Technical Performance, Overall Accuracy and Complications of EUS-Guided Interventional Procedures: A Dynamic Landscape.

Endoscopic ultrasound (EUS) gained wide acceptance as the diagnostic and minimally invasive therapeutic approach for intra-luminal and extraluminal gastrointestinal, as well as various non-gastrointestinal lesions. Since its introduction, EUS has undergone substantial technological advances. This multi-centric study is a retrospective analysis of a prospectively maintained database of patients who underwent EUS for the evaluation of lesions located within the gastrointestinal tract and the proximal organs. It aimed to extensively assess in dynamic the dual-center EUS experience over the course of the past 20 years. Hence, we performed a population study and an overall assessment of the EUS procedures. The performance of EUS-FNA/FNB in diagnosing pancreatic neoplasms was evaluated. We also investigated the contribution of associating contrast-enhanced ultrasound imaging (CE-EUS) with EUS-FNA/FNB for differentiating solid pancreatic lesions or cystic pancreatic lesions. A total of 2935 patients undergoing EUS between 2002-2021 were included, out of which 1880 were diagnostic EUS and 1052 EUS-FNA/FNB (80% FNA and 20% FNB). Therapeutic procedures performed included endoscopic transmural drainage of pancreatic fluid collections, celiac plexus block and neurolysis, while diagnostic EUS-like CE-EUS (20%) and real-time elastography (12%) were also conducted. Most complications occurred during the first 7 days after EUS-FNA/FNB or pseudocyst drainage. EUS and the additional tools have high technical success rates and low rates of complications. The EUS methods are safe, cost effective and indispensable for the diagnostic or therapeutic management in gastroenterological everyday practice.

Real-time computer-aided diagnosis of focal pancreatic masses from endoscopic ultrasound imaging based on a hybrid convolutional and long short-term memory neural network model.

Differential diagnosis of focal pancreatic masses is based on endoscopic ultrasound (EUS) guided fine needle aspiration biopsy (EUS-FNA/FNB). Several imaging techniques (i.e. gray-scale, color Doppler, contrast-enhancement and elastography) are used for differential diagnosis. However, diagnosis remains highly operator dependent. To address this problem, machine learning algorithms (MLA) can generate an automatic computer-aided diagnosis (CAD) by analyzing a large number of clinical images in real-time. We aimed to develop a MLA to characterize focal pancreatic masses during the EUS procedure. The study included 65 patients with focal pancreatic masses, with 20 EUS images selected from each patient (grayscale, color Doppler, arterial and venous phase contrast-enhancement and elastography). Images were classified based on cytopathology exam as: chronic pseudotumoral pancreatitis (CPP), neuroendocrine tumor (PNET) and ductal adenocarcinoma (PDAC). The MLA is based on a deep learning method which combines convolutional (CNN) and long short-term memory (LSTM) neural networks. 2688 images were used for training and 672 images for testing the deep learning models. The CNN was developed to identify the discriminative features of images, while a LSTM neural network was used to extract the dependencies between images. The model predicted the clinical diagnosis with an area under curve index of 0.98 and an overall accuracy of 98.26%. The negative (NPV) and positive (PPV) predictive values and the corresponding 95% confidential intervals (CI) are 96.7%, [94.5, 98.9] and 98.1%, [96.81, 99.4] for PDAC, 96.5%, [94.1, 98.8], and 99.7%, [99.3, 100] for CPP, and 98.9%, [97.5, 100] and 98.3%, [97.1, 99.4] for PNET. Following further validation on a independent test cohort, this method could become an efficient CAD tool to differentiate focal pancreatic masses in real-time.

Clinical impact of strain histogram EUS elastography and contrast-enhanced EUS for the differential diagnosis of focal pancreatic masses: A prospective multicentric study.

