Background and Aims The use of contrast-harmonic EUS (CH-EUS) in routine clinical practice is increasing rapidly but is not yet standardized. We present the levels of evidence (LEs) found in the ...literature to put its clinical outcomes in the appropriate perspective. Methods We conducted a systematic review of the available English-language articles. The LEs were stratified according to the Oxford Centre for Evidence-Based Medicine guidelines. Results Overall, 210 articles were included and presented according to different pathologic conditions. For pancreatic solid neoplasms, the pooled sensitivity and specificity in the diagnosis of pancreatic carcinoma were very high (LE 1); quantitative analysis and guidance of FNA were reported as investigational research (LE 2-3). For pancreatic cystic lesions, the identification of neoplastic solid components as hyperenhanced lesions represented a promising application of CH-EUS (LE 2). For lymph nodes, CH-EUS increased the diagnostic yield of B-mode EUS for the detection of malignancy (LE 2). For submucosal tumors, CH-EUS seemed useful for differential diagnosis and risk stratification (LE 2-3). For other applications, differential diagnosis of gallbladder and vascular abnormalities by CH-EUS were reported (LE 2-3). Conclusions The LEs of CH-EUS in the literature have evolved from the initial descriptive studies to multicenter and prospective trials, and even meta-analyses. The differential diagnosis between benign and malignant lesions is the main field of application of CH-EUS. With regard to pancreatic solid neoplasms, the concomitant use of both CH-EUS and EUS-FNA may have additive value in increasing the overall accuracy by overcoming the false-negative results associated with each individual technique. Other applications are promising but still investigational.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Current imaging modalities are limited in their ability to distinguish pancreatic cancer (PC) from non‐neoplastic pancreatic lesions. The diagnostic use of contrast‐enhanced endoscopic ...ultrasonography (CE‐EUS) has increased, and its utility has been reported. Recently, contrast‐enhanced harmonic EUS (CH‐EUS) was reported to facilitate imaging of parenchymal perfusion and microvessels in pancreatobiliary diseases, leading to a high diagnostic accuracy for PC. The present meta‐analysis aims to investigate the usefulness of CH‐EUS with enhancement pattern for PC diagnosis.
Methods
A systematic meta‐analysis of all potentially relevant articles identified in PubMed, the Cochrane library, and Medline was carried out. Fixed‐effects or random‐effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence interval (CI).
Results
The study enrolled 887 patients from nine eligible studies. Pooled estimates of sensitivity and specificity were 93% (95% CI, 0.91–0.95) and 80% (95% CI, 0.75–0.85), respectively. Subgroup analyses were carried out on the main results after excluding two outliers. Area under summary receiver operating characteristics curve was 0.97. No publication bias was found using funnel plots. No significant relationship was found between the diagnostic odds ratios and the characteristics of the studies including continent and contrast agent.
Conclusions
This meta‐analysis showed that CH‐EUS with qualitative analysis of enhancement pattern is useful for the diagnosis of PC, and has high sensitivity and accuracy, regardless of the type of contrast agent used. This modality may provide improved diagnostic accuracy for PC in clinical practice.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
This document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 (www.tncd.org).
All French medical ...societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019.
The management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET.
These guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Histology is the gold standard for the diagnosis of pancreatic adenocarcinoma. However, the negative predictive value of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the ...diagnosis remains low. The aims of this prospective multicenter study were: (1) to compare the performance of contrast-harmonic EUS (CH-EUS) with that of EUS-FNA for the diagnosis of pancreatic adenocarcinoma; (2) to assess the intra- and interobserver concordances of CH-EUS.
A total of 100 consecutive patients with a solid pancreatic mass of unknown origin were prospectively included at three centers (July 2009 - April 2010). All patients were examined by CH-EUS followed by EUS-FNA. Absence of vascular enhancement at CH-EUS was regarded as a sign for pancreatic adenocarcinoma. The final diagnosis (gold standard) was based on pathological examination (EUS-FNA, surgery) or 12-month follow-up.
