Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: a prospective non-randomized controlled trial.

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. STUDY: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.

Targeted transcriptomic analysis of pancreatic adenocarcinoma in EUS-FNA samples by NanoString technology.

Background: Integration of transcriptomic testing into EUS-FNA samples is a growing need for precision oncology in pancreatic ductal adenocarcinoma (PDAC). The NanoString platform is suitable for transcriptome profiling in low yield RNA samples. Methods: Inclusion of patients that underwent EUS-FNA cytological diagnosis of pancreatic ductal adenocarcinoma using 19G and/or 22G needles and subsequent surgical resection. Formalin-fixed, paraffin-embedded (FFPE) cytological and surgical samples underwent RNA extraction and transcriptomic analysis using a custom 52-gene NanoString panel of stromal PDAC features. Cell type abundance was quantified in FFPE specimens and correlated. Results: 18 PDAC patients were included. Mean EUS-FNA passes was 2 + 0.7. All FFPE passed the RNA quality control for genomic analysis. Hierarchical clustering on the global gene expression data showed that genes were differentially expressed between EUS and surgical samples. A more enriched cancer-associated fibroblasts and epithelial-mesenchymal transition transcriptomic profile was observed across surgical specimens whereas immunological biomarkers were more represented in EUS-FNA samples. Cytological examination confirmed a scanty representation of CAF and more immunological cell abundance in cytological samples in comparison to surgical specimens. Conclusion: Targeted transcriptomic NanoString profiling of PDAC samples obtained by EUS-FNA is a feasible approach for pre-surgical molecular analysis although stromal CAF/EMT mRNA biomarkers are underrepresented.

Telemedicine and intraductal papillary mucinous neoplasms: Analysis of a new follow-up strategy during COVID-19 outbreak.

BACKGROUND: The Coronavirus pandemic outbreak in 2019 and the saturation of healthcare system led to an increased use of digital tools for surveillance. In this study we described our experience using telemedicine to follow-up on patients with intraductal papillary mucinous neoplasms during the COVID-19 era and analyze those factors associated to patients' satisfaction. METHODS: This 1-year retrospective observational study enrolled patients with intraductal papillary mucinous neoplasms followed-up by telemedicine during COVID-19 outbreak. Patients with high-risk features needing on-site physical examination or declining remote follow-up were excluded. A 13-question survey was conducted; demographic, geographic, and employment information was collected. Univariate and multivariate analyses were performed to evaluate those factors associated to patients' satisfaction. RESULTS: Out of 287, a total of 177 patients with intraductal papillary mucinous neoplasms were included: the mean age was 69 (44-87) years and the male/female ratio was 0.78. A total of 80 (45.2%) patients had previously experienced abdominal pain. Most patients (85.3%) were satisfied with telemedicine: at univariate analysis, age ≥70 years (P = .007), retirement (P = .001), and absence of previous abdominal pain (P = .05) were significantly associated with patient satisfaction. At multivariate analysis, the absence of previous abdominal pain was the only factor independently associated with patient satisfaction (odds ratio 5.964, 95% confidence interval 2.21-16.11, P < .001). CONCLUSION: Telemedicine allows a new follow-up strategy that can be used in selected patients with intraductal papillary mucinous neoplasms. The absence of previous abdominal pain is associated with patient satisfaction during follow-up. Further studies are needed to evaluate safety of remote follow-up in patients with intraductal papillary mucinous neoplasms.

Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about endoscopic ultrasound (EUS)-guided sampling in gastroenterology, including EUS-guided fine needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB), of submucosal tumors, diffuse esophageal/gastric wall thickening, pancreatic solid masses and cystic-appearing lesions, mediastinal lesions unrelated to lung or esophageal cancer, cancer of the esophagus, stomach, and rectum, lymph nodes of unknown origin, adrenal gland masses, and focal liver lesions. False-positive cytopathological results and needle tract seeding are also discussed. The present Clinical Guideline describes the results of EUS-guided sampling in the different clinical settings, considers the role of this technique in patient management, and makes recommendations on circumstances that warrant its use. A two-page executive summary of evidence statements and recommendations is provided. A separate Technical Guideline describes the general technique of EUS-guided sampling, particular techniques to maximize the diagnostic yield depending on the nature of the target lesion, and sample processing. The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling.

UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy.

BACKGROUND: The impact of thymidylate synthase (TYMS) and UDP-glucoronosyltransferase 1A (UGT1A) germline polymorphisms on the outcome of colorectal cancer (CRC) patients treated with irinotecan plus 5-fluorouracil (irinotecan/5FU) is still controversial. Our objective was to define a genetic-based algorithm to select patients to be treated with irinotecan/5FU. METHODS: Genotyping of TYMS (5'TRP and 3'UTR), UGT1A1(*)28, UGT1A9(*)22 and UGT1A7(*)3 was performed in 149 metastatic CRC patients treated with irinotecan/5FU as first-line chemotherapy enrolled in a randomised phase 3 study. Their association with response, toxicity and survival was investigated by univariate and multivariate statistical analysis. RESULTS: TYMS 3TRP/3TRP genotype was the only independent predictor of tumour response (OR=5.87, 95% confidence interval (CI)=1.68-20.45; P=0.005). UGT1A1(*)28/(*)28 was predictive for haematologic toxicity (OR=6.27, 95% CI=1.09-36.12; P=0.04), specifically for neutropenia alone (OR=6.40, 95% CI=1.11-37.03; P=0.038) or together with diarrhoea (OR=18.87, 95% CI=2.14-166.67; P=0.008). UGT1A9(*)1/(*)1 was associated with non-haematologic toxicity (OR=2.70, 95% CI=1.07-6.82; P=0.035). Haplotype VII (all non-favourable alleles) was associated with non-haematologic toxicity (OR=2.11, 95% CI=1.12-3.98; P=0.02). CONCLUSION: TYMS and UGT1A polymorphisms influence on tumour response and toxicities derived from irinotecan/5FU treatment in CRC patients. A genetic-based algorithm to optimise treatment individualisation is proposed.

Severe complications limit long-term clinical success of self-expanding metal stents in patients with obstructive colorectal cancer.

OBJECTIVES: Self-expanding metal stents (SEMS) are increasingly being used to treat malignant colorectal obstruction. However, complications have been reported in up to 50% of patients. There is limited information on long-term outcomes of these patients. The aim of this study was to retrospectively assess the long-term clinical success of SEMS in patients with malignant colorectal obstruction in a single tertiary center and to identify possible predictive factors of developing complications. METHODS: A total of 47 attempts to insert colorectal SEMS were made in 47 patients during a 5-year period. Stents of 9-cm length were placed under endoscopic and radiologic monitoring. After 24 h, all patients underwent abdominal X-ray to verify correct positioning of the stent. Patients were followed at the outpatient clinic. RESULTS: Insertion success was achieved in 44 (94%) patients. Acceptable initial colonic decompression was observed in 44 out of 47 (94%) attempts and in all (100%) successfully inserted stents. The stents were placed in the rectum (n=7, 15%), sigmoid (n=33, 70%), left colon (n=4, 9%), or anastomosis (n=3, 6%). The majority of patients had stage IV disease (n=40, 85%). SEMS served as a bridge to scheduled surgery in 9 (20%) patients and as a palliative definitive treatment in 38 (80%) cases. Three patients were lost to follow-up, so the outcome was evaluated in 41 patients. Long-term clinical failure occurred in 21 (51%) patients and was due to complications such as: migration (n=9, 22%), obstruction (n=7, 17%), perforation (n=3, 7%), and tenesmus (n=2, 5%). Perforations occurred 3, 4, and 34 days after insertion, and all patients died. In the bridge-to-surgery group, primary anastomosis was possible in only four of nine patients (44%). Clinical failure was not associated with any tumor-related factor. However, eight of nine patients with stent migration and two of three patients with perforation had been previously treated with chemotherapy. CONCLUSIONS: Placement of SEMS does not seem to be as effective as suggested because of late complications. For patients with potentially curable lesions, the use of colonic stents for malignant obstruction should only be considered when surgery is scheduled shortly after the stent insertion. Moreover, in patients with incurable obstructing colorectal cancer eligible for chemotherapy and a long life expectancy, palliative treatments other than SEMS should be considered.