BACKGROUND: Recent advances in EUS techniques (real-time EUS elastography and contrast-enhanced EUS) have allowed a better characterization of focal pancreatic masses. Mean strain histograms (SHs) are considered a good parameter for the semi-quantitative evaluation of focal pancreatic masses, alongside complementary contrast-enhanced EUS parameters which can be quantified during both the early arterial and late venous phase. MATERIALS AND METHODS: The study design was prospective, blinded, and multicentric, assessing real-time EUS elastography and contrast-enhanced EUS results for the characterization of focal pancreatic masses using parametric measurements, in comparison with pathology which is the gold standard. SHs were performed based on the embedded software of the ultrasound system, with the values being reversed as opposed to our initially published data on hue histograms. Consequently, a cutoff of 80 was derived from previous multicentric trials. Contrast-enhanced EUS also allowed the focal masses to be classified as hyper-, iso-, or hypoenhanced in comparison with the normal pancreatic parenchyma. EUS-FNA was then performed for all patients, with a positive cytological diagnosis taken as a final proof of malignancy for the pancreatic masses. The diagnoses obtained by EUS-FNA were verified further either by surgery or during a clinical follow-up of at least 6 months. RESULTS: A total number of 97 consecutive patients with focal pancreatic masses were included in the study. Based on previously defined cutoffs of 80, the values of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the mean SHs for the diagnosis of pancreatic cancer were 100%, 29.63%, 78.65%, 100%, and 80.41%, respectively. Corresponding values for contrast-enhanced EUS (taking into consideration hypoenhencement as a predictive factor of malignancy) were 98.57%, 77.78%, 92%, 95.45%, and 92.78%, respectively. Combining contrast enhancement-EUS (hypoenhencement) and semi-quantitative EUS elastography (SH cutoffs <80), the resulting values corresponding for sensitivity, specificity, and accuracy were 98.57%, 81.48%, and 93.81%, respectively. CONCLUSION: The current study using objective parametric tools for both EUS elastography and contrast-enhanced EUS confirmed the results of previous studies and meta-analyses that indicated a complementary role for the differential diagnosis of focal pancreatic masses. Moreover, the best values for the receiver operating curves were obtained using a sequential clinical algorithm based on the initial use of elastography, followed by contrast enhancement.

Clinical impact of EUS elastography followed by contrast-enhanced EUS in patients with focal pancreatic masses and negative EUS-guided FNA.

AIMS: It is well known that endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has a high sensitivity (over 85%) and specificity (100%) for diagnosis of pancreatic cancer. The aim of the study was to establish a EUS based clinical diagnostic algorithm in patients with pancreatic masses and negative cytopathology after EUS-FNA, based on previously published results and cut-offs of real-time elastographic (RTE) EUS and contrast-enhanced harmonic (CEH) EUS. MATERIAL AND METHODS: We included in the study a subgroup of 50 consecutive patients with focal pancreatic masses which underwent EUS examinations with negative EUS-FNA. RTE-EUS and CEH-EUS were performed sequentially in all patients. The sensitivity, specificity and accuracy of these methods were calculated separately. A clinical decision algorithm based on elastography followed by CEH was established. RESULTS: For the diagnosis of possible malignancy, the sensitivity, specificity and accuracy of RTE-EUS were: 97.7%, 77.4%, and 84% respectively. CEH-EUS had similar results: 89.5%, 80.7%, and 84%, respectively. In 25 patients with soft/mixed appearance during elastography,sequential assessment using contrast-enhanced EUSwas performed. The specificity of CEH-EUS for detection of chronic pancreatitis in this sub-set of patients was excellent (100%). In other 25 patients with hard appearance in elastography (low strain) CEH-EUS had an excellent specificity (100%) and accuracy (93%) in the detection of pancreatic cancer. CONCLUSIONS: The proposed algorithm with sequential use of elastography followed by CEH could be a good clinical tool in the set of patients with negative EUS-FNA results for the differentiation between benign and malignant focal pancreatic masses.

More than 9 years of continuous trastuzumab treatment in metastatic breast cancer without cardiac toxicity: a case report and literature review.

