Nobutsugu Abe

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue.

The altered form of the high-mobility group A2 (HMGA2) gene is somehow related to the generation of human benign and malignant tumours of mesenchymal origin. However, only a few data on the expression of HMGA2 in malignant tumour originating from epithelial tissue are available. In this study, we examined the HMGA2 expression level in pancreatic carcinoma, and investigated whether alterations in the HMGA2 expression level are associated with a malignant phenotype in pancreatic tissue. High-mobility group A2 mRNA and protein expression was determined in eight surgically resected specimens of non-neoplastic tissue (six specimens of normal pancreatic tissue and two of chronic pancreatitis tissue) and 27 pancreatic carcinomas by highly sensitive reverse transcriptase–polymerase chain reaction (RT–PCR) techniques and immunohistochemical staining, respectively. Reverse transcriptase–polymerase chain reaction analysis revealed the expression of the HMGA2 gene in non-neoplastic pancreatic tissue, although its expression level was significantly lower than that in carcinoma. Immunohistochemical analysis indicated that the presence of the HMGA2 gene in non-neoplastic pancreatic tissue observed in RT–PCR reflects its abundant expression in islet cells, together with its focal expression in duct epithelial cells. Intense and multifocal or diffuse HMGA2 immunoreactivity was noted in all the pancreatic carcinoma examined. A strong correlation between HMGA2 overexpression and the diagnosis of carcinoma was statistically verified. Based on these findings, we propose that an increased expression level of the HMGA2 protein is closely associated with the malignant phenotype in the pancreatic exocrine system, and accordingly, HMGA2 could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignant cells from non-neoplastic pancreatic exocrine cells.

Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas

Matrix metalloproteinases play a crucial role in tumour invasion and mestasis. Matrilysin (MMP-7) has been shown to correlate with nodal or distant metastasis in colorectal carcinomas; however, its implication in early invasive colorectal carcinomas has not been determined. This study was undertaken to clarify the association of matrilysin expression with clinicopathologic parameters in early invasive colorectal carcinomas. 38 early invasive colorectal carcinomas treated by local excision or radical surgery were examined. Tumour budding was evaluated as the number of dedifferentiation units along the entire invasive margin. Matrilysin protein levels were determined using immunohistochemical study. Univariate analysis showed that matrilysin expression alone was significantly associated with distant metastasis (P= 0.0339), and both tumour budding and matrilysin expression were significantly associated with adverse outcome (P= 0.0005, 0.0341). Histological differentiation, vessel invasion, and depth of invasion were not significantly associated with either distant metastasis or adverse outcome. Multivariate analysis confirmed that tumour budding and matrilysin expression were independently associated with adverse outcome, although the significance of matrilysin expression was marginal (P= 0.0488). Tumour budding at the invasive margin and matrilysin expression are more useful in identifying high-risk groups for adverse outcome in patients with early invasive colorectal carcinomas.

Risk factors predictive of lymph node metastasis in depressed early gastric cancer

BACKGROUND This study was conducted to identify risk factors predictive of regional lymph node metastasis in depressed early gastric cancer and further to establish an objective criterion useful to indicate additional surgical treatment in cases in which submucosal tumor extension becomes evident by endoscopic mucosal resection (EMR). METHODS Data from 276 patients surgically treated for depressed early gastric cancer were collected, and the relationship between the patient and tumor characteristics, and the lymph node metastasis was retrospectively evaluated by multivariate analysis. RESULTS In the multivariate logistic regression model, female sex, a larger tumor size (20 mm or more), submucosal invasion, and presence of lymphatic vessel involvement were found to be independent risk factors for lymph node metastasis. Among 145 patients with submucosally invasive carcinoma, no lymph node metastasis was observed in patients who showed none of the other three risk factors, whereas 14.3% and 23.3% of patients with one and two of these factors had lymph node metastasis, respectively. The lymph node metastasis rate was calculated to be 86.7% in patients who had all three factors. CONCLUSIONS Submucosal invasion, female sex, tumor size of 20 mm or more, and lymphatic vessel involvement were significantly and independently related to the presence of lymph node metastasis in depressed early gastric cancer. The positive number of the latter three risk factors is a simple criterion to indicate additional surgical treatment in cases with submucosal invasion revealed first by EMR.

Laparoscopic pancreatic cystgastrostomy

Internal drainage of acute pancreatic pseudocysts is indicated 6 weeks after the first documentation of pseudocyst. It is also indicated for symptomatic chronic pseudocysts 6 cm or more in diameter. When pseudocysts are located in close contact with the posterior wall of the stomach, they are best drained by pseudocyst-gastrostomy. This procedure can also be completed making use of intragastric surgical techniques. Under standard laparoscopic observation, three intragastric ports are placed through the abdominal and anterior gastric walls, establishing working channels for a telescope and hand instruments. After the presence of pseudocysts is confirmed, the posterior wall of the stomach and the cyst wall can be incised by electrocautery. After a sufficient drainage orifice is made and the cyst contents are thoroughly debrided, the intragastric ports are removed and defects in the gastric wall are closed with sutures placed via the standard laparoscopic approach. This approach is much less invasive than the conventional approach, which entails a large gastrotomy in the anterior wall of the stomach. This procedure should be the method of choice when interventional radiology or endoscopic intervention fails to effectively drain retrogastric pseudocysts.

High mobility group HMGI(Y) protein expression in human colorectal hyperplastic and neoplastic diseases.

HMGI(Y) proteins are overexpressed in experimental and human malignancies, including colon, prostate and thyroid carcinomas. To determine at which step of the carcinogenic process HMGI(Y) induction occurs, we analysed the expression of the HMGI(Y) proteins in hyperplastic, preneoplastic and neoplastic tissues of colorectal origin by immunohistochemistry. All the colorectal carcinomas were HMGI(Y)‐positive, whereas no expression was detected in normal colon mucosa tissue. HMGI(Y) expression in adenomas was closely correlated with the degree of cellular atypia. Only 2 of the 18 non‐neoplastic polyps tested were HMGI(Y)‐positive. These data indicate that HMGI(Y) protein induction is associated with the early stages of neoplastic transformation of colon cells and only rarely with colon cell hyperproliferation.

Management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts. IPMNs have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. IPMNs are classified into main duct and branch duct types, based on the site of tumor involvement. IPMN patients have a favorable prognosis if appropriately treated. The postoperative 5-year survival rate is nearly 100% for benign tumors and noninvasive carcinoma, and approximately 60% