A multicenter validation of an endoscopic classification with narrow band imaging for gastric precancerous and cancerous lesions.

BACKGROUND AND STUDY AIM: The reliability and external validity of narrow band imaging (NBI) in the stomach have not been described consistently. The aim of the current study was to describe and estimate the accuracy and reliability of a simplified classification system for NBI in the diagnosis of gastric lesions. METHODS: Consecutive patients undergoing NBI endoscopy at two reference centers (n=85, 33% with dysplasia) were included in two studies. In total, 224 different areas were biopsied and recorded onto video. In the derivation study, previously described NBI features were analyzed in order to develop a simplified classification. In the validation study the accuracy and reliability of this classification were estimated among three groups of endoscopists with different levels of expertise in NBI. RESULTS: The reliability/accuracy results from the derivation study allowed the creation of a simplified NBI classification. In the validation study, "regular vessels with circular mucosa" (pattern A) was associated with normal histology (accuracy 83%; 95% confidence interval [CI] 75 %-90%); "tubulo-villous mucosa" (pattern B) was associated with intestinal metaplasia (accuracy 84%; 95CI 77%-91%; positive likelihood ratio [LR+]=4.75); and "irregular vessels and mucosa" (pattern C) was associated with dysplasia (accuracy 95%; 95CI 90%-99%; LR+=44.33). The reproducibility of these patterns was high (k=0.62). "Light-blue crest" was moderately reliable (k=0.49) but specific (87%) for intestinal metaplasia. A variable vascular density (additional pattern+) was the best feature for Helicobacter pylori gastritis (accuracy 70%; 95CI 59%-80%) but showed only fair reliability (k=0.38). Non-experienced endoscopists presented lower agreement (k=0.6 vs. k=0.75) and accuracy (74% vs. 86%) than international experts/experienced endoscopists. CONCLUSION: A simplified NBI classification is accurate and reliable for the diagnosis of intestinal metaplasia and dysplasia. The classification should be further assessed and validated on a per-patient assessment of NBI, and by comparing NBI with other imaging technologies.

Our perspective on endoscopic resection for colorectal neoplasms.

Endoscopic mucosal resection (EMR) is a minimally invasive technique for effective treatment of early stage colorectal lesions with no invasive potential. However, the high frequency of local recurrence after piecemeal EMR for large lesions is considered a serious problem. In contrast, endoscopic submucosal dissection (ESD) allows en-bloc resection, irrespective of the lesion's size. ESD has been established as a standard method for the endoscopic removal of early cancers in the upper gastrointestinal tract in Japan. Although the use of ESD for colorectal lesions has been studied clinically, ESD is not yet established as a standard therapeutic method. We define the indications for en-bloc resection, based on extensive clinicopathological analyses, as a laterally spreading tumor (LST) non-granular type (LST-NG) lesion greater than 20 mm and an LST granular (LST-G) type lesion greater than 40 mm. Both of these lesions had a high submucosal invasion rate. Especially, LST-NG type lesions greater than 20 mm are technically difficult to remove completely even by piecemeal EMR and are considered a "definite indication for en-bloc resection". The ESD procedure is undoubtedly an ideal method to achieve en-bloc resection, however, the prevalences of suitable lesions among all neoplastic lesions and among all early cancers were not high (1.0% and 5.0%, respectively). Therefore, it is crucial to master more fundamental therapeutic techniques and have knowledge of surveillance strategy after endoscopic treatment.

Diagnosis and endoscopic resection of early gastric cancer.

The overall prognosis of gastric cancer is generally poor due to late presentation and diagnosis. When detected early, the prognosis for gastric cancer is excellent, and curative endoscopic resection may be possible, without the need for surgery. Careful endoscopic examination is important so as to avoid missed lesions. Endoscopic resection, especially with the technique of endoscopic submucosal dissection, is a viable alternative to surgery for the curative treatment of early gastric cancer, with similar long term results, as long as strict inclusion criteria are adhered to.

Endoscopic resection of early gastric cancer treated by guideline and expanded National Cancer Centre criteria.