Endoscopic ultrasound-guided fine-needle aspiration and trucut biopsy in the diagnosis of gastric stromal tumors: a randomized crossover study.

BACKGROUND AND AIM: The diagnosis of gastrointestinal stromal tumors (GISTs) has important prognostic and therapeutic implications. The specific diagnosis of GIST has to be based on immunocytochemistry. This study aimed to prospectively compare in a crossover manner the accuracy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB) in the specific diagnosis of gastric GISTs. We hypothesized that EUS-TCB is superior to EUS-FNA in this respect. PATIENTS AND METHODS: Forty patients with gastric subepithelial tumors suspected on the basis of EUS of being a GIST underwent both EUS-FNA and EUS-TCB. The sequence in which the techniques were employed was randomly assigned to avoid bias. RESULTS: Forty tumors were sampled (mean number of passes: 2.1 +/- 0.9 with EUS-TNB and 1.9 +/- 0.8 with EUS-FNA; P = not significant, NS). Final diagnoses were: GIST (n = 27), carcinoma (n = 2), leiomyoma (n = 1), schwannoma (n = 1), and no diagnosis possible (n = 9). Device failure occurred in 6 patients with EUS-TCB. A cytohistological diagnosis of mesenchymal tumor (n = 29) and carcinoma (n = 2) was made in 70 % of cases by EUS-FNA and in 60 % of cases by EUS-TCB ( P = NS). Among the samples that were adequate, immunohistochemistry could be performed in 74 % of EUS-FNA samples and in 91 % of EUS-TCB samples ( P = 0.025). When inadequate samples were included, the overall diagnostic accuracy of EUS-FNA was 52 % and that of EUS-TCB was 55 % ( P = NS). There were no complications. CONCLUSIONS: EUS-TCB is not superior to EUS-FNA in GISTs because of the high rate of technical failure of trucut. However, when an adequate sample is obtained with EUS-TCB, immunohistochemical phenotyping is almost always possible. EUS-TCB can be safely performed in this set of patients.

The role of a computed tomography-based image registered navigation system for natural orifice transluminal endoscopic surgery: a comparative study in a porcine model.

BACKGROUND AND STUDY AIMS: Most natural orifice transluminal endoscopic surgery (NOTES) procedures have been performed in animal models through the anterior stomach wall, but this approach does not provide efficient access to all anatomic areas of interest. Moreover, injury of the adjacent structures has been reported when using a blind access. The aim of the current study was to assess the utility of a CT-based (CT: computed tomography) image registered navigation system in identifying safe gastrointestinal access sites for NOTES and identifying intraperitoneal structures. METHODS: A total of 30 access procedures were performed in 30 pigs: anterior gastric wall (n = 10), posterior gastric wall (n = 10), and anterior rectal wall (n = 10). Of these, 15 procedures used image registered guidance (IR-NOTES) and 15 procedures used a blind access (NOTES only). Timed abdominal exploration was performed with identification of 11 organs. The location of the endoscopic tip was tracked using an electromagnetic tracking system and was recorded for each case. Necropsy was performed immediately after the procedure. The primary outcome was the rate of complications; secondary outcome variables were number of organs identified and kinematic measurements. RESULTS: A total of 30 animals weighting a mean (± SD) of 30.2 ± 6.8 kg were included in the study. The incision point was correctly placed in 11 out of 15 animals in each group (73.3 %). The mean peritoneoscopy time and the number of properly identified organs were equivalent in the two groups. There were eight minor complications (26.7 %), two (13.3 %) in the IR-NOTES group and six (40.0 %) in the NOTES only group ( P = n. s.). Characteristics of the endoscope tip path showed a statistically significant improvement in trajectory smoothness of motion for all organs in the IR-NOTES group. CONCLUSION: The image registered system appears to be feasible in NOTES procedures and results from this study suggest that image registered guidance might be useful for supporting navigation with an increased smoothness of motion.

EUS-guided tissue acquisition in the study of the adrenal glands: Results of a nationwide multicenter study.

