Endoscopic ligation with elastic bands in the prevention of hemorrhage recurrence caused by esophageal varices. Study of 45 patients

The aim of the present study was to determine the usefulness of elastic band ligation in the prevention of hemorrhage recurrence by esophageal varices. Forty-five patients without known hepatocarcinoma who had survived a hemorrhagic variceal episode were included in the study. Seventeen patients (38%) were Child-Pugh A, 22 (49%) B, and 6 (13%) C, with the hepatitis C virus and alcohol being the etiology of cirrosis in 55 and 20% of the cases, respectively. The first ligation session was performed between the third and fifth days after the hemorrhagic episode and the posterior sessions were carried out at intervals of 2-4 weeks. The ligation sessions were performed without antibiotic prophylaxis and with placement of an overtube. A mean of 4 +/- 2 bands were placed per session (range, 1-8) and the mean number of sessions required per patient to achieve erradication of the varices was 3.5 +/- 1.5 (range, 2-8). The rate of bleeding recurrence was 17.7% (9 episodes, five by variceal rupture and four by ulcer secondary to ligation). All the episodes of bleeding recurrence occurred between the sessions, with the mortality being 11% (5/45 patients). In the 40 remaining patients the varices were erradicated although 19 (47.5%) required one or two additional sessions of sclerotherapy. The accumulated percentage of patients free of bleeding recurrence was 82% during a mean follow-up of 10.2 +/- 6.7 months. Ten lesions of dislaceration of the esophageal mucosa caused by placement of the were observed overtube. In conclusion, endoscopic elastic band ligation is a useful technique for the erradication of esophageal varices an in the prevention of bleeding recurrence.     

Management of esophageal varices in children by endoscopic variceal ligation

Endoscopic variceal sclerotherapy (EVS) has been considered the mainstay of therapy for bleeding esophageal varices in adults. However, recent data have shown that endoscopic variceal ligation (EVL) is just as efficacious and has fewer complications than EVS. Although there are many reports concerning EVL in adults, only a few studies have been done in children. This report describes experience with EVL in 22 children with esophageal variceal hemorrhage. Eighty-seven EVL procedures were performed during a 9-year period in 22 children. The causes of portal hypertension were biliary atresia (10), portal vein thrombosis (8), chronic active hepatitis (1), cirrhosis secondary to cystic fibrosis (2), and primary sclerosing cholangitis (1). The age range at the onset of variceal bleeding was 8 months to 19 years. Twelve patients had EVS before EVL treatment was begun. Distal esophageal varices (one to four per session) were mechanically ligated using an elastic band ligature device attached to a flexible endoscope. The aim of therapy was obliteration of distal esophageal varices by EVL, every 2 to 4 weeks, until eradication. Subsequent EVL was dictated by the status of the varices. Outcome was assessed with respect to survival, rebleeding, status of varices, and complications. The patients underwent a mean of four sessions of EVL (range, one to eight). Four patients subsequently underwent liver transplantation. Of the 18 patients remaining (average follow-up period, 5.3 years), 12 had their varices eradicated (average of four EVL sessions), four are still in treatment, one has not been evaluated in the past 4 years, and one died of liver failure. Complications included bleeding between sessions (6 patients), cervical esophageal perforation (1 patient), and transient fever (2 patients). No child has experienced symptoms of esophageal stenosis or gastroesophageal reflux. Two patients died of liver disease, unrelated to bleeding from portal hypertension. EVL is effective in controlling variceal hemorrhage in children with portal hypertension, regardless of etiology. The complication rate is low, and EVL is an acceptable and perhaps preferable alternative to EVS in children with esophageal varices.     

Disconnection as the last possible therapy of hemorrhage in esophageal varices

The authors draw attention to their favourable results of disconnection in haemorrhage of oesophageal varices. This favourable result applies to immediate results as well as long-term results. They emphasize in particular the fact that disconnection can be used also when other methods are not feasible for various reasons. This fact is demonstrated by the authors on three patients whose complicated history and general condition were such that disconnection was the only solution of the situation.     

Emerging role of endoscopic variceal band ligation in the treatment of esophageal varices

Quantitative EEG techniques are becoming more available. Eventually, all EEG will be digital. Various digital utility programs can help even now with storage and viewing the polygraph EEG itself. Techniques of frequency analysis, topographic mapping and discriminant functions are also available but have limited clinical use. Applications as a monitoring tool and careful analysis of epileptic spikes have been shown some promise but need further study to identify their proper clinical roles.     