BACKGROUND: Criteria for endoscopic resection in patients with early gastric cancer (EGC) have been expanded recently by the National Cancer Centre (NCC). This study compared long-term outcomes in patients with EGC who underwent endoscopic treatment according to guideline criteria with those treated according to expanded criteria. METHODS: Baseline and outcome data from patients undergoing curative endoscopic resection for EGC between January 1999 and December 2005 were collected from electronic medical records. Survival time hazard ratios and 95 per cent confidence intervals were calculated using the Cox proportional hazards model. RESULTS: Of 1485 patients who had a curative resection, 635 (42.8 per cent) underwent resection according to traditional criteria and 625 (42.1 per cent) according to expanded criteria. There was no significant difference in overall survival between the groups. CONCLUSION: Patients who have treatment following the expanded criteria have similar long-term survival and outcomes to those treated according to guideline criteria.

Use of Gascon and Pronase either as a pre-endoscopic drink or as targeted endoscopic flushes to improve visibility during gastroscopy: a prospective, randomized, controlled, blinded trial.

OBJECTIVE: To assess whether endoscopic flushes of the bubble-bursting agent Gascon and the mucolytic agent Pronase are as effective in terms of improving endoscopic mucosal visibility as a pre-endoscopic drink of the same agents. MATERIAL AND METHODS: A total of 112 patients attending a Japanese tertiary referral centre for upper gastrointestinal endoscopy were randomized to receive either the standard Japanese procedure of a pre-endoscopic drink of water containing Gascon and Pronase with endoscopic flushes of 20-ml aliquots of water, or no pre-endoscopic therapy but endoscopic flushes of 20-ml aliquots of water containing Gascon, with or without Pronase as necessary. RESULTS: Visibility scores were significantly better in the pre-endoscopic drink group than in either of the endoscopic flush groups. The group receiving a pre-endoscopic drink required fewer flushes during the procedure and there was no difference in the endoscopic time between the three groups. CONCLUSIONS: Our results suggest that endoscopic spraying of these bubble-bursting and mucolytic agents is not able to offer equivalent improvements in endoscopic mucosal visibility when compared with the standard Japanese therapy of a pre-endoscopic drink of these agents. The addition of Pronase to the spray solution had no measurable benefit over Gascon alone. We therefore cannot recommend endoscopic spraying of mucous clearing agents over their use as a pre-endoscopic drink.

The indolent course and high incidence of t(14;18) in primary duodenal follicular lymphoma.

BACKGROUND: Information on the clinical behavior of the recently proposed primary duodenal follicular lymphoma (DFL) is limited. PATIENTS AND METHODS: Demographic data, signs, symptoms, disease stage, and treatment of the patients diagnosed in National Cancer Center Hospital from 1999 to 2007 were collected and analyzed. RESULTS: Twenty-seven patients were studied. Nineteen patients were asymptomatic at the time of diagnosis. Twenty patients had stage I disease. The histological grade was 1 or 2 in 26 patients. IgH/BCL2 fusion was shown in 20 of the examined 24 cases (83%). Fourteen patients received therapy upon diagnosis (local radiotherapy in 2 patients and chemotherapy in 12 including rituximab therapy), their response rate was 85%, and the estimated progression-free survival (PFS) rate at 3 years was 70%. One patient developed histological transformation. The other 13 patients were followed up; their estimated PFS rate at 3 years was 74%. Five among six cases responded to treatment even after progressive disease. All 27 patients have survived with a median follow-up time of 47.9 months. CONCLUSIONS: The majority of primary DFL patients have a localized tumor of low-grade histology and are positive for t(14;18). Watchful waiting might be an alternative approach for its indolent course; however, further studies are warranted.

Risk factors for cardiac and pyloric stenosis after endoscopic submucosal dissection, and efficacy of endoscopic balloon dilation treatment.

BACKGROUND AND STUDY AIMS: Bleeding and perforation are major complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), but post-ESD stenosis represents a severe delayed complication that can result in clinical symptoms such as dysphagia and nausea. The aims of this study were to determine the risk factors and evaluate the clinical treatment for post-ESD stenosis. METHODS: A total of 2011 EGCs resected by ESD at our institution between 2000 and 2005 were reviewed retrospectively. Resection was defined as cardiac when any mucosal defect was located in the squamocolumnar junction, and as pyloric when any mucosal defect was located < 1 cm from the pylorus ring. Post-ESD stenosis was defined when a standard endoscope could not be passed through the stenosis. We examined the incidence of post-ESD stenosis, its relationship with relevant factors, and the clinical course of post-ESD stenosis patients. RESULTS: Post-ESD stenosis occurred with seven of 41 cardiac resections (17 %) and eight of 115 pyloric resections (7 %). Circumferential extent of the mucosal defect of > 3/4 and longitudinal extent > 5 cm were each significantly related to occurrence of post-ESD stenosis with both cardiac and pyloric resections. All 15 affected patients were successfully treated by endoscopic balloon dilation. CONCLUSIONS: A circumferential extent of the mucosal defect of > 3/4 or longitudinal extent of > 5 cm in length were both demonstrated to be risk factors for post-ESD stenosis, in both cardiac and pyloric resections, and endoscopic balloon dilation was shown to be effective in treating post-ESD stenosis.

Total endoscopic resection of Barrett esophagus.

Barrett's esophagus with high grade intraepithelial neoplasia is associated with disease progression at rates of greater than 10% per year. Endoscopic resection is a lower risk alternative to surgery for the management of high grade intraepithelial neoplasia and intramucosal cancer. Two endoscopic approaches have been used, namely localized resection of the lesion and total endoscopic resection of all Barrett's mucosa. The latter strategy removes all at-risk mucosa. Currently it is performed mainly using piecemeal endoscopic mucosal resection techniques. In recent years endoscopic submucosal dissection has been attempted to obtain en bloc resection. This review will describe the techniques of total endoscopic resection, and summarize the key published data.

Treatment strategy after non-curative endoscopic resection of early gastric cancer.

BACKGROUND: Endoscopic resection (ER) is indicated for patients with early gastric cancer who have a negligible risk of lymph node metastasis (LNM). Histological examination of the resected specimen may indicate a possible risk of LNM or a positive resection margin. These patients are considered to have undergone non-curative ER. The aim of this study was to determine the appropriate treatment strategy for such patients. METHODS: A total of 298 patients who had non-curative ER were classified into those with a positive lateral margin only (group 1; 72 patients) and those with a possible risk of LNM (group 2; 226 patients). RESULTS: Surgery was performed within 6 months of non-curative ER in 19 patients in group 1 and 144 in group 2. In group 1, nine patients were found to have local residual tumours, all limited to the mucosal layer without LNM. In Group 2, 13 patients had residual disease, including four local tumours without LNM, two local tumours with LNM and seven cases of LNM alone. The rate of LNM after surgery was 6.3 per cent in group 2. CONCLUSION: Surgery remains the standard treatment after non-curative ER in patients with a possible risk of LNM.

Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection--an analysis of risk factors.

BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) has been reported to be associated with a higher complication rate than standard endoscopic mucosal resection. We aimed to clarify the risk factors for delayed bleeding after ESD for early gastric cancer (EGC). METHODS: 1083 EGCs in 968 consecutive patients undergoing ESD during a 4-year period were reviewed. Post-ESD coagulation (PEC) preventive therapy of visible vessels in the resection area, using a coagulation forceps, was introduced and mostly performed during the later 2 years. Various factors related to patients, tumors, and treatment including PEC were investigated using univariate and multivariate analysis with regard to delayed post-ESD bleeding, evidenced by hematemesis or melena, that required endoscopic treatment. RESULTS: Delayed bleeding occurred after ESD of 63 lesions (5.8 % of all lesions and 6.5 % of patients), controlled in all cases by endoscopic hemostasis; blood transfusion was required in only one case. Tumor location in the upper third of the stomach and PEC were independent factors indicating a lower rate of delayed bleeding according to both univariate and multivariate analysis. CONCLUSIONS: This retrospective study suggested that preventive coagulation of visible vessels in the resection area after ESD may lead to a lower bleeding rate.

Gastric perforation during endoscopic resection for gastric carcinoma and the risk of peritoneal dissemination.

BACKGROUND: The potential risk of peritoneal seeding following perforation caused by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is unknown. METHODS: Between January 1991 and December 2003, 90 patients suffered gastric perforation during EMR or ESD at the National Cancer Centre Hospital, Tokyo. The clinical and pathological evidence for peritoneal dissemination in these patients was assessed retrospectively. RESULTS: Eighty-four patients were followed up at this hospital for a median of 53.6 (range 7.0-136.6) months; the remaining six patients were followed up at other institutions. In 83 patients the perforation was repaired by endoscopic clip application and seven patients underwent emergency surgery. Gastrectomy was carried out in 33 patients who had non-curative endoscopic surgery. Among these, peritoneal fluid was sampled during operation in nine patients and was cytologically negative for malignancy. The other 24 patients who had a gastrectomy did not have ascites so cytology was not performed. No peritoneal dissemination was noted during follow-up. CONCLUSION: This study suggests that perforation associated with EMR and ESD does not lead to peritoneal dissemination even in the long term.

Cancer of the gastric stump following distal gastrectomy for cancer.

BACKGROUND: Cancer of the gastric stump (CGS) after distal gastrectomy for cancer has not been characterized in a large study. The aim of this study was to investigate the clinicopathological features and outcome of CGS following distal gastrectomy for cancer. METHODS: Patients with CGS following distal gastrectomy for gastric cancer diagnosed between 1970 and 2002 were reviewed retrospectively. RESULTS: A total of 108 patients was identified. The median interval between the initial gastrectomy and resection for CGS was 7.5 (range 1-41) years. The depth of tumour invasion was T1 in 67 patients, T2 in 16, T3 in eight and T4 in 17 patients. Endoscopic mucosal resection was performed in 25 patients with T1 tumours. R0 resection was achieved in 103 patients. The overall 5-year survival rate was 53.1 per cent. The 5-year survival rates for patients with T1, T2, T3 and T4 disease were 76, 40, 13 and 9 per cent respectively. CONCLUSION: The outcome for patients with non-early CGS was poor. Early detection of CGS is important following distal gastrectomy for gastric cancer and strict surveillance is recommended for at least 10 years after the initial gastrectomy.

Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum.

BACKGROUND: Laterally spreading tumours (LSTs) in the colorectum are usually removed by endoscopic mucosal resection (EMR) even when large in size. LSTs with deeper submucosal (sm) invasion, however, should not be treated by EMR because of the higher risk of lymph node metastasis. AIMS: To determine which endoscopic criteria, including high magnification pit pattern analysis, are associated with sm invasion in LSTs and clarify indications for EMR. METHODS: Eight endoscopic criteria from 511 colorectal LSTs (granular type (LST-G type); non-granular type (LST-NG type)) were evaluated retrospectively for association with sm invasion, and compared with histopathological findings. RESULTS: LST-NG type had a significantly higher frequency of sm invasion than LST-G type (14% v 7%; p<0.01). Presence of a large nodule in LST-G type was associated with higher sm invasion while pit pattern (invasive pattern), sclerous wall change, and larger tumour size were significantly associated with higher sm invasion in LST-NG type. In 19 LST-G type with sm invasion, sm penetration determined histopathologically occurred under the largest nodules (84%; 16/19) and depressed areas (16%; 3/19). Deepest sm penetration in 32 LST-NG type was either under depressed areas (72%; 23/32) or lymph follicular or multifocal sm invasion (28%; 1/32 and 8/32, respectively). CONCLUSIONS: When considering the most suitable therapeutic strategy for LST-G type, we recommend endoscopic piecemeal resection with the area including the large nodule resected first. In contrast, LST-NG type should be removed en bloc because of the higher potential for malignancy and greater difficulty in diagnosing sm depth and extent of invasion compared with LST-G type.

Why does Japan have a high incidence of gastric cancer? Comparison of gastritis between UK and Japanese patients.

