Konstantinos Mimidis

Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis

BACKGROUND/AIMS The usual clinical practice is to screen all patients with established cirrhosis at the time of diagnosis by upper endoscopy for the presence of varices. Patients with large varices should be treated with non-selective beta blockers to reduce the incidence of first variceal bleeding. However, fewer than 50% of cirrhotic patients have varices at screening endoscopy and most have small sized varices, with a low risk of bleeding. The aim of the present study was to determine whether clinical or laboratory non-endoscopic parameters could predict the presence of large oesophageal varices. PATIENTS/METHODS Seventeen variables considered relevant to the prevalence of oesophageal varices were tested in 184 patients with cirrhosis, who underwent screening endoscopy. Small varices were regarded as those which flatten with insufflation or slightly protrude into the lumen, while large varices are those which protrude into the lumen or touch each other. None of the patients was on beta blockers or other vasoactive drugs or had a history of variceal bleeding. RESULTS Oesophageal varices were present in 92 patients (50%), and large varices in 33 patients (17.9%). Variables associated with the presence of large oesophageal varices on univariate analysis were the presence of ascites and splenomegaly either by clinical examination or by ultrasound (p < 0.01), the presence of spiders (p = 0.02), platelet count (p < 0.0001), and bilirubin (p = 0.01). Factors independently associated with the presence of large oesophageal varices on multivariate analysis were platelet count, size of spleen and presence of ascites by ultrasound. Using mean values as cut-off points, it is noteworthy that only five out of 39 patients (12.8%) with platelets > or = 18(x 10(9)/l), spleen length < or = 135 mm and no ascites had varices. Moreover, all these patients had small sized varices. On the other hand, 15 out of 18 patients (83.3%) with a platelet count < 118 x 10(9)/l, spleen length > 135 mm and ascites had varices. Moreover, five out of those 18 patients had large varices (28.3%). CONCLUSION Thrombocytopenia, splenomegaly and ascites are independent predictors of large oesophageal varices in cirrhotic patients. We suggest that endoscopy could be avoided safely in cirrhotic patients with none of these predictive factors, as large varices are absent in this group of patients.

Increased frequency of mutations in the gene responsible for familial Mediterranean fever (MEFV) in a cohort of patients with ulcerative colitis: evidence for a potential disease-modifying effect?

The MEFV gene, responsible for familial Mediterranean fever (FMF), is involved in inflammatory reactions through altered leukocyte apoptosis, secretion of interleukin (IL)-1β, and activation of the NF-κ B pathway. Ulcerative Colitis (UC) and FMF are both characterized by a recurrent pattern of presentation with periods of remission and flares associated with neutrophilic infiltration at the site of injury. The aim of this study was to investigate the possible correlation between UC and MEFV gene alterations. Twenty-five consecutive, first-diagnosed and untreated UC patients, 28 control patients with rheumatoid arthritis, and 65 normal individuals were analyzed. Nonisotopic RNase Cleavage Assay (NIRCA) was applied as a first-step mutational screening method of exons 10 and 2 of MEFV gene; direct sequencing was subsequently performed to confirm the results. MEFVmutations were identified in 7 (3 M694V/0, 2 M680I/0, 1 E148Q/E148Q, and 1 A744S/0) out of 25 UC patients versus 1 (M694V/0) out of 28 rheumatoid arthritis patients (P = .0199) and 1 (M694V/0) out of 65 healthy controls (P = .0004). Four out of 7 patients with MEFVmutations had inflammatory arthritis, a clinical finding that was not observed in the 18 UC patients with unmutated MEFV (P = .0028). Patients with UC almost universally carried the T A C G MEFV exon 2 haplotype in contrast with normal individuals (P < .0001) and FMF patients (P = .0310). In conclusion the increased frequency of mutations of MEFV in UC patients, especially in those with episodic arthritis, suggests a possible modifying effect of MEFV in the disease process and its localization within the joint. The difference in distribution of MEFV exon 2 haplotypes between UC patients and both FMF patients and normal individuals, suggests that UC patients constitute a genetically distinct population. Larger, longitudinal studies are needed to confirm these initial findings.

Mucocele of the appendix: a report of five cases

Abstract.Mucocele of the appendix is an uncommon disorder, characterized by a cystic dilatation of the lumen. It is often diagnosed clinically from signs and symptoms of acute appendicitis or, if it is asymptomatic, as an incidental finding during ultrasonography, computed tomography, and radiographic examinations of the gastrointestinal tract, or laparotomy. The incidence of mucocele ranges from 0.2% to 0.3% of all appendectomy specimens. We report five cases of appendiceal mucocele (all women, aged 19–90 years), who were admitted from January 1993 to January 2003 to our hospital. These cases represent 0.29% of the 1720 appendectomies performed during this period. Three of the patients were symptomatic and had appendectomies. The final diagnosis for mucocele was given at laparotomy. No colon neoplasms were identified during surgery, and subsequent colonoscopic examinations were also negative. The other two patients were asymptomatic of appendiceal tumor. Colonoscopy revealed two colonic malignant tumors in one patient and an adenocarcinoma of the sigmoid colon in the other. Mucocele of the appendix was diagnosed pre–operatively by ultrasound and computed tomography. One of the two patients underwent a right hemicolectomy and sigmoidectomy; the other one underwent an appendectomy, cecostomy and sigmoidectomy. Four of the patients recovered and are doing well today; one patient died on the twenty–fifth postoperative day. The most common symptom of mucocele is abdominal pain, although many patients may be asymptomatic. Mucocele is often associated with concomitant colon cancer, thus patients with this tumor should be systematically checked for other colonic lesions.