Sclerotherapy versus sclerotherapy and propranolol in the prevention of rebleeding from oesophageal varices: a randomised study

BACKGROUND: This trial was carried out to assess the value of propranolol in the prevention of recurrent variceal bleeding when combined with longterm endoscopic sclerotherapy. PATIENTS AND METHODS: Two hundred patients (161 male, 39 female, age range 20-68 years) with portal hypertension resulting mainly from schistosomal periportal fibrosis or posthepatitic cirrhosis presenting with their first episode of haematemesis or melena, or both were included. This was confirmed endoscopically to result from ruptured oesophageal varices. After initial control of bleeding, patients were randomised into two groups: group 1 treated with endoscopic sclerotherapy alone and group 2 treated with sclerotherapy plus propranolol. They were followed up for two years. RESULTS: Group (2) had a lower rebleeding rate (14.3% v 38.6% in group 1), lower variceal recurrence after obliteration (17% v 34% in group 1), longer period between variceal obliteration and recurrence (36 weeks v 21 weeks in group 1); but no change in mortality (12% in both groups). CONCLUSIONS: Patients treated with sclerotherapy should be given propranolol for longterm management.     

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.     

Fatal hemorrhage from rupture of the intracranial internal carotid artery caused by aspergillus arteritis

To the best of our knowledge, this is the first reported case of combined intracranial and extracranial hemorrhage due to aspergillus cerebral arteritis. Knowledge of the imaging and the importance of early diagnosis and treatment are emphasized. A 78 year old man developed progressive right-sided visual impairment and diplopia. Magnetic resonance imaging demonstrated a mass lesion located in the right orbital apex, with extension to the cavernous sinus and the right middle cranial fossa. Cerebral angiography showed no aneurysmal dilatation. He was scheduled for transnasal biopsy. However, the patient died of massive epistaxis and intracranial hemorrhage. Postmortem examination revealed an aspergillus granuloma of the orbit and the skull base involving the intracranial and extracranial internal carotid artery. Aspergillus fumigatus was identified by culture. The characteristic feature of the fungal infection is a low-intensity signal on T2-weighted magnetic resonance images. This finding may be useful in diagnosing fungal infection.     

Does expressive writing reduce health care utilization? A meta-analysis of randomized trials.

This meta-analysis examined whether writing about stressful experiences affects health care utilization (HCU) compared with writing on neutral topics or no-writing control groups. Randomized controlled trials of 30 independent samples representing 2,294 participants were located that contained sufficient information to calculate effect sizes. After omitting one study as an outlier, the effects were combined within 3 homogeneous groups: healthy samples (13 studies), samples with preexisting medical conditions (6 studies), and samples prescreened for psychological criteria (10 studies). Combined effect sizes, Hedges's g (95% confidence interval), with random effects estimation were 0.16 (0.02, 0.31), 0.21 (-0.02, 0.43), and 0.06 (-0.12, 0.24), respectively. Writing about stressful experiences reduces HCU in healthy samples but not in samples defined by medical diagnoses or exposure to stress or other psychological factors. The significance of these effects for individuals' health is unknown. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials

OBJECTIVE: To evaluate the efficacy of pentoxifylline therapy in improving the walking capacity of patients with moderate intermittent claudication. DATA SOURCES: A search of MEDLINE for trials published between 1976 and 1994 inclusive, and a bibliographic review of all articles retrieved. STUDY SELECTION: Randomized, placebo-controlled, double-blind clinical trials were selected that evaluated the pain-free walking distance (the distanced walked on a treadmill before the onset of calf pain) and the absolute claudication distance (the maximum distance walked on a treadmill) among patients with moderate intermittent claudication. Twelve study groups in 11 trials were included in the analysis. DATA EXTRACTION: In addition to information regarding the trial design, patient characteristics, dosages and treatment periods, the means and standard deviations were collected for both the pain-free walking and absolute claudication distances. Trial quality was also assessed. DATA SYNTHESIS: Overall, there was a statistically significant improvement in the pain-free walking distance after pentoxifylline therapy (weighted mean difference 29.4 m [95% confidence interval (CI) 13.0 to 45.9 m]); this finding was based on a total sample of 612 patients (308 in the treatment groups and 304 in the control groups). A significant improvement was also noted in the absolute claudication distance (weighted mean difference 48.4 m [95% CI 18.3 to 78.6 m]); this was based on a total sample of 511 patients (258 in the treatment group and 253 in the control group). In a sensitivity analysis of the pain-free walking distance, significant treatment effects and no statistically significant heterogeneity were found when only trials were included that were "medically eligible" (involved patients with stage II disease and a pain-free walking distance of 50 to 200 m). In a similar sensitivity analysis of the absolute claudication distance, the two conditions resulting in a significant treatment effect and no significant heterogeneity were the inclusion of "medically eligible" trials and those with a shorter treatment duration (13 weeks or less). CONCLUSION: Pentoxifylline therapy may be efficacious in improving the walking capacity of patients with moderate intermittent claudication. However, properly conducted clinical trials are required to provide a true estimate of the benefit.     