The main concern of long-term use of trastuzumab remains its association with potential cardiac side effects. Although these side effects are real, they are probably overemphasized. We report the case of a woman with metastatic breast cancer, who is currently in complete remission, and who received trastuzumab continuously for more than 9 years, without any significant cardiac toxicity.

Multicenter randomized controlled trial comparing the performance of 22 gauge versus 25 gauge EUS-FNA needles in solid masses.

BACKGROUND AND AIMS: Few randomized studies have assessed the clinical performance of 25-gauge (25G) needles compared with 22-gauge (22G) needles during endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy of intra-abdominal lesions. We aimed to compare the diagnostic yield, as well as performance characteristics of 22G versus 25G EUS biopsy needles by determining their diagnostic capabilities, the number of needle passes as well as cellularity of aspirated tissue specimen. METHODS: The study is a prospective, randomized, multicenter study. Patients were referred between January 2009 and January 2010 for diagnostic EUS including EUS-guided FNA of different lesions adjacent to the upper GI tract. All patients were randomized to EUS-FNA performed with either a 22G or 25G aspiration needle. RESULTS: EUS-FNA was performed in 135 patients (62 patients with a 22G needle). Sensitivity and specificity of the 22G needle was 94.1% and 95.8%, respectively, and for the 25G needle 94.1% and 100%, respectively. Investigators reported better visualization and performance for the 22G needle compared to the 25G (p < 0.0001). The number of tissue slides obtained was higher for the 22G needle during the second and third needle passes (p < 0.05). We did not observe significant differences between the number and preservation status of obtained cells (p > 0.05). CONCLUSIONS: A significant difference was found between the two types of needles in terms of reduced visualization of the 25G needle and suboptimal performance rating. However, this did not impact on overall results since both needles were equally successful in terms of a high diagnostic yield and overall accuracy.

Power Doppler endoscopic ultrasound for the assessment of pancreatic neuroendocrine tumors.

OBJECTIVE: Pancreatic neuroendocrine tumors (PNET) represent rare, heterogeneous tumors with clinical, imaging and treatment particularities. The aim of this study was to assess the role of power Doppler endoscopic ultrasound (EUS) in the diagnosis and characterization of PNET. METHODS: All consecutive patients with PNET assessed by power Doppler EUS in the Research Centre of Gastroenterology and Hepatology Craiova, Romania, in the past 51 months were included in the study. All EUS examinations were performed initially in gray-scale mode, followed by power Doppler mode examinations, before and after contrast-enhancement. Each recorded EUS movie was further subjected to post-processing using a computer-enhanced dynamic analysis using a special plug-in which permitted assessment of vascularity index (EUS-VI). RESULTS: Based on the analysis of all consecutive malignant focal pancreatic masses diagnosed in the study period, a total number of 131 consecutive patients were included: 14 patients with pancreatic neuroendocrine tumors and 117 patients with pancreatic adenocarcinoma. The sensitivity of the pre-contrast EUS-VI for the diagnosis of PNET was 71.43%, similar to EUS-FNA. After contrast enhancement, the EUS-VI is also higher in PNET (27.07%) as compared to pancreatic adenocarcinoma where it was significantly lower 9.82% (P < 0.001). However, the sensitivity of EUS-VI after contrast enhancement for the diagnosis of PNET was 100%, higher than pre-contrast EUS-VI, with an acceptable specificity (79.49%) and better accuracy (81.68%). CONCLUSION: Power Doppler EUS represents a useful method in the initial assessment of PNET. Using evaluation of vascularity through EUS-VI, the differentiation between PNET and pancreatic cancer could be possible, especially in the subgroup of patients where EUS-guided fine needle aspiration is falsely negative.

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.

Intraductal papillary mucinous tumors of the pancreas.