A viral kinetic study using pegylated interferon alfa‐2b and/or lamivudine in patients with chronic hepatitis B/HBeAg negative

We studied viral dynamic parameters in 44 chronic hepatitis B/hepatitis B e antigen (HBeAg)(−) patients treated with pegylated interferon alfa‐2b (PEG‐IFN) 100 or 200 μg weekly or lamivudine 100 mg daily or the combination of PEG‐IFN 100 or 200 μg with lamivudine. Patients receiving PEG‐IFN monotherapy exhibited viral load oscillations between weekly injections, which were resolved by the addition of lamivudine. The median pharmacological delay was estimated at 4.1, 5.8, and 1.8 hours in PEG‐IFN monotherapy, PEG‐IFN 100/200 μg + lamivudine, and lamivudine monotherapy, respectively (P = .44). The median half‐life of free virus was 12.7 hours (range, 2.4‐69.2 hours). The mean antiviral effectiveness of PEG‐IFN 100/200 μg monotherapy was lower than that of lamivudine (82.6% vs. 96.4%; P = .005). The mean effectiveness of PEG‐IFN 100 μg + lamivudine and PEG‐IFN 200 μg + lamivudine was 92.8% and 94.4%, respectively. The half‐life of infected cells ranged from 2.7 to 75 days. The median half‐life of infected cells in patients receiving the combination regimens of PEG‐IFN and lamivudine was similar to that of lamivudine patients (5.0 days vs. 6.0 days, P = .77). In conclusion, the addition of pegylated interferon alfa‐2b in lamivudine treatment was found to neither enhance the potency of blocking HBV production nor the decay rates of infected cells. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270‐9139/suppmat/index.html). (HEPATOLOGY 2005;42:77–85.)

Predisposing factors and clinical symptoms in HIV-negative patients with Candida oesophagitis: are they always present?

Candida oesophagitis (CO) is scarce among immunocompetent patients. This study aimed at evaluating predisposing factors, clinical symptoms and endoscopic findings in this group. We retrospectively reviewed 55 patients diagnosed as CO endoscopically (whitish plaques) and cytologically (fungal mycelia on brush cytology). Carcinoma, diabetes, acid suppression, steroids, gastric surgery and oesophageal motility disorders were considered as predisposing factors. Twenty of 55 patients lacked any predisposing factor for CO. These patients were more frequently asymptomatic (8/20) when compared with those with known predisposing factors (5/35) (p = 0.031). Moreover, dysphagia was more prevalent in the latter group (24/35 vs. 8/20; p = 0.039). Endoscopic findings correlated with the presence of neither predisposing factors nor symptoms (Wilcoxon p > 0.05). Thus, CO can be discovered in patients without apparent predisposing risk factors and clinical symptoms. Further studies are needed to elucidate the mechanisms of transition from colonisation to infection.

Factors associated with failure of endoscopic injection haemostasis in bleeding peptic ulcers.

BACKGROUND The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. METHODS In the period 1992 to 1998, we prospectively studied all patients suffering from peptic ulcer bleeding and identified endoscopically as being either bleeding actively or carrying a visible vessel. A total of 427 patients (343 men and 84 women; mean age 58.6 +/- 16.6 years) were all subjected to endoscopic injection with adrenaline solution on an emergency basis. Patients who eventually required surgical intervention for permanent haemostasis were considered as endoscopic haemostasis failures, whereas those who did not were considered as endoscopic treatment successes. We evaluated all clinical and endoscopic parameters that might have been related to failure of endoscopic injection therapy. RESULTS Endoscopic injection haemostasis was successful in 341 patients (79.9%) and a failure in 86 (20.1%) who finally underwent emergency surgical haemostasis. On analysing the examined parameters, failure was significantly related to shock on admission (OR 2.31, 95% CI 1.33, 6.97), spurt bleeding at endoscopy (OR 2.45, 95% CI 1.51, 3.98), posteriorly located duodenal ulcer (OR 2.48, 95% CI 1.37, 7.01) and anastomotic ulcer (OR 3.39, 95% CI 1.37, 7.29). Endoscopic injection haemostasis therapy was less effective in patients with chronic ulcers compared to those who had acute NSAID-related ulcers. A history of peptic ulcer (OR 1.57, 95% CI 1.14, 3.05), previous peptic ulcer bleeding (OR 2.45, 95% CI 1.51, 3.98) or non-use of NSAIDs (OR 2.81, 95% CI 1.33, 4.62) were negative predictors for the outcome of endoscopic haemostasis. CONCLUSION With the use of specific clinical and endoscopic characteristics it is possible to define a subgroup of high-risk patients for continued bleeding or rebleeding despite endoscopic injection therapy. These patients may be candidates for intensive monitoring, early surgical intervention or possibly complementary endoscopic haemostatic methods.Background: The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. Methods:

