Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos).

BACKGROUND AND AIMS: Confocal laser endomicroscopy enables real-time in vivo microscopy during endoscopy and can predict relapse in patients with inflammatory bowel disease in remission. However, little is known about how endomicroscopic features change with time. The aim of this longitudinal study was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment. METHODS: Twenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were enrolled. The colonic mucosa was examined with high-definition colonoscopy, histopathology, and CLE at 4 colonic sites. Subsequently, patients requiring medical treatment escalation were referred for repeat endoscopy with CLE after 6 to 8 weeks. RESULTS: The baseline frequency of fluorescein leakage (P < .001), microerosions (P < .001), tortuosity of the crypts (P = .001), distortion of the crypts openings (P = .001), presence of inflammatory infiltrates (P < .001), and decreased crypt density (P < .001) were significantly higher in active ulcerative colitis compared with inactive ulcerative colitis and control subjects. A decrease in histopathologic score after medical treatment escalation was correlated with improvement in crypt tortuosity (rs = .35, P = .016), distortion of crypt openings (rs = .30, P = .045), and decreased crypt density (rs = .33, P = .026) but not in other features. CONCLUSIONS: CLE is an emerging endoscopic technique that reproducibly identifies mucosal changes in ulcerative colitis. With the exception of crypt changes, endomicroscopic features appear to improve slowly with time after medical treatment. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01684514.).

The Clinical Value of Multimodal Ultrasound for the Differential Diagnosis of Hepatocellular Carcinoma from Other Liver Tumors in Relation to Histopathology.

Recent advances in the field of ultrasonography offer promising tools for the evaluation of liver tumors. We aim to assess the value of multimodal ultrasound in differentiating hepatocellular carcinomas (HCCs) from other liver lesions. We prospectively included 66 patients with 72 liver tumors. The histological analysis was the reference standard for the diagnosis of malignant liver lesions, and partially for benign tumors. All liver lesions were assessed by multiparametric ultrasound: standard ultrasound, contrast-enhanced ultrasound (CEUS), the point shear wave elastography (pSWE) using shear wave measurement (SWM) method and real-time tissue elastography (RTE). To diagnose HCCs, CEUS achieved a sensitivity, specificity, accuracy and positive predictive value (PPV) of 69.05%, 92.86%, 78.57% and 93.55%, respectively. The mean shear-wave velocity (Vs) value in HCCs was 1.59 ± 0.29 m/s, which was lower than non-HCC malignancies (p < 0.05). Using a cut-off value of 1.58 m/s, SWM achieved a sensitivity of 54.76%, and 82.35% specificity, for differentiating HCCs from other malignant lesions. The combination of SWM and CEUS showed higher sensitivity (79.55%) compared with each technique alone, while maintaining a high specificity (89.29%). In RTE, most HCCs (61.53%) had a mosaic pattern with dominant blue areas corresponding to type "c" elasticity. Elasticity type "c" was 70.59% predictive for HCCs. In conclusion, combining B-mode ultrasound, CEUS, pSWE and RTE can provide complementary diagnostic information and potentially decrease the requirements for other imaging modalities.

Diagnostic Performance of an Artificial Intelligence Model Based on Contrast-Enhanced Ultrasound in Patients with Liver Lesions: A Comparative Study with Clinicians.

Contrast-enhanced ultrasound (CEUS) is widely used in the characterization of liver tumors; however, the evaluation of perfusion patterns using CEUS has a subjective character. This study aims to evaluate the accuracy of an automated method based on CEUS for classifying liver lesions and to compare its performance with that of two experienced clinicians. The system used for automatic classification is based on artificial intelligence (AI) algorithms. For an interpretation close to the clinical setting, both clinicians knew which patients were at high risk for hepatocellular carcinoma (HCC), but only one was aware of all the clinical data. In total, 49 patients with 59 liver tumors were included. For the benign and malignant classification, the AI model outperformed both clinicians in terms of specificity (100% vs. 93.33%); still, the sensitivity was lower (74% vs. 93.18% vs. 90.91%). In the second stage of multiclass diagnosis, the automatic model achieved a diagnostic accuracy of 69.93% for HCC and 89.15% for liver metastases. Readers demonstrated greater diagnostic accuracy for HCC (83.05% and 79.66%) and liver metastases (94.92% and 96.61%) compared to the AI system; however, both were experienced sonographers. The AI model could potentially assist and guide less-experienced clinicians to discriminate malignant from benign liver tumors with high accuracy and specificity.

