Rifaximin modulates 5-fluorouracil-induced gastrointestinal mucositis in rats.

OBJECTIVE: This study assessed the protective potential of rifaximin in 5-fluorouracil (5-FU) induced intestinal mucositis in the Wistar rats'. MATERIALS AND METHODS: Twenty-nine Wistar rats were divided into 4 interventional groups of 6 animals (A, B, C and F) and one control group (M) of 5 animals. Groups A, B and C received for three days consecutively rifaximin orally: 50 mg/kg (group A), 100 mg/kg (group B) and 200 mg/kg (group C). In the fourth day, 500 mg/kg of 5-FU was administered intraperitoneally to the groups A, B, C and F. A semi-quantitative histological assessment for duodenum, jejunum and colon were obtained by rating 11 histological characteristics of mucositis from 0 (normal) to 3 (severe). Semi-quantitative grades were a measure for TLR4 immunopositive cells. Statistical comparisons used - U Test, with a Bonferroni correction for alpha (p ≤ 0.016). RESULTS: In the group F the most affected areas were the jejunum (median histological score 25) and the duodenum (median histological score 22). The assessment of duodenum histological lesions depicted significant difference between F and B groups (U = 1.5, p = 0.007) and between F and C groups (U = 0, p = 0.003). Graded microscopic degenerative lesions on jejunum were significantly different between F and C groups (U = 0, p = 0.004). Graded TLR4 immunopositive cells in the jejunum surface epithelium was significantly different between groups F and C (U = 2.5, p = 0.006). In the colonic mucosa, significantly differences were noted on microscopic degenerative lesions between F and A groups (U = 0, p = 0.004) and between F and C groups (U = 0, p = 0.004). CONCLUSIONS: Pretreatment with 200 mg/kg of rifaximin for 3 consecutive days proved efficient in preventing intestinal mucosal degenerative lesions induced by 5-FU.

Adalimumab and Infliximab in Crohn's disease - real life data from a national retrospective cohort study.

AIM: to compare the efficacy and safety of Adalimumab(ADA) and Infliximab(IFX), in a large Romanian population and to identify predictors of response. Methods We performed a national retrospective cohort study including 265 patients (136 ADA, 129 IFX) between 2008-2014. Binary logistic regression was performed with the statistical program Minitab. RESULTS: Patients were half women, with a median age of 36, a median disease duration of 2.5 years, 80% received Azathioprine. Mean therapy duration was 20 months in ADA group and 36 months in IFX group. Complete response to Adalimumab respectively Infliximab was recorded in 77%vs.65%, secondary loss of response in 18%vs.28%, statistically comparable. We failed to identify predictors of response. In 79.2%of patients with secondary loss of response to ADA, the dose was escalated, 12.5% were switched to Infliximab. In 70%of patients that lost response to IFX, the dose was increased, 30% were switched to Adalimumab. CONCLUSIONS: Adalimumab and Infliximab have similar efficacy, with a complete response rate of~70%. In case of secondary loss of response to IFX, the best solution is to switch to ADA, with 83% response rate, while in case of secondary loss of response to ADA, increasing the dose leads to 84 % response rate.

Factors affecting colonoscopy comfort and compliance: a questionnaire based multicenter study.

AIMS: Colonoscopy screening reduces colorectal cancer-related mortality and incidence. However, many patients are reluctant to undergo colonoscopy or return for follow-up because of the investigation's cumbersome and unpleasant nature. We aimed to identify patient-related factors significantly influencing comfort and quality of colonoscopy analyzing responses to a self-administered validated questionnaire. METHODS: Patients undergoing colonoscopy under sedation in two high-volume endoscopy units were invited to answer a short prevalidated questionnaire regarding preprocedure anxiety, satisfaction with information provided, most worrisome aspect of the procedure and knowledge of the benefits of colonoscopy. Self-reported comfort during colonoscopy as graded on a 10 point visual analog scale was the main variable considered. Univariate analysis identified factors possibly associated with a higher degree of comfort during colonoscopy that were then tested through multivariate logistical regression. RESULTS: 452 questionnaires were returned. Most patients reported an acceptable degree of discomfort during colonoscopy but 70.2% of the respondents considered the information provided prior to the procedure to be insufficient. On multivariate analysis older age, higher degree of satisfaction with information provided (p = 0.04), lower preprocedure anxiety levels (p < 0.01) and endoscopy center (p < 0.01) were shown to correlate with increased comfort during colonoscopy. Education level, previous colonoscopy, gender and bowel prep quality did not influence patient comfort. CONCLUSIONS: Patient comfort during colonoscopy is dependent on satisfaction with the information provided before the procedure. Higher availability of the physician and better interaction with the patient might decrease patient perceived burden of colonoscopy and lead to higher return rates in the screening and surveillance setting.

