The role of computed tomography for the prediction of esophageal variceal bleeding: Current status and future perspectives.

Esophageal variceal bleeding (EVB) is one of the most common and severe complications related to portal hypertension (PH). Despite marked advances in its management during the last three decades, EVB is still associated with significant morbidity and mortality. The risk of first EVB is related to the severity of both PH and liver disease, and to the size and endoscopic appearance of esophageal varices. Indeed, hepatic venous pressure gradient (HVPG) and esophagogastroduodenoscopy (EGD) are currently recognized as the "gold standard" and the diagnostic reference standard for the prediction of EVB, respectively. However, HVPG is an invasive, expensive, and technically complex procedure, not widely available in clinical practice, whereas EGD is mainly limited by its invasive nature. In this scenario, computed tomography (CT) has been recently proposed as a promising modality for the non-invasive prediction of EVB. Although CT is only a diagnostic modality, thus being not capable of supplanting EGD or HVPG in providing therapeutic and physiological data, it could potentially assist liver disease scores, HVPG, and EGD in a more effective prediction of EVB. However, to date, evidence concerning the role of CT in this setting is still lacking. Our review aimed to summarize and discuss the current evidence concerning the role of CT in predicting the risk of EVB.

Stocky/Packed Pancreas: A Case of Focal Drug-Induced Acute Pancreatitis Mimicking Cancer.

Drug-induced acute pancreatitis (DIP) is a recognised but underreported entity in the literature. Immunotherapy drugs have been described as one possible emerging cause, although the pathogenic mechanism is still largely unclear. To date, only a few cases have been reported, even if in recent times there is an over-increasing awareness of this pathologic entity. The imaging-based diagnosis of DIP can be difficult to establish, representing a real challenge for a radiologist, especially when the inflammatory disease appears as a focal mass suspicious for a malignancy. Case report: We herein report the case of a 71-year-old man with a known history of partially responsive lung adenocarcinoma subtype with high programmed cell death ligand 1 (PD-L1) expression, who underwent positron emission tomography (PET)/computed tomography (CT) imaging follow-up after one year of immunotherapy. The exam revealed a stocky/packed lesion in the pancreatic body, with increased 18F-fluorodeoxyglucose (FDG) accumulation highly suggestive of pancreatic cancer, which finally was proven to be a DIP induced by immunotherapy. Conclusion: Distinguishing between focal DIP and pancreatic neoplasm is, therefore, crucial for timely therapeutic management and prognostic stratification. A deep knowledge of possible imaging pitfalls coupled with a comprehensive clinical and laboratory assessment is pivotal to avoid any delays in diagnosis.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic neuroendocrine tumors: a systematic review of the literature.

Background and study aims Surgery is the mainstay therapy for pancreatic neuroendocrine tumors (P-NETs), but it is associated with significant adverse events (AEs). In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been described for treating P-NETs. We performed a systematic literature review aimed at exploring the feasibility, effectiveness, and safety of EUS-RFA in treatment of P-NETs. Methods The literature review was performed in PubMed/MEDLINE, EMBASE, and SCOPUS to identify all case reports of EUS-RFA for treatment of P-NETs. Results Sixyt-one patients (males 49.2 %, mean age 64.5 years) and 73 tumors (mean size 16 mm, insulinomas 30.1 %) treated with EUS-RFA were included from 12 studies. The overall effectiveness of EUS-RFA was 96 % (75 % - 100 %) without differences between functional vs. non-functional P-NETs ( P  = 0.3) and without relevant issues about safety (mild AEs 13.7 %). While tumor location was not predictive for incomplete/non-response to EUS-RFA, greater tumor dimensions predicted treatment failure (21.8 ±â€Š4.71 mm in the non-response group vs 15.07 ±â€Š7.34 mm in the response group, P  = 0.048). At ROC analysis, a P-NET size cut-off value ≤18 mm predicted response to treatment, with a sensitivity of 80 % (95 % CI 28.4 % - 99.5 %), a specificity of 78.6 % (95 % CI 63.2 % - 89.7 %), a positive predictive value of 97.1 % (95 % CI 84.7 % - 99.9 %) and a negative predictive value of 30.8 % (95 % CI 9.1 % - 61.4 %), with an area under the curve of 0.81 (95 % CI 0.67 - 0.95). Conclusions EUS-RFA is safe and effective for treating P-NETs. It may be reasonable to consider EUS-RFA for small P-NETs, irrespective of the functional status.