Liver Function Tests and FIB-4 Score as Predictors of Severity in COVID-19 Patients from the South-West of Romania.

BACKGROUND: The coronavirus disease 2019 pandemic (COVID-19) is the most important global health crisis to date. In this study, we performed an analysis to find the association between liver damage, FIB-4 score and the severity of COVID-19 disease. METHODS: We included a total of 580 patients that tested positive for SARS-CoV-2 infection and were hospitalized. No patient included had any known history of liver disease. Liver function tests were performed, and FIB-4 score was calculated in order to assess their involvement in the disease progression. RESULTS: More than half of the patients had elevated liver function tests. Age, high body mass index, associated heart disease and diabetes were associated with poor outcome. Corticosteroids, antibiotics, and anticoagulants strongly correlated with liver injuries. Liver impairment and injury, as well as a FIB-4 score higher than 3.5, also correlated with higher degrees of disease severity. CONCLUSION: Liver injury and elevated FIB-4 score were associated with poor clinical outcome and disease severity, as well as being a valuable tool to predict COVID-19-related mortality.

EndoCuff-Assisted Colonoscopy Versus Standard Colonoscopy in Colonic Polyp Detection-Experience from a Single Tertiary Centre.

BACKGROUND: Standard colonoscopy fails to visualize the entire colon mucosa and consequently a significant amount of polyps are still being missed. New device, such as EndoCuff, have been developed to improve mucosal visualisation, hence the quality in colonoscopy. The aim of this study was to assess the diagnostic yield of EndoCuff-assisted colonoscopy in comparison with standard colonoscopy by taking into consideration several quality indicators. METHODS: In this study, 965 adults ≥ 18 years referred for colonoscopy were randomly divided into two groups. The main statistical investigation compared the difference between EndoCuff-assisted colonoscopy (EC) vs. standard colonoscopy (SC) in the detection of colonic polyps and adenoma detection rate (ADR). The second inquiry sought to compare experienced vs. recently trained and female vs. male operators. RESULTS: The ADR was higher for EC than for SC (37.50% vs. 26.64%). Regarding the mean number of detected polyps per procedure (MPP), the result was statistically significant when generally comparing the EC vs. SC (p=0.0009). There were no differences in MPP between EC and SC for recently trained endoscopists (p=0.7446), while a significant difference for experienced doctors (p=0,0020) was noted. A significant difference was observed between female doctors and male doctors only when using SC. EC was more helpful for female doctors when assessing MPP (p=0.0118). No serious adverse events related to EndoCuff-assisted colonoscopy was noted. CONCLUSIONS: EndoCuff-assisted colonoscopy seems to be safe and may bring benefits for improving the polyp/adenoma detection rates in regard to missed lesions, usually located in blind areas.

Role of Contrast-Enhanced Ultrasonography in Hepatocellular Carcinoma by Using LI-RADS and Ancillary Features: A Single Tertiary Centre Experience.

Clinical utility of ancillary features (AFs) in contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS®) is yet to be established. In this study, we assessed the diagnostic yield of CEUS LI-RADS and AFs in hepatocellular carcinoma (HCC). We retrospectively included patients with risk factors for HCC and newly diagnosed focal liver lesions (FLL). All lesions have been categorized according to the CEUS LI-RADS v2017 by an experienced sonographer blinded to clinical data and to the final diagnosis. From a total of 143 patients with 191 FLL, AFs favoring HCC were observed in 19.8% cases as hypoechoic rim and in 16.7% cases as nodule-in nodule architecture. From the total of 141 HCC cases, 83.6% were correctly classified: 57.4%- LR-5 and 26.2%- LR-4. In 9.21% cases, CEUS indicated LR-M; 2.12% cases- LR-3. The LR-5 category was 96.2% predictive (PPV) of HCC. LR-5 had 60.4% sensitivity and 93.6% specificity. PPV for primitive malignancy (LR-4 + LR-5) was 95.7%, with 88% sensitivity, 89.3% specificity and 88.4% accuracy for HCC. LR-4 category had 94.8% PPV and 26.2% sensitivity. CEUS LR4 + LR5 had 81,8% sensitivity for HCCs over 2 cm and 78.57% sensitivity for smaller HCCs. CEUS LR-5 remains an excellent diagnostic tool for HCC, despite the size of the lesion. The use of AFs might improve the overarching goal of LR-5 + LR-4 diagnosis of high specificity for HCC and exclusion of non-HCC malignancy.