BACKGROUND: There are limited data about the role of endoscopic ultrasound-guided tissue acquisition (EUS-TA), by fine needle aspiration (EUS-FNA) or biopsy (EUS-FNB), in the evaluation of the adrenal glands (AG). The primary aim was to assess the diagnostic yield and safety. The secondary aims were the malignancy predictors, and to create a predictive model of malignancy. METHODS: This was a retrospective nationwide study involving all Spanish hospitals experienced in EUS-TA of AGs. Inclusion period was from April-2003 to April-2016. Inclusion criteria: all consecutive cases that underwent EUS-TA of AGs. EUS and cytopathology findings were evaluated. Statistical analyses: diagnostic accuracy of echoendoscopist's suspicion using cytology by EUS-TA, as gold standard; multivariate logistic regression model to predict tumor malignancy. RESULTS: A total of 204 EUS-TA of AGs were evaluated. Primary tumor locations were lung70%, others19%, and unknown11%. AG samples were adequate for cytological diagnosis in 91%, and confirmed malignancy in 60%. Diagnostic accuracy of the endosonographer's suspicion was 68%. The most common technique was: a 22-G (65%) and cytological needle (75%) with suction-syringe (66%). No serious adverse events were described. The variables most associated with malignancy were size>30mm (OR2.27; 95%CI, 1.16-4.05), heterogeneous echo-pattern (OR2.11; 95%CI, 1.1-3.9), variegated AG shape (OR2.46; 95%CI, 1-6.24), and endosonographer suspicion (OR17.46; 95%CI, 6.2-58.5). The best variables for a predictive multivariate logistic model of malignancy were age, sex, echo-pattern, and AG-shape. CONCLUSIONS: EUS-TA of the AGs is a safe, minimally invasive procedure, allowing an excellent diagnostic yield. These results suggest the possibility of developing a pre-EUS procedure predictive malignancy model.

Impact of endoscopic ultrasonography and physician specialty on the management of patients with esophagus cancer.

While endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are the most accurate techniques for locoregional staging of esophageal cancer, little evidence exists that these innovations impact on clinical care. The objective on this study was to determine the frequency with which EUS and EUS-FNA alter the management of patients with localized esophageal cancer, and assess practice variation among specialists at a tertiary care center. Three gastroenterologists, three medical oncologists, three radiation oncologists and four thoracic surgeons were asked to independently report their management recommendations as the anonymized staging information of 50 prospectively enrolled patients from another study were sequentially disclosed on-line. Compared to initial management recommendations, that were based upon history, physical examination, upper endoscopy and CT scan results, EUS prompted a change in management 24% (95% CI: 12-36%) of the time; usually to a more resource-intensive approach (71%), for example from recommending palliation to recommending neoadjuvant chemoradiation therapy. EUS-FNA plus cytology results altered management an additional 8% (95% CI: 6-15%) of the time. Agreement between specialists ranged from fair (intraclass correlation [ICC=0.32) to substantial (ICC=0.65); improving with additional information. Among specialists, agreement was greatest for patients with stage I disease. EUS and EUS-FNA changed patient management the most for patients with stages IIA, IIB or III disease. EUS, with or without FNA, significantly impacts the management of patients with localized esophageal cancer. With respect to the optimal treatment for each patient, agreement among physicians incrementally increases with endoscopic ultrasound results. Specialty training appears to influence therapeutic decision-making behavior.

Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis.

This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM) proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017) [1].

Lithium as a disease-modifying agent for prion diseases.

Prion diseases still remain incurable despite multiple efforts to develop a treatment. Therefore, it is important to find strategies to at least reduce the symptoms. Lithium has been considered as a neuroprotective agent for years, and the objective of this preclinical study was to evaluate the efficacy of lithium delivered as a water-in-oil microemulsion (Aonys®). This delivery system allows using low doses of lithium and to avoid the toxicity observed in chronic treatments. C57BL/6J mice were intracranially inoculated with ME7 prion-infected brain homogenates and then were treated with lithium from day 90 post inoculation until their death. Lithium was administered at traditional doses (16 mg/kg/day) by the gavage route and at lower doses (40 or 160 µg/kg/day; Aonys®) by the rectal mucosa route. Low doses of lithium (Aonys®) improved the survival of prion-inoculated mice, and also decreased vacuolization, astrogliosis, and neuronal loss compared with controls (vehicle alone). The extent of the protective effects in mice treated with low-dose lithium was comparable or even higher than what was observed in mice that received lithium at the traditional dose. These results indicate that lithium administered using this innovative delivery system could represent a potential therapeutic approach not only for prion diseases but also for other neurodegenerative diseases.

Incidence and clinical significance of hyperamylasemia after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions: a prospective and controlled study.

BACKGROUND AND STUDY AIM: Acute pancreatitis as a complication of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions is rarely observed. However, there is little information on the incidence of hyperamylasemia after EUS-FNA of the pancreas and its clinical significance. This study aimed to supply this lack of information. PATIENTS AND METHODS: Patients who underwent EUS-FNA of a pancreatic lesion between October 2004 and October 2005 were studied prospectively. Exclusion criteria were: (i) platelet count under 50,000/mm (3) and/or prothrombin time < 50 %; (ii) performance of surgery, endoscopic retrograde cholangiopancreatography (ERCP), a percutaneous biopsy attempt, or another invasive procedure within 7 days before EUS-FNA; (iii) lack of informed consent. Serum amylase levels were determined before and 8 and 24 h after the procedure. Hyperamylasemia was defined by amylase levels above 104 UI/L (and higher than baseline levels) 8 h after the procedure. Acute pancreatitis was defined by upper abdominal pain (with or without nausea and/or vomiting) accompanied by elevation of serum amylase or lipase to at least twice baseline levels. RESULTS: A total of 100 patients underwent EUS-FNA of a pancreatic lesion (58 men, 42 women; mean age 60 +/- 13 years). Eleven patients (11 %) showed hyperamylasemia 8 h after the puncture (298 +/- 293 UI/L, range 105 - 1044 UI/L), but only two of them developed acute mild pancreatitis after EUS-FNA. Hyperamylasemia was not related either to the type of lesion (cystic or solid) or to its location, the duration of the procedure, or the number of passes performed. CONCLUSIONS: Pancreatitis after pancreatic EUS-FNA occurs in 2 % of patients, with some more cases of silent hyperamylasemia. This complication may have to be included in the information given to patients for their informed consent.

EUS FNA in intraductal papillary mucinous tumors of the pancreas.

BACKGROUND/AIMS: There is little information concerning the potential role of fine-needle aspiration guided by endoscopic ultrasonography in the pathologic diagnosis of intraductal papillary mucinous tumors of the pancreas. METHODOLOGY: Patients with an intraductal papillary mucinous tumor of the pancreas suggested by endoscopic ultrasonography underwent fine-needle aspiration guided by endoscopic ultrasonography in order to investigate the presence of mucin and/or cytologic changes consistent with this diagnosis. A group of 111 patients with other pancreatic lesions explored during the same period of time was used as a control group. RESULTS: Fine-needle aspiration guided by endoscopic ultrasonography was safely performed in 19 patients and supported the diagnosis in 17 of them. Nine out of the 17 patients with suspicion of intraductal papillary mucinous tumors of the pancreas went to surgery and this diagnosis was confirmed in the resected specimen in all of them. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS FNA in the diagnosis of IPMT were 82%, 100%, 100%, 92% and 94% respectively. CONCLUSIONS: Fine-needle aspiration guided by endoscopic ultrasonography is a good technique to support the diagnosis of intraductal papillary mucinous tumors of the pancreas and should be considered in this group of patients if pathologic confirmation is judged to be necessary.

Prospective assessment of the role of antibiotic prophylaxis in ERCP.