Intraductal papillary mucinous tumors (IPMTs) are benign and malignant lesions that arise from the epithelial lining of main pancreatic duct and/or branch pancreatic ducts, with excessive mucin production (especially hyperplastic/adenomatous variety). Based on the degree of cytoarchitectural atypia on microscopic examination, IPMTs are classified as benign, borderline, carcinoma in situ and invasive tumors. Imaging examinations are very important to establish the diagnosis. Two or more tests are usually required. Transabdominal ultrasound, endoscopic ultrasound, computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangio-pancreatography have been used for the diagnosis of IPMTs. The correct diagnosis, achieved until recently only with endoscopic retrograde cholangiopancreatography, can be currently obtained with non-invasive imaging modalities, particularly computed tomography and magnetic resonance imaging. Confirmation of the diagnosis requires, however, endoscopic-ultrasound fine-needle aspiration biopsy, followed by cytological or microhistological exams. The natural evolution of IPMTs is still not clear and the management is consequently still evolving.

Plaque-type morphea in children.

We present the case of a girl, aged 8-year-old, with a history of acrocyanosis and repeated respiratory infections with beta-hemolytic streptococcus, which was consulted for the presence of skin lesions in the right buttock area. Clinical examination showed, in the right buttock region, an oval plaque with a diameter about 12 cm, hard, well defined, with irregular outline. The biopsy was performed and it revealed typical aspects of plaque-type morphea. The epidermis was mostly atrophic, with areas of ridge reduction; an important proliferation of collagen fibers within superficial and deep dermis and an abundant lymphocytic inflammatory infiltrate throughout the dermal thickness reaching hypodermic level and infiltrating it. General treatment consisted of antibiotics; vitamin E; local treatment with topical cortisone; analogues of vitamin D3 to which we associated topical adjuvants with repairing and healing role applied to the biopsied area. Evolution was favorable after three months of treatment, with obvious improvement of skin lesions; skin became more elastic and the purple red contour ring disappeared.

Dowling-Degos disease.

Dowling-Degos disease (DDD) is a rare autosomal dominant inherited pigmentary disorder of the flexures with a reticulate aspect and with presence of prominent comedone-like lesions and pitted scars. The diagnosis includes acanthosis nigricans as well as other reticulate pigmentary disorders classified into: dyschromatrosis symmetrica hereditaria (DSH), dyschromatosis universalis hereditaria (DUH) and reticulate acropigmentation of Kitamura (RAPK). We present a 35-year-old woman, which presented with flexural hyperpigmentation considerate as acanthosis nigricans. At a close clinical and histopathological examination, we obtained sure data for Dowling-Degos disease, with a possible familial history of this disease in her son. We review the literature data concerning this disease.

Clinical and cytopathological aspects in phyllodes tumors of the breast.

The frequency of mesenchymal breast tumors is very low, being represented mostly by tumors with biphasic proliferation (phyllodes tumors) and less by other types of non-epithelial tumors. From clinical point of view, phyllodes tumors (PT) can mimic a breast carcinoma. Therefore, the preoperative diagnosis by cytological examination on material obtained by fine needle aspiration (FNA) is very important for adequate treatment of these tumors. In current study, we assessed clinical aspects of 79 phyllodes tumors regarding patient's age and localization of the tumors. In 17 out of 79 cases, it has been performed FNA within the tumors with further cytological examination on the smears obtained. The median age of the patients was 46.07-year-old, being progressively higher with grade of the tumors with significant values between benign and borderline tumors (p=0.04954) and between benign and malignant ones (p=0.02890). The distinguish on the smears of stromal fragments and naked stromal nuclei with variable grade of atypia regarding the tumoral type, in detriment of epithelial elements have been conclusive for fibroepithelial lesion as cytopathological diagnosis. The preoperative differentiation between a breast phyllodes tumor and a breast carcinoma is extremely important for avoiding of a useless radical surgery for the patient. If the fine needle aspiration was correctly performed, the accuracy of the cytodiagnosis has been 82% in current study.

Correlations between gonadotropins level, vaginal cytology and menopause vessel-active phenomena.

INTRODUCTION: Vessel active phenomena from menopause as hot flushes have unknown cause but is demonstrated that the hormone substitution treatment has a very good efficiency in the disproof of the symptomatology. OBJECTIVES: To establish if there is a correlation between gonadotropins level, the presence of the vessel active manifestations and the atrophy of the vaginal epithelium in menopause. MATERIAL AND METHODS: The study design is cross-sectional, done on the 40 and 60-year-old women from the general population list of a family doctor. We studied the blood values of LH and FSH and the vagina cytology and the relations of these parameters with the presence of hot flushes and others vessel active phenomena in menopause. RESULTS: The group consists of 136 women aged between 40 and 60-year-old. Their blood tests prove: LH with normal levels in 79% of cases, FSH has high values in 85%, the vagina cytology marked out the epithelium atrophy in 76% of cases. DISCUSSION: The augmentation of the FSH values is associated with the presence of hot flashes. The ratio LH/FSH under 0.40 is strong associated with vessel active phenomena (p-value 0.000012). We could not establish a statistical correlation between the presence of the vessel active phenomena and vagina atrophy (p-value 0.098). CONCLUSIONS: Vessel active manifestations on the menopause have morphological substratum. The increase of FSH is statistic correlated to the vessel active disorders. It is possible that FRH be the trigger for the hypothalamic thermo detection.

BRCA1 expression in invasive breast carcinomas and clinicopathological correlations.

BRCA1-positive tumors characterize a heterogeneous group of breast cancers with a specific range of histopathological and immuno-histochemical features. We evaluated the relationship between morphological characteristics and immunohistochemical profile of 14 BRCA1-positive breast tumors from an initial study group of 40 breast tumors. Morphological parameters of all cases were studied on Hematoxylin-Eosin-stained sections and their immunophenotypic profile was assessed using antibodies against estrogen receptors (ER), progesteron receptors (PR), c-erbB2 oncoprotein (Her2/neu), BRCA1-protein, and the proliferative rate of the tumoral cells was assessed by Ki-67-proliferative index. All patients were females with an average age of 43.71-year-old. Fourteen out of the 40 tumors were BRCA1-positive. All breast carcinomas in this study were invasive. The most common histological type in our study was invasive ductal carcinoma. The majority of the tumors were high-grade G3. The examination of the lymph node found metastasis in eight cases. We found 11 cases of triple negative (ER, PR and Her2/neu), while the rest showed positivity for all these three markers. We observed a high-celullar proliferation index in all cases. The immunohistochemical study of BRCA1-protein is important to the study of the development and progression of the disease.

Subungual exostosis of the big toe.

The subungual exostosis is a benign bone tumor on the distal phalanx of a digit, beneath or adjacent to the nail, often bringing in discussion many differential diagnosis. We present a 14-year-old boy with a cutaneous nodular lesion, painful to the easy touch on the latero-internal half of the nail of right big toe with extension in the cutaneous part of this. He suffered many treatments, especially cauterization, but with recurrence. In the present, the radiological findings of the affected finger and the histopathological ones from the fragment excised confirmed the diagnosis of subungual exostosis. The local excision of the entire region with the removal of the cartilaginous cap has been followed by a silent period without recurrences of almost two years when he as revised.

Clinical and cytological correlations in pericardial effusions with cardiac tamponade.

We studied 27 patients diagnosed with pericardial effusion with cardiac tamponade on which pericardiocentesis was performed. The purpose of the study was to evaluate the benefits and limits of the cytological examination of the pericardial liquid in the etiological diagnosis and the treatment of patients with cardiac tamponade. The pericardial liquid taken was examined macroscopically, biochemically (content of proteins, glucose, cholesterol, and LDH), cytologically (MGG stained smears from pericardial liquid) and bacteriologically. The obtained results were compared to the clinical data, the laboratory and paraclinical tests, to differentiate the cause and therapeutically procedure. The cardiac tamponade remitted after pericardiocentesis in all patients. The pericardial liquid was exudate (Ligth criteria) in 82% of all patients. The cytological examination of the pericardial liquid showed malignant smear in 40.74% of the patients, smear of the TBC specific inflammation type in 7.40% patients, smear of non-specific inflammation type in 25.94% of patients, reactive type smear in 25.9% of patients.