Predictors of advanced colorectal neoplasia at initial and surveillance colonoscopy after positive screening immunochemical faecal occult blood test.

BACKGROUND: Characteristics such as gender and lifestyle are not taken in account in colorectal cancer screening and surveillance recommendations. AIMS: To identify factors associated with advanced neoplasia at initial and surveillance colonoscopy. METHODS: In this observational study, 750 individuals with positive faecal occult blood test, aged 50-74 years, underwent a first screening colonoscopy in 2007-2009. We collected anthropometric data as well as data on physical activity, smoking and drinking habits, fruit and vegetable consumption and low-dose aspirin use through a questionnaire. RESULTS: At initial colonoscopy advanced neoplasia (n=399, 53.2%) was positively associated with age, male gender, smoking and alcohol drinking, and inversely associated with physical activity, fruit and vegetables consumption and long-term use of aspirin. These 7 factors were used to calculate a risk score, ranging from 0 (no unfavourable characteristics) to 7 (all unfavourable characteristics present), which was significantly associated with advanced neoplasia (odds ratio 1.55 for one point increase, P<0.01). Among the 372 adenoma patients who returned for follow-up surveillance colonoscopy, the score remained associated with advanced neoplasia (odds ratio 1.28 for one point increase, P=0.01). CONCLUSION: Besides age and gender, modifiable factors such as lifestyle and aspirin use were associated with the risk of advanced neoplasia at initial and surveillance colonoscopy.

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy.

AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. METHODS: Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. CONCLUSION: Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy.

Confocal laser endomicroscopy for in vivo diagnosis of Barrett's oesophagus and associated neoplasia: a pilot study conducted in a single Italian centre.

BACKGROUND: Diagnosis and management of Barrett's oesophagus are controversial. Technical improvements in real-time recognition of intestinal metaplasia and neoplastic foci provide the chance for more effective target biopsies. Confocal laser endomicroscopy allows to analyze living cells during endoscopy. AIMS: To assess the diagnostic accuracy, inter- and intra-observer variability of endomicroscopy for detecting in vivo neoplasia (dysplasia and/or early neoplasia) in Barrett's oesophagus. METHODS: Prospective pilot study. Patients referred for known Barrett's oesophagus were screened. Endomicroscopy was carried out in a circular fashion, every 1-2 cm, on the whole columnar-lined distal oesophagus. Visible lesions, when present, were analyzed first. Targeted biopsies were taken. Confocal images were classified according to confocal Barrett classification. Endomicroscopic and histological findings were compared. RESULTS: Forty-eight out of 50 screened patients underwent endomicroscopy. Visible lesions were observed in 3 patients. In a per-biopsy analysis, Barrett's-oesophagus-associated neoplasia could be predicted with an accuracy of 98.1%. The agreement between endomicroscopic and histological results was substantial (κ=0.76). CONCLUSIONS: This study suggests that endomicroscopy can provide in vivo diagnosis of Barrett's oesophagus-associated neoplasia. Because it allows for the study of larger surface areas of the mucosa, endomicroscopy may lead to significant improvements in the in vivo screening and surveillance of Barrett's oesophagus.

Linear array ultrasonography to stage rectal neoplasias suitable for local treatment.