Prospective study of bacteremia rate after elastic band ligation and sclerotherapy of esophageal varices in patients with hepatosplenic schistosomiasis

Bone scintigraphy was performed in a 69-year-old male patient with adult T-cell leukemia suffering from right lower limb pain. Numerous sites of increased uptake were seen in the skull, left clavicle, bilateral humeri, bilateral radii and right femur and tibia. Bone radiographs showed multiple osteolytic lesions, most of which corresponded to the abnormal deposits on the bone scans with 740 MBq of 99mTc-hydroxymethylene diphosphonate. This pattern is rarely reported, but bone involvement of adult T-cell leukemia is not uncommon. Bone involvement was remarkable on the appendicular skeleton when compared with common metastatic bone tumors. Bone scintigraphy may be useful in detecting bone involvement in adult T-cell leukemia.     

Cholesterol reduction and the risk for stroke in men. A meta-analysis of randomized, controlled trials

OBJECTIVE: Reducing serum cholesterol lowers the risk for ischemic heart disease, but its effects on other vascular diseases are unknown. Published trials were reviewed to determine the effect of cholesterol-lowering interventions on fatal and nonfatal stroke. DESIGN: Meta-analysis of randomized, controlled trials. DATA IDENTIFICATION: A literature search of English-language studies examining the effect of modified diets or medications on cardiovascular end points from 1965 to 1992 using MEDLINE and a review of references of five quantitative overviews of cholesterol reduction and coronary disease. DATA ANALYSIS: Thirteen studies met three eligibility criteria: patients randomized to intervention or control; fatal or nonfatal stroke reported separately; and end points assessed without knowledge of treatment status. Heterogeneity among studies and overall effects of treatment on fatal and nonfatal stroke were estimated using the Mantel-Haenszel-Peto method to combine independent study results. The influence of various study designs and interventions was explored using subgroup comparisons. RESULTS: For fatal stroke, the overall odds ratio associated with cholesterol-lowering interventions in 13 trials was 1.32 (95% Cl, 0.94 to 1.86), and the odds ratio for the 10 single-intervention trials was 1.34 (Cl, 0.91 to 1.96). Among eight trials reporting nonfatal events, the summary odds ratio for nonfatal stroke for treated participants compared with controls was 0.88 (Cl, 0.70 to 1.11), and the odds ratio for total strokes was 0.98 (Cl, 0.80 to 1.19). Among three trials using clofibrate, treatment significantly increased the risk for fatal stroke (odds ratio, 2.64; Cl, 1.42 to 4.92) but not for nonfatal stroke (odds ratio, 0.87; Cl, 0.61 to 1.26). Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the risk for fatal stroke. CONCLUSIONS: Lowering serum cholesterol through modified diets or medications does not reduce stroke mortality or morbidity in middle-aged men. Clofibrate appears to increase the risk for fatal strokes, but the mechanism for this effect is unknown.     