BACKGROUND/AIMS: Despite the existence of published recommendations, various studies of antibiotic prophylaxis have reached conflicting conclusions, and controversy exists regarding the role of antibiotic prophylaxis in ERCP. The aim of this study was to analyze the efficacy of the intramuscular administration of clindamicine and gentamicine before ERCP. METHODOLOGY: Sixty-one consecutive patients referred for ERCP were prospectively randomized to receive either clindamicine 600mg and gentamicine 80mg, both intramuscularly one hour before the ERCP (group I; 31 patients) or not (group II; 30 patients). Two blood samples were obtained from every patient (just before endoscopy and within 5 minutes of withdrawal of the endoscope) and were incubated for 7 days and examined daily for growth of bacteria. Patients were closely monitored for 7 days after endoscopy to detect the development of infectious complications. RESULTS: Only 7 cultures from 7 patients were positive. Four were obtained post-ERCP (two patients in group I and two in group II) and the remaining three before endoscopy. The post-ERCP isolated bacteria were: Streptococcus mitis, Peptoestreptococcus anaerobious, Moraxella spp and Escherichia coli. Two patients, one from each group, developed post-ERCP cholangitis that were solved with medical treatment. CONCLUSIONS: Our findings indicate that ERCP induce bacteremia in a small group of patients and suggest that prophylactic administration of clindamicine plus gentamicine does not reduce the incidence of bacteremia and cholangitis, and do not support the routine use of prophylactic antibiotics prior to ERCP.

The European panel on the appropriateness of gastrointestinal endoscopy guidelines colonoscopy in an open-access endoscopy unit: a prospective study.

BACKGROUND: The demand for gastrointestinal endoscopy is increasing in most developed countries, resulting in an important rise in overall costs and waiting lists for endoscopic procedures. Therefore, adherence to appropriate indications for these procedures is essential for the rational use of finite resources in an open-access system. AIM: To assess indications and appropriateness of colonoscopy according to the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria. METHODS: From May to June 2004, all consecutive patients referred to our Unit for open-access colonoscopy were considered for inclusion in this prospective study. Appropriateness of each colonoscopy was established according to the EPAGE criteria. In order to evaluate whether appropriateness of use correlated with the diagnostic yield of colonoscopy, relevant endoscopic findings were also recorded. RESULTS: A total of 350 consecutive patients were included in the study. In 38 of them, the colonoscopy indication was not listed in the EPAGE guidelines and, consequently, they were not evaluated. In the remaining 312 patients, the indication for the procedure was considered inappropriate in 73 (23%) patients. Both referring doctor characteristics (specialty and health care setting) and patient data (age) correlated with appropriateness of endoscopy. The diagnostic yield was significantly higher for appropriate colonoscopies (42%) than in those judged inappropriate (21%) (P = 0.001). CONCLUSIONS: A noteworthy proportion of patients referred for colonoscopy to an open-access endoscopy unit are considered inappropriate because of their indication, with significant differences among specialties. These results suggest that implementation of validated guidelines for its appropriate use could improve this situation and, considering the correlation between appropriateness and diagnostic yield, even contribute to improve the prognosis of patients with colorectal diseases.

Wireless capsule endoscopy in patients with obscure gastrointestinal bleeding: a comparative study with push enteroscopy.

BACKGROUND: The identification and treatment of lesions located in the small intestine in obscure gastrointestinal bleeding is always a clinical challenge. AIM: To examine prospectively the diagnostic precision and the clinical efficacy of capsule endoscopy compared with push enteroscopy in obscure gastrointestinal bleeding. METHODS: Forty-two patients (22 men and 20 women) with obscure gastrointestinal bleeding (overt bleeding in 26 cases and occult blood loss with chronic anaemia in 16) and normal oesophagogastroduodenoscopy and colonoscopy were analysed. All patients were instructed to receive the capsule endoscopy and push enteroscopy was performed within the next 7 days. Both techniques were blindly performed by separate examiners. The diagnostic yield for each technique was defined as the frequency of detection of clinically relevant intestinal lesions carrying potential for bleeding. RESULTS: A bleeding site potentially related to gastrointestinal bleeding or evidence of active bleeding was identified in a greater proportion of patients using capsule endoscopy (74%; 31 of 42) than enteroscopy (19%; eight of 42) (P = 0.05). The most frequent capsule endoscopy findings were: angiodysplasia (45%), fresh blood (23%), jejunal ulcers (10%), ileal inflammatory mucosa (6%) and ileal tumour (6%). No additional intestinal diagnoses were made by enteroscopy. In seven patients (22%), the results obtained with capsule endoscopy led to a successful change in the therapeutic approach. CONCLUSIONS: Compared with push enteroscopy, capsule endoscopy increases the diagnosis yield in patients with obscure gastrointestinal bleeding, and allows modification on therapy strategy in a remarkable proportion of patients.