BACKGROUND: Because of the many therapeutic options available, a reliable staging is crucial for rectal neoplasia management. Adenomas and cancers limited to the submucosa without lymph node involvement may be treated locally. AIMS: The aim of this study is to evaluate the diagnostic accuracy of endorectal ultrasonography in the staging of neoplasias suitable for local treatment. METHODS: We considered all patients who underwent endorectal ultrasonography between 2001 and 2010. The study population consisted of 92 patients with 92 neoplasias (68 adenocarcinomas and 24 adenomas). A 5 and 7.5MHz linear array echoendoscope was used. The postoperative histopathologic result was compared with the preoperative staging defined by endorectal ultrasonography. Adenomas and cancers limited to the submucosa were considered together (pT0-1). RESULTS: The sensitivity, specificity, overall accuracy rate, positive predictive value, and negative predictive value of endorectal ultrasonography for pT0-1 were 86%, 95.6%, 91.3%, 94.9% and 88.7%. Those for nodal involvement were 45.4%, 95.5%, 83%, 76.9% and 84%, with 3 false positive results and 12 false negative. For combined pT0-1 and pN0, endorectal ultrasonography showed an 87.5% sensitivity, 95.9% specificity, 92% overall accuracy rate, 94.9% positive predictive value and 90.2% negative predictive value. CONCLUSION: Endorectal linear array ultrasonography is a reliable tool to detect rectal neoplasias suitable for local treatment.

Gastroesophageal reflux disease management according to contemporary international guidelines: a translational study.

AIM: To test the Genval recommendations and the usefulness of a short trial of proton pump inhibitor (PPI) in the initial management and maintenance treatment of gastroesophageal reflux disease (GERD) patients. METHODS: Five hundred and seventy seven patients with heartburn were recruited. After completing a psychometric tool to assess quality of life (PGWBI) and a previously validated GERD symptom questionnaire (QUID), patients were grouped into those with esophagitis (EE, n = 306) or without mucosal damage (NERD, n = 271) according to endoscopy results. The study started with a 2-wk period of high dose omeprazole (omeprazole test); patients responding to this PPI test entered an acute phase (3 mo) of treatment with any PPI at the standard dose. Finally, those patients with a favorable response to the standard PPI dose were maintained on a half PPI dose for a further 3-mo period. RESULTS: The test was positive in 519 (89.9%) patients, with a greater response in EE patients (96.4%) compared with NERD patients (82.6%) (P = 0.011). Both the percentage of completely asymptomatic patients, at 3 and 6 mo, and the reduction in heartburn intensity were significantly higher in the EE compared with NERD patients (P < 0.01). Finally, the mean PGWBI score was significantly decreased before and increased after therapy in both subgroups when compared with the mean value in a reference Italian population. CONCLUSION: Our study confirms the validity of the Genval guidelines in the management of GERD patients. In addition, we observed that the overall response to PPI therapy is lower in NERD compared to EE patients.

Is it possible to clinically differentiate erosive from nonerosive reflux disease patients? A study using an artificial neural networks-assisted algorithm.

BACKGROUND: The use of either symptom questionnaires or artificial neural networks (ANNs) has proven to improve the accuracy in diagnosing gastroesophageal reflux disease (GERD). However, the differentiation between the erosive and nonerosive reflux disease based upon symptoms at presentation still remains inconclusive. AIM: To assess the capability of a combined approach, that is, the use of a novel GERD questionnaire - the QUestionario Italiano Diagnostico (QUID) questionnaire - and of an ANNs-assisted algorithm, to discriminate between nonerosive gastroesophageal reflux disease (NERD) and erosive esophagitis (EE) patients. METHODS: Five hundred and fifty-seven adult outpatients with typical GERD symptoms and 94 asymptomatic adult patients, were submitted to the QUID questionnaire. GERD patients were then submitted to upper gastrointestinal endoscopy to differentiate them between EE and NERD patients. RESULTS: The QUID score resulted significantly (P<0.001) higher in GERD patients versus controls, but it was not statistically significantly different between EE and NERD patients. ANNs assisted diagnosis had greater specificity, sensitivity and accuracy compared with the linear discriminant analysis only to differentiate GERD patients from controls. However, no single technique was able to satisfactorily discriminate between EE and NERD patients. CONCLUSION: Our study suggests that the combination between QUID questionnaire and an ANNs-assisted algorithm is useful only to differentiate GERD patients from healthy individuals but fails to further discriminate erosive from nonerosive patients.