BACKGROUND AND AIMS: The incidence of gastric cancer in Japan is four times higher than in the UK. It usually arises in a stomach with corpus predominant or pangastritis that has undergone extensive atrophy and intestinal metaplasia. We hypothesised that a Japanese population would have a more severe gastritis with a corpus predominant or pangastritis pattern and a greater degree of atrophy and intestinal metaplasia than that found in the UK. To test this we designed a comparative trial. METHODS: A total of 252 age matched consecutive patients were recruited from the endoscopy services in Leeds and Tokyo. In each centre, 21 patients were prospectively selected from each decennial, between the ages of 20-80 years. All had epigastric discomfort as their predominant symptom. Patients with peptic ulcer, cancer, and oesophagitis were excluded. Five gastric biopsies were examined by two histopathologists using the updated Sydney system. Helicobacter pylori infection was assessed by histology and culture of biopsies and enzyme linked immunosorbent assay and immunoblot of plasma. RESULTS: Gastritis was found by both pathologists in 59 (47%) UK and 76 (60%) Japanese patients (chi(2) test, p = 0.04). In those patients with gastritis, corpus predominant or pangastritis was commoner in the Japanese (63% Japan v 36% in the UK (chi(2) test, p = 0.003) Atrophy and intestinal metaplasia were more extensive and severe (Mann-Whitney U test, p<0.001) and chronic inflammation and polymorph activity were also greater, especially in the corpus (Mann-Whitney U test, p<0.001). Fifty three of 59 UK gastritis patients (90%) and 67/76 (88%) (chi(2) test, p = 1) Japanese gastritis patients were positive for H pylori. Using a previously described "gastric cancer risk index" among H pylori positive patients, there were significantly more Japanese than UK subjects with a "high risk" score. CONCLUSION: In Japanese as opposed to English patients, gastritis is more prevalent and severe with more corpus predominant atrophy and intestinal metaplasia. These differences may partially explain the higher incidence of gastric cancer in Japan.

Development of an aggressive depressed cancer in a case of familial adenomatous polyposis.

In 1977, Kariya et al. reported a case of a small depressed cancer in a patient with familial adenomatous polyposis (FAP) raising the possibility that not all cancers in FAP develop from polypoid adenomas. It is now becoming widely recognized that colonic adenomas may appear as flat or depressed lesions. However, colorectal cancers developing in patients with familial adenomatous polyposis (FAP) are still thought to evolve from adenomatous polyps following the polyp-carcinoma sequence. We report the case of a patient with FAP in whom rectal carcinoma developed 23 years after subtotal colectomy and ileorectal anastomosis. We suggest that this malignancy may have developed de novo because of the depressed shape of the lesion and the aggressive growth pattern. This case raises the possibility that carcinomas may not always evolve from polyps in FAP. Aggressive cancers with a depressed appearance should be searched for when surveying the rectal stump in patients with FAP.

Endoscopic mucosal resection.

We are now finding more malignancies in their early stages than previously. Attempts to ablate these lesions are difficult and do not provide the histological information required to decide on further treatment. Surgery is difficult to justify, as only a minority of lesions are associated with lymph node metastases and lesions may not become clinically relevant within the lifetime of an elderly patient. Endoscopic mucosal resection allows cancers to be resected at minimal cost, morbidity and mortality. It is also the most reliable investigation when assessing lesions which are suspicious for containing early cancer. After endoscopic removal, histological assessment of depth of penetration and a search for invasion into lymphatics or venules allows the risk of microscopic lymph node metastases to be predicted. The risk of developing metastatic disease can then be balanced against the risks of surgery in view of the patient's age and health.

Metastatic tumors to the stomach: analysis of 54 patients diagnosed at endoscopy and 347 autopsy cases.

BACKGROUND AND STUDY AIMS: There have been several published reports on metastatic lesions in the stomach, but the numbers of cases have been limited due to the low frequency of the condition. The present study examined the clinicopathological features of metastatic tumors in the stomach from distant sites in a large series of cases. PATIENTS AND METHODS: A total of 389 patients with gastric metastases from solid malignant tumors were examined between 1968 and 1998 at our institution. Of these, 347 were identified from a series of 6380 autopsy cases; 54 patients were diagnosed endoscopically while alive, 12 of whom had confirmation of the condition at autopsy. RESULTS: In the endoscopically diagnosed cases, the metastases presented as solitary (65%) or multiple lesions (35 %), and were more frequently located in the middle or upper third of the stomach. Although the endoscopic appearance often resembled that of submucosal tumor (51%) or primary gastric cancer (39%), the final diagnosis was easily obtained in over 90% of cases from endoscopic biopsies. In two cases of lung cancer and breast cancer, gastric metastases were found before the primary tumors. In the autopsy cases with solid malignancies, metastatic lesions to the stomach were found in 5.4%, and the lung, breast, and esophagus were common primary sites. Malignant melanoma was the most frequent tumor to metastasize to the stomach (29.6%). CONCLUSIONS: Since metastatic lesions to the stomach are rare, the above characteristics of the lesions should be borne in mind, and biopsies should be taken for precise diagnosis during endoscopic examinations.