Development of an E-learning System for the Endoscopic Diagnosis of Early Gastric Cancer: An International Multicenter Randomized Controlled Trial.

BACKGROUND: In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness. METHODS: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results. FINDINGS: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001). INTERPRETATION: This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).

Magnifying endoscopy for diagnosing and delineating early gastric cancer.

We describe the basic principles and clinical usefulness of modern magnifying endoscopy techniques, using white-light imaging or narrow-band imaging, for precise diagnosis of small flat gastric cancers. Regarding technology, first, the resolution provided by the endoscope is important in order to consistently visualize the precise morphology of microvascular architecture, and second, the use of a distal attachment (soft hood or cap) is essential in order to maintain a constant distance between the tip of the scope and the mucosal surface. Regarding methodology, a systematic but simple classification system based on microvascular pattern and microsurface pattern (the "VS classification") is proposed. The technique based on the principles described here can be applied not only in routine endoscopic examination but also in the detailed preoperative assessment of the lateral extent of early gastric cancer, before endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD).

Narrow-band imaging with magnification in Barrett's esophagus: validation of a simplified grading system of mucosal morphology patterns against histology.

BACKGROUND AND STUDY AIMS: Validation of a simplified classification of mucosal morphology in prediction of histology in Barrett's esophagus using narrow-band imaging with magnification (NBI-Z) and assessing its reproducibility by endoscopists experienced in the use of NBI (NBI-experts) and by endoscopists who were new to NBI (non-NBI-experts). PATIENTS AND METHODS: In a prospective cohort study of 109 patients with Barrett's esophagus at a single tertiary referral center, mucosal patterns visualized in Barrett's esophagus on NBI-Z were classified into four easily distinguishable types: A, round pits with regular microvasculature; B, villous/ridge pits with regular microvasculature; C, absent pits with regular microvasculature; D, distorted pits with irregular microvasculature. The NBI-Z grading was compared with the final histopathological diagnosis, and positive (PPV) and negative predictive values (NPV) were calculated. The reproducibility of the grading was then assessed by NBI-expert and non-NBI-expert endoscopists, and interobserver and intraobserver agreement were calculated using kappa statistics. RESULTS: Per-biopsy analysis: In 903 out of 1021 distinct areas (87.9%) the NBI-Z grading corresponded to the histological diagnosis. Per-patient analysis: The PPV and NPV for type A pattern (columnar mucosa without intestinal metaplasia) were 100% and 97% respectively; for types B and C (intestinal metaplasia) they were 88% and 91% respectively, and for type D (high-grade dysplasia) 81% and 99% respectively. Inter- and intraobserver agreement: The mean kappa values in assessing the various patterns were 0.71 and 0.87 in the non-expert group; 0.78 and 0.91 in the expert group. CONCLUSIONS: This study has validated a simplified classification of the various morphologic patterns visualized in Barrett's esophagus and confirmed its reproducibility when used by NBI-expert and non-NBI-expert endoscopists.

Expression of Bax protein in gastric carcinomas. A clinicopathological and immunohistochemical study.

BACKGROUND AND STUDY AIMS: Reduced Bax protein expression has been shown to be a negative prognostic factor in patients with breast, ovarian, colorectal, esophageal and pancreatic cancer. Our aim was to immunohistochemically study Bax protein expression in gastric carcinomas and correlate its expression with clinicopathological parameters and prognosis. PATIENTS AND METHODS: Immunohistochemistry was performed, using a monoclonal antibody against bax, in paraffin-embedded tumor specimens from 47 cases of gastric cancer. RESULTS: Positive staining for the Bax protein was found in 20/47 (42.4%) adenocarcinomas examined. Negative Bax protein expression in tumour cells was correlated with lymph node metastasis (P < 0.05), and degree of differentiation (p < 0.05). Univariate analysis showed that the variables with a significant negative impact on survival were: high TNM tumour stage, depth of penetration in the gastric wall, lymph node involvement, and Bax protein expression. Multivariate analysis showed that the only variable with an impact on survival was Bax protein expression (p < 0.05, Relative Risk: 3.34). Kaplan-Meier curves showed that the 5-year survival was 36.8% in cases with positive compared with 16% in cases with negative Bax protein expression (p = 0.0427). CONCLUSION: Negative Bax expression in gastric cancer is associated with de-differentiation, lymph node metastases, and poor clinical prognosis. Bax protein expression might play an important role in the development and phenotypic differentiation of gastric carcinomas and tumor progression.

