Contrast enhancement and elastography in endoscopic ultrasound: an overview of clinical applications in pancreatic diseases.

Endoscopic ultrasound is a very accurate imaging technique with a relevant clinical impact in the diagnosis and staging of various conditions such as pancreaticobiliary lesions, esophageal cancer, lung cancer, submucosal lesions and lymph nodes. Despite its increasing importance in everyday clinical routine, endoscopic ultrasound outcomes are still highly operator-dependent and tissue confirmation with fine needle aspiration is very often required for definitive differential diagnosis of tumors. Several techniques of image enhancement have been developed in recent years in the attempt to make the technique less operator-dependent. Among them the most important appear to be contrast harmonic-endoscopic ultrasound and endoscopic ultrasound-elastography. Contrast harmonic-endoscopic ultrasound is performed with a dedicated harmonic which displays the fine vascular network of both normal and pathological tissues after injection of an ultrasound contrast agent. Endoscopic ultrasound-elastography displays with different colors the differences in hardness between tissues, thus estimating elasticity in soft normal tissues which appear red and hard neoplastic tissues which appear blue. While contrast harmonic-endoscopic ultrasound has been introduced into clinical practice, endoscopic ultrasound-elastography mainly represents an investigational tool. The purpose of this paper was to review the mechanism of action and the clinical outcomes of contrast harmonic-endoscopic ultrasound and endoscopic ultrasound-elastography in pancreatic diseases. Both techniques show promising applications in the study of pancreatic tumors including differential diagnosis and providing guidance to fine needle aspiration.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats.

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Usefulness of a second endoscopic arm to improve therapeutic endoscopy in the lower gastrointestinal tract. Preliminary experience - a case series.

Endoscopic submucosal dissection is a difficult procedure with frequent complications. Our aim was to test the feasibility of utilizing a second endoscopic arm to improve the dissection. An Olympus prototype blind probe, with an external diameter of 6 mm and a 2.8-mm working channel, was used as a second endoscopic arm. Its purpose was to lift the lesion during dissection. The main endoscope served both to perform the dissection and to visualize the second endoscopic arm in the monitor. Eight patients with polypoid lesions in the rectum or distal sigmoid were treated successfully. The procedure was feasible, and submucosal exposure was ameliorated allowing easier dissection. The resection was curative in all cases. No recurrences have been detected during up to 18-months of follow-up. A small perforation and two cases of delayed bleeding were managed nonsurgically. Applying counter-traction with a second endoscopic arm can facilitate submucosal dissection of distal colorectal lesions.

The influence of endoscopic biliary stents on the accuracy of endoscopic ultrasound for pancreatic head cancer staging.

BACKGROUND AND STUDY AIMS: Biliary stents have been found to interfere with endoscopic ultrasound (EUS) tumor (T) and nodal (N) staging in patients with periampullary cancer. Our aim was to determine whether this also occurs in patients with pancreatic head cancer. PATIENTS AND METHODS: We studied a consecutive series of patients who were undergoing preoperative EUS for diagnosis and staging of suspected pancreatic cancer, some of whom had biliary stents in situ and some of whom did not. The main end point was the uni- and multivariate association of biliary stenting with T and N mis-staging by EUS. The surgical T and N stages were used as gold standards. RESULTS: A total of 65 patients were identified (19 with biliary stents in situ and 46 without). Surgical stage T4 was found more frequently in patients with stents (53% vs. 22%, P = 0.014). The T stage by EUS was correct in 85% of the patients without biliary stents and in 47% of the patients with stents. The frequency of mis-staging by EUS was significant only among patients with a biliary stent. The distribution by EUS N stage did not differ significantly from the surgical N-stage distribution in the two groups of patients. According to the multivariate analysis, patients with stents were 6.55 times more likely to be incorrectly T staged (95% confidence interval [CI] 1.69-25.49) and 3.71 times more likely to be incorrectly N staged (95% CI 1.11-12.45) than patients without stents. CONCLUSIONS: The results add support to the recommendation that EUS staging of pancreatic head neoplasms should be performed prior to stent placement.

Real-time detection of Helicobacter Pylori infection and atrophic gastritis: comparison between conventional methods and a novel device for gastric juice analysis during endoscopy.