Prophylactic endoscopic sclerosing treatment of the esophageal wall in varices -- a prospective controlled randomized trial

From January 1, 1978 to January 1, 1980 a controlled randomized trial comparing conservative treatment with prophylactic sclerotherapy of esophageal varices prior to hemorrhage was carried out. In all 71 patients liver cirrhosis was histologically confirmed. The two randomly assigned groups were comparable. Indications of endoscopic treatment were the existence of varices III-IV bearing erosions, varices II-IV without erosions but coagulation factors below 30%, or both. Six patients left the trial. In group Ia -- treatment by conservative means -- a high rate of variceal bleeding and death was observed. Comparing these results with those of group Ib treated by sclerotherapy, bleeding and death rates were found to be highly significantly lower. -- Thus the investigated criteria for predicting a recent variceal hemorrhage are confirmed. Prophylactic sclerotherapy in esophageal varices with erosions and/or poor coagulation reserve of the liver can largely prevent an esophageal hemorrhage from varices, and prolongs the life of these chronically ill patients.     

Sclerosis of esophageal varices. Results of 10 years experience

Before they give their results, the authors, whose experience of sclerosis of oesophageal varices under the oesophagoscope has so far involved 157 patients, deal specifically with the problems facing the anaesthetist and resuscitator when this technique is used, tolerance of the product injected and possible accidents. Firstly, they point out the unsuitability of the patients referred to them by their medical or surgical colleagues. By implication therefore, treatment should only be undertaken with the assistance of a team of experienced resuscitators and every precaution taken to mitigate the effects of possible accidents to these patients who are particularly at risk. These cases are mainly characterized by serious haemorrhages (seven cases described, one resulting in death). Oesophageal injury is, on the other hand, the exception where trained personnel are involved (2 minor mucosal tears out of more than 800 oesophagoscopies). Finally, secondary parietal oesophageal necrosis occurs. Quininaemia assessment after injection of quinine-urea confirms that the product is being efficiently eliminated. Overall results reveal a survival rate of 61 p. 100 after more than a year and 20 p. 100 after more than than three years. These figures underline the limitations of therapeutic possibilities and the serious prognosis for this result of portal hypertension. This leads the authors to express a wish that the procedure should be used as a measure to prevent haemorrhage as soon as the presence of varices is realized. On the other hand, they reject on practical grounds emergency sclerosis of oesophageal varices, as a direct heamostatic method, since, according to their statistics, this almost invariably results in failure.     

Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials

CONTEXT: Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke. OBJECTIVE: To estimate the risk of hemorrhagic stroke associated with aspirin treatment. DATA SOURCES: Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors' reference files. STUDY SELECTION: All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported. DATA EXTRACTION: Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol. DATA SYNTHESIS: Data from 16 trials with 55462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10000 persons (95% confidence interval [CI], 107-167; P<.001) and in ischemic stroke, a reduction of 39 events per 10000 persons (95% CI, 17-61; P<.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10000 persons (95% CI, 5-20; P<.001). This risk did not differ by participant or study design characteristics. CONCLUSIONS: These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.     

Management of steroid-dependent asthma with methotrexate: a meta-analysis of randomized clinical trials

Our objective was to determine whether methotrexate is an effective steroid-sparing agent for patients with severe asthma. Published reports of controlled trials assessing the use of methotrexate in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in any language were identified and assessed for inclusion in the meta-analysis. We selected randomized, double-blind, placebo-controlled trials in which low-dose methotrexate was administered to corticosteroid-dependent asthmatics, and oral steroids were subsequently tapered according to the patients' clinical status. Data were extracted independently by two reviewers. For all eligible trials, the mean reduction in oral corticosteroid dose, the mean change in FEV1, and the standard deviations, were calculated for the treatment and control groups. Data concerning side-effects of therapy were also extracted. Data from 12 studies, reporting on a total of 250 patients, were pooled using a weighted average method, with weights proportional to the inverse of the variance of the treatment effect. Compared to placebo, the use of methotrexate was associated with a pooled 6.0% improvement in FEV1 (95% CI, 1.0-11%) and an 18.2% reduction in oral steroid use (95% CI, 11.7-24.7%). This corresponded to a 3.3 mg day-1 greater reduction in oral steroid use for patients taking methotrexate than for those taking placebo (95% CI, 2.1-4.4 mg day-1). Gastrointestinal complications and transient increases in liver enzymes were more common in patients randomized to methotrexate. Three potentially life-threatening side-effects (two pneumonias and one liver dysfunction) occurred in 159 patients randomized to methotrexate vs. none in those patients on placebo. It was concluded that methotrexate allowed a modest reduction in oral corticosteroid compared to patients receiving placebo. The benefit is relatively small, however, and should be balanced against the potential for side-effects associated with the use of methotrexate.     

Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials

PURPOSE: An overview is presented of reports published since 1980, in which postoperative adjuvant chemotherapy is compared with surgery alone for patients with gastric cancer. A MEDLINE literature review yielded 123 reports, 14 of which were relevant randomized trials; data from 11 of these trials were (or became) available for analysis of crude mortality odds. These 11 trials included 2,096 patients. METHODS: Odds ratios were calculated by comparing the adjuvant treatment arm with the observation-only arm. Those odds ratios that could be considered homogeneous yielded an estimated common odds ratio of 0.88 (95% confidence interval [CI], 0.78 to 1.08), which was slightly, but far from significantly, in support of adjuvant treatment. RESULTS: The results confirm the common opinion that the adjuvant chemotherapy regimens prescribed in these trials, although effective in phase II studies, do not improve survival. Furthermore they indicate that postoperative chemotherapy in general offers no additional survival benefit for patients with curatively resected gastric cancer. CONCLUSION: In conclusion, at present, postoperative chemotherapy cannot be considered as standard adjuvant treatment. New trials of adjuvant therapy for gastric cancer must include a no-treatment control arm.     

Clinico-radiological dissociation in cerebral hemorrhage caused by afibrinogenemia

INTRODUCTION: Congenital afibrinogenemia is a very rare hereditary anomaly of coagulation. Only 150 cases have been published. Clinical manifestation in the form of some type of bleeding is similar to that of other congenital coagulopathies, although the pattern of presentation is different. Spontaneous bleeding is rare, but slight injury, which may be unnoticed, may trigger it off. In spite of being a congenital condition, it may be of late onset, as in our patient, with bleeding episodes occurring in the second decade of life. CLINICAL CASE: We describe a woman who had several episodes of bleeding, two of which were intracerebral. The principal feature of this was dissociation between the clinical findings and their detection by neuro-imaging. Substitutive therapy led to the disappearance of symptoms. CONCLUSION: Cerebral haemorrhage in the presence of afibrinogenemia may fail to be detected early on CT. On clinical suspicion of bleeding, early substitutive treatment should be started.     

Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials

Well-founded pharmacokinetic information is one of the cornerstones of a New Drug Application (NDA) to the Food and Drug Administration (FDA) required to introduce a new drug or a generic equivalent (ANDA) to the marketplace. The service that laboratories engaged in therapeutic drug monitoring provide to support clinical activities is also needed by the pharmaceutical industry during the evaluation and introduction of drugs to the marketplace. In considering this alternative service activity, one must be aware of and compliant with rules established by the FDA for performance of such studies. As specified in CFR 21, Parts 58, 211, and 320, good clinical and laboratory practice indicates that the laboratory should employ a Lab Study Director, who is responsible for the validation of all procedures implemented to support a study protocol, ensures that the laboratory carries out the study following these defined procedures, and personally reviews the results of all testing. The laboratory must validate each procedure by demonstrating and documenting that the procedure does what it is designed to do while meeting the analytical performance specifications required by the study. Laboratory records of all activities must be maintained and available for inspection by the FDA on request. The FDA has authority over all activities related to NDA and ANDA submissions and can bring criminal charges if results of a study are changed because a laboratory deviates from standard procedure. Competent drug monitoring laboratories are fully capable of participating in clinical trials testing activities. Laboratory staff should be fully versed in the FDA rules governing these activities, validate all procedures, and establish systems to verify the procedures are carried out as specified.     

Treatment of hemorrhages by rupture of cardio-tuberous varices with transjugular intrahepatic portasystemic shunt

Twelve consecutive patients admitted for bleeding from ruptured gastric varices were treated with transjugular intrahepatic portosystemic shunts and followed for a mean of 6 +/- 3 months (range: 8-293 days). The shunt was performed successfully in all 12 patients. The shunt occluded in 3 patients (respectively 19, 101 and 103 days after insertion) of whom one remained asymptomatic and two experienced rebleeding. Four patients presented with acute encephalopathy, spontaneously in two and after rebleeding in two. Three patients died, two after rebleeding and one of septic shock secondary to pneumonia. Overall, 9 patients survived a mean of 211 +/- 92 days with no rebleeding, 8 of whom have not yet experienced any complications. These results suggest that transjugular intrahepatic portosystemic shunts could be useful in treating hemorrhages from ruptured gastric varices and in preventing their recurrence.