A short course of preoperative radiotherapy improves prognosis of operable rectal carcinoma: a case control study.

BACKGROUND/AIMS: Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single Greek institution over a 10-year period, with a similar regimen. METHODOLOGY: During the period of 1995-2000, 150 consecutive patients with Dukes' B or C rectal cancer were matched to receive preoperative radiotherapy (Group I) or not (Group II). Seventy-five patients received pelvic radiotherapy of 2500cGY/5 fractions, followed by surgery within one week. Radiotherapy was delivered through 4 portals, with the patient lying in the prone position. A CT scan was used to define treatment volume. The 5-fraction course was used for lesions that seemed readily resectable. Patients in both groups received adjuvant chemotherapy. Local recurrence, disease-free interval and 5-year survival were evaluated and analyzed. RESULTS: The disease-free interval was significantly longer in Group I (p < 0.0005). This benefit was mainly due to a significantly lower incidence of local recurrence in Group I (9/75, 12%) compared with Group II (30/75, 40%) (p < 0.0005). The incidence of distant metastases was not significantly different between the 2 groups. The 5-year survival for all patients, who underwent "curative" surgery was significantly higher in Group I (77.3%) as compared to Group II (39%), (p < 0.0005). CONCLUSIONS: Patients with resectable rectal cancer who received 2500cGy/5 fractions preoperative radiotherapy to the pelvis had excellent local control of disease, longer disease-free interval and higher 5-year survival than patients who did not. These patients were able to undergo sphincter preserving surgery and adjuvant chemotherapy.

Diffuse idiopathic colonic varices presenting with lower gastrointestinal bleeding in an elderly patient: a case report and review of the literature.

We report a case of lower gastrointestinal bleeding caused by idiopathic colonic varices. A 74-year-old woman presented with rectal bleeding. Colonoscopy revealed numerous varices of the entire colon, which, after an extensive work-up, proved to be idiopathic. No specific therapy or transfusions were required and there has been no further bleeding to date (follow-up 10 months). Review of the literature demonstrates that diffuse idiopathic colonic varices are a rare cause of lower gastrointestinal bleeding, especially as the first presentation in an elderly patient.

Lamivudine monotherapy in HBeAg-negative chronic hepatitis B: prediction of response-breakthrough and long-term clinical outcome.

BACKGROUND: Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined. AIM: To determine pre-treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg-negative chronic hepatitis B receiving long-term lamivudine. METHODS: Seventy-nine patients, with chronic HBeAg-negative hepatitis B, who received lamivudine for a median of 31 months were included in the study. RESULTS: Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre-treatment serum hepatitis B virus DNA concentrations of more than 10(6) copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated. CONCLUSIONS: In HBeAg-negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 10(6) copies/mL is a strong predictor for breakthrough because of drug-resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre-existing cirrhosis.

Endoscopic ultrasonography in the diagnosis and management of portal hypertension. Where are we next?

Endoscopic ultrasonography has recently emerged as an accurate, non-invasive and reproducible alternative means of providing data for patients with portal hypertension. It is well established that endoscopic ultrasonography is more sensitive than endoscopy in the diagnosis of gastric varices. Dilated venous abnormalities outside the gastrooesophageal lumen, which cannot be diagnosed by endoscopy, are readily visible with endoscopic ultrasonography or miniature probes. Endoscopic ultrasonography is also useful to predict the risk of variceal recurrence and thus the risk of rebleeding after endotherapy which cannot be reliably predicted using endoscopy alone. The introduction of echo endoscopes equipped with Doppler facilities has allowed the sonographic visualisation of the vessels and the evaluation of vascular blood flow along with possible morphologic and haemodynamic changes after endoscopic or pharmacological therapy. However, despite its theoretical advantages, relative evidence suggests that in the clinical setting of portal hypertension, endoscopic ultrasonography remains an investigational tool with limited clinical applications.

Somatostatin and its analogues in peptic ulcer bleeding: facts and pathophysiological aspects.

Peptic ulcer bleeding remains a common medical emergency and despite recent advances in management is still associated with high mortality. Endoscopic treatment remains the cornerstone for the effective management of high-risk patients. Recent evidence suggests that potent antisecretory drugs that inhibit gastric acid secretion, such as proton pump inhibitors, may be of help alone or in combination with endotherapy in the management of peptic ulcer bleeding. Somatostatin appears to offer a distinct advantage over antisecretory drugs, as it inhibits both acid and pepsin secretion and combines these effects with a reduction in gastroduodenal mucosal blood flow which seems to be important in the pathophysiology of peptic ulcer bleeding. Additionally, the inhibition of pepsin secretion might induce a decreased proteolytic activity preventing the dissolution of freshly formed clots at the site of bleeding. Despite its theoretical advantages, there has been very little evidence in the recent past in setting of randomised, controlled, clinical trials. In reviewing the available data, we found that the efficacy of somatostatin and its analogue octreotide are different in the control of peptic ulcer bleeding and this might be due to the different distribution of its receptors through the GI tract. Further studies are needed to define the exact role, if any, of somatostatin and its analogues, in high-risk patients with peptic ulcer bleeding and this might be a rather interesting area for future research.

