Lorenzo Fuccio

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

BACKGROUND AND AIMSnEndoscopic 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.nnnMETHODSnElectronic 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.nnnRESULTSnNinety-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.nnnCONCLUSIONSnIn 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.

Clinical outcomes following stent placement in refractory benign esophageal stricture: a systematic review and meta-analysis

BACKGROUND AND AIMSnThe management of refractory benign esophageal strictures (RBESs) is challenging. Stent placement has been proposed as a possible rescue strategy. We performed a systematic review and meta-analysis to examine the efficacy of this strategy in the long-term resolution of dysphagia.nnnMETHODSnPubMed, SCOPUS, and Google Scholar were searched (up to January 2015). Studies recruiting adults with RBES treated with stent placement were eligible. The success, adverse event, and migration rates were pooled by means of a random-effect model to obtain odds with a 95u200a% confidence interval (CI).nnnRESULTSnEighteen studies (444 patients) were eligible for inclusion. The pooled clinical success rate was 40.5u200a% (95u200a%CI 31.5u200a%u200a-u200a49.5u200a%), yielding odds of 0.68 (95u200a%CI 0.46u200a-u200a0.98) with high heterogeneity (I(2)u200a=u200a65.0u200a%). The meta-regression analysis showed stricture etiology as the only influencing factor. Treatment with self-expanding plastic (SEPSs) and metal stents (SEMSs) did not result in significantly higher success rates than treatment with biodegradable stents (BDSs) (46.2u200a% vs. 40.1u200a% vs. 32.9u200a%, respectively). The migration rate was 28.6u200a% (95u200a%CI 21.9u200a%u200a-u200a37.1u200a%), yielding odds of 0.40 (95u200a%CI 0.28u200a-u200a0.59), with migration rates for SEPSs and SEMSs reported as being not significantly higher than BDSs (33.3u200a% vs. 31.5u200a% vs. 15.3u200a%, respectively). The adverse event rate was 20.6u200a% (95u200a%CI 15.3u200a%u200a-u200a28.1u200a%), yielding odds of 0.26 (95u200a%CI 0.18u200a-u200a0.39) with no significant difference between stent types (19.4u200a% vs. 21.9u200a% vs. 21.9u200a%, respectively).nnnCONCLUSIONSnStent placement in patients with RBES is effective in about 40u200a% of cases. Further studies should investigate whether the clinical success rate varies according to the stricture etiology.(PROSPERO registration number: CRD42015019017.).

Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn

BackgroundHypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance–pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by negative SAP/SI and PPI refractoriness. The clinical value of SAP and SI has been questioned. We aimed to investigate whether impairment of chemical clearance and of mucosal integrity, expressed by the postreflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), characterize HE independently of SAP and SI.MethodsImpedance–pH tracings from PPI-responsive endoscopy-negative patients, 125 with nonerosive reflux disease and 108 with HE, distinguished by an abnormal and a normal acid exposure time, and from 70 patients with FH were retrospectively selected and blindly reviewed.ResultsThe mean PSPW index and MNBI were significantly lower in nonerosive reflux disease (30xa0%, 1378xa0Ω) than in HE (51xa0%; 2274xa0Ω) and in both of them as compared with FH (76xa0%; 3445xa0Ω) (Pxa0=xa00.0001). Both the PSPW index (adjusted odds ratio 0.863, Pxa0=xa00.001) and the MNBI (adjusted odds ratio 0.998, Pxa0=xa00.001) were independent predictors of HE; with their combined assessment, the area under the curve on receiver operating characteristic analysis was 0.957. SAP and/or SI was positive in 67 of the 108 HE patients (62xa0%), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92xa0%; Pxa0<xa00.0001).ConclusionsHE is characterized by impairment of chemical clearance and mucosal integrity, which explains the increased reflux perception. When SAP and SI afford uncertain results, the PSPW index and MNBI should be analyzed.

Barriers against split-dose bowel preparation for colonoscopy

Objective Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients attitude towards split regimen and patient-related factors associated with its uptake. Design In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4u2005L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. Results Of the 1447 patients (mean age 59.2±13.5u2005years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p<0.001, χ2 for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service >1u2005h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). Conclusion Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. Trial registration number NCT02287051; pre-result.

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

BACKGROUND AND AIMSnPer-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.nnnMETHODSnA 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.nnnRESULTSnAfter 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.nnnCONCLUSIONnThe 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.

Postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance can link PPI-responsive heartburn to reflux better than acid exposure time

Acid exposure time (AET) is considered the most useful parameter to predict response of reflux‐related heartburn to medical or surgical treatment. However, recent studies showed high rates of heartburn response to proton pump inhibitor (PPI) therapy in patients with normal AET.