Spitz nevus with an uncertain malignant potential.

We present the case of 10-year-old girl who have had from birth a plane tumor, of tan color, 3-4 mm of diameter, localized on the face on the cutaneous part of the superior lip. This tumor has been stabile until 8-year-old. Then, after repeated sunlight exposures, the lesion has become more stark, hemispheric in shape, has increased in size becoming about 5-6 mm, with irregular borders, and after an accidental traumatism it began to bleed. We have performed the electroexcision of the lesion for diagnostic and therapeutic purpose. The histopathologic exam distinguished typical images of Spitz nevus on some of the histological sections but also of melanocytary tumor with uncertain malignant potential on the others where atypical mitoses localized in the deeper component of the tumor are being noticed. The immunohistochemical assessment of the tumoral cells showed positivity for the melanocytic markers HMB45 and Melan A, within junctional intraepidermic nevic cells and in the nevic cells from superficial dermis, and also for CD44 protein (belonging to the adhesion molecules family). However, cyclin D1 was positive in rare nevic cells, and the proliferation rate of the tumor was small, with a proliferation index for Ki67 lesser than 5%. The correlation between histopathological and immunohistochemical data conducive to final diagnosis of Spitz nevus with uncertain malignant potential. The clinical evolution confirmed the histopathological diagnosis by the fact that the patient did not presented clinical signs of local recurrences or metastasis at three years after the excision of the tumor.

Clinical and histopathological correlations of the modifications of fetal membranes in amniochorial infection.

The paper aims at analyzing the histopathological modifications induced by the amniotic infection on present fetal membranes and in the absence of clinical signs of chorioamnionitis. Such an evaluation is important in the context of postpartum fetomaternal complications. The objective was to determine the relation between the microbial invasion in the amniotic cavity and the severity of inflammatory lesions of the placenta, of the membranes and the umbilical chord.

Correlations among the serum levels of some interleukins and the histopathological aspects in chronic viral hepatitis C.

UNLABELLED: PREMISES AND OBJECTIVES: The evolution of the infection with the hepatic virus C depends on the defense of the organism, found under the control of a network of cytokines and chemokines. The mechanisms that are causing both viral persistence as well as hepatic pathology are not entirely elucidated. We have proposed to study the amount in which different categories of cytokines are incriminated in the pathogenesis of the chronic liver disease, as well as the eventual correlations between the serum levels of these cytokines and certain histopathological aspects in the chronic viral hepatitis C. PATIENTS AND METHODS: Thirty-five patients with chronic viral hepatitis C (persistent - nine, active - 15, cirrhosis - 11) have been studied, constituting group P, and 20 healthy subjects constituting the reference group (R). In both groups have been determined the serum concentrations of some proinflammatory interleukins (TNF-alpha, IL-6, IL-8), and antiinflammatory (IL-10) cytokines, through the immunoenzymatic technique ELISA. Results. For the proinflammatory cytokines taken into consideration (TNF-alpha, IL-6, IL-8) increased serum values have been determined to the patients with chronic hepatitis C, the maximal level being observed to the patients active chronic hepatitis and cirrhosis (24/35 patients - 68.57%, 19/35 patients - 54.28% and, namely, 18/35 patients - 51.42%). The serum values of IL-10 are increased in 19/35 patients - 54.28%. The direct relationship among the increased levels of IL-10, the astringency of the inflammation and the hepatic functional insufficiency has been taken into consideration. CONCLUSIONS: The immune cellular answer has a fundamental role in the pathogenesis of the liver disease in the patients with chronic viral hepatitis C. The disequilibrium between the pro- and antiinflammatory cytokines participates to the installation of hepatic lesions of cytolysis and/or to the progression of fibrosis. The serum concentrations of the studied cytokines (TNF-alpha, IL-6, IL-8 and IL-10) are correlated to the histopathological spoilages of the liver.