The final diagnoses were: 69 adenocarcinoma, 10 neuroendocrine tumors, 13 chronic pancreatitis, and 8 other lesions. In diagnosing adenocarcinoma, CH-EUS and EUS-FNA had respective accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 95 %, 96 %, 94 %, 97 %, and 91 %, and of 95 %, 93 %, 100 %, 100 %, and 86 % without significant difference. Five false-negative cases with EUS-FNA were correctly classified by CH-EUS. Interobserver agreement (seven endosonographers) was good (kappa 0.66). Intraobserver agreement was good to excellent (kappa 0.76 for junior, 0.90 for senior).
The performance of CH-EUS for the diagnosis of pancreatic adenocarcinoma was excellent. The good intra- and interobserver concordances suggest an excellent reproducibility. CH-EUS could help to guide the choice between surgery and follow-up when EUS-FNA is inconclusive.
Acute hepatitis E virus infection during pregnancy has a high fatality rate in developing countries. Little data are available on chronic infection in pregnant women. We report a case of chronic ...hepatitis E during treatment with infliximab and azathioprine, without adverse event during pregnancy and with spontaneous resolution after delivery.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As duodenal neuroendocrine tumors (NETs) are rare, their optimal management has not been clearly established. The aim of this study was to evaluate the feasibility and outcome of endoscopic treatment ...of duodenal NETs.
We reviewed the files of all patients who underwent endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and 2014 at two centers.
A total of 29 patients with 32 uT1N0M0 NETs < 20 mm were included. Treatment consisted of endoscopic mucosal resection in 19 cases, and cap aspiration in 13 cases. Prior submucosal saline injection was used in 15 cases. Mortality was 3 % (one severe bleeding). Morbidity was 38 % (11/29). At post-resection analysis, mean tumor size was 8.9 mm (range 3 - 17 mm), 29 lesions were stage pT1, one was pT2, and 2 were pTx because of piecemeal resection. All NETs were well differentiated. A total of 27 lesions were classified as grade 1 and 5 were grade 2. The resection was R0, R1, and Rx for 16, 14, and 2 lesions, respectively. Three R1 patients underwent additional surgical treatment, with no residual tumor on the surgical specimen but with positive metastatic lymph nodes in two cases. One patient was lost to follow-up. Finally, 24 patients were included in the follow-up analysis. The median follow-up period was 56 months (range 6 - 175 months). Two patients presented a tumor recurrence during the follow-up period.
Endoscopic treatment of small duodenal NETs was associated with significant morbidity, a difficulty in obtaining an R0 specimen, and the risk of lymph node metastasis. Nevertheless, it represents an interesting alternative in small grade 1 duodenal lesions and in patients at high surgical risk.
Contrast harmonic EUS (CH-EUS) has the ability to depict tumor microvasculature. Decreased microvascular density has been identified as a factor associated with tumor aggressiveness. We aimed to ...study the accuracy of CH-EUS for the prediction of pancreatic neuroendocrine tumor (PNET) aggressiveness.
Between June 2009 and March 2015, all consecutive patients with histology-proven PNETs and CH-EUS examination were included. Nine endosonographers blindly analyzed all videos. CH-EUS tumor aggressiveness was defined as a heterogeneous enhancement at the early arterial phase. The final diagnosis of tumor aggressiveness was defined as follows: G3 tumors, morphologic and/or histologic findings of metastatic disease in G1/G2 tumors. Diagnostic values were calculated. Intratumoral microvascular density and fibrosis were assessed on pathologic specimens.
Eighty-one tumors were included, of which 26 were aggressive (32.1%). In CH-EUS 35 tumors (43.2%) had a heterogeneous enhancement. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CH-EUS for the diagnosis of tumor aggressiveness were 86%, 96%, 82%, 71%, and 98%, respectively. The interobserver agreement among the 9 endosonographers was good (k = .66). The intraobserver agreement was excellent for the junior (κ = .83) and senior (κ = .82) endosonographers. Heterogeneous tumors at CH-EUS corresponded to fewer vascular and more fibrotic tumors (P < .01).
