Neven Ljubičić

Comparison of Surgical Treatments of Gallstone Ileus: Preliminary Report

Gallstone ileus is an uncommon cause of small bowel obstruction, accounting for only 1% to 4% of all intestinal obstructions. In the group of patients over 65 years of age, gallstones cause about 25% of all non-strangulated obstructions of the small bowel. Gallstone ileus is burdened with high mortality rate, ranging from 12% to 18%, and most patients are of advanced age, with many other concomitant diseases that may increase the operative risk. The purpose of this study was to compare the two investigated surgical procedures: treatment of intestinal obstruction alone or combined with urgent cholecystectomy and fistula repair. Analysis of 30 patients undergoing operation for gallstone ileus at the Clinical Hospital “Sestre milosrdnice” between 1985 and 2001 is presented. Patients were treated either for ileus alone (group 1, 11 patients) or as one-stage procedure with urgent fistula closure (group 2, 19 patients). Operating time was significantly longer for the one-stage procedure. Complications occurred in 3 of 11 patients (27.3%) from group 1 and in 11 of 18 patients (61.1%) from group 2 (one tailed, p = 0.043). One patient in group 1 died and two patients in group 2 died. Urgent fistula repair was significantly associated with the occurrence of complications (odds ratio [OR] 12.1, 95% confidence internal [95% CI] 1.2–121.5). Simple enterotomy should be the procedure of choice for patients with gallstone ileus. The one-stage procedure including urgent fistula repair should be reserved only for highly selected patients with absolute indications.

Influence of the Degree of Liver Failure on Portal Blood Flow in Patients with Liver Cirrhosis

Portal vein haemodynamics as demonstrated by the pulsed Doppler system were studied in 37 patients with cirrhosis who had been classified in three groups (A, B, and C) in accordance with the degree of liver failure. Maximal inner diameter of the portal vein was significantly lower in patients who were considered to be in good condition (group A) than in patients with moderate and severe liver failure (group B and group C) (p less than 0.001). A significant difference was also found between group A and group B and between group A and group C with regard to the portal blood velocity and portal blood flow (p less than 0.001). In accordance with the presence and size of the oesophageal varices, in patients with large varices the portal blood velocity and portal blood flow were significantly lower than in patients without varices (p less than 0.001), whereas maximal inner portal vein diameter was significantly higher (p less than 0.001). This study demonstrated that in patients with cirrhosis circulatory alterations in the portal vascular bed may be, at least in part, an indicator of the stage of liver disease.

Effect of cyclosporine in a murine model of experimental colitis.

The use of immunosuppressive therapy may be associated with significant toxicity. The aim of this study was to investigate the effect of cyclosporine A (CsA) in murine model of experimental colitis. Experimental colitis was induced in NMRI mice using an enema of 0.2% solution of dinitrofluorobenzene, combined with skin sensitization. After inducing colitis, experimental groups of animals were treated with CsA (1, 3, 5, 10, 25, 50 mg/kg/day) intraperitoneally (i.p.) or intracolonically (i.c.), and control groups were treated with phosphate-buffered saline intraperitoneally or intracolonically, respectively. Colonic inflammatory changes were assessed using a histopathologic score of 0–30, and pooled whole blood samples were processed with monoclonal antibodies for cyclosporine concentration. In addition, two groups of animals with experimental colitis were treated intraperitoneally or intracolonically with 3 mg/kg/day of CsA, and the colons were also taken for immunohistochemistry for CD25. CsA diminished the extent of colitis in groups treated with 3, 5, 10, or 25 mg/kg intraperitoneally or intracolonically, and in groups treated with 1 and 50 mg/kg intracolonically (P < 0.05). The effect of intracolonic application of CsA was not related to whole blood cyclosporine concentrations. In addition, the effect of CsA at 3 mg/kg, applied intraperitoneally or intracolonically was, in part, expressed in decreasing the numbers of CD25+ cells within colonic mucosa/submucosa (P < 0.05). In conclusions, the results of this study indicate the possibility of intracolonic application of cyclosporine in order to widen the therapeutic window for effective, but possibly toxic drug, such as cyclosporine.

Doppler Ultrasound of Hepatic and System Hemodynamics in Patients with Alcoholic Liver Cirrhosis

OBJECTIVE The progression of liver cirrhosis eventually increases cardiac output, while blood pressure and systemic vascular resistance are reduced. A complex behavior of portal hemodynamic to hepatic artery and system circulation has not yet been presented. There is a lack in knowledge about the correlation of local and systemic circulation parameters to the degree of liver failure, with respect to presence of ascites and esophageal varices. PATIENTS AND METHODS The study sample was 76 patients hospitalized for established alcoholic liver cirrhosis. Patients were divided into groups according to Child-Pugh clinical score; grade A (n = 24), B (n = 18) and C (n = 18). Ascites was found in 28 patients and esophageal varices in 46. Portal vein flow velocity (PVFV), hepatic artery resistance index (HARI), heart and great vessels within mediastinal cavity were assessed with ultrasound devices equipped with spectral Doppler. RESULTS Significant differences in mean blood pressure, systemic vascular resistance index (SVRI) minute volume, cardiac index and PVFV were found in the group of patients with the most severe stage (C). In regard to presence of ascites statistically significant difference was observed in elevated mean blood pressure and SVRI. Correlation was found between conjugated HARI to blood pressure and to SVRI. CONCLUSIONS In patients with liver cirrhosis there is an inversely reciprocal relationship of conjugated HARI with PVFV, correlating to disease grade. PVFV in cirrhosis decreases and HARI values were over 0.7. Study demonstrated that combining echocardiography with abdominal Doppler ultrasound served as valuable non-invasive diagnostic insight in liver and systemic circulation among different grade of cirrhosis.

Glasgow Blatchford, pre-endoscopic Rockall and AIMS65 scores show no difference in predicting rebleeding rate and mortality in variceal bleeding

Abstract Objective: To compare the performance of the Glasgow Blatchford score (GBS), pre-endoscopic Rockall score (PRS) and AIMS65 score in predicting specific clinical endpoints following variceal upper gastrointestinal hemorrhage (UGIH). Material and methods: Between January 2008 and December 2013, we retrospectively analyzed 225 consecutive hospitalized patients managed for endoscopically confirmed UGIH. Results: A total of 225 patients (mean age 61.3 years), mostly diagnosed with alcoholic cirrhosis (195/86.7%), presented with variceal UGIH during the study period. Rebleeding occurred in 22 (9.8%) patients and 30-day mortality was 39 (17.3%). Initial hemostasis was achieved with N-butyl cyanoacrylate (151/79.1%) and endoscopic variceal ligation (40/20.9%), while secondary rebleeding prophylaxis in 110 (48.9%) patients was accomplished using endoscopic variceal ligation (92%). The majority of patients died from the underlying disease, while 12 (30.8%) died from bleeding. Median hospital stay was 6 (1–35) days. There was no statistically significant difference among AIMS65, GBS and PRS in predicting mortality (AUROC 0.70 vs. 0.64 vs. 0.66) or rebleeding rates (AUROC 0.74 vs. 0.60 vs. 0.67). The GBS was superior in predicting the need for blood transfusion compared to AIMS65 score (AUROC 0.75 vs. 0.61, p = 0.01) and PRS (AUROC 0.75 vs. 0.58, p = 0.009). Conclusions: The AIMS65, GBS and PRS scores are comparable but not useful for predicting outcome in patients with variceal UGIH because of poor discriminative ability. The GBS is superior in predicting the need for transfusion compared to AIMS65 score and PRS.

Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent bleeding

AIM To compare the recurrent bleeding after endoscopic injection of different epinephrine volumes with hemoclips in patients with bleeding peptic ulcer. METHODS Between January 2005 and December 2009, 150 patients with gastric or duodenal bleeding ulcer with major stigmata of hemorrhage and nonbleeding visible vessel in an ulcer bed (Forrest IIa) were included in the study. Patients were randomized to receive a small-volume epinephrine group (15 to 25 mL injection group; Group 1, n = 50), a large-volume epinephrine group (30 to 40 mL injection group; Group 2, n = 50) and a hemoclip group (Group 3, n = 50). The rate of recurrent bleeding, as the primary outcome, was compared between the groups of patients included in the study. Secondary outcomes compared between the groups were primary hemostasis rate, permanent hemostasis, need for emergency surgery, 30 d mortality, bleeding-related deaths, length of hospital stay and transfusion requirements. RESULTS Initial hemostasis was obtained in all patients. The rate of early recurrent bleeding was 30% (15/50) in the small-volume epinephrine group (Group 1) and 16% (8/50) in the large-volume epinephrine group (Group 2) (P = 0.09). The rate of recurrent bleeding was 4% (2/50) in the hemoclip group (Group 3); the difference was statistically significant with regard to patients treated with either small-volume or large-volume epinephrine solution (P = 0.0005 and P = 0.045, respectively). Duration of hospital stay was significantly shorter among patients treated with hemoclips than among patients treated with epinephrine whereas there were no differences in transfusion requirement or even 30 d mortality between the groups. CONCLUSION Endoclip is superior to both small and large volume injection of epinephrine in the prevention of recurrent bleeding in patients with peptic ulcer.

New insight into the role of NT-proBNP in alcoholic liver cirrhosis as a noninvasive marker of esophageal varices

Aim To investigate the association between plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and formation of esophageal varices. Methods Thirty-five patients with alcoholic cirrhosis were divided into three groups according to the Child-Pugh classification: grade A (n = 11, 32%), B (n = 12, 34%), and C (n = 12, 34%). System hemodynamic parameters were measured using sphygmomanometry, electrocardiography, and echocardiography. NT-proBNP was analyzed by using an electrochemiluminiscence sandwich immunoassay. Results The presence of esophageal varices was associated with a higher serum NT-proBNP level, with a cut-off value of >101 pg/mL (sensitivity, 87.60% and specificity, 72.73%; P < 0.001). Conclusions NT-proBNP was found to be a marker of the presence of esophageal varices, but not a marker of progression of liver cirrhosis. In cirrhotic patients, NT-proBNP value >101 pg/mL was shown to be a valuable noninvasive parameter in predicting the presence of varices.