Two different types of diabetes mellitus in pancreatic cancer population. Comparative study between new onset and long standing diabetes mellitus on 76 patients with pancreatic cancer.

BACKGROUND: There are some studies which have reported a higher diagnosis probability for PC if the DM occurred within the past 2-3 years. Information on the clinical profile of pancreatic cancer (PC) associated with diabetes mellitus (DM) is limited. The aim of the study was to compare clinic-morphological features in patients with new onset DM and PC and long lasting DM and PC, in order to detect new factors or markers which can help in early diagnosis of PC. METHODS: This study included 76 patients with pancreatic cancer admitted between 2000-2009 in the 4th Medical Clinic Cluj-Napoca; in group A 56 patients with PC and new onset of DM (< 24 months duration) were included and in group B 20 patients with PC and long standing diabetes (> 60 months duration) were included. We compared the demographic, clinical, biochemical and morphological characteristics of new onset or long lasting DM and pancreatic cancer. RESULTS: New onset DM was more prevalent (74% vs. 26%, p < .05) than long lasting DM among patients with PC. The patients with long lasting DM had a greater frequency of urban environment (100% vs. 55.6% p = .02), a higher body mass index (BMI)(32.1 SD 8.4 vs. 29.9 SD 6.7 kg/m2, p = .05), higher fasting blood glucose levels (182 mg/dL vs. 134 mg/dL, p = .008) and urinary ketone bodies (60% vs. 10.7%, p = .002) compared with those with new-onset DM and PC. There was no statistical difference regarding gender, median age, blood group, location and staging of tumours, long and hard alcohol and cigarettes consumption, between group A and B. CONCLUSIONS: New onset DM was more significantly frequent than long lasting DM in patients with PC. New onset diabetes DM associated with PC is frequent, mild and non-decompensated. In patients with PC and long lasting DM, the metabolic status and diabetes are imbalanced.

Effects of rifaximin on indomethacin-induced intestinal damage in guinea-pigs.

AIM: Enterobacterial translocation into the gut mucosa is the first step required for activation of neutrophils and inducible nitric oxide synthase (iNOS), involved in the pathogenesis of indomethacin-induced intestinal lesions. Rifaximin may limit NSAID-associated intestinal damage by decreasing the bacterial load. We aimed to study the effect of rifaximin on indomethacin-induced intestinal damage in guinea-pigs. MATERIALS AND METHODS: Twenty-four guinea pigs, equally divided in four interventional groups (A-D), received indomethacin, given orally once daily (30 mg/kg) for three consecutive days. In groups B, C, D different doses of rifaximin (50 mg/kg, 100 mg/kg and 200 mg/kg) were given orally two hours before indometachin administration. Semi-quantitative grades were measure for gross findings, degenerative lesions, neutrophils and eosinophils infiltrates and iNOS immunopositivity. Statistical comparisons used Mann Whitney Test, with a Bonferroni correction for alpha (p ≤ 0.016). RESULTS: Statistical analysis of graded gross findings, microscopic degenerative lesions, endothelium damage and iNOS immunopositivity found no difference between A and B groups. Significant fewer gross findings (U = 3, p = 0.015), microscopic degenerative lesions (U = 2, p = 0.008) and lower grades for iNOS immunopositivity (U = 0, p = 0.002) were found in group C compared with group A. In group D, significant lower grades for iNOS immunopositivity were obtained (U = 0, p = 0.002) compared with group A and fewer degenerative lesions without reaching statistical significance (U = 4, p = 0.026). CONCLUSIONS: 100 mg/kg of rifaximin proved efficient in preventing gut degenerative lesions induced by indomethacin in a guinea pig model, the iNOS activity being significantly decreased.

Surgical outcome of inflammatory bowel disease - experience of a tertiary center.

