurodevelopmental disorders. These models may even mimic the relevant neurodevelopmental aspects of at least some forms of schizophrenia, especially the early developmental disconnection of circuits between the hippocampus and frontal cortex.