Nutritional Screening Model in Tertiary Medical Unit in Croatia

Background/Aims: Malnutrition of hospitalized patients is often undetected and untreated due to poor awareness and insufficient knowledge of the attending hospital staff. Nutritional screening has not been part of the daily routine in Croatian hospitals. Our aim was to implement nutritional screening as part of the routine medical examination and to assess the nutritional risk at admission for all hospitalized patients. Methods: All patients hospitalized in departments of internal medicine in tertiary hospitals in Croatia were screened at entry using the Nutrition Risk Screening 2002 (NRS 2002). Results: Between October and December 2010, 1,696 patients were screened and analyzed (948 males and 748 females). 329 (19.4%) had an NRS 2002 score ≥3 and were considered to be at nutritional risk. An NRS 2002 score ≥3 was identified as a significant predictor of the length of hospital stay (beta coefficient = 0.06, p = 0.027) and fatal outcome (OR = 6.18, p < 0.001). Only 32.8% of malnourished patients received some nutritional support. Conclusions: Every fifth patient hospitalized in a general medical department in Croatia is at nutritional risk and the majority of them does not receive nutritional support. More effort is needed to implement nutritional standards in daily clinical practice.

Decrease in insulin resistance has a key role in improvement of metabolic profile during intragastric balloon treatment

To the Editor, Obesity is a chronic polygenic disease in most cases [1]. Despite the different pathogenesis, all obese individuals have something in common: low growth hormone (GH) levels and increased insulin levels [2]. This hormonal imbalance plays an important role in other metabolic disorders, such as glucose intolerance and dyslipidemia. Adipose tissue mass is also important factor. It is an endocrine organ that secrets several metabolic hormones and proinflammatory cytokines. The intensity of their secretion positively correlates with adipose tissue mass [3]. Weight loss improves metabolic profile, although the exact mechanism is poorly understood. A detailed study regarding this matter was published only 1 year ago. The authors disclosed that diet-induced weight loss increases GH and ghrelin levels and decreases insulin and leptin levels [2]. However, neither one study analyzed parallel changes in metabolic hormones and metabolic profile in short time intervals during weight loss. Hence, the exact causative relations between these hormones are unknown. BioEnterics intragastric balloon (BIB) is a endoscopic method in obesity treatment. The balloon placed in the stomach delays stomach emptying and enhances the feeling of satiety [4]. We aimed to investigate changes in serum insulin, C-peptide, GH, blood glucose, glycated hemoglobin, insulin resistance and lipid profile in first, third and sixth month after BIB placement. Since our previous study showed that the change in ghrelin and leptin levels during BIB treatment considerably depends on body mass index (BMI) [5], we analyzed those changes separately in obese (BMI \40 kg/m) and morbid obese (BMI \40 kg/m) patients.

Lack of prognostic significance of connexin-43 labeling in a series of 46 gastrointestinal stromal tumors

Background Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors with variable malignant potential. Connexin-43 (C×43) is the commonest gap-junction protein and has been frequently investigated in oncology. Our aim was to establish the immunohistochemical expression of C×43 in relation to GIST location, size, Ki67 index, tumor grade and follow-up. Materials and methods The study included postoperative samples of 46 patients treated for GIST in the 1999–2010 time frame. Complete clinical workup was available for 38 patients (82.6%); total surgical resection was carried out in 32 (84.2%) patients, while 13 (34.2%) patients underwent chemotherapy. Median follow-up was 40.7 months (range, 1-134). Results The calculated incidence of GIST in our setting was 11.5 per million. C×43 was expressed in 43/46 (93.5%) GIST cases, with a significant difference between stomach- and small intestine-derived tumors (p=0.006). Ki67 was 10% on average (range, 1–22) and was not correlated with tumor location (p=0.194). C×43 did not show significance with regard to tumor size (p=0.264) or higher tumor grade (p=0.658), as opposed to Ki67, which significantly correlated with both (p=0.0048 and p<0.001, respectively). C×43 and Ki67 were not significantly correlated (p=0.708). Ki67 correlated with time to recurrence (p=0.022). Ki67 >11% was taken as the indication to start imatinib chemotherapy (sensitivity 61.5%, specificity 92.0%, p=0.022). Ten (66.7%) of 15 patients with long-term (>5 years) follow-up were in remission. Conclusion C×43 was frequently expressed in GISTs regardless of tumor site. However, no significant relationships to histopathological parameters suggestive for prognosis were found. Further investigations might clarify the roles of C×43 in GIST oncogenesis.