UNLABELLED: BACKGROUNDS/AIM: Despite advances in medical treatment, a large number of patients with inflammatory bowel disease(IBD) require surgery. We aim to evaluate the efficacy and outcome of surgical interventions in patients with chronic inflammatory bowel diseases. MATERIAL AND METHODS: We retrospectively analysed the medical records from 221 patients admitted to our institution between 2009-2012 with the diagnosis of IBD. Out of these patients, 55 (24.88 %) were diagnosed with Crohn's disease,while the remaining 166 patients (75.11%) had ulcerative colitis. RESULTS: Seventeen of 55 patients with Crohn's disease (30.91%)required surgical management before or during this period. Nine with disease proximal to the transverse colon underwent segmental resections (enteral or colonic) with primary anastomosis, without morbidity. The other 8 patients, with disease distal to the transverse colon, underwent segmental colonic resections (two with primary anastomosis, three with stoma formation) or major colonic resection- subtotal colectomy with ileostomy (1 case) and total proctocolectomy with ileostomy(2 cases). Sixteen of 166 patients with ulcerative colitis(9.64%) required surgery before or during this period. The surgical procedure used included total proctocolectomy with definitive ileostomy (3 cases) and total colectomy with ileostomy(13 cases). 7 of the 13 patients had restorative surgery after total colectomy, 1 remaining with definitive ileostomy due to short vascular pedicle and 5 patients refused restorative surgery. Median daily stool frequency after reconstructive surgery was 7(range 3-12). CONCLUSION: For patients with Crohn's disease proximal to the transverse colon, limited resection with primary anastomosis is safe. Major colonic resection (subtotal colectomy or proctocolectomy)is indicated if the disease is located distal to the transverse colon and primary anastomosis should be avoided. Due to unsatisfactory quality of live after reconstructive surgery(stool frequency remains high), total proctocolectomy with end-ileostomy remains a viable alternative for patients with ulcerative colitis.

Nutritional risk screening and prevalence of malnutrition on admission to gastroenterology departments: a multicentric study.

BACKGROUND AND AIMS: There is little awareness and a lack of data on the prevalence of hospital malnutrition in gastro-enterology departments. Since part of these patients are referred for surgical treatment and poor nutritional status is a known risk factor for perioperative morbidity, we conducted a prospective study aimed to screen for the nutritional risk and assess the prevalence and risk factors of malnutrition in gastro-enterology departments in Romania. METHODS: We included patients consecutively admitted to 8 gastroenterology units over a period of three months in our study. Nutritional risk was evaluated using NRS 2002. Malnutrition was defined using BMI ( 20 kg m2) or and 10% weight loss in the last six months. RESULTS: 3198 patients were evaluated, 51.6% males and 48.4% females, with the mean age of 54.5 Â+- 14.3 years. Overall percentage of patients at nutritional risk was 17.1%, with the highest risk for patients with advanced liver diseases (49.8%), oncologic (31.3%), inflammatory bowel diseases (20.2%), and pancreatic diseases (18.9%). The overall prevalence of malnutrition was of 20.4%, higher for advanced liver diseases (39.4%), inflammatory bowed diseases (30.6%), oncologic (26.8%) and pancreatic diseases (23%). Independent risk factors for malnutrition were younger age (p 0.0001), female gender (p 0.0001), a higher (A ≥ 3) NRS (p 0.0001), presence of neoplasm (p 0.0001), of advanced liver disease (p=0.0003) and a reduction of 25% of dietary intake (p 0.0001). CONCLUSIONS: One in five patients admitted to gastroenterology units could benefit from prompt nutritional intervention. Correction of nutritional status is mandatory before any surgical procedure. Emphasis on nutritional evaluation at admission and beginning of nutritional therapy where needed are particularly required in patients with advanced liver diseases, digestive neoplasms, inflammatory bowel diseases and pancreatic diseases. ABBREVIATIONS: NRS= nutritional risk score, BMI = body mass index, IBD = inflammatory bowel diseases.

Mortality and need of surgical treatment in acute upper gastrointestinal bleeding: a one year study in a tertiary center with a 24 hours / day-7 days / week endoscopy call. Has anything changed?

BACKGROUND: Acute upper gastrointestinal bleeding, previously often a surgical problem, is now the most common gastroenterological emergency. AIM: To evaluate the current situation in terms of mortality and need of surgery. SUBJECTS AND METHODS: Retrospective non-randomised clinical study performed between 1st January-31st December 2011, at "Professor Dr. Octavian Fodor" Regional Institute of Gastroenterology and Hepatology in Cluj Napoca. 757 patients with upper gastrointestinal bleeding were endoscopically examined within 24 hours from presentation in the emergency unit. Data were collected from admission charts and Hospital Manager programme. Statistical analysis was performed with GraphPad 2004, using the following tests: chi square, Spearman, Kruskall-Wallis, Mann-Whitney, area under receiver operating curve. RESULTS: Non-variceal etiology was predominant, the main cause was bleeding being peptic ulcer. In hospital global mortality was of 10.43%, global rebleeding rate was 12.02%, surgery was performed in 7.66% of patients. Urgent haemostatic surgery was needed in 3.68% of patients with nonvariceal bleeding. The need for surgery correlated with the postendoscopic Rockall score (p=0.0425). In peptic ulcer, the need for surgery was not influenced by time to endoscopy or type of treatment (p=0.1452). Weekend (p=0.996) or night (p=0.5414) admission were not correlated with a higher need for surgery. CONCLUSIONS: Over the last decade, the need for urgent surgery in upper gastrointestinal bleeding has decreased by half, but mortality has remained unchanged.

