Kazuoki Hizawa

Predictive value of endoscopic ultrasonography for regression of gastric low grade and high grade MALT lymphomas after eradication of Helicobacter pylori

BACKGROUND While a close association between gastric mucosa associated lymphoid tissue (MALT) lymphoma and Helicobacter pyloriinfection has been established, there are still cases which do not respond to H pylori eradication. AIMS To investigate the clinicopathological factors which may help predict the therapeutic efficacy of H pylori eradication in gastric MALT lymphoma. PATIENTS Forty one patients with gastric MALT lymphoma, including low and high grade lesions. METHODS After endosonographic staging was determined, H pylori was eradicated in all patients, and the subsequent gastric pathological course was then investigated. RESULTS Complete regression of MALT lymphoma was observed in 29(71%) patients, partial regression in five (12%), and no regression in seven (17%). Twenty six (93%) of 28 MALT lymphomas restricted to the mucosa but only three (23%) of 13 lymphomas which invaded the deep portion of the submucosa or beyond completely regressed. Kaplan-Meier analysis for the probability of complete regression of MALT lymphoma revealed a significant difference between tumours restricted to the mucosa and those invading the submucosa deeply or beyond (p<0.05). Neither the presence of a high grade component, perigastric lymphadenopathy, nor clinical staging prior to eradication correlated with the probability of lymphoma regression. CONCLUSIONS Assessment of deep submucosal invasion by endosonography is valuable for predicting the efficacy of H pylorieradication in gastric MALT lymphoma.

Neoplastic transformation arising in Peutz-Jeghers polyposis

PURPOSE AND METHODS: To clarify the potential for malignancy of Peutz-Jeghers polyposis, we investigated 75 gastrointestinal polyps resected surgically or endoscopically from seven patients with this syndrome. RESULTS: There were 19 polyps in the stomach, 18 in the duodenum, 22 in the small intestine, and 16 in the large intestine, and these were histologically composed of 1 pyogenic granuloma, 1 cancer in adenoma, 2 adenomas, and 71 Peutz-Jeghers polyps. Nine of these Peutz-Jeghers polyps were accompanied by an adenomatous component, and, in addition, two of these showed a cancerous transformation with stalk invasion. A total of 12 neoplastic polyps (16 percent) were found in three relatively young patients (aged 20, 25, and 43 years), all of which were pedunculated and located either in the duodenum or in the jejunum. There was no statistical significance in size between the neoplastic polyps (mean ±SD, 20.1±10.8 mm) and the completely hamartomatous polyps (mean ±SD, 15.8±9.0 mm). Moreover, the configuration of these types of polyps seemed similar. CONCLUSION: Neoplastic transformation is not a rare event, and our results may indicate evidence of a hamartoma-adenoma-carcinoma sequence in Peutz-Jeghers polyposis.

Preventive effect of nutritional therapy against postoperative recurrence of Crohn disease, with reference to findings determined by intra-operative enteroscopy

Objective. The aim of this study was to elucidate the predictive value of intra-operative enteroscopy (IOE) and the effect of enteral nutrition (EN) with regard to the postoperative recurrence of Crohn disease (CD). Material and methods. Forty patients requiring surgery for severe intestinal complications of CD were examined by IOE, and the severity of the remnant small intestine was determined. Patients were subclassified into either an EN group (>1,200 kcal/day) or a non-EN group (<1,200 kcal/day) according to the amount of daily EN intake after surgery. Contributions of IOE findings and EN to postoperative recurrence were analysed retrospectively. Results. IOE identified intestinal lesions in 39 patients and active intestinal lesions in 24 patients. The cumulative rate of postoperative recurrence was significantly higher in patients with cobblestone appearance confirmed by IOE (p=0.006). However, other active intestinal lesions were not related to postoperative recurrence. EN reduced the cumulative rate of postoperative recurrence (p=0.017), especially in patients with penetrating type (p=0.005), in patients who did not have colitis (p=0.051) and in patients who did not have active intestinal lesions confirmed by IOE (p=0.02). Conclusions. EN is a prophylactic that prevents the postoperative recurrence of small intestinal CD. Patients with the penetrating type of CD, and those who do not have active lesions in the small intestine according to IOE, are candidates for EN after surgery.

Natural history of ampullary adenoma in familial adenomatous polyposis: reconfirmation of benign nature during extended surveillance

OBJECTIVE:Surgical or endoscopic papillectomy may be one of the therapeutic strategies for patients with familial adenomatous polyposis (FAP). To determine whether prophylactic papillectomy is necessary for FAP, we investigated the natural history of the ampullary adenoma in FAP.METHODS:Eighteen subjects with FAP were surveyed by duodenoscopy with biopsy for >10 yr. Endoscopic appearance, histological findings, and immunohistochemical stainings for Ki-67 of ampulla were compared between initial and final endoscopic examinations.RESULTS:The endoscopic grade in the ampulla remained unchanged in 16 subjects, whereas in two subjects an increase in the endoscopic grade was noted. In two subjects adenoma developed from an endoscopically and histologically normal ampulla. The histological grade of dysplasia increased in three of 12 subjects who initially had adenoma. The labeling index for Ki-67 was not different between initial and final examinations.CONCLUSIONS:These data suggest that most ampullary adenoma of patients with FAP is static and that aggressive endoscopic or surgical removal is unnecessary for the adenoma.

Comparison of EUS and magnifying colonoscopy for assessment of small colorectal cancers

BACKGROUND Prediction of invasion depth and lymph node metastasis is mandatory when local treatment is considered for small colorectal cancer. The aim of this study was to compare the accuracy of EUS with a catheter probe (probe-EUS) and magnifying colonoscopy for prediction of invasion depth and lymph node metastasis for small colorectal cancer. METHODS Small colorectal cancers were imaged by both probe-EUS and magnifying colonoscopy. Invasion depth by probe-EUS was determined by the presence or absence of distortion of the third sonographic layer. Findings by magnifying colonoscopy were divided into regular, distorted, and amorphous patterns. Histopathologically, depth of invasion was classified as intramucosa/slight or deep invasion. Findings by probe-EUS and magnifying colonoscopy were compared with respect to deep invasion and lymph node metastasis. RESULTS There were 22 small colorectal cancers with intramucosa/slight invasion and 28 with deep invasion. Four of 30 cancers had associated lymph node metastasis. Accuracy for depth of invasion was 91.8% for probe-EUS and 63.3% in magnifying colonoscopy, the difference being statistically significant (p = 0.0013). Negative predictive value of probe-EUS for deep invasion was higher than that for magnifying colonoscopy (respectively, 90.9% vs. 54.1%) in the population studied (prevalence deep invasion 56%). The accuracy for lymph node metastasis was 24.1% for probe-EUS and 72.4% for magnifying colonoscopy, the difference being statistically significant (p < 0.001). Positive predictive value for lymph node metastasis was higher when the amorphous pattern was noted by magnifying colonoscopy compared with the positive predictive value for deep invasion by probe-EUS (respectively, 33.3% vs. 8.7%) in the population studied (prevalence lymph node metastasis 13.3%). CONCLUSIONS Probe-EUS is superior to magnifying colonoscopy for determination of invasion depth in small colorectal cancer. Magnifying colonoscopy may be predictive of lymph node metastasis, thereby suggesting that the procedures provide complementary information with respect to the decision for local versus surgical therapy.

Juvenile polyposis of the stomach: clinicopathological features and its malignant potential.

AIMS: To clarify a clinical entity of juvenile polyposis of the stomach compared with generalised juvenile gastrointestinal polyposis. METHODS: The clinicopathological features of juvenile polyposis dominantly involving the stomach at initial presentation were reviewed in 12 patients (three new patients and nine from the literature). These were compared with 29 cases of generalised juvenile gastrointestinal polyposis. RESULTS: There were three men and nine women with juvenile polyposis of the stomach, aged 10-63 years. Hypoproteinaemia was present in nine patients, anaemia in seven, and a family history of intestinal polyposis in seven. No patient presented with a congenital abnormality. During the observation period, two patients developed colonic juvenile polyps. Gastric polyps invariably affected the antrum and extended to the fundus, eventually becoming more numerous, larger, and more pedunculated. Ten patients required gastrectomy for associated malignancy or uncontrolled protein losing gastropathy. Histological examinations of the resected specimens demonstrated neoplastic tissue arising from juvenile polyps in four of the 12 patients. Atypism in these mixed polyps varied from adenoma to well or moderately differentiated adenocarcinoma. CONCLUSIONS: Juvenile polyposis of the stomach has malignant potential, and may be a separate entity from generalised juvenile gastrointestinal polyposis.

Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene mutation

Background: Serrated adenoma is a precursor of colorectal cancer. Aim: To clarify possible genotype-phenotype correlations of serrated adenomas in familial adenomatous polyposis (FAP). Patients: Eleven patients from eight families with FAP. Methods: We performed total colonoscopy with multiple biopsies in patients. Neoplasia with a serrated glandular structure was regarded as a serrated adenoma. In each patient, germline mutations of the APC gene were determined. Colonic phenotype was compared with germline mutations of the APC gene. Results: Serrated adenomas were found in three patients. These patients had macroscopic polyps <100 in number. Pedigrees with serrated adenomas had the truncating germline APC mutation at codon 161, 332, or 1556 while in the other pedigrees mutations were found between codons 554 and 1324. Conclusions: In FAP, serrated adenoma may be a phenotype characteristic of the attenuated form.

Genetic predisposition to clinical manifestations in familial adenomatous polyposis with special reference to duodenal lesions

OBJECTIVE:In familial adenomatous polyposis (FAP), genetic predisposition for duodenal adenomatosis has not been investigated precisely. The aim of this study was to investigate the correlation between adenomatous polyposis coli (APC) gene mutation and duodenal adenomatosis in FAP.METHODS:APC gene mutation was determined by means of a protein truncation test in 34 patients from 25 families with FAP. The prevalence and grade of duodenal adenomatosis were compared among the proximal mutation group (exons 1–9), the distal mutation group (exons 10–15), and the undetermined groups. The correlation between the course of duodenal adenomatosis and APC gene mutation was retrospectively investigated in 19 patients.RESULTS:The prevalence of duodenal adenomatosis was lower in the proximal mutation group (44%) than in the distal mutation (100%) and undetermined (83%) groups. In patients with positive duodenal adenomatosis, the endoscopic grade did not differ among the groups. The endoscopic grade increased in two of the four patients with the proximal mutation group (50%), in three of 10 patients with the distal mutation group (30%), and in two of five patients (40%) with the undetermined group.CONCLUSIONS:Truncating APC gene mutation proximal to exon 9 may contribute to the less frequent development of duodenal adenomatosis in FAP, but severity and progression of duodenal adenomatosis do not seem to be determined by APC gene mutation alone.

Gastrointestinal Manifestations of Cowdenʼs Disease: Report of Four Cases

Four patients with an established diagnosis of Cowdens disease underwent barium meal study, upper gastrointestinal endoscopy, barium enema examination, and colonoscopy. In three, the esophagus was affected by small protrusions, which were diagnosed as glycogenic acanthosis. Numerous hyperplastic polyps were found in the stomach in three patients, and in one an inflammatory fibroid polyp was also detected. Either lymphangiectasia or lymphoid polyps were found in the duodenum in two patients. In all patients, the colon showed polyps that varied in histology and included adenoma, hamartomatous polyp, and ganglioneurofibroma. In addition, jejunal lymphangiomas were found in one of the three patients in whom the small intestine could be precisely evaluated. These findings suggest that the gastrointestinal involvement in Cowdens disease is characterized by various benign lesions, especially esophageal glycogenic acanthosis, numerous gastric hyperplastic polyps, and multiple hamartomatous polyps in the rectosigmoid colon. Detection of these gastrointestinal manifestations may lead to early diagnosis of this potentially malignant disease.

Association between thyroid cancer of cribriform variant and familial adenomatous polyposis.

A case of a 20 year old Japanese woman who developed thyroid cancer exhibiting unusual cribriform structures while being followed up for familial adenomatous polyposis/Gardners syndrome is reported. The patient presented with osteomas, pigmented retinal lesions, and adenomas of the duodenum and the papilla of Vater, in addition to numerous adenomatous polyps in the colorectum. On ultrasonography, the thyroid cancer was localised to the right lobe and was identified as an irregular, internal echo tumour with a peripheral hypoechoic zone, measuring 1.8 cm in diameter. Histological examination of the resected tumour showed a concomitance of papillary proliferation and cribriform structures with follicles of varying sizes. These features can be distinguished from sporadic thyroid cancer.