Xavier Cussó

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.

Norfloxacin Prevents Bacterial Infection in Cirrhotics With Gastrointestinal Hemorrhage

To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group 2 (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = 0.001), bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than 0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage.

Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors

BACKGROUND & AIMS Exogenous cholecystokinin (CCK) decreases lower esophageal sphincter (LES) pressure and increases transient LES relaxations (TLESRs) in humans. The aims of this study were to determine whether endogenous CCK increases gastroesophageal reflux in humans and whether this is a direct effect on the LES. METHODS Esophageal pH, LES pressure, and gallbladder volume were measured in 8 healthy volunteers after ingestion of a 181-kcal meal alone or adding 12 g cholestyramine to increase endogenous CCK release. In 7 additional volunteers, the effect of cholestyramine was studied during intravenous perfusion of saline or the CCK-A receptor antagonist loxiglumide. In circular LES strips from 9 transplant donors, we measured the effect of CCK-8 (10(-11) to 3 x 10(-8) mol/L) on basal tension and on electrical field-induced relaxation. RESULTS Cholestyramine increased gallbladder emptying, reflux episodes, TLESRs, and time of esophageal pH of <4. Loxiglumide inhibited postprandial gallbladder emptying, reflux episodes, TLESRs, and time of pH of <4 and prevented the decrease in LES pressure induced by cholestyramine. In vitro, CCK-8 contracted LES strips through a tetrodotoxin-insensitive pathway but did not modify electrical field-induced LES relaxations. CONCLUSIONS Endogenous CCK enhances postprandial gastroesophageal reflux in humans by increasing the rate of TLESRs and reduces postprandial LES pressure. These actions seem mediated by extrasphincteric CCK-A receptors that override a direct contractile effect of CCK on the LES muscle.

Clinical usefulness of K-ras gene mutation detection and cytology in pancreatic juice in the diagnosis and screening of pancreatic cancer.

Background The significance of K-ras codon 12 mutation in pancreatic juice is still unclear. Although considerable controversy surrounds this question, the diagnostic utility of K-ras in patients with clinical suspicion of pancreatic cancer (PC) and in PC-risk patients remains unknown. Objective To study prospectively the utility of the K-ras gene mutation and cytology in the diagnosis and screening of PC, and to assess its contribution to clinical decision making. Methods Pancreatic juice samples obtained from 90 patients were evaluated prospectively. Group I (n = 40) comprised patients with clinical suspicion of PC; group II (n = 50) comprised 49 patients with chronic pancreatitis and one patient proceeding from a PC family screening. The K-ras mutation was detected by means of artificial restriction fragment length polymorphisms (RFLP) in DNA after polymerase chain reaction (PCR) amplification. Results In group I, of those patients with a definitive diagnosis of PC, malignant cells were found in 27% and K-ras mutation in 44%. In five cases, molecular analysis contributed to diagnosis (4/11 with negative cytology and 1/2 with insufficient cytological material). K-ras mutation revealed an early tumour in one patient, and was the only sample available for diagnosis in another. In group II, the K-ras gene mutation was detected in 8/49 patients (16%) with chronic pancreatitis, one of whom developed PC (2%). Conclusions K-ras mutation analysis of pancreatic juice may complement cytological evaluation in the diagnosis of PC, in spite of its limited contribution to clinical decision making. The presence of K-ras mutation in chronic pancreatitis classifies a subgroup of PC-risk patients who should be evaluated carefully by long-term follow-up.

An evaluation of gastric biopsy in the diagnosis of gastric cancer.

The number of positive biopsy fragments obtained endoscopically in 174 cases of gastric cancer has been compared to the total number of biopsies taken in each instance. All cases in which more than 8 specimens had been taken included at least 1 fragment positive for malignancy. This suggests that at least 8 biopsy samples should be taken from each lesion, whatever its gross appearance may be.

Pharmacologic treatment of portal hypertension in the prevention of community-acquired spontaneous bacterial peritonitis.

Introduction Given that &bgr;-blockers reduce the incidence of bacterial translocation in cirrhotic rats, the aim of this study was to compare the long-term incidence of spontaneous bacterial peritonitis in cirrhotic patients submitted to pharmacologic versus endoscopic treatment to prevent variceal rebleeding. Patients and methods Two hundred and thirty patients with variceal hemorrhage were included in two previous randomized trials performed to compare the efficacy of medication (nadolol plus isosorbide mononitrate, n=115) versus endoscopic treatment (n=115) with sclerotherapy or ligation for the prevention of rebleeding. Results The mean follow-up was 23±1.4 months. The characteristics of the patients and the number of patients on long-term prophylaxis with norfloxacin were similar in both groups. The incidence of spontaneous bacterial peritonitis was lower in the medication group (9 versus 14.7%, P=NS). The probability of spontaneous bacterial peritonitis was also lower in the medication group (6 versus 12% at 1 year, 22 versus 36% at 5 years; P=0.08), due to a significantly lower probability of community-acquired spontaneous bacterial peritonitis in this group (1 versus 10% at 1 year, 18 versus 32% at 5 years; P=0.02). Patients with no hemodynamic response to therapy had a significantly higher probability to develop community-acquired spontaneous bacterial peritonitis during follow-up than hemodynamic responders (P<0.03). Long-term probability of developing community-acquired spontaneous bacterial peritonitis is lower in patients submitted to pharmacologic treatment for preventing variceal rebleeding than in those submitted to endoscopic treatment. Conclusion Long-term pharmacologic prophylaxis of variceal rebleeding contributes to the prevention of community-acquired spontaneous bacterial peritonitis.

Endoscopic cytology of cancer of the esophagus and cardia: a long-term evaluation

Between January 1979 and December 1986, 858 endoscopic cytological examinations of the esophagus were performed, including 309 patients with confirmed malignancies. A positive cytological diagnosis of cancer was made in 289 (93.5%). Adequate biopsies were obtained in 269 instances (87.0%), being positive in 238 cases (overall positivity of biopsy, 77.02%). The combined use of biopsy and cytology provided a correct diagnosis in 98.0% of cases. The cytological examinations were positive in 30 of 40 patients (75.0%) with obstructing lesions in whom no satisfactory biopsies could be obtained. No false positive diagnosis was made among the 550 patients with benign conditions. In this series, cytology increased the yield of biopsy by 20.8%.

Is endoscopic gastric cytology worthwhile ? An evaluation of 903 cases of carcinoma

From 1978 to 1989, 4,772 endoscopic cytological examinations of the stomach have been done in our laboratory, including 903 patients with a final diagnosis of gastric carcinoma. There were seven false-positive results among 3,810 examinations done in patients without malignant disease (specificity 99.8%). Cytology yielded positive results in 785 of 903 carcinomas (sensitivity 86.9%), while biopsies were positive in 826 of 895 cases (sensitivity 92.3%). Both techniques combined resulted in positive diagnoses in 886 of 903 malignancies (sensitivity 98.1%). Cytology was positive in 52 patients with negative biopsies as well as in eight patients in whom biopsies had not been obtained. Thus cytology added 60 positive diagnoses (6.7%) to the overall diagnostic results. These results suggest that endoscopic cytology is useful for avoiding unnecessary delays caused by having to perform repeated endoscopic biopsies. It should be done as a routine procedure in those institutions in which significant numbers of gastric carcinomas are studied and where an experienced gastrointestinal cytology laboratory is available.