Effect of polyethylene glycol electrolyte balanced solution on patients with acute colonic pseudo obstruction after resolution of colonic dilation: a prospective, randomised, placebo controlled trial.

BACKGROUND AND AIMS: Conservative therapy for patients with acute colonic pseudo obstruction (Ogilvie's syndrome) may be successful initially but relapses are common. The aim of the present study was to evaluate the effect of polyethylene glycol (PEG) electrolyte balanced solution on the relapse rate of the syndrome after initial resolution with neostigmine or endoscopic decompression. PATIENTS AND METHODS: The study was performed on 30 consecutive patients who presented with abdominal distension and radiographic evidence of colonic dilation, with a caecal diameter > or = 10 cm, that resolved conservatively. Patients then were randomised to receive daily 29.5 g of PEG (n = 15) or similar placebo (n = 15). Patients were monitored daily for a seven day period for stool and flatus evacuations, and colonic diameter on abdominal radiographs. Administration of the test solutions and assessment of patient symptoms and x rays were performed in a blinded fashion. A caecal diameter > or = 8 cm with a concomitant > or =10% increase after initial successful therapeutic intervention was considered as a relapse and these patients, after a second therapeutic intervention, were eligible to receive open label PEG. RESULTS: Twenty five patients received neostigmine as the initial therapeutic intervention which resulted in resolution of colonic dilation in 88% of cases. Eight patients had successful endoscopic decompression. Five (33.3%) patients in the placebo group had recurrent caecal dilation compared with none in the PEG group (p = 0.04). Therapy with PEG resulted in a significant increase in stool and flatus evacuations (p = 0.001 and 0.032, respectively) as well as in a significant decrease in the diameter of caecum, ascending and transverse colon, and abdominal circumference (p = 0.017, 0.018, 0.014, and 0.008, respectively). CONCLUSIONS: Administration of PEG in patients with Ogilvie's syndrome after initial resolution of colonic dilation may increase the sustained response rate after initial therapeutic intervention.

Primary prophylaxis of variceal bleeding in cirrhotics unable to take beta-blockers: a randomized trial of ligation.

AIM: To compare endoscopic banding ligation vs. no treatment in cirrhotics with intolerance or contraindications to beta-blockers for prevention of first bleeding in portal hypertension. METHODS: A sample size of 214 was planned with all sizes of varices. However, the trial was stopped due to increased bleeding in 52 patients in the ligation group. The baseline severity liver disease and endoscopic features were similar. Ligation group: 25 (M/F = 21/4, mean age: 60 +/- 9.37 years); 27 not-treated group: 27 (M/F = 17/10, mean age: 63 +/- 10.27). RESULTS: The mean follow-up period was 19.5 +/- 13.3 months: five bled in the ligation group (20%), three from varices (two after banding at 11 and 17 days; one during the procedure), and two from gastropathy; two bled in the not-treated group (7%- two both varices) (P = 0.24). There were seven deaths in the ligation group and 11 in the not-treated group (P = 0.39). CONCLUSION: Sixty per cent of the bleeding in the banding group was probably iatrogenic, requiring the study to be stopped. Endoscopic banding ligation was no better than no treatment. This study suggests that ligation may be harmful when used as primary prophylaxis, similar to prophylactic sclerotherapy in the past.

Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study.

BACKGROUND: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. METHODS: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. RESULTS: H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR) = 1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P = 0.008). Current smoking (OR = 2.65; 95% CI, 1.14-6.15; P= 0.02), CagA status (OR = 2.28; 95% CI, 1.24-4.19; P = 0.008), dyspepsia (OR = 6.89; 95% CI, 1.84-25.76; P = 0.004) and past history of peptic ulcer disease (OR=3.15; 95% CI, 1.43-6.92; P=0.004) were associated significantly with increased risk of bleeding peptic ulcer. CONCLUSIONS: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.

A randomized trial to assess the efficacy of interferon alpha in combination with ribavirin in the treatment of interferon alpha nonresponders with chronic hepatitis C: superior efficacy of high daily dosage of interferon alpha in genotype 1.