The proton pump inhibitor test for gastroesophageal reflux disease: optimal cut-off value and duration.

BACKGROUND: There is no accepted gold standard for the diagnosis of gastroesophageal reflux disease (GERD). AIM: To assess the optimal cut-off value and duration of the proton pump inhibitor (PPI) test in GERD patients with and without oesophagitis. METHODS: Prospective study of 544 patients undergoing upper GI endoscopy and treated for 2 weeks with PPIs at double dose, and for 3 additional months at standard dose. The status of the patient at end of treatment was used as an independent diagnostic standard, i.e. patients completely asymptomatic were considered as "true" GERD patients. RESULTS: PPI test was positive in 89.7-97.8% of the patients according to the cut-off or duration of test used. Test sensitivity ranged from 95.5% to 98.8%, whereas specificity did not exceed 36.3%. Positive predictive values ranged from 87% to 80%, negative predictive values ranged from 58% to 70%, respectively. CONCLUSIONS: The PPI test is a sensitive but poorly specific test in GERD patients. Its optimal duration is 1 week, and the optimal cut-off value is a decrease of heartburn score ≥75%. The diagnostic yield is higher in erosive oesophagitis compared with non-erosive reflux disease patients, similarly to the symptomatic response to 3-month PPI therapy.

Endoscopic surveillance for hereditary non-polyposis colorectal cancer (HNPCC) family members in a Southern Italian region.

BACKGROUND: Surveillance in hereditary non-polyposis colorectal cancer (HNPCC) family members recommends baseline colonoscopy starting at age 20 and then surveillance colonoscopy every 1-2 years. AIMS: To verify adherence to the guidelines for HNPCC family members enrolled in endoscopic surveillance. METHODS: Data regarding 11 HNPCC families was retrieved from our database. Excluding 11 probands, 106 family members were evaluated and 40 underwent surveillance. RESULTS: At baseline colonoscopy, 7 colorectal cancers (CRC), 14 polyps (PO) [1 inflammatory, 2 hyperplastic, 10 adenomas with low grade dysplasia (LGD-AD) and 1 adenoma with high-grade dysplasia (HGD-AD)] were diagnosed in sixteen individuals. Twenty-eight HNPCC family members underwent endoscopic surveillance, with a total of 94 surveillance colonoscopies. Of these, 45 were positive (4 CRC, 3 inflammatory PO, 34 hyperplastic PO, 21 LGD-AD and 5 HGD-AD). Mean time between two consecutive surveillance colonoscopies was 24.6 months (range 4-168). Median time to first positive surveillance colonoscopy was 84 months for HNPCC family members with negative baseline colonoscopy, and 60 months for those with positive baseline colonoscopy (p=0.21). CONCLUSIONS: Our data suggests that surveillance colonoscopy every 2 years is adequate to diagnose advanced lesions in HNPCC family members, and improves their compliance with surveillance.

Outcome of nonerosive gastro-esophageal reflux disease patients with pathological acid exposure.

