Daniele Mandolesi

Review article: the diagnosis of non‐alcoholic fatty liver disease – availability and accuracy of non‐invasive methods

Non‐alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of clinical conditions, actually representing an emerging disease of great clinical interest. Currently, its diagnosis requires liver biopsy, an invasive procedure not free from potential complications. However, several non‐invasive diagnostic strategies have been proposed as potential diagnostic alternatives, each with different sensitivities and accuracies.

Spleen stiffness measurement can predict clinical complications in compensated HCV-related cirrhosis: A prospective study

BACKGROUND & AIMS Hepatic venous pressure gradient (HVPG) measurement represents the best predictor of clinical decompensation (CD) in cirrhotic patients. Recently data show that measurement of spleen stiffness (SS) has an excellent correlation with HVPG levels. Aim of the present prospective study was to assess SS predictive value for CD compared to HVPG, liver stiffness (LS), and other non-invasive tests for portal hypertension in a cohort of patients with HCV-related compensated cirrhosis. METHODS From an initial cohort of 124 patients, 92 underwent baseline LS, SS, HVPG measurements and upper gastrointestinal endoscopy at enrolment and then followed-up for 2 years or until the occurrence of the first CD. Univariate and multivariate logistic regression models were used for determining judgement criteria associated parameters. Accuracy of predictive factors was evaluated using c statistic. The final model was internally validated using the bootstrap method. RESULTS During follow-up, 30 out 92 (32.6%) patients developed CD. At univariate analysis varices at enrolment, all non-invasive parameters, HVPG, and model for end-stage liver disease (MELD) resulted clinical predictors of CD. At multivariate analysis only SS (p=0.0001) and MELD (p=0.014) resulted as predictive factors. A decision algorithm based on the results of a predictive model was proposed to detect patients with low risk of decompensation. CONCLUSIONS This study shows that in compensated cirrhotic patients a SS and MELD predictive model represents an accurate predictor of CD with accuracy at least equivalent to that of HVPG. If confirmed by further studies, SS and MELD could represent valid alternatives to HVPG as prognostic indicator of CD in HCV-related cirrhosis.

Clinical outcomes after endoscopic submucosal dissection for colorectal neoplasia: a systematic review and meta-analysis

BACKGROUND AND AIMS Endoscopic submucosal dissection (ESD) is an endoscopic resection technique for lesions suspicious of superficial malignancy. It is performed using an ESD knife on its own (standard technique) or by the sequential use of a knife and a snare (hybrid technique). The experience with these techniques is different in Asian and non-Asian countries. We performed a systematic review and meta-analysis of available evidence on colorectal ESD. METHODS Electronic databases were searched up to August 2016 for studies evaluating R0, en bloc resection, and adverse event rates of both techniques for the treatment of colorectal lesions. Proportions were pooled by a random effects model. RESULTS Ninety-seven studies (71 performed in Asia) evaluated the standard technique and 12 studies (7 in Asia) the hybrid technique. The R0 resection rate of the standard technique was 82.9%, and it was significantly lower in non-Asian versus Asian countries: 71.3% versus 85.6%. The en bloc resection rate was 91% and was significantly lower in non-Asian versus Asian countries (81.2% vs 93%, respectively). Surgery was needed in 1.1% of the ESD-related adverse events, with a significant difference between non-Asian and Asian countries (3.1% vs 0.8%). The R0 and en bloc resection rates with the hybrid technique were significantly lower than those achieved with the standard technique: 60.6% and 68.4%, respectively, with similar adverse event rates. CONCLUSIONS In non-Asian countries the standard ESD technique is still failing to achieve acceptable levels of performance. The hybrid technique showed low R0 resection rates and should not be considered as an adequate alternative to the standard technique.

Liver and spleen stiffness and other noninvasive methods to assess portal hypertension in cirrhotic patients: a review of the literature.

Portal hypertension (PH) is one of the most important causes of morbidity and mortality in patients with chronic liver disease. PH measurement is crucial to stage and predict the clinical outcome of liver cirrhosis. Measurement of hepatic vein pressure gradient is considered the gold standard for assessment of the degree of PH; however, it is an invasive method and has not been used widely. Thus, noninvasive methods have been proposed recently. We critically evaluated serum markers, abdominal ultrasonography, and particularly liver and spleen stiffness measurement, which represent the more promising methods to stage PH degree and to assess the presence/absence of esophageal varices (EV). A literature search was carried out on MEDLINE, EMBASE, Web of Science, and Scopus for articles and abstracts. The search terms used included ‘liver cirrhosis’, ‘portal hypertension’, ‘liver stiffness’, ‘spleen stiffness’, ‘ultrasonography’, and ‘portal hypertension serum biomarker’. The articles cited were selected on the basis of their relevance to the objective of the review. The results of available studies indicate that individually, these methods have a mild accuracy in predicting the presence of EV, and thus they cannot substitute endoscopy to predict EV. When these tests were used in combination, their accuracy increased. In addition to the PH staging, several serum markers and spleen stiffness measurement can predict the clinical outcome of liver cirrhosis with a good accuracy, comparable to that of hepatic vein pressure gradient. In the future, noninvasive methods could be used to select patients requiring further investigations to identify the best tailored clinical management.

