Szabolcs Ábrahám

Kupffer cell blockade improves the endotoxin-induced microcirculatory inflammatory response in obstructive jaundice

Cholestasis predisposes to hypersensitivity to LPS, leading to potential septic complications. We set out to characterize the involvement of Kupffer cell (KC) activation in the hepatic microcirculatory and structural consequences of obstructive jaundice in the presence and absence of acute endotoxemia. The hepatic microcirculatory consequences of 3-day extrahepatic bile duct ligation (BDL) were assessed in rats. The contributions of changes in hepatic perfusion, leukocyte influx, and proinflammatory cytokine release to the development of hepatic structural damage were also determined. Furthermore, the corresponding consequences of BDL in combination with acute (2-h) endotoxemia (1 mg kg−1 LPS, i.v.) were compared with those observed after LPS alone. In a second series, the same protocols were applied in identical groups of rats where the KC function was inhibited with 24-h gadolinium chloride pretreatment (10 mg kg−1, i.v.). Bile duct ligation induced minor inflammatory reactions but caused a marked reduction in hepatic sinusoidal perfusion and severe histological damage. LPS treatment, however, elicited an approximately 5-fold increase in leukocyte adherence in the central venules and pronounced IL-6 and TNF-&agr; release, but without significant structural damage. The combination of BDL with LPS enhanced the perfusion failure, leukocyte sticking/deposition, and proinflammatory cytokine release; most of these changes can be effectively ameliorated by gadolinium chloride. In conclusion, when obstructive jaundice is followed by a second hit of LPS, perfusion failure, liver inflammation, and structural damage are enhanced, the KCs playing a decisive role in this scenario. Therapeutic strategies aimed at KC blockade can potentially reduce the risk of inflammatory complications in cholestasis.

The effects of laparoscopic Nissen fundoplication on Barrett's esophagus: Long-term results

Abstract Objective. The aim of our study was to conduct a retrospective investigation of the efficacy of laparoscopic Nissen fundoplication in patients with Barretts esophagus. Material and methods. A total of 78 patients with Barretts esophagus underwent surgery. Patients were divided into three groups on the basis of the preoperative endoscopic biopsies: a non-intestinal group (n = 63) with fundic or cardiac metaplasia, an intestinal group (n = 18) with intestinal metaplasia, and a dysplastic group (n = 7) with low-grade dysplasia. Clinical follow-up was available in the case of 64 patients at a mean of 42 ± 16.9 months after surgery. Results. Check-up examination revealed total regression of Barretts metaplasia in 10 patients. Partial regression was seen in 9 cases, no further progression in 34 patients, and progression into cardiac or intestinal metaplasia in 11 patients. No cases of dysplastic or malignant transformation were registered. Where we observed the regression of BE, among the postoperative functional examinations results of manometry (pressure of lower esophageal sphincter) and pH-metry were significantly better compared with those groups where no changes occurred in BE, or progression of BE was found. Discussion. Our results highlight the importance of the cases of fundic and cardiac metaplasia, which can also transform into intestinal metaplasia. Conclusions. Antireflux surgery can appropriately control the reflux disease in a majority of the patients who had unsuccessful medical treatment, and it may inhibit the progression and induce the regression of Barretts metaplasia in a significant proportion of these patients.

A pilot study on faecal MMP-9: a new noninvasive diagnostic marker of colorectal cancer.

Background:Colorectal cancer (CRC) is one of the leading malignancies worldwide, therefore cheap noninvasive screening methods are of great importance. Matrix-metalloproteinase-9 (MMP-9) has a role in the progression of CRC, and its level is elevated in tumour biopsies. Faecal MMP-9 levels are increased in active ulcerative colitis patients, but in CRC patients, they have never been measured. We aimed to assess the faecal MMP-9 levels in patients undergoing total colonoscopy according to endoscopic and histological diagnosis.Methods:One hundred and nine patients provided faecal samples for MMP-9 analysis. A total colonoscopy was performed; suspicious lesions were evaluated by histology. Faecal MMP-9 levels were measured by ELISA.Results:The number of patients allocated to different groups were: negative/diverticulosis: 34 (referred to as controls); hyperplastic polyps: 15; adenomas: 32 (22 at high risk); and CRC: 28. Faecal MMP-9 was significantly increased in CRC compared with all other groups (P<0.001). Faecal MMP-9 was suitable to distinguish CRC patients from controls (sensitivity: 89.3%; specificity: 91.2%). By means of a lower cutoff level, faecal MMP-9 identified high-risk adenomas besides CRC (sensitivity: 76%; specificity: 85.3%). This lower cutoff level screened 59% of high-risk adenomas.Conclusions:Faecal MMP-9 may be a promising new noninvasive marker in CRC.

Effects of Kupffer cell blockade on the hepatic expression of metallothionein and heme oxygenase genes in endotoxemic rats with obstructive jaundice.

AIMS Heme oxygenase (HO) and metallothionein (MT) genes are rapidly upregulated in the liver by pro-inflammatory cytokines and/or endotoxin as protection against cellular stress and inflammation. Gadolinium chloride (GdCl₃)-induced Kupffer cell blockade has beneficial consequences in endotoxemia following bile duct ligation. Herein we further characterized the effects of Kupffer cell inhibition on the activation of the antioxidant defense system (HO and MT gene expressions, and antioxidant enzyme activities) in response to endotoxemia and obstructive jaundice. MAIN METHODS The isoform-specific expression of MT and HO genes was assessed (RT-PCR) in rat livers following 3-day bile duct ligation, 2-h lipopolysaccharide treatment (1mg/kg) or their combination, with or without GdCl₃ pretreatment (10 mg/kg, 24h before endotoxin). Lipid peroxidation, DNA damage and hepatic antioxidant enzyme activities were also assessed. KEY FINDINGS All these challenges induced similar extents of DNA damage, whereas the lipid peroxidation increased only when endotoxemia was combined with biliary obstruction. The MT and HO mRNA levels displayed isoform-specific changes: those of MT-1 and HO-2 did not change appreciably, whereas those of MT-2 and HO-1 increased significantly in 2-h endotoxemia, with or without obstructive jaundice. Among the enzymes reflecting the endogenous protective mechanisms, the catalase and copper/zinc-superoxide dismutase levels decreased, while that of Mn-SOD slightly increased. Interestingly, GdCl₃ alone induced lipid peroxidation, DNA damage and MT-2 expression. In response to GdCl₃, HO-1 induction was significantly lower in each model. SIGNIFICANCE Despite its moderate hepatocellular toxicity, the ameliorated stress-induced hepatic reactions provided by GdCl₃ may contribute to its protective effects.

Prospective Comparison of Magnetic Resonance Imaging, Transrectal and Transperineal Sonography, and Surgical Findings in Complicated Perianal Crohn Disease

Magnetic resonance imaging (MRI) and transrectal sonography are the two accepted imaging modalities for evaluation of perianal fistulas and abscesses. Transperineal sonography is a new technique that is easy to learn and can be performed at any time. The purpose of this study was to prospectively compare the diagnostic accuracy of MRI, transrectal sonography, and transperineal sonography with surgical findings in patients with perianal Crohn disease.

Role of laparoscopic surgery in the treatment of ulcerative colitis; short- and mid-term results

Abstract Objectives. Laparoscopy is used more widely for the surgery of ulcerative colitis. The objective of this study was a comparison of the surgical and 3-year follow-up results of patients treated with conventional and minimally invasive methods. Materials and methods. A total of 45 patients received surgery for ulcerative colitis, 16 as emergency and 29 as elective cases. Laparoscopy was used in 23 and a conventional method in 22 cases. No difference was found between the two groups from the aspects of American Society of Anesthesiologists physical status (ASA) class, mean body mass index (BMI) and age. There were 4 emergency cases in the laparoscopy group, and 12 in the open group. Nineteen elective surgeries were performed in the laparoscopy group, and 10 in the open group. Results. There was no significant difference between the groups as concerns the length of hospital or intensive care unit (ICU) stay, the time to bowel function recovery, but the duration of open surgery was significantly shorter. There was no difference between the groups in the rate of early postoperative complications, whereas among potential late complications, the rates of intestinal obstruction (8.7% vs. 45%) and a septic condition (0% vs. 27%) were significantly lower in the laparoscopy group. There was a significant improvement in the quality of life after surgery in both groups, and better cosmetic results were observed in the laparoscopy group. Conclusion. Laparoscopy can be used for ulcerative colitis both emergency and elective cases, it provides a good quality of life and the mid-term rate of complications is lower as compared with open surgery.

Efficacy of combined anti-TNF-alpha and surgical therapy in perianal and enterocutaneous fistulizing Crohn’s disease – clinical observations from a tertiary Eastern European center

Abstract Background and aims. Recently, anti-TNF-alpha therapy has increasingly been used in the treatment of perianal Crohn’s disease (PCD), but there is only limited data regarding its short- and long-term efficacy. Material and methods. The medical records of 68 patients treated with anti-TNF-alpha for PCD were assessed retrospectively. Rate of complex fistulas was 75%. Every patient received induction therapy, but in 20 cases the treatment was discontinued before week 52 due to funding regulations, an allergic reaction, or compliance problems. On week 12, the luminal activity decreased in more than 80% of the cases and the complete remission (CR) rate was about 60%; by the end of the first year, this ratio did not change substantially. Complete fistula closure was achieved in 26 cases (38.3%) and 53 patients (51.5%) showed a partial response during the 1-year period. Regarding both perianal and luminal activities, CR rate was achieved in 23 cases (33.8%). However, after the biological therapy was discontinued, recurrence of fistulas could be detected in every second patient. Additional surgical intervention was performed in 45% of patients during the 1-year period (seton drainage of fistulas and abscess drainage). Conclusion. The anti-TNF-alpha therapy combined with surgery is an effective treatment of PCD. Approximately every third patient revealed complete fistula closure, while half of the other cases showed a partial response. Due to the high rate of fistula recurrence after stopping the biological therapy, more than 1 year of anti-TNF-α treatment may be beneficial.

Laparoscopic Splenectomy Is a Safe Method in Cases of Extremely Large Spleens

INTRODUCTION The aim of this study was to assess if there is a relationship between the outcome of laparoscopic splenectomy (LS) procedures and the size of the spleen, the learning curve, or the method of specimen retrieval. PATIENTS AND METHODS Between January 1, 2002 and December 31, 2013, 70 LS procedures were performed at our department. Based on the weight of the removed spleen, patients were divided into three groups: Group 1, <350 g (n=32); Group 2, 350-1000 g (n=15); and Group 3, >1000 g (n=7). The role of the learning curve was also analyzed with the first 20 surgeries considered as the learning period. The specimen was retrieved with morcellation through the lateral port site in 54 cases, whereas in 11 cases, the large spleen was retrieved through a Pfannenstiel incision. RESULTS The mean duration of surgery was 122 minutes. When considered by spleen weight, durations for Groups 1-3 were 117, 128, and 134 minutes, respectively. When considered by the learning curve, durations for learning and later periods were 149 and 111 minutes, respectively (P=.002). After the learning period, larger spleens were removed (208 versus 519 g; P=.02), and there were fewer conversions. The mean postoperative hospital stay was 5.1 days. In the 11 cases where the specimen was retrieved through a Pfannenstiel incision, the mean duration of surgery was 108 minutes, and the mean spleen weight was 1032 g. CONCLUSIONS Our study supports that the proposal that LS is safe and has numerous advantages, even in the case of massive splenomegaly. Our results were mainly affected by the spleen size and the learning curve.

Tenziós típusú fejfájás és colitis ulcerosa

Background and purpose Tension-type headache is a very common disease with a high socio-economic impact as its lifetime prevalence is 30-78% in the general population. The incidence of inflammatory bowel diseases is continuously rising. Limited data are accessible on quality of life in patients with surgically treated ulcerative colitis. The aim of our study is to examine quality of life, concerning headache, among patients who had undergone surgery due to ulcerative colitis. Methods Between 1 January 2005 and 1 March 2016, surgery was performed due to ulcerative colitis in 75 patients. During this retrospective analysis the average duration of the follow-up was 46 (1-124) months. The pre-sence of headache was evaluated by the use of Brief Illness Perception and Headache Questionnaires. Results Among the primary headache disorders (n=27), tension-type headache occurred in 19 (70.4%) cases, and 8 (29.6%) patients had migraine (without aura). Among tension-type headache cases 17 (89.5%) patients experienced episodic form and 2 (10.5%) suffered from chronic form. Patients with headache had obtained a significantly higher score on Brief Illness Perception Questionnaire. Conclusion According to our study tension-type headache is common among patients with ulcerative colitis. This observation raises the question whether stress plays role in the pathogenesis of both diseases, which influences and worsens considerably quality of life. Neurological examination, psychological and psychiatric guidance are worth considering in patients with ulcerative colitis.

Colitis ulcerosa minimálisan invazív sebészi kezelése-hosszú távú eredmények

Absztrakt Bevezetes: A colitis ulcerosa sebeszi kezeleseben egyre szelesebb korben alkalmazzak a laparoszkopos technikat, azonban hosszu tavu magyarorszagi eredmenyekkel eddig meg nem rendelkeztunk. Celkitűzes: A szerzők celja a hagyomanyos es a minimalisan invaziv modszerrel operalt betegek műteti es 47,8 honapos utankovetesi eredmenyeinek osszehasonlitasa. Modszer: 2005. januar 1. es 2014. december 31. kozott osszesen 56 beteg kerult műtetre colitis ulcerosa diagnozissal, akik kozul 20-at surgősseggel, 36-ot tervezetten műtottek. Laparoszkopos technikaval 33, nyitottan 23 műtetet vegeztek. Eredmenyek: A perioperativ időszakban az apolasi idő, passzazsmegindulas, az intenziv osztalyos es transzfuzios igeny es szovődmenyek teren a csoportok kozott kulonbseget nem eszleltek. Hosszu tavu szovődmenyek tekinteteben az intestinalis obstrukcio, a szeptikus allapot es az egyeb komplikaciok előfordulasa szignifikansan alacsonyabb volt a laparoszkopos műteten atesett betegek csoportjaban. Mindket csoport eletminős...INTRODUCTION For the surgical treatment of ulcerative colitis, laparoscopy is used more widely, but less data are available on long-term results in Hungary. AIM The aim of the authors was to compare the mean 47.8-month follow-up results of patients treated with conventional and minimally invasive surgical methods. METHOD Between January 1, 2005 and December 31, 2014, 56 patients were treated with surgery (20 emergencies, and 36 elective cases). Laparoscopy was used in 33 and conventional method in 23 cases. RESULTS There was no difference between the two groups in hospital and intensive care unit stay, bowel function recovery, need for transfusion, and complications during the perioperative period. Regarding long-term complications, the occurrence of intestinal obstruction, septic condition and other complications were significantly fewer in the laparoscopy group. The quality of life improved in both groups after the surgery. CONCLUSIONS Laparoscopy can be used safely; it provides good quality of life and better cosmetic results, and the long-term rate of complications is lower as compared to open surgery.