The presence of rapid on-site evaluation did not increase the adequacy and diagnostic accuracy of endoscopic ultrasound-guided tissue acquisition of solid pancreatic lesions with core needle

AbstractBackgroundnRapid on-site evaluation (ROSE) improves the adequacy and accuracy of EUS-guided tissue acquisition, although it is not routinely widely available. Evidence suggested that core needles might overcome the absence of ROSE. The aim of this study was to evaluate the influence of ROSE on the adequacy and accuracy of EUS-guided tissue acquisition with core needles in patients with pancreatic solid lesions.MethodsPatients who underwent EUS-guided tissue acquisition of pancreatic mass lesions were retrospectively identified at three tertiary referral centers and those performed with the core needle were included. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without ROSE was the primary outcome measure. The diagnostic accuracy and tissue core acquisition were the secondary outcome measures.ResultsA total of 333 patients with pancreatic solid mass lesions were included in the study; 140 cases sampled with ROSE and 193 cases without ROSE. The adequacy was 92.1xa0% in the group sampled with ROSE and 88.1xa0% in the group without ROSE (pxa0=xa00.227). In the ROSE group sensitivity, specificity, and accuracy were 90.7, 100 and 92.1xa0%, respectively. In the group without ROSE, sensitivity, specificity, and accuracy were 87.2, 100, and 88.1xa0%, respectively. No difference for all these figures was observed between the two groups. The tissue core was available in 61.4 and 53.4xa0% of cases with and without ROSE, respectively (pxa0=xa00.143).ConclusionIn the absence of ROSE, EUS-based tissue acquisition with Core needle should be considered since it achieves comparable tissue sampling adequacy and accuracy.

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

BACKGROUNDnThe 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.nnnMETHODSnProspective 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.nnnRESULTSnSix 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.nnnCONCLUSIONnBrachytherapy 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.

Preoperative Chemoradiation With VMAT-SIB in Rectal Cancer: A Phase II Study

Purpose The aim of this study was to investigate the efficacy and toxicity of volumetric modulated arc therapy (VMAT)–simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer. Methods Radiation therapy was performed using the VMAT‐SIB technique. The dose to mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered on GTV + 2‐cm margin with a total dose of 57.5 Gy (2.3 Gy/fraction). The following concomitant chemotherapy was administered: capecitabine (825 mg/m2 twice daily, 5 days per week) and oxaliplatin (130 mg/m2 on days 1, 17, and 35). Efficacy was evaluated in terms of complete pathological response (pCR). Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 3.0 criteria. Results A total of 18 patients (7 women; median age 62 years; clinical stage: 4 local recurrences, 6 cT4, 5 cT3, 3 cT2, 2 cN0, 7 cN1, 9 cN2) were enrolled. Sixteen patients underwent surgical resection (9 low anterior resection, 6 abdominal perineal amputations; 1 transanal excision) and 2 patients did not undergo surgery for early metastatic progression or death from acute pulmonary edema. R0 resection was achieved in all patients who underwent surgery. Overall, 4 patients had a pCR and 7 patients only a microscopic residual of disease (pT0‐Tmic: 11/18 = 61.1%; 95% CI, 36.2‐86.1). Acute grade ≥ 3 toxicity was as follows: 1 case of leukopenia, 1 skin toxicity, 1 genitourinary toxicity, and 5 gastrointestinal toxicities, with an overall incidence of 8 (44.4%) of 18 patients. One‐, 3‐, and 5‐year cumulative local control was 100%, 68.6%, and 68.6%, respectively. One‐, 3‐, and 5‐year cumulative disease‐free survival was 88.9%, 66.7%, and 66.7%, respectively. One‐, 3‐, and 5‐year cumulative overall survival was 85%, 63.8%, and 63.8%, respectively. Conclusion The regimen used in this study showed excellent results in terms of pathologic responses. However, despite the use of the VMAT technique, more than one‐third of patients had severe acute toxicity. Micro‐Abstract The efficacy and toxicity of volumetric modulated arc therapy (VMAT)–simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer were investigated. VMAT‐SIB with concomitant capecitabine and oxaliplatin showed a good efficacy: 11 (61.1%) of 18 patients had complete or near complete response. Severe acute toxicity was not negligible and reported in 44.4% patients.

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 ≤1000u2009µm 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 11u2009260 colorectal dissected lesions were included. Most resected lesions (82.2%; 95%u2009CI 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%u2009CI 6.1% to 10.3%) had an infiltration depth of ≤1000u2009µm, 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.