Gastroesophageal reflux disease after per-oral endoscopic myotomy as compared with Heller's myotomy with fundoplication: a systematic review with meta-analysis

BACKGROUND AND AIMS Per-oral endoscopic myotomy (POEM) represents a less invasive alternative to conventional laparoscopic Hellers myotomy (LHM) for patients with achalasia. It cannot be excluded, however, that the lack of fundoplication after POEM may result in a higher incidence of reflux disease, as compared with LHM. The aim of our study was to conduct a systematic review of prospective studies reporting the incidence of reflux disease developed after POEM and LHM. METHODS A literature search with electronic databases was performed (up to February 2017) to identify full articles on the incidence of gastroesophageal reflux symptoms and endoscopic monitoring and pH monitoring findings after POEM and LHM (with fundoplication). Proportions and rates were pooled by means of random or fixed-effects models, according to the level of heterogeneity between studies. RESULTS After we applied the selection criteria, 17 and 28 studies, including 1542 and 2581 participants who underwent POEM and LHM, respectively, were included. The pooled rate of postprocedural symptoms was 19.0% (95% confidence interval [CI], 15.7%-22.8%) after POEM and 8.8% (95% CI, 5.3%-14.1%) after LHM, respectively. The pooled rate estimate of abnormal acid exposure at pH monitoring was 39.0% (95% CI, 24.5%-55.8%) after POEM and 16.8% (95% CI, 10.2%-26.4%) after LHM, respectively. The rate of esophagitis after POEM was 29.4% (95% CI, 18.5%-43.3%) after POEM and 7.6% (95% CI, 4.1%-13.7%) after LHM. At meta-regression, heterogeneity was explained partly by the POEM approach and study population. CONCLUSION The incidence of reflux disease appears to be significantly more frequent after POEM than after LHM with fundoplication. Monitoring pH and ensuring appropriate treatment after POEM should be considered in order to prevent long-term reflux-related adverse events.

Brachytherapy for the palliation of dysphagia owing to esophageal cancer: A systematic review and meta-analysis of prospective studies

BACKGROUND The management of dysphagia owing to esophageal cancer is challenging. Brachytherapy has been proposed as an alternative option to stent placement. We performed a systematic review to examine its efficacy and safety in the resolution of dysphagia. METHODS Prospective studies recruiting at least 20 patients with malignant dysphagia and published up to April 2016 were eligible. The dysphagia-free survival (DFS) and adverse event rates were pooled by means of a random effect model. RESULTS Six studies for a total of 9 treatment arms (623 patients) were eligible for inclusion. After 1month since treatment, the DFS rate was 86.9% [95%CI: 76.0-93.3%]; after 3months, it was 67.2% [95%CI: 56.1-76.7%]; after 6months, it was 47.4% [95%CI: 38.5-56.5%]; after 9months, it was 37.6% [95%CI:30.0-45.9%]; and, finally, after 12months, it was 29.4% [95%CI: 21.6-38.7%]. The heterogeneity between studies was high at 1-, 3- and 6-month assessment; the values of I2 were 86.3%, 80.0% and 57.8%, respectively. The meta-regression analysis showed total radiation dose and number of fractions as the only positively influencing factors. Severe adverse event rate was 22.6% (95%CI 19.4-26.3). The main reported adverse events were brachytherapy-related stenosis (12.2%) and fistula development (8.3%). Two cases (0.3%) of deaths were reported due to esophageal perforation. CONCLUSION Brachytherapy is a highly effective and relatively safe treatment option therefore its underuse is no longer justified. Further studies should investigate the optimal radiation dose and number of fractions able to achieve the highest DFS rates.