CH-EUS is accurate in the prediction of PNET aggressiveness and could be a decision-making element in their management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background
The aim of this prospective multicenter study was to compare a flexible 19 G needle with nitinol shaft (19 G Flex) with a standard 22 G needle for transduodenal endoscopic ...ultrasound (EUS)-guided sampling of pancreatic head tumors.
Methods
Patients with pancreatic head tumors requiring tissue diagnosis were randomized into two arms: puncture with either a 19 G Flex needle or a 22 G needle. The primary end point was diagnostic accuracy for malignancy. The secondary end points were ergonomic scores, sample cytohistological quality, and complications. A 6-month follow-up was performed.
Results
125 patients were randomized and 122 were analyzed: 59 patients in the 19 G Flex arm and 63 patients in the 22 G arm. The final diagnosis was malignancy in 111 patients and benign condition in 11. In intention-to-treat analysis, the diagnostic accuracy for malignancy of the 19 G Flex and 22 G needles was 69.5 % (95 % confidence interval CI 56.1 % – 80.8 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %), respectively (
P
= 0.02). In per-protocol analysis excluding eight technical failures in the 19 G Flex group, the diagnostic accuracy of the 19 G Flex and 22 G needles was not statistically different: 80.4 % (95 %CI 66.9 % – 90.2 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %;
P
= 0.12). Technical success was higher in the 22 G arm than in the 19 G Flex arm: 100 % (95 %CI 94.3 % – 100 %) vs. 86.4 % (95 %CI 75.0 % – 94.0 %), respectively (
P
= 0.003). Transduodenal EUS-guided sampling was more difficult with the 19 G Flex (odds ratio 0.68, 95 %CI 0.47 – 0.97).
Conclusion
The 19 G Flex needle was inferior to a standard 22 G needle in diagnosing pancreatic head cancer and more difficult to use in the transduodenal approach.
Endoscopic papillectomy of early tumors of the ampulla of Vater is an alternative to surgery. This large prospective multicenter study was aimed at evaluating the long-term results of endoscopic ...papillectomy.
Between September 2003 and January 2006, 10 centers included all patients referred for endoscopic papillectomy and meeting the inclusion criteria: biopsies showing at least adenoma, a uT1N0 lesion without intraductal involvement at endoscopic ultrasound (EUS), and no previous treatment. A standardized endoscopic papillectomy was done, with endoscopic monitoring with biopsies 4 - 8 weeks later where complications were recorded and complementary resection performed when necessary. Follow-up with duodenoscopy, biopsies, and EUS was done at 6, 12, 18, 24 and 36 months. Therapeutic success was defined as complete resection (no residual tumor found at early monitoring) without duodenal submucosal invasion in the resection specimen in the case of adenocarcinoma and without relapse during follow-up.
93 patients were enrolled. Mortality was 0.9 % and morbidity 35 %, including pancreatitis in 20 %, bleeding 10 %, biliary complications 7 %, perforation 3.6 %, and papillary stenosis in 1.8 %. Adenoma was not confirmed in the resection specimen in 14 patients who were therefore excluded. Initial treatment was insufficient in 9 cases (8 carcinoma with submucosal invasion; 1 persistence of adenoma). During follow-up, 5 patients had tumor recurrence and 7 died from unrelated diseases without recurrence. Finally, 81.0 % of patients were cured (95 % confidence interval 72.3 % - 89.7 %).
Endoscopic papillectomy of selected ampullary tumors is curative in 81.0 % of cases. It must be considered to be the first-line treatment for early tumors of the ampulla of Vater without intraductal invasion.
Background and aim
The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound ...fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs.
Methods
Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case.
Results
The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (
p
< 0.001). nCLE significantly increased the interobserver agreement of 0.28 (
p
< 0.0001), from 0.36 (CI 95% 0.33–0.49) to 0.64 (CI 95% 0.61–0.67). nCLE improved the rates of full agreement among the five experts of 24% (
p
< 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76).
Conclusion
The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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