AIM: To assess the management and outcome of nonerosive gastro-esophageal reflux disease (NERD) patients who were identified retrospectively, after a 5-year follow-up. METHODS: We included patients with gastro-esophageal reflux disease (GERD) symptoms who had a negative endoscopy result and pathological 24-h esophageal pH-monitoring while off therapy. We interviewed them after an average period of 5 years (range 3.5-7 years) by means of a structured questionnaire to assess presence of GERD symptoms, related therapy, updated endoscopic data and other features. We assessed predictors of esophagitis development by means of univariate and multivariate statistical analysis. RESULTS: 260 patients (137 women) were included. Predominant GERD symptoms were heartburn and regurgitation in 103/260 (40%). 70% received a maintenance treatment, which was proton pump inhibitor (PPI) in 55% of cases. An average number of 1.5 symptomatic relapses per patient/year of follow-up were observed. A progression to erosive gastro-esophageal reflux disease (ERD) was found in 58/193 (30.0%) of patients undergoing repeat endoscopy; 72% of these were Los Angeles grade A-B. CONCLUSION: This study shows that progression to ERD occurs in about 5% of NERD cases per year, despite therapy. Only two factors consistently and independently influence progression: smoking and absence of PPI therapy.

Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins.

BACKGROUND: Portal hypertension leads to the formation of portosystemic collateral veins in liver cirrhosis. The resulting shunting is responsible for the development of portosystemic encephalopathy. Although ammonia plays a certain role in determining portosystemic encephalopathy, the venous ammonia level has not been found to correlate with the presence or severity of this entity. So, it has become partially obsolete. Realizing the need for non-invasive markers mirroring the presence of esophageal varices in order to reduce the number of endoscopy screening, we came back to determine whether there was a correlation between blood ammonia concentrations and the detection of portosystemic collateral veins, also evaluating splenomegaly, hypersplenism (thrombocytopenia) and the severity of liver cirrhosis. METHODS: One hundred and fifty three consecutive patients with hepatic cirrhosis of various etiologies were recruited to participate in endoscopic and ultrasonography screening for the presence of portosystemic collaterals mostly esophageal varices, but also portal hypertensive gastropathy and large spontaneous shunts. RESULTS: Based on Child-Pugh classification, the median level of blood ammonia was 45 mcM/L in 64 patients belonging to class A, 66 mcM/L in 66 patients of class B and 108 mcM/L in 23 patients of class C respectively (p < 0.001).The grade of esophageal varices was concordant with venous ammonia levels (rho 0.43, p < 0.001). The best area under the curve was given by ammonia concentrations, i, e., 0.78, when comparing areas of ammonia levels, platelet count and spleen longitudinal diameter at ultrasonography. Ammonia levels predicted hepatic decompensation and ascites presence (Odds Ratio 1.018, p < 0.001). CONCLUSION: Identifying cirrhotic patients with high blood ammonia concentrations could be clinically useful, as high levels would lead to suspicion of being in presence of collaterals, in clinical practice of esophageal varices, and pinpoint those patients requiring closer follow-up and endoscopic screening.

Potential role for the common cystic fibrosis DeltaF508 mutation in Crohn's disease.

BACKGROUND: Inflammatory bowel disease (IBD) is an epithelial barrier disease that is thought to result from a dysregulated interaction with bacteria in the intestine of genetically predisposed individuals. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in the autosomal recessive disease cystic fibrosis, modulates gut permeability, mucus production, and epithelial interactions with bacteria. The cystic fibrosis DeltaF508 mutation is commonly found in the general population and has been shown to result in a reduced number of CFTR molecules at the surface of epithelial cells. Given the important biological functions of CFTR in the intestine, we tested whether this mutation is of relevance to IBD. METHODS: Using DNA heteroduplex analysis, we investigated the distribution of DeltaF508 heterozygosity in 2568 subjects from three independent cohorts of Italian, Swedish, and Scottish IBD patients and controls. RESULTS: In all three cohorts an association between DeltaF508 and Crohn's disease (CD) was observed. Specifically, DeltaF508 heterozygosity was markedly underrepresented in CD patients from Italy and Sweden (P = 0.021 and 0.027 versus controls, respectively), while stratification for disease location revealed an absence of DeltaF508 carriers among Scottish CD patients with right-sided colitis (P = 0.023 versus all other locations). CONCLUSIONS: DeltaF508 heterozygosity might exert a protective effect in CD.