BACKGROUND AND STUDY AIMS: Gastric juice may represent a valuable source of clinicopathological information if properly analyzed. We evaluated the reliability and clinical validity of data obtained using an innovative device (the "Mt 21-42") that analyzes gastric juice, thus allowing the identification of Helicobacter pylori infection and atrophic gastritis of the oxyntic mucosa during endoscopy. METHODS: Validation studies were carried out to evaluate the measuring performance of the device. In addition, the H. pylori status and the presence of atrophic gastritis were assessed in 150 patients undergoing upper gastrointestinal endoscopy. In all these patients the Mt 21-42 device was used to assist endoscopy. Conventional tests (involving histology, urease testing, urea breath testing, anti- H. pylori IgG, serum gastrin, pepsinogen, intrinsic factor and parietal cells autoantibodies, vitamin B12, and folate) were also performed for comparison with the Mt 21-42 results. RESULTS: The measuring performance of the Mt 21-42 was good; for pH, the relative percent error and the coefficient of variation were 1.9 % +/- 4.2 and 1.3 %, respectively, and for ammonium they were 0.1 % +/- 0.2 % and 2.1 %. For the detection of H. pylori infection, the sensitivity and specificity of the device (96.7 % and 94.3 %) were similar to those of the urea breath test (90.5 % and 93.3 %) and serology (87.1 % and 88.8 %), and higher than those of the urease test (78.6 % and 98.7 %; P < 0.01) and routine histology (94.3 % and 76.3 %; P < 0.05). When compared with the currently available standard methods, use of the Mt 21-42 was found to be the most sensitive technique for the detection of atrophy (94.7 % vs. 5.3 % - 47.4 %; P < 0.001); the device failed to detect the disease in only one case (5 %), whereas failure rates of 53 % - 95 % were reported with the conventional methods. CONCLUSION: Atrophic gastritis of the oxyntic mucosa is a risky condition that often goes undetected in current clinical practice. The Mt 21-42 is an effective, useful, and desirable tool that may help to overcome this diagnostic limitation; it produces time and cost savings and also allows the detection of H. pylori infection.

Present and future of endoscopic ultrasonography.

Endoscopic ultrasonography and endoscopic ultrasonography-guided fine needle aspiration are well-established techniques, encompassing a variety of diagnostic and therapeutic applications. Along with traditional indications that constitute everyday clinical practice in all endoscopic ultrasonography centres, new indications are emerging that resemble the continuing research carried on in this field. Some of these are innovative applications, developed by highly experienced endosonographers and with a putative role for clinical practice in the near future. Others are merely experimental applications, carried out on in animal models or in highly selected groups of patients, opening up new fascinating areas of research but not for imminent introduction in clinical practice. The purpose of this review, after summarising the present indications of endoscopic ultrasonography, is to focus on the future applications and try to establish their possible advent, either in the near or in the far future.

Endoscopic treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease is a common chronic disorder which has a severe effect on the patient's quality of life. In view of the high cost of medical therapy and the limitations of surgery, a variety of endoscopic techniques have been developed for the treatment of this condition, and these have shown apparently encouraging results, at least in the short term. However, promising results have been obtained in only around two-thirds of patients over a short-term follow-up period of about 6 months. Moreover, several inconsistencies have emerged between the efficacy of this form of treatment in improving symptoms and quality of life and a lack of improvement of objective parameters, such as lower esophageal sphincter pressure and esophageal acid exposure. The authors strongly endorse the need for comprehensive evaluation of clinical evidence on this topic. After an extensive evaluation of existing literature, we suggest that controlled studies are urgently needed in order to clarify the potential of endoscopic therapy, either in terms of cost-effectiveness or in comparison with standard therapy. Meanwhile, with regard to current practice, the use of endoscopic treatment should be limited to clinical trials, which should incorporate the provision of comprehensive and unbiased information to study patients.

Endoscopic ultrasonography.

This paper covers the literature published between June 2003 and August 2004 on endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (FNA). During this period, more than 120 original studies were published on the topic, not to mention editorials and case reports--indirect evidence of the ever-increasing importance of EUS in everyday clinical practice. However, due to limitations of space, this review will focus only on a few articles selected for their importance and originality. The studies presented deal either with the outcome of EUS--i. e., its real importance in affecting the choices physicians are faced with in their clinical work--or definitively clarify certain technical issues that have often been a matter of debate at EUS meetings. Finally, a few papers describing new potential diagnostic or interventional applications of EUS are presented. Many other relevant papers in addition to those discussed in detail are cited in the references.