Issues and controversies in esophageal inlet patch.

The proximal esophagus is rarely examined, and its inspection is often inadequate. Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus, a region in which their prevalence is likely underestimated. Various studies have reported correlations between these esophageal marks with different issues such as Barrett's esophagus, but these findings remain controversial. Conflicting reports complicate the process of interpreting the clinical features of esophageal inlet patches and underestimate their importance. Unfortunately, the limited clinical data and statistical analyses make reaching any conclusions difficult. It is hypothesized that inlet patches are correlated with various esophageal and extraesophageal symptoms, diagnoses and the personalized therapeutic management of patients with inlet patches as well as the differential diagnosis for premalignant lesions or early cancers. Due to its potential underdiagnosis, there are no consensus guidelines for the management and follow up of inlet patches. This review focuses on questions that were raised from published literature on esophageal inlet patches in adults.

Current strategies for malignant pedunculated colorectal polyps.

Despite significant advances in imaging techniques, the incidence of colorectal cancer has been increasing in recent years, with many cases still being diagnosed in advanced stages. Early detection and accurate staging remain the main factors that lead to a decrease in the cost and invasiveness of the curative techniques, significantly improving the outcome. However, the diagnosis of pedunculated early colorectal malignancy remains a current challenge. Data on the management of pedunculated cancer precursors, apart from data on nonpolypoid lesions, are still limited. An adequate technique for complete resection, which provides the best long-term outcome, is mandatory for curative intent. In this context, a discussion regarding the diagnosis of malignancy of pedunculated polyps, separate from non-pedunculated variants, is necessary. The purpose of this review is to provide a critical review of the most recent literature reporting the different features of malignant pedunculated colorectal polyps, including diagnosis and management strategies.

Narrow band imaging endoscopy for detection of precancerous lesions of upper gastrointestinal tract.

Gastric cancer (GC) is an important health problem despite the advances in surgery and chemotherapy and although the incidence is decreasing, GC is still considered the second most common cause of deceases produced by cancer. Survival rates in gastric cancer are low, mainly because most patients are often diagnosed in late stages. The current interest in the diagnostic of GC is the detection of early gastric cancer. Advances in high-resolution endoscopic techniques such as narrow band imaging (NBI) allow the detection of early precancerous lesions like polyps or metaplastic mucosa. Performing only white light imaging endoscopy in order to detect gastric cancer can lead to omission or misdiagnose of a considerable number of early gastric cancers. NBI endoscopy associated with other high-resolution examinations is viable in detecting early gastric cancer, though few studies also indicate that the endoscopist's expertise plays an important factor as well.

Narrow band imaging with near-focus mode for colorectal polyps' characterization.

Conventional white light endoscopy is far from being an ideal tool to detect, characterize, and confirm the nature of colorectal lesions in order to indicate targeted biopsies or polyp resections only when necessary. Minimally invasive imaging techniques have gradually emerged to reveal previously unseen abnormalities to the operator during endoscopic examination. In this respect, technology and applications of narrow band imaging (NBI) are rapidly evolving. Magnification using NBI with near-focus mode has been introduced recently to enable closer examination under the control of a single button. The aim of this article is to offer an in-depth overview of this topic with emphasis on colorectal polyps through a literature review by using PubMed search tools including full-text articles, up-to-date guidelines and recent abstracts with obvious conclusions.

Tumor neoangiogenesis detection by confocal laser endomicroscopy and anti-CD105 antibody: Pilot study.