A randomized trial was conducted to assess the efficacy of daily (QD) or thrice weekly (TIW) administration of interferon-alpha (IFN) in high doses in combination with ribavirin (1.0-1.2 g/day) in patients with chronic hepatitis C (CHC) who were nonresponders to previous IFN monotherapy. Interferon was administered as 10 MU IFN (QD or TIW) for 4 weeks, followed by 5 MU IFN (QD or TIW) for 20 weeks, and then by 3 MU IFN (QD or TIW) for 24 weeks. Sustained virological response (SVR) was evaluated in 142 patients who received at least one dose of medication. One-fourth of the patients achieved SVR, 26% of those treated with IFN QD and 25% of those treated with IFN TIW (P = 0.85). For genotype 1 patients, SVR rates were 32.4 and 15.8% for IFN QD and IFN TIW, respectively, whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4%, respectively (test of homogeneity: P = 0.031). This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction (P = 0.012) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas, among genotype non-1 patients, the two treatments were similar (odds ratio of SVR in IFN QD vs IFN TIW: 3.33 among genotype 1 patients, 95% CI: 1.00-11.14). In conclusion, re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients.

Differences in self-reported perceived and objective measures of duration and intensity of physical activity for adults in skiing.

The effect of physical activity (PA) on health is well documented. The assessment of PA is a valuable and important issue, however, there are several methodological issues among the available methods of measurement that may have implications for the prevention of specific diseases. The purpose of this study was to examine the differences between an objective method of measurement and the subjective estimation of the PA for novice skiers. Seventy-five students aged 19-21 years old with no previous experience in ski participated in this study. Participants wore a heart rate monitor during practice in order to record the exercise intensity. Simultaneously, a trained observer recorded their time on task. A day after the objective measurement, the participants filled a questionnaire in order to estimate their perceived exertion during practice as well as their perceived time on task. The results showed (1) differences between the observed time on task and the perceived recalled time, (2) no differences overall between the recorded and perceived recalled intensity of exercise but when groups were split according to their objective intensity a difference was found for each group respectively. Participants overall had overestimated the time on task, but they had underestimated the intensity of their effort recalled 1 day after their practice. These results raise the question whether a questionnaire as method of measuring PA is reliable, especially when it is used to estimate energy expenditure. However, further studies must be made in order to examine the implications of such a question.

Endoscopic sclerotherapy plus propranolol versus propranolol alone in the primary prevention of bleeding in high risk cirrhotic patients with esophageal varices: a prospective multicenter randomized trial.

BACKGROUND: Analysis of primary prevention studies of the use of beta-blockers has shown clear reductions in variceal bleeding in cirrhotic patients with varices. In contrast, the usefulness of prophylactic endoscopic sclerotherapy, alone or in combination with propranolol, in the management of these patients is still under investigation. The present study compared the efficacy of combined sclerotherapy and propranolol versus propranolol alone in the primary prevention of hemorrhage in cirrhotic patients with varices and high (greater than 18 mm Hg) intraesophageal variceal pressure. METHODS: Patients were randomly assigned to propranolol (42 patients) or to propranolol plus sclerotherapy (44 patients). The mean duration of follow-up was 26.8 +/- 7.7 and 24.6 +/- 9.8 months, respectively. RESULTS: During this period 23% of the patients in the combination group experienced at least 1 episode of bleeding due to varices or congestive gastropathy as compared with 14% in the propranolol group (not significant). Twenty-three patients (52%) in the combination group developed complications as compared with 8 (19%) in the propranolol group (p = 0.002). The mortality rate was similar in both groups (14% and 18%, respectively). The only independent factor predictive of survival was the level of serum albumin. CONCLUSIONS: Endoscopic sclerotherapy should not be used for the primary prevention of hemorrhage in cirrhotic patients at high risk of variceal bleeding who are undergoing treatment with propranolol.

Determination of lansoprazole in biological fluids and pharmaceutical dosage by HPLC.

A simple and rapid (extractionless) high-performance liquid chromatographic method with UV detection at 230 nm was developed for the determination of lansoprazole in biological fluids and pharmaceutical dosage. Niflumic acid was added as internal standard. The separation was performed at ambient temperature on a C18 Spherisorb column with acetonitrile + 0.1 M sodium acetate (40:60, v/v, pH 7) as mobile phase. The retention time was 5.2 min for niflumic acid and 6.7 min for lansoprazole. The detection limit was 20 ng/ml using a 100 microl loop. The method was successfully applied to a pharmacokinetic study of lansoprazole in humans.

Approach to the management of bleeding esophageal varices: role of somatostatin.

