Masaki Kunihiro

Electrocautery snare resection stimulates cellular proliferation of residual colorectal tumor: an increasing gene expression related to tumor growth.

PURPOSE: Recently, endoscopic mucosal resection has been performed commonly for colorectal tumors. However, incomplete endoscopic mucosal resection produces a residual tumor that grows rapidly. The aim of this study was to clarify the characteristics of the residual tumor using the nude mouse model. METHODS: Human colon cancer cells (colo201 or colo320DM) were implanted subcutaneous into nude mice. We then removed more than one-half of the tumor with an electrocautery snare or a surgical knife, and compared the tumor growth rate with that of control tumors. Before and after resection, we examined the Ki-67 labeling index of the tumors with an immunohistochemical assay and mRNA expression for epidermal growth factor receptor, vascular endothelial growth factor, and transforming growth factor alpha. RESULTS: Residual tumors showed a higher growth rate in tumor volume than control tumors using both methods (electrocautery snare and surgical knife). Colo201 groups showed a higher total volume change per day than colo320DM groups after resection. Furthermore, these tumors also showed a higher Ki-67 labeling index, and a stronger epidermal growth factor receptor and transforming growth factor alpha mRNA expression than primary and control tumors in the colo201 implanted groups. There was no significant difference in vascular endothelial growth factor mRNA expression between groups implanted with colo201 or colo320DM. CONCLUSION: Our results suggest that residual tumors caused by incomplete endoscopic mucosal resection may have a higher growth potential than the tumors before resection.

Magnifying colonoscopic features of ulcerative colitis reflect histologic inflammation.

Background:Colonoscopy plays an important role in the diagnosis of ulcerative colitis and the determination of disease activity. Standard colonoscopic findings, however, do not often agree with histologic findings. The aim of this study was to clarify the relation between magnifying colonoscopic features and histologic inflammation in the course of ulcerative colitis. Methods:We performed magnifying colonoscopy examinations in 60 patients with ulcerative colitis. We classified the features into six types and analyzed the relations among these features, standard colonoscopic features (Matts grades), and pathohistological findings. Results:It was difficult to distinguish the remission stage from the active stage by standard colonoscopy in cases of Matts grade 2 disease. There was a relation, however, between the magnifying colonoscopic types and the degrees of histologic inflammation. The magnifying colonoscopic types reflected histologic inflammation status more accurately than did standard colonoscopic findings. Conclusion:Magnifying colonoscopy is useful for determining the degree of histologic change without biopsy in patients with ulcerative colitis.

Combined Expression of HLA-DR Antigen and Proliferating Cell Nuclear Antigen Correlate with Colorectal Cancer Prognosis

HLA-DR antigen expression and the proliferating cell nuclear antigen labeling index (PCNA-LI) were examined immmunohistochemically in 59 surgically resected advanced colorectal cancers to clarify the clinicopathologic significance of the HLA-DR antigen. HLA-DR antigen expression was detected in 33 (56%) of the 59 lesions, which showed less frequent liver metastasis than lesions without HLA-DR antigen expression (40 vs. 68%; p < 0.05). Five-year survival rates of patients with and without HLA-DR antigen expression were 50 and 19%, respectively. Lesions combining HLA-DR antigen expression and a relatively low PCNA-LI had the best prognosis. These results indicate that HLA-DR antigen expression, particularly combined with a low PCNA-LI, is an important outcome predictor in colorectal cancer.

A combination of the Helicobacter pylori stool antigen test and urea breath test is useful for clinical evaluation of eradication therapy: A multicenter study

Background:  Helicobacter pylori stool antigen (HpSA) test is a new tool for evaluating the H. pylori infection. The present study was carried out to investigate the clinical usefulness of the HpSA test in the evaluation of eradication therapy by comparing it with the 13C‐urea breath test (UBT).

Clinical Features of Gastrointestinal Follicular Lymphoma: Comparison with Nodal Follicular Lymphoma and Gastrointestinal MALT Lymphoma

We retrospectively compared the clinicopathological features of primary intestinal follicular lymphomas (FL-GIs), nodal follicular lymphomas (FL-LNs) and gastrointestinal MALT lymphomas (MALT-GIs), and investigated the distribution and the endoscopic appearances of FL-GI to evaluate the effectiveness of treatment modality. The subjects were 28 FL-GI patients, 135 FL-LN patients and 70 MALT-GI patients. In FL-LNs the clinical stage III–IV was 83%, while in FL-GIs clinical stage I–II was 68%. In MALT-GIs clinical stage I–II was 87%. The overall survival was significantly better in MALT-GI patients than in FL-LN patients. All FL-GI patients were alive at the time of evaluation. Regarding the histological grade (WHO), grade 1 was 81% in FL-GI, whereas in FL-LN grade 2 was 28% and grade 3 was 11%. The Follicular Lymphoma International Prognostic Index was low in 61% of FL-GIs, while in FL-LNs it was equally distributed to low, intermediate and high, suggesting that the prognosis is better in FL-GIs than in FL-LNs. The clinicopathological studies revealed the FL-GI has intermediate characteristics between FL-LN and MALT-GI. We recommend a ‘watch-and-wait’ policy or chemotherapy with rituximab for the therapy of FL-GIs because the lesions are often located in broader areas from the lower duodenum to the small intestine.