Clinical usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by means of endosonography-guided fine-needle aspiration biopsy.

AIM: To establish the usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by comparing this technique with conventional cytology in aspirates obtained by endosonography-guided fine-needle aspiration. METHODS: All consecutive patients with pancreatic focal lesions undergoing endosonography-guided fine-needle aspiration were included. Samples were obtained with the concurrence of an attendant cytopathologist. Detection of codon-12 KRAS mutations was performed by the restriction fragment length polymorphism-polymerase chain reaction method. The effectiveness of conventional cytology, KRAS mutational analysis and their combination was established with respect to the definitive diagnosis. A cost-effectiveness analysis was also performed. RESULTS: Thirty-three patients had pancreatic adenocarcinoma and 24 patients had other lesions. A total of 136 samples was obtained. In patients in whom specimens were adequate (93% for cytology; 100% for mutational analysis), the specificity of both techniques was 100%, whereas the sensitivity favoured cytology (97% vs. 73%). When inadequate samples were considered as misdiagnosed, a combination of both techniques reached the highest overall accuracy (cytology, 91%; mutational analysis, 84%; combination of both, 98%). CONCLUSIONS: Cytology from aspirates obtained by endosonography-guided fine-needle aspiration is the most precise single technique for the diagnosis of pancreatic adenocarcinoma. However, when adequate specimens are not available to reach a cytological diagnosis, the addition of KRAS mutational analysis represents the best strategy.

Endoscopic sclerotherapy to arrest uncontrolled variceal bleeding in cirrhotic patients with high surgical risk.

BACKGROUND/AIMS: In 20-50% of patients bleeding from esophageal varices, conservative procedures fail to obtain hemostasis and prevent early recurrence. METHODOLOGY: We retrospectively analyzed the efficacy and safety of endoscopic sclerotherapy in 66 cirrhotic patients with high surgical risk and persistence or recurrence of variceal bleeding in spite of adequate medical treatment (somatostatin and/or balloon tamponade). RESULTS: Emergency sclerosis controlled bleeding in 46 out of 66 patients (70%). The remaining 20 patients underwent additional procedures to arrest the hemorrhage, and 6 died because of massive bleeding. Early rebleeding occurred in 5 patients (10%). The mortality within 2 days, 1 week, and 6 weeks was 9%, 17% and 32%, respectively. Death was attributed to hemorrhage in 9 cases. Sclerotherapy was associated with complications in 9 patients (14%). CONCLUSION: These results suggest that emergency sclerotherapy is a safe and effective procedure in cirrhotic patients with high surgical risk and persistence or recurrence of bleeding after conservative hemostatic procedures.

Sphincterotomy in the treatment of biliary leakage.

BACKGROUND/AIMS: Endoscopic procedures such as sphincterotomy and endobiliary stenting have proved useful to solve postoperative bile leakage. We have assessed the outcome of a series of such patients initially treated with endoscopic sphincterotomy, having reserved stent placement for treatment failures only. METHODOLOGY: Twenty-five consecutive patients referred for endoscopic assessment of postoperative bile leaks and fistulas after cholecystectomy (n = 15), orthotopic liver transplantation (n = 9) and hepatic resection due to cystic hydatid disease (n = 1) underwent endoscopic retrograde cholangiopancreatography and sphincterotomy using a standard papillotome. Sphincterotomy was followed by stone extraction using a Dormia basket if common bile duct lithiasis were present. RESULTS: Bile leaks healed early after endoscopic sphincterotomy in 22 out of 25 patients (88%). Common bile duct stones were also retrieved in 6 of these patients. Bile duct stenosis due to surrounding pancreatic inflammation was demonstrated in two of the patients in which sphincterotomy failed to stop bile leakage. CONCLUSIONS: Endoscopic sphincterotomy alone should at present be considered a highly effective treatment to resolve postsurgical bile leaks unless bile strictures are present.