Seasonality in the prevalence of acute upper gastrointestinal bleeding

The seasonal fluctuations of acute upper gastrointestinal bleeding treated from 1991 to 1996 in Patras, Greece, were analyzed retrospectively. During that period, 1992 patients with acute upper gastrointestinal bleeding were admitted to our hospital. After patients who were not residents of the region served by our hospital were excluded, the remaining 1879 cases were reviewed. We observed seasonal fluctuation with low prevalence in winter and an increase in spring and autumn with two peaks in April and October (p < 0.00001). The seasonal prevalence parallels that of duodenal ulcer bleeding, which follows a similar fluctuation (p < 0.00001). Bleeding due to gastric ulcers or other causes presented no periodicity. Seasonal fluctuation, both in total numbers of upper gastrointestinal bleeding and in duodenal ulcer bleeding, was statistically significant only in patients not receiving nonsteroidal anti-inflammatory drugs (p < 0.00001). We conclude that upper gastrointestinal bleeding shows a seasonal fluctuation parallel to duodenal ulcer bleeding and is not related to nonsteroidal anti-inflammatory drugs. The seasonal pattern supports the traditional view of duodenal ulcer exacerbations.

The usefulness of PCR amplification of the IS6110 insertion element of M. tuberculosis complex in ascitic fluid of patients with peritoneal tuberculosis

Background: The diagnosis of tuberculous peritonitis (TP) may be difficult and elusive. The present study was designed to demonstrate the diagnostic usefulness of a nested polymerase chain reaction (PCR) assay, specific for the IS6110 insertion element of M. tuberculosis complex, in patients with ascites who were suspected of having TP in order to achieve a more timely diagnosis and treatment. Methods: Three HIV-negative patients suffering from fever and ascites were evaluated for suspected TP. Specimens were obtained from ascitic fluid, bone marrow, and peripheral blood and analyzed by both conventional methods and nested PCR for the presence of bacilli. Response to antituberculous treatment was considered as the final criterion for diagnosis of peritoneal tuberculosis. Results: All three patients had an excellent response to antituberculous therapy. Our PCR-based protocol detected M. tuberculosis complex DNA in the ascitic fluid of all patients, whereas conventional methods failed to establish the disease. Furthermore, in one patient, M. tuberculosis was also detected in both bone marrow and peripheral blood. Conclusions: PCR amplification of the IS6110 sequence of M. tuberculosis complex in ascitic fluid is a useful tool when peritoneal tuberculosis is suspected. However, its validity still needs to be established.

In vivo induction of the autophagic machinery in human bone marrow cells during Leishmania donovani complex infection.

Autophagy is a homeostatic process promoting cell survival in periods of stress. The induction of the autophagic machinery has also been implicated in both innate and adaptive immunity. Leishmania donovani, which is the causative pathogen of visceral leishmaniasis, is an intracellular parasite that invades and multiplies in bone marrow macrophages. We describe the induction of host cell autophagic machinery during acute natural bone marrow infection by L. donovani complex, detected by LC3B immunoblot. The successful treatment with liposomal amphotericin B resulted in the resolution of this phenomenon. Even though the role of autophagy in parasite biology has been previously studied, our findings show for the first time the in vivo host cell LC3B conversion as a marker of the induction of the autophagic machinery during infection with Leishmania parasite in real time conditions.

Esophageal and small bowel obstruction by occupational bezoar: report of a case

BackgroundPhytobezoar may be a cause of bowel obstruction in patients with previous gastric surgery. Most bezoars are concretions of poorly digested food, which are usually formed initially in the stomach. Intestinal obstruction (esophageal and small bowel) caused by an occupational bezoar has not been reported.Case presentationA 70-year old male is presented suffering from esophageal and small bowel obstruction, caused by an occupational bezoar. The patient has worked as a carpenter for 35 years. He had undergone a vagotomy and pyloroplasty 10 years earlier. The part of the bezoar, which caused the esophageal obstruction was removed during endoscopy, while the part of the small bowel was treated surgically. The patient recovered well and was discharged on the 8th postoperative day.ConclusionsSince occupational bezoars may be a cause of intestinal obstruction (esophageal and/or small bowel), patients who have undergone a previous gastric surgery should avoid occupational exposures similar to the presented case.