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.

Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding.

BACKGROUND: After an episode of acute bleeding from esophageal varices, patients are at high risk for recurrent bleeding and death. We compared two treatments to prevent recurrent bleeding--endoscopic ligation and combined medical therapy with nadolol and isosorbide mononitrate. METHODS: We randomly assigned 144 patients with cirrhosis who were hospitalized with esophageal variceal bleeding to receive treatment with endoscopic ligation (72 patients) or the combined medical therapy (72 patients). Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The initial dose of nadolol was 80 mg orally once daily, with adjustment according to the resting heart rate; isosorbide mononitrate was given in increasing doses, beginning at 20 mg once a day at bed time and rising over the course of one week to 40 mg orally twice a day, unless side effects occurred. The primary end points were recurrent bleeding, complications, and death. RESULTS: The median follow-up period was 21 months. A total of 35 patients in the ligation group and 24 in the medication group had recurrent bleeding. The probability of recurrence was lower in the medication group, both for all episodes related to portal hypertension (P=0.04) and for recurrent variceal bleeding (P=0.04). There were major complications in nine patients treated with ligation (seven had bleeding esophageal ulcers and two had aspiration pneumonia) and two treated with medication (both had bradycardia and dyspnea) (P=0.05). Thirty patients in the ligation group died, as did 23 patients in the medication group (P=0.52). The probability of recurrent bleeding was lower for patients with a hemodynamic response to therapy, defined as a decrease in the hepatic venous pressure gradient of more than 20 percent from the base-line value or to less than 12 mm Hg (18 percent, vs. 54 percent in patients with no hemodynamic response at one year; P<0.001), and the probability of survival was higher (94 percent vs. 78 percent at one year, P=0.02). CONCLUSIONS: Combined therapy with nadolol and isosorbide mononitrate is more effective than endoscopic ligation for the prevention of recurrent bleeding and is associated with a lower rate of major complications. A hemodynamic response to treatment is associated with a better long-term prognosis.

Somatostatin alone or combined with emergency sclerotherapy in the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

Recent trials have shown that somatostatin (SMT) is as effective as sclerotherapy in the treatment of acute variceal bleeding and that the combination of both treatments is more effective than sclerotherapy alone. To assess whether the addition of sclerotherapy improves the efficacy of SMT alone, all patients admitted to our unit with gastrointestinal bleeding and with suspected cirrhosis received a continuous infusion of SMT (250 micrograms/h). Endoscopy was performed between 1 and 5 hours later, and patients with esophageal variceal bleeding were randomized to receive or not to receive sclerotherapy. In both groups, SMT infusion was continued for 5 days. Fifty patient admissions were allocated to each group. Therapeutic failure occurred in 21 cases of the SMT group and in 7 cases of the combined-therapy group (P =.002). Failure to control the acute episode occurred in 24% vs. 8% (P =.03) and early rebleeding in 24% vs. 7% (P =.03), respectively. Transfusional requirements were significantly higher in the SMT group, while the incidence of complications was lower (8% vs. 24%; P =.029). In the multivariate analysis, the presence of shock at admission and active bleeding during endoscopy were the variables that better predicted the failure of therapy with SMT alone. Mortality at 6 weeks was similar. These data demonstrate that the addition of sclerotherapy significantly improves the efficacy of SMT alone for the treatment of acute variceal bleeding, although it also increases the rate of complications. Patients with shock and those with active bleeding are more likely to benefit from this combined therapy.

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.

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.

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.

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.

[Endoscopic cytology in the diagnosis of carcinoma of Vater's ampulla]. / Citología endoscópica en el diagnóstico de carcinoma de la ampolla de Vater.

An endoscopic cytology procedure was performed in 25 patients with a final diagnosis of carcinoma of the ampulla of Vater. A diagnosis of malignancy was made cytologically in 22 instances, and in 9 patients cytology was the only positive finding before operation. In two cases endoscopic biopsy was positive while the cytologic examination did not confirm the histological diagnosis.

[Usefulness of laparoscopy as a second-look method in neoplasms of the ovary]. / Utilidad de la laparoscopia como método de "second-look" en las neoplasias de ovario.