Stem-like cells in colorectal oncology.

Although the treatment for colorectal cancer has seen considerable progress during the past few years, the mortality associated with this type of tumor remains high. This article presents the existing methods of treatment, focusing on the new treatments made possible by the advances in the field of normal and tumor stem cells. Starting from the normal architecture of the colon and the properties of the cells identified in it, we sought to present a few notions concerning these cells which have a direct relevance for both pathology and treatment. The manner in which they divide (symmetrically or asymmetrically) as well as the molecules which control their circulation through the body are just a few examples which are likely to influence the treatment of colorectal cancer in the future.

[Laparoscopic treatment of a large trichobezoar in the stomach with gastric perforation and abdominal wall abscess]. / Tratamentul laparoscopic al unui tricobezoar gastric de mari dimensiuni complicat cu perforatie gastrica blocata in peretele abdominal anterior.

Trichobezoar represents a mass of swallowed hair inside the stomach. Here we report a 17-year-old girl who presented in our department with symptoms of gastric ulcer. Ultrasound examination followed by upper endoscopy revealed a large trichobezoar in the stomach with simultaneous gastric perforation. Laparoscopy also revealed a penetration into the anterior abdominal wall accompanied by abscess at this level. We performed a laparoscopic gastrotomy with trichobezoar extraction and laparoscopic treatment of perforation and abdominal wall abscess. The postoperative evolution was normal and the patient was discharged on the fifth postoperative day. We show that laparoscopic approach may be safely used in the treatment of the large gastric complicated trichobezoar. Several laparoscopic approaches were described for the treatment of tricobezoar and its complications but as far as we know this is the first report of laparoscopic treatment of large tricobezoar and associate gastric perforation.

Therapeutic approach to the malignant tumors of the biliary tract.

Cholangiocarcinomas (CCA) are malignant tumors that originate in the cholangiocytes, occur at any level of the biliary tract, are very aggressive and have a 5-year survival rate of 7-8%. Their diagnosis is late and difficult, and the prognosis is very poor. The only curative treatment of these tumors is the complete surgical resection. Signs of unresectability can be detected in most patients with CCA when establishing the diagnosis. Thus, only certain palliative measures can be employed in most cases. The ideal palliative method should be minimally invasive, accompanied by few complications, should offer an increased quality of life, require reduced hospitalization and the lowest costs. The palliative treatment of the obstructive jaundice may be achieved by means of surgical bypass, endoscopic insertion of biliary stents, percutaneous stents, transhepatic stents, photodynamic therapy and/or radio-chemotherapy.

[Minimally invasive treatment of common bile duct calculi]. / Tratamentul miniinvaziv al litiazei caii biliare principale.

UNLABELLED: Miniinvasive treatment of lithiasis of the common bile duct hasn't reached yet a standard end point. There are multiple techniques used for it. In this study we evaluate its indications, possibilities and limits. MATERIAL AND METHOD: In a series of 14,024 biliary patients operated over 9 years 719 patients underwent open choledocolithotomy. In 173 (1.2%) of patients we used miniinvasive procedures as follows: 71 cases underwent sequential treatment, 91 laparoscopic treatment and in 11 cases the remnant calculi were extracted 1-6 days postoperative. RESULTS: Sequential treatment was the preferred treatment when the lithiasis of the common bile duct was detected preoperative. Transcistic extraction was more often performed for the lithiasis diagnosed intraoperative. The conversion to open surgery was performed in 13 cases, remnant calculi were early diagnosed in 11 patients and late diagnosed in 14 cases (the calculi were extracted by endoscopic sphyncterotomy). All patients were healed. DISCUSSIONS: The miniinvasive procedures have to be practiced as frequently as possible because of rapid healing and early recovery of the patients, despite some disadvantage of them. The choledocotomy and choledocoduodenostomy are exceptional techniques to be used in specific cases.