Various treatment strategies have been used to control variceal bleeding, including drugs, esophageal tamponade, endoscopic sclerotherapy (ES), endoscopic variceal ligation, transjugular intrahepatic portosystemic shunt and emergency surgery. None of these procedures are ideal and treatment frequently requires a combination of techniques. Sclerotherapy is one of the most widely used methods to control variceal bleeding; however, success is largely dependent on an experienced endoscopist. Vasoactive drugs act by decreasing pressure and blood flow in the gastroesophageal collaterals and they offer the advantage of being administered by inexperienced personnel. Drugs currently used in the treatment of variceal hemorrhage include vasopressin, terlipressin, somatostatin and octreotide. In the clinical studies to date, somatostatin was more effective than vasopressin and as effective as terlipressin in the control of bleeding esophageal varices (BEV), with an improved safety profile. In contrast, octreotide has shown conflicting results and more data are required to support the drug in this indication. More recently the ABOVE (Acute Bleeding Esophageal Variceal Episodes) study has provided further evidence that early administration of vasoactive drugs such as somatostatin is significantly more effective than placebo in the overall control of acute BEV episodes in cirrhotic patients undergoing ES. Therefore, the administration of a vasoactive drug as early as possible before emergency sclerotherapy is recommended for the effective management of BEV.

Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial.

BACKGROUND: Sclerotherapy is widely used for acute variceal bleeding, although in emergencies bleeding makes it difficult to obtain the clear view required for safe and effective treatment. We investigated whether early administration of somatostatin would improve the efficacy of sclerotherapy. METHODS: In this double-blind, prospective trial, patients who had cirrhosis with upper-gastrointestinal bleeding were randomly assigned natural somatostatin (6 mg per 24 h) or placebo for 120 h. In addition, intravenous bolus doses of somatostatin (250 micrograms) or placebo were injected after the start of the infusion, before emergency endoscopy or sclerotherapy, and when active bleeding was observed. The primary endpoint was treatment failure, defined as the occurrence during the infusion period of at least one of: excess transfusion of blood products, haematemesis, haemodynamic instability, need for rescue therapy, or death. FINDINGS: 205 patients were enrolled: 101 received somatostatin and 104 received placebo. Treatment failed in 35 somatostatin and 57 placebo recipients (p = 0.004); death or use of rescue therapy occurred in nine and 19 patients, respectively (p = 0.05). The mean quantity of blood products transfused over 120 h (adjusted for baseline haemoglobin) was 2.64 (SD 0.35) units in the somatostatin group versus 3.62 (0.35) units in the placebo group (p = 0.05). At endoscopy, active bleeding from oesophageal varices was less frequent (27 vs 42 patients, p = 0.012) and the sclerotherapy procedure was easier (2.8 vs 4.7 cm, p = 0.0027) in the somatostatin than in the placebo group. INTERPRETATION: Early administration of natural somatostatin continued for 120 h, combined with additional bolus injections, is more effective than placebo in the overall control of acute variceal haemorrhage in patients with cirrhosis undergoing sclerotherapy.

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.

Extractionless high-performance liquid chromatographic method for the simultaneous determination of piroxicam and 5'-hydroxypiroxicam in human plasma and urine.

A simple and rapid (extractionless) high-performance liquid chromatographic method with UV detection, at 330 nm, was developed for the simultaneous determination of piroxicam and its major metabolite, 5'-hydroxypiroxicam, in human plasma and urine. Acidified plasma and alkali-treated urine samples are used and naproxen is added as internal standard. The separation is performed at 40 degrees C on a C18 Spherisorb column with acetonitrile--0.1 M sodium acetate (33:67, v/v, pH 3.3) as mobile phase. The retention time is 2.2 min for 5'-hydroxypiroxicam, 2.6 min for piroxicam and 3.2 min for naproxen. The detection limit is 0.05 micrograms/ml using a 100-microliters loop.

Somatostatin and octreotide in the management of acute variceal hemorrhage.

In recent years, somatostatin and its long-acting analogue octreotide have been used as the initial treatment in acute variceal hemorrhage, with conflicting results. The aim of this study was to meta-analyse all the randomised controlled trials published in English, in which somotostatin or octreotide was compared with other vasoactive drugs, balloon tamponade and endoscopic sclerotherapy in variceal hemorrhage. Concerning the control of bleeding, somatostatin or octreotide therapy was shown to be significantly better than the other vasoactive drugs (p < 0.0012, x2 = 10.55). In contrast, the effectiveness of both agents appeared to be similar to that of balloon tamponade and sclerotherapy in arresting acute variceal hemorrhage during the infusion period. Regarding the complication rate, it appears that treatment with somatostatin or octreotide is followed by a significantly lower complication rate as compared with the other vasoactive drugs (p < 0.0001, x2 = 16.47) as well as than endoscopic sclerotherapy (p, 0.0002, x2 = 14.16). In conclusion, the results of this study suggest that in acute variceal hemorrhage, somatostatin or octreotide is better than any other combination of vasoactive drugs. As regards comparison with sclerotherapy or balloon tamponade, further evidence of benefit is needed before a recommendation can be made for the use of instead of these two kind of treatments of the former procedures.