The usefulness of second-look laparoscopy in the follow-up of ovarian cancer is evaluated. This procedure has been included in the protocol for the treatment of these tumors. During the period 1980-1987 a total of 3038 laparoscopies were performed; 205 (7%) were for ovarian cancer. We present the results of 72 explorations in 52 patients; after surgery and chemotherapy all of them were in complete remission. 44 explorations were second-look laparoscopy and 28 third-look laparoscopy. All the examinations were done under local anesthesia. There were two failures due to the presence of adhesions secondary to the previous surgery which prevented the pneumoperitoneum. In 35 (48.6%) explorations a neoplasia was found and a laparotomy was avoided. There were 31% (4/13) false negative in second-look laparotomy post-laparoscopy. The correlation between gross and microscopic findings was excellent. There were no complications in spite of the previous abdominal surgery. We recommend second-look laparoscopy in patients under treatment of ovarian cancer which in our experience avoided laparotomy almost in half of the cases; no complications were observed and the procedure was well-tolerated.

Efficacy of ethanolamine and polidocanol in the eradication of esophageal varices. A prospective randomized trial.

A prospective randomized trial has been undertaken to compare the efficacy of two sclerosing agents, Ethanolamine oleate (Et) and Polidocanol (Pl), in the eradication of esophageal varices (EV). Fifty consecutive cirrhotic patients, 22 in the Et and 28 in the Pl group, were included. Clinical data were comparable in both groups. Eradication of the EV was achieved in 81% (18/22) in the Et group and 64.1% (18/28) in the Pl group (p = NS). There was a significant difference in the rate of rebleeding (4 episodes in 3 patients in the Et group and 18 episodes in 13 patients in the Pl group, p less than 0.05). No differences were noted in the number of other complications or mortality. Both sclerosants have proved useful in the eradication of EV, but Et was superior to Pl in the preventation of recurrent bleeding in the course of repeated endoscopic injection sclerotherapy (EIS).

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%.

Endoscopic hemostasis by local injection of epinephrine and polidocanol in bleeding ulcer. A prospective randomized trial.

The present prospective randomized trial has been carried out to assess the efficacy of the endoscopic injection of epinephrine plus polidocanol, in the prompt treatment of upper gastrointestinal bleeding due to peptic lesions. Over a period of one year, 72 patients were admitted to the study. Thirty-six of these underwent endoscopic treatment (group A), while the others received medical treatment (group B). Definitive hemostasis was achieved in 29 patients in group A, and in 21 in group B (p less than 0.05). Seven patients in group A and 12 in group B underwent emergency surgery for persistent or recurrent bleeding (p = NS). Three patients from group B received endoscopic treatment owing to relative surgical contraindications. It was successful in all of them. Patients from group A needed a significantly lower number of units of packed red cells (p less than 0.05). Our results show that it is justified to employ endoscopic injection as the first therapeutic step in upper GI bleeding due to peptic gastroduodenal lesions.

Laparoscopic cytology--an evaluation.

Cytological sampling by abrasion and/or aspiration was done in a consecutive series of 927 patients at the time of laparoscopy. Cytological examination confirmed the diagnosis of malignancy in 312 out of 335 cases of primary or secondary liver cancer (93.1%). Biopsy was positive in 262 out of 303 patients (86.4%). The combined use of cytology and biopsy provided a positive diagnostic accuracy of 97.6%). The cytological report was positive in 215 out of 239 (89.9%) proven extrahepatic malignancies (gallbladder, gynecological, peritoneal). Biopsy was positive in 180 out of 199 cases (90.4%). The combined use of cytology and biopsy provided an accuracy of 95.8%). There was only one false positive diagnosis of malignancy. The sensitivity of laparoscopic cytology was 93.1% and its specificity 100% in liver disease. Sensitivity was 90.3% and specificity 99.4% in other types of abdominal cancer. In these series, cytological examination added 15.6% positive results (liver) and 11.7% (other lesions) to those of biopsy, which was not performed in 89 patients in whom it was considered too risky or technically too difficult.