Endoscopic ultrasonography.

This review again uses a practical arrangement of the topics of endoscopic ultrasonography (EUS) into clinical categories rather than single diseases. The clinical categories include established indications, such as staging of gastrointestinal tract cancers, differential diagnosis of submucosal tumors, evaluation of solid and cystic pancreatic masses, detection of lymph nodes, evaluation of the biliary tree, and fine-needle aspiration (FNA). In addition to established indications, surgical and investigational techniques are presented, such as fine-needle therapeutic procedures and methods of studying portal hypertension and hepatic, abdominal, and retroperitoneal masses. This year, the new techniques and instruments presented have not included new probes or endoscopes, as these have already gained wide application in published papers and clinical practice. However, new techniques capable of facilitating the use of existing equipment are discussed, such as computer-aided EUS image analysis. Finally, some fascinating studies investigated outcomes with EUS and the cost-effectiveness of the method - stimulating both endosonographers and non-endosonographers to think about current practices and ways of improving them.

The importance of endoscopic ultrasonography in the management of low-grade gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Anti-Helicobacter pylori therapy has been reported to cause regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma in a high percentage of patients. However, in some patients, these lesions persist despite antibiotic treatment. AIM: To determine the various endosonographic findings that may predict the regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma post-antibiotics. METHODS: Seventy-six patients with Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma were studied. Follow-up data were available on 51 patients. All patients were treated with antibiotics. Participants underwent pre- and post-anti-Helicobacter pylori therapy endoscopy with gastric biopsies, followed by endoscopic ultrasonography examination of the stomach. RESULTS: Helicobacter pylori was eradicated in 45 of 51 (88%) patients. At the 2-year follow-up, complete regression of mucosa-associated lymphoid tissue lymphoma was seen in 28 of 51 (55%) patients: 12 of 16 (75%) patients in stage T1m N0, 11 of 19 (58%) patients in stage T1sm N0, four of eight (50%) patients in stages T1m N1 and T1sm N1, and one of four (25%) patients in stage T2 N0. None of the stage T2 N1 patients achieved clinical regression. CONCLUSIONS: Endoscopic ultrasonography evaluation of gastric mucosa-associated lymphoid tissue lymphoma plays a pivotal role in the initial staging and post-treatment follow-up evaluation of these lesions. Accurate staging is essential in the determination of the optimal treatment modality.

Scientific publications in endoscopic ultrasonography: a 20-year global survey of the literature.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound imaging of mediastinum, gastrointestinal tract and pancreas, and endoscopic ultrasound-guided fine-needle aspiration of suspicious lesions, have now been available for several years. Although many papers have been published on endoscopic ultrasonography, a comprehensive overview of the subject matter presented has not yet been carried out. An extensive survey of the literature on endoscopic ultrasonography since its inception in the 1980 s was conducted in this study; key points are summarized. METHODS: A computer-based PubMed search system was used to retrieve all available abstracts pertaining to endoscopic ultrasound from 1980 to the present. Data were collected concerning the impact factor, the various EUS instruments and fine-needle aspiration biopsy techniques used, and the subject matter, as well as the journals publishing the abstracts. RESULTS: A total of 1259 articles were published in 65 journals: 440 (35 %) Western European studies, 404 (32 %) American studies, and 321 (26 %) Japanese studies were retrieved. The total and average impact factor per paper was highest for American papers, followed by European papers and Japanese papers. Forty-seven percent of the papers were published in Gastrointestinal Endoscopy and Endoscopy. The most frequently discussed topics concerned the staging of various malignancies, including esophageal, gastric, pancreatic, and colorectal cancer. The average sample size per paper was in the range 25 - 50. The various types of study included retrospective inquiries (25 %), reviews (24 %), prospective studies (17 %), and case reports (15 %). CONCLUSIONS: Over the course of the past 20 years, there has been a progressive increase in the number of publications pertaining to endoscopic ultrasonography. Large-scale prospective studies are now needed to validate earlier reports. In addition, the diagnostic and therapeutic role of endoscopic ultrasound needs to be more widely publicized among physicians in all health-care fields, so that appropriate patients may be referred.