Why attempt en bloc resection of non-pedunculated colorectal adenomas? A systematic review of the prevalence of superficial submucosal invasive cancer after endoscopic submucosal dissection

Objective Endoscopic submucosal dissection (ESD) aims to achieve en bloc resection of non-pedunculated colorectal adenomas which might be indicated in cases with superficial submucosal invasive cancers (SMIC), but the procedure is time consuming and complex. The prevalence of such cancers is not known but may determine the clinical necessity for ESD as opposed to the commonly used piecemeal mucosal resection (endoscopic mucosal resection) of colorectal adenomas. The main aim was to assess the prevalence of SMIC SM1 (ie, invasion ≤1000 µm or less than one-third of the submucosa) on colorectal lesions removed by ESD. Design A literature review was conducted using electronic databases (up to March 2017) for colorectal ESD series reporting the histology of the dissected lesions. Results 51 studies with data on 11 260 colorectal dissected lesions were included. Most resected lesions (82.2%; 95% CI 78.8% to 85.3%) were adenomas (low- and high-grade dysplasia, 26.8% and 55.4%, respectively). Overall, 15.7% were submucosal cancers, but only slightly more than half (8.0%; 95% CI 6.1% to 10.3%) had an infiltration depth of ≤1000 µm, providing a number needed to treat (NNT) to avoid one surgery of 12.5. Estimating an oncologically curative (R0; G1/2; L0/V0) resection rate of 75.3% (95% CI 52.2% to 89.4%) for malignant lesions, the prevalence of curative resection lowered to 6% (95% CI 4.2% to 7.2%) with an NNT of 16.7. Conclusion The low prevalence of SMIC SM1 in lesions selected for ESD as well as the even lower rate of curative resection limits the clinical applicability of endoscopic en bloc resection. This calls for caution over an indiscriminate use of this technique in the resection of colorectal neoplasia.

Underuse of brachytherapy for the treatment of dysphagia owing to esophageal cancer. An Italian survey

BACKGROUND International guidelines strongly recommend brachytherapy as valid alternative or in addition to stenting in patients with dysphagia owing to esophageal cancer. However, for not well understood reasons, brachytherapy is definitively underused for the palliative treatment of malignant dysphagia. Aim of the current survey was to investigate the use of brachytherapy for the treatment of malignant dysphagia in Italy. METHODS A structured questionnaire was submitted to the 1510 members of the Italian Association of Radiation Oncologists (AIRO). These members refer to 177 centres of radiotherapy across Italy and in 68 (38.4%) of them brachytherapy is routinely performed. RESULTS Of the 1510 invited members, 178 completed the survey (11.7%). The answers provided by the 178 participants allowed to get information on 40 out of 68 brachytherapy centres (58.8%). Seven out of 40 (17.5%) centres perform brachytherapy of the oesophagus, in 3 out of 40 (7.5%) centres brachytherapy represents the first line of treatment. The main reason why brachytherapy is not routinely performed is the lack of experience. CONCLUSION Despite the strong recommendations of the international guidelines and the wide diffusion of brachytherapy centres across Italy, only very few of them routinely considered brachytherapy for the treatment of dysphagia due to esophageal cancer.

The management of ‘hard-to-prepare’ colonoscopy patients

ABSTRACT Introduction: Effective bowel cleansing is crucial for high quality colonoscopy. A notable portion of patients still present with low quality bowel preparation prior to their colonoscopy, compromising the overall quality of their colonoscopy. Areas covered: This review focuses on the main strategies that can improve the cleansing quality with a special interest on those clinical conditions that have been associated with a poor bowel preparation quality, such as patients with chronic constipation, history of bowel resection, liver cirrhosis, diabetes mellitus and chronic kidney disease. The review provides a practical and evidence-based approach to help clinicians in the management of ‘hard-to-prepare’ patients. Expert commentary: In the past few years, the quality of colonoscopy has become a hot topic and bowel cleansing is a crucial part of it; however, the approach to patients with an increased risk of poor bowel preparation quality is still not always supported by high-quality evidence, since most of these patients are routinely excluded from the clinical studies. Trials focused on this subgroup of patients are recommended to provide tailored bowel preparation regimens and guarantee high-quality procedures.

A new mechanism of gastroesophageal reflux in hiatal hernia documented by high-resolution impedance manometry: a case report.

Gastroesophageal reflux disease (GERD) is recognized to be a multifactorial disease and several mechanisms leading to reflux have been described, nevertheless its pathophysiology has not been fully clarified. Hiatus hernia is a known risk factor for GERD since it impairs the esophagogastric junction, leading to: reduction in lower esophageal sphincter pressure; increase in the frequency of the transient lower esophageal sphincter relaxation; and impairment of esophageal clearance. Last generation diagnostic techniques have improved the understanding of these mechanisms. A 72-year-old woman with hiatus hernia and GERD underwent a high resolution impedance manometry (HRIM) after a partial response to treatment with pantoprazole. None of the proposed pathophysiological mechanisms for GERD could explain the presence of reflux: HRIM showed normal lower esophageal sphincter (LES) pressure and contractile integral, complete bolus clearance in all test swallows, and absence of transient LES relaxation. However, after the end of each peristaltic wave, as the LES pressure returned to resting values, a gastroesophageal reflux was detected until the following swallow. We describe an interesting case of a patient with a sliding hiatus hernia, with symptoms suggestive of GERD, in which HRIM revealed a new possible mechanism through which hiatus hernia may lead to GERD.