Usefulness of positron emission tomography in primary intestinal follicular lymphoma

Double-balloon enteroscopy (DBE) and video capsule endoscopy are useful for the diagnosis of lymphoma in the small intestine. However, DBE cannot be safely performed in cases with passage disturbance due to wall thickening and stenosis. Additionally, video capsule endoscopy cannot be performed in such cases because of the risk of retention. Here, we report 4 cases of primary follicular lymphoma of the gastrointestinal tract that could be detected using (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET-CT). The endoscopic findings of these 4 cases included lesions with wall thickening, which comprised macroscopically clusters of nodules, dense clusters of whitish granules or small nodules, fold thickening and ulcers with irregular margins that occupied the whole lumen with edematous mucosa. All patients fulfilled the World Health Organization grade 1 criteria. (18)F-fluorodeoxyglucose PET-CT can help predict the risks that may result from certain endoscopic examinations, such as DBE and video capsule endoscopy.

A duodenal follicular lymphoma associated with the lesion mimicking MALT lymphoma in terminal ileum and Bauhin valve

This is a case report of a 66-year-old woman who consulted us with a 1-week history of postprandial epigastric discomfort and dyspepsia. Upper and lower gastrointestinal endoscopy and double-balloon enteroscopy revealed lesions in three parts: a swelling with a shallow depression in the ampulla of Vater, flat and rough nodules in the jejunum, and a mixture of lymphoid polyposis and rough surface of follicular lymphoma of the terminal ileum and Bauhin valve. The histological, immunophenotypic, and molecular findings of the duodenal lesion confirmed the diagnosis of follicular lymphoma. We initially diagnosed the ileal lesion as MALT lymphoma immunohistochemically. However, Southern blot hybridization analysis for immunoglobulin heavy chain gene rearrangement showed identical monoclonal bands in both the duodenal and ileal lesions. The molecular cytogenetic studies were also positive for the 14;18 translocation in both lesions. Therefore, the true diagnosis of this ileal lesion should be a follicular lymphoma with marginal zone differentiation. Primary follicular lymphomas of gastrointestinal tract were suggested to have intermediate features between nodal follicular lymphoma and MALT lymphoma. This case is an important clue to prove the similarity of follicular lymphoma of gastrointestinal tract to MALT lymphoma and will be crucial in considering the therapeutic strategy.

The Progression of Esophageal Mucosa-associated Lymphoid Tissue Lymphoma after Helicobacter pylori Eradication Therapy: A Case Report and Discussion of Therapeutic Options

A 50-year-old woman with epigastric discomfort was referred to our hospital. Esophagogastroduodenoscopy showed flat, elevated, submucosal tumor-like lesions in the esophagus. Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) of the esophagus was diagnosed based on the examination of an endoscopic biopsy specimen. Computed tomography showed the enlargement of a lymph node in the gastric cardia. The present case showed disease progression despite Helicobacter pylori eradication therapy and achieved partial remission after rituximab monotherapy. The patient remained in partial remission for 20 months. This case suggests that esophageal MALT lymphoma with lymph node involvement does not respond to H. pylori eradication therapy and that it requires systemic treatment.

Gastric type adenoma with submucosal invasive carcinoma: A case study

A 75-year-old woman visited our hospital for the examination of esophagogastroduodenoscopy (EGD) without any major complaint. The patients medical history included hypertension, but no carcinoma. EGD revealed a 30-mm elevated lesion located in the anterior wall of the upper region of the stomach. The lesion, which was a 0-IIa+I type lesion with fading-like and light flare-like domains, was surgically removed using endoscopic submucosal dissection (ESD) and then the patient was diagnosed with gastric type adenoma with submucosal invasive carcinoma. To the best of our knowledge, this is the first report of a gastric type adenoma with submucosal invasive carcinoma and may therefore provide significant insights into the malignant potential of gastric type adenoma lesions.

Dexmedetomidine for conscious sedation with colorectal endoscopic submucosal dissection: a prospective double-blind randomized controlled study

Objective: Conscious sedation for colorectal endoscopic submucosal dissection (ESD) has not been standardized, and there are no studies of sedation for colorectal ESD. Methods: We conducted a prospective double‐blind randomized controlled trial to clarify the usefulness of DEX during colorectal ESD. In total 80 patients with colorectal ESD from April 2016 to May 2017 were assigned to the placebo group or the DEX group (40 cases each). The primary outcome was patient satisfaction (visual analogue scale: VAS). Secondary outcomes were evaluated for 13 factors, including patient pain level (VAS), endoscopist satisfaction (VAS), objective patient pain level viewed from the endoscopists perspective (VAS), rate of patient response, rate of side effects, etc., from the patients and endoscopists perspectives. Results: Patient satisfaction was 8.4 and 9.1 (P = 0.018) in the placebo group and the DEX group, respectively. Secondary outcomes of patient pain level, endoscopist satisfaction, objective patient pain level from the endoscopists perspective for the placebo and DEX groups were 1.2 and 0.4 (P = 0.045), 8.2 and 9.3 (P < 0.001), and 1.2 and 0.5 (P = 0.002), respectively. All of these were significantly positive results (more comfortable and less pain) in the DEX group. The rate of a patient response was 100% in all cases. The side effects (hypoxia/bradycardia/hypotension) were 0%/0%/0% and 7.5%/7.5%/5% (P = 0.030). However, these rates were less than the reported side effect occurrence rate, and no additional medication was needed. Conclusion: DEX enables conscious sedation, and is useful not only for patient and endoscopist satisfaction but also for pain relief. DEX is an effective sedation method for colorectal ESD.