AIM: To evaluate neoangiogenesis in patients with colon cancer by two fluorescently labeled antibodies on fresh biopsy samples imaged with confocal laser endomicroscopy (CLE). METHODS: CLE is an imaging technique for gastrointestinal endoscopy providing in vivo microscopy at subcellular resolution. An important question in validating tumor angiogenesis is what proportion of the tumor vascular network is represented by pre-existing parent tissue vessels and newly formed vessels. CD105 (endoglin) represents a proliferation-associated endothelial cell adhesion molecule. In contrast to pan-endothelial markers, such as CD31, CD105 is preferentially expressed in activated endothelial cells that participate in neovascularization. Thus, we evaluated CD105 and CD31 expression from samples of ten patients with primary rectal adenocarcinoma, using a dedicated endomicroscopy system. A imaging software was used to obtain the Z projection of the confocal serial images from each biopsy sample previously combined into stacks. Vascular density and vessel diameters were measured within two 50 µm x 475 µm rectangular regions of interest centered in the middle of each image in the horizontal and vertical direction. The results were averaged over all the patients and were expressed as the mean ± SE. RESULTS: The use of an anti-CD105 antibody was found to be suitable for the detection of blood vessels in colon cancer. Whereas anti-CD31 antibodies stained blood vessels in both normal and pathologic colon equally, CD105 expression was observed primarily in malignant lesions, with little or no expression in the vessels of the normal mucosa (244.21 ± 130.7 vessels/mm(3) in only four patients). The average diameter of anti-CD105 stained vessels was 10.97 ± 0.6 µm in tumor tissue, and the vessel density was 2787.40 ± 134.8 vessels/mm(3). When using the anti-CD31 antibody, the average diameter of vessels in the normal colon tissue was 7.67 ± 0.5 µm and the vessel density was 3191.60 ± 387.8 vessels/mm(3), while in the tumors we obtained an average diameter of 10.88 ± 0.8 µm and a vessel density of 4707.30 ± 448.85 vessels/mm(3). Thus, there were more vessels stained with CD31 than CD105 (P < 0.05). The average vessel diameter was similar for both CD31 and CD105 staining. A qualitative comparison between CLE vs immunohistochemistry lead to similar results. CONCLUSION: Specific imaging and quantification of tumor microvessels are feasible in human rectal cancer using CLE examination and CD105 immunostaining of fresh tissue samples.

Evaluation of new morphometric parameters of neoangiogenesis in human colorectal cancer using confocal laser endomicroscopy (CLE) and targeted panendothelial markers.

The tumor microcirculation is characterized by an abnormal vascular network with dilated, tortuous and saccular vessels. Therefore, imaging the tumor vasculature and determining its morphometric characteristics represent a critical goal for optimizing the cancer treatment that targets the blood vessels (i.e. antiangiogenesis therapy). The aim of this study was to evaluate new vascular morphometric parameters in colorectal cancer, difficult to achieve through conventional immunohistochemistry, by using the confocal laser endomicroscopy method. Fresh biopsies from tumor and normal tissue were collected during colonoscopy from five patients with T3 colorectal carcinoma without metastasis and were marked with fluorescently labeled anti-CD31 antibodies. A series of optical slices spanning 250 µm inside the tissue were immediately collected for each sample using a confocal laser endomicroscope. All measurements were expressed as the mean ± standard error. The mean diameter of tumor vessels was significantly larger than the normal vessels (9.46±0.4 µm vs. 7.60±0.3 µm, p = 0.0166). The vessel density was also significantly higher in the cancer vs. normal tissue samples (5541.05±262.81 vs. 3755.79±194.96 vessels/mm3, p = 0.0006). These results were confirmed by immunohistochemistry. In addition, the tortuosity index and vessel lengths were not significantly different (1.05±0.016 and 28.30±3.27 µm in normal tissue, vs. 1.07±0.008 and 26.49±3.18 µm in tumor tissue respectively, p = 0.5357 and p = 0.7033). The daughter/mother ratio (ratio of the sum of the squares of daughter vessel radii over the square of the mother vessel radius) was 1.15±0.09 in normal tissue, and 1.21±0.08 in tumor tissue (p = 0.6531). The confocal laser endomicroscopy is feasible for measuring more vascular parameters from fresh tumor biopsies than conventional immunohistochemistry alone. Provided new contrast agents will be clinically available, future in vivo use of CLE could lead to identification of novel biomarkers based on the morphometric characteristics of tumor vasculature.

Confocal laser endomicroscopy for the morphometric evaluation of microvessels in human colorectal cancer using targeted anti-CD31 antibodies.

INTRODUCTION: Numerous anti-angiogenic agents are currently developed to limit tumor growth and metastasis. While these drugs offer hope for cancer patients, their transient effect on tumor vasculature is difficult to assess in clinical settings. Confocal laser endomicroscopy (CLE) is a novel endoscopic imaging technology that enables histological examination of the gastrointestinal mucosa. The aim of the present study was to evaluate the feasibility of using CLE to image the vascular network in fresh biopsies of human colorectal tissue. For this purpose we have imaged normal and malignant biopsy tissue samples and compared the vascular network parameters obtained with CLE with established histopathology techniques. MATERIALS AND METHODS: Fresh non-fixed biopsy samples of both normal and malignant colorectal mucosa were stained with fluorescently labeled anti-CD31 antibodies and imaged by CLE using a dedicated endomicroscopy system. Corresponding biopsy samples underwent immunohistochemical staining for CD31, assessing the microvessel density (MVD) and vascular areas for comparison with CLE data, which were measured offline using specific software. RESULTS: The vessels were imaged by CLE in both normal and tumor samples. The average diameter of normal vessels was 8.5±0.9 µm whereas in tumor samples it was 13.5±0.7 µm (p = 0.0049). Vascular density was 188.7±24.9 vessels/mm(2) in the normal tissue vs. 242.4±16.1 vessels/mm(2) in the colorectal cancer samples (p = 0.1201). In the immunohistochemistry samples, the MVD was 211.2±42.9/mm(2) and 351.3±39.6/mm(2) for normal and malignant mucosa, respectively. The vascular area was 2.9±0.5% of total tissue area for the normal mucosa and 8.5±2.1% for primary colorectal cancer tissue. CONCLUSION: Selective imaging of blood vessels with CLE is feasible in normal and tumor colorectal tissue by using fluorescently labeled antibodies targeted against an endothelial marker. The method could be translated into the clinical setting for monitoring of anti-angiogenic therapy.

Utility of endoscopic ultrasound multimodal examination with fine needle aspiration for the diagnosis of pancreatic insulinoma - a case report.

Insulinomas are benign insulin-secreting neuroendocrine tumors originating in the pancreatic beta cells. Symptoms are caused by hypoglycemia and clinical diagnosis is based on establishing their relationship to fasting, usually via a fasting test. The most conclusive imaging tests are endoscopic ultrasound (EUS) and CT. Surgery is the treatment of choice. A 33 year old male presented with a 2-year history of hunger which had intensified in the previous 6 months with added accompanying symptoms, culminating with an acute episode - loss of consciousness and seizures - which resolved after administering i.v. glucose. A fasting test was performed, with results suggestive for an insulinoma. Dual-phase CT showed a mass in the tail of the pancreas but no contrast enhancement. EUS was used for further assessment: B-mode showed a hypoechoic focal mass with a cystic component, on contrast enhancement the pattern was hypovascular, and elastography showed soft tissue. EUS fine needle aspiration (FNA) was performed and the immunohistochemistry (IHC) assay was conclusive for a neuroendocrine tumor of the pancreas. Treatment consisted of caudal pancreatectomy, with no recurrence after 1-year follow-up. Although this case started with a classic clinical presentation of an insulinoma, imaging studies related to tumor vascularization raised doubts about the actual diagnosis. Nevertheless, multimodal EUS assessment with FNA was considered to be the most appropriate diagnostic technique for detection, characterization and staging of the mass. EUS findings together with the IHC assay were able to offer the definite diagnosis of a benign neuroendocrine tumor and allowed us to refer the patient for appropriate treatment.