EUS-guided tissue sampling: comparison of "dual sampling" (Trucut biopsy plus FNA) with "sequential sampling" (Trucut biopsy and then FNA as required).

BACKGROUND AND STUDY AIMS: Both endoscopic ultrasound- (EUS-) guided tissue sampling techniques, fine-needle aspiration (FNA) and Trucut biopsy, have advantages and limitations. The aim of this study was to develop a strategy of combining these two EUS-guided sampling techniques in order to maximize the diagnostic accuracy and minimize duplication. PATIENTS AND METHODS: In this multicenter study we performed "dual sampling" (i. e. with both FNA and Trucut biopsy) in 95 patients during phase 1 of the study and "sequential sampling" (i. e. performing FNA only when Trucut biopsy tissue cores were macroscopically inadequate) in 72 patients during phase 2. RESULTS: During the study period, 167/401 patients referred for EUS-guided sampling were eligible for the study; only solid lesions were included. In 143/167 patients (86 %), sampling was performed via the transesophageal or transgastric routes. When the dual sampling strategy was used, an accurate diagnosis was achieved in 78/95 patients by FNA, compared with 85/95 by Trucut biopsy ( P = 0.21). The combined accuracy of the dual sampling strategy was higher than FNA alone (88/95 vs. 78/95, P = 0.048), but was not significantly higher than Trucut biopsy alone (88/95 vs. 85/95, P = 0.61). Using the sequential sampling strategy, an accurate diagnosis was achieved in 66/72 patients (92 %) compared with 88/95 (93 %) for dual sampling ( P = 1.0), and 8/72 patients (11 %) had to undergo FNA after Trucut biopsy failed to obtain an adequate sample. One patient with mediastinal tuberculosis developed a cold abscess following Trucut biopsy. CONCLUSION: A sequential sampling strategy, in which EUS-guided Trucut biopsy is attempted first, and FNA performed only when Trucut biopsy fails to obtain a macroscopically adequate sample, achieves a diagnostic accuracy of 92 %, with 11 % of patients requiring both sampling procedures.

Novel endoscopic observation in Barrett's oesophagus using high resolution magnification endoscopy and narrow band imaging.

BACKGROUND: High resolution magnification endoscopy with narrow band imaging (NBI) may improve the detection of specialised intestinal metaplasia (SIM) and dysplasia in Barrett's oesophagus. AIMS: To describe the magnified endoscopic features with the use of NBI in Barrett's oesophagus. METHODS: Three hundred and forty-four areas from 50 patients with Barrett's oesophagus were studied using high resolution magnification endoscopy (HRME) with NBI and targeted biopsies were obtained. The sensitivity, specificity, predictive values of the various patterns for the prediction of SIM and dysplasia were calculated. RESULTS: The magnified endoscopic features of Barrett's oesophagus with the use of NBI consist of microstructural/microvascular patterns. The yield of SIM according to the patterns was: (i) Regular microstructural pattern with tubular/linear/villous pattern 90.6% and with circular pattern 0%; and (ii) Absent microstructural pattern 98.9%. The sensitivity, specificity, positive and negative predictive values of the combination of regular microstructural pattern (tubular/villous/linear) and absent microstructural pattern to detect SIM were 100%, 78.8%, 93.5% and 100%, respectively. The sensitivity, specificity, positive and negative predictive values of the irregular microvascular/microstructural pattern for the prediction of high grade dysplasia were 90%, 100%, 99.2% and 100%, respectively. CONCLUSION: High resolution magnification endoscopy with NBI allows clear visualisation of microstructural and microvascular patterns within Barrett's oesophagus, and allows targeted biopsy with a high yield of SIM and high grade dysplasia.

High-resolution magnification endoscopy can reliably identify normal gastric mucosa, Helicobacter pylori-associated gastritis, and gastric atrophy.

BACKGROUND AND STUDY AIMS: The aims of the study were to describe the magnified endoscopic findings in the gastric body, correlate these with histology, and evaluate their reproducibility in the assessment of the magnified endoscopic patterns seen. PATIENTS AND METHODS: A total of 95 consecutive dyspeptic patients underwent upper gastrointestinal endoscopy with a magnifying endoscope. The endoscopists classified the magnified endoscopic patterns and correlated them with the histological findings. In the second part of the study, 200 images were shown to five endoscopists in order to examine inter- and intraobserver variability in image assessment. RESULTS: The magnified endoscopic findings in the gastric body were categorized into four types: type 1, honeycomb-type subepithelial capillary network (SECN) with regular arrangement of collecting venules and regular, round pits; type 2, honeycomb-type SECN with regular, round pits, but loss of collecting venules; type 3, loss of normal SECN and collecting venules, with enlarged white pits surrounded by erythema; and type 4, loss of normal SECN and round pits, with irregular arrangement of collecting venules. The sensitivity, specificity, and positive and negative predictive values of the type 1 pattern for predicting normal gastric mucosa were 92.7% (95% confidence interval [CI] 93.2-97.3%), 100% (95% CI 83.9-100%), 100% (95% CI 92.9-100%), and 83.8% (95% CI 65.5-93.9%). The sensitivity, specificity, and positive and negative predictive values of types 2 and 3 patterns for predicting a Helicobacter pylori-infected stomach were 100% (95% CI 83.9-100%), 92.7% (95% CI 93.2-97.3%), 83.8% (95% CI 65.5-93.9%), and 100% (95% CI 92.9-100%). The sensitivity, specificity, and positive and negative predictive values of a type 4 pattern for predicting gastric atrophy were 90% (95% CI 66.8-98.2%), 96% (95% CI 87.9-98.9%), 85.7% (95% CI 62.6-96.2%), and 97.3% (95% CI 89.6-99.5%. The kappa values for inter- and intraobserver agreement in predicting normal gastric mucosa, H. pylori gastritis, and gastric atrophy were 0.864 and 0.913 respectively. CONCLUSION: High-resolution magnification endoscopy can reliably identify the normal gastric mucosa, H. pylori-associated gastritis, and gastric atrophy in a Western population.

Barrett's esophagus specialist clinic: what difference can it make?

A 'Barrett's specialist clinic' was set up in our institution consisting of a specialist nurse, research fellow, and a consultant gastroenterologist. The aim of our study was to examine the impact of this clinic in the management of patients with Barrett's esophagus (BE). Patients with the diagnosis of BE seen in the outpatient departments or in the endoscopy unit were referred to this clinic. Guidelines were introduced modelling the American College of Gastroenterology recommendation. Patients were assessed based on their comorbidity and willingness to undergo surveillance. Reflux symptom control and acid suppression was addressed. All patients were invited to undergo high-resolution enhanced magnification endoscopy (EME) and targeted biopsy to confirm the diagnosis and to form a management plan. During the appointment in the clinic, patients were given an option to fill a questionnaire that inquired about the information given to them regarding BE. One hundred and forty-three patients (92 men, mean age: 62 years) with a diagnosis of BE were seen in the specialist clinic. In 16 patients surveillance was stopped. In 25 patients treatment was changed due to poor control of reflux symptoms. Sixty-five patients (51%) answered the questionnaire. Seventy-five patients (58%) underwent high resolution EME. Twelve patients, had a histological upgrade after EME, in spite of a short mean screening interval (5.5 months). The 'Barrett's specialist clinic' introduced a more structured approach in our institution and changed the way these patients were managed. Our results indicate the need for local guidelines and Barrett's specialist clinics in the UK, and perhaps in the rest of the Western world, wherein the burden of this condition is increasing.

Acetic acid-enhanced magnification endoscopy in the diagnosis of specialized intestinal metaplasia, dysplasia and early cancer in Barrett's oesophagus.

BACKGROUND: Barrett's surveillance is prone to sampling error. Aim To determine whether enhanced magnification endoscopy using acetic acid instillation improves diagnostic accuracy of specialized intestinal metaplasia/dysplasia in Barrett's oesophagus. METHODS: We examined the detection rate of the specialized intestinal metaplasia/dysplasia in 64 consecutive patients with Barrett's oesophagus using acetic acid to enhance mucosal pit patterns. Histology was compared with the previous findings at recent conventional surveillance in 62 patients. We also examined the inter-/intra-observer agreement in the assessment of the enhanced magnification endoscopy pit pattern findings. RESULTS: Histology revealed columnar-lined oesophagus in six (9%) patients, specialized intestinal metaplasia in 49 (77%), low-grade dysplasia in five (8%), high-grade dysplasia in one (2%), and adenocarcinoma in three (5%). There was discordance between the histologic findings from conventional surveillance with random biopsy. Fifteen patients (24%) had a histological upgrade with enhanced magnification endoscopy. There was a high detection rate of specialized intestinal metaplasia even in short segment Barrett's oesophagus (74%), and additionally, there were two cancers, one with 2-cm Barrett's oesophagus and one ultra-short (1 cm). The mean kappa values for inter- and intra-observer agreement in assessing the pit patterns were 0.571 (0.041) and 0.709 (0.038), respectively. CONCLUSIONS: Enhanced magnification endoscopy allows clear visualization of the epithelial pit patterns within Barrett's oesophagus, and targeted biopsy results in a high yield of specialized intestinal metaplasia and dysplasia.

Unusual case of pulmonary hypertension.

Truly reversible pulmonary hypertension is rare. Acquired systemic arteriovenous (A-V) fistulas following spinal surgery (laminectomy) are a less recognized cause of secondary pulmonary hypertension. We describe a patient who presented with symptoms and clinical evidence of pulmonary hypertension and underwent endovascular correction of an acquired A-V fistula, which led to improvement according to clinical and noninvasive hemodynamic criteria.

Lateral cervical cyst with unsuspected metastasis from an occult tonsillar carcinoma.

Lateral cervical cysts containing squamous cell carcinoma is a diagnostic and therapeutic challenge for the clinician since they usually represent a cystic metastasis from an occult carcinoma. Various imaging modalities or even blind biopsies will help identify the primary tumour. If the primary tumour is identified, an appropriate treatment decision can be made that incorporates both the primary tumour and the cervical node. If the primary remains unidentified, the neck is treated with a modified or radical neck dissection, depending on the extent of metastatic disease, and radiation therapy is administered to Waldeyer's ring and both necks. We present in this paper, a case with a large cervical cyst where histology showed the presence of a poorly differentiated squamous cell carcinoma in the wall of the cyst. A diagnostic evaluation of the patient was negative. Blind biopsies of the right tonsil revealed occult squamous cell carcinoma. The patient was treated by combined chemo/radiotherapy and she is doing well nine months following excision of the mass. The relevant literature is briefly reviewed.

A case of gallstone ileus with an unusual impaction site and spontaneous evacuation.

Gallstone ileus is an unusual cause of colonic obstruction. The formation of a fistula between the gall bladder and the bowel wall may allow a gallstone to enter the intestinal tract. Plain abdominal films, abdominal ultrasound and abdominal computed tomography aid in the diagnosis. Although surgery is the treatment of choice in cases of colonic gallstone ileus, colonoscopic removal of the impacted stone should be attempted. We describe the case of an 85-year-old man who presented with symptoms and signs of large bowel obstruction. Diagnostic evaluation revealed a large gallstone impacted in the sigmoid colon, which is a rather unusual impaction site. Despite our efforts we could not extract the stone endoscopically, mainly due to its large size. Yet, despite its large size, the stone was spontaneously evacuated a few hours later.

Combined carcinoid-adenocarcinoma tumour of the anal canal.

The concurrence of carcinoid admixed with adenocarcinoma in the gastrointestinal tract is an unusual phenomenon that has been reported in the oesophagus, stomach, small intestine, appendix, colon and rectum. These mixed or 'composite' tumours seem to be derived from a multipotential stem cell capable of bidirectional differentiation and have a worse prognosis than ordinary adenocarcinoma. Chromogranin-A staining has increased the diagnostic yield for detecting these tumours and provides information for perioperative management and long-term prognosis. We describe a patient who presented to our department due to painful defecation. Sigmoidoscopy demonstrated a mass in the anal canal. Histology revealed that the tumour was a mixed carcinoid-adenocarcinoma neoplasm. To our knowledge, this is the first report in the English literature of a composite tumour of the anal canal.

Buried bumper syndrome with a fatal outcome, presenting early as gastrointestinal bleeding after percutaneous endoscopic gastrostomy placement.

Percutaneous Endoscopic Gastrostomy (PEG) has gained wide acceptance among patients who require prolonged tube-feeding support. A rather unusual complication of PEG placement is migration of the internal bumper through or into the abdominal wall. This was first described in 1988 and is called the buried bumper syndrome (BBS). The syndrome is a late complication of PEG tube placement. The manifestations of the syndrome must be recognised and the patient referred for emergency endoscopy and removal of the bumper. Failure to recognise this syndrome may result in serious complications including gastrointestinal bleeding, perforation of the stomach, peritonitis and death. We describe a case where a patient developed the buried bumper syndrome quite early after PEG placement. The syndrome manifested with gastrointestinal bleeding. Although we removed the buried bumper endoscopically, and placed another PEG tube, the patient developed peritonitis and died 16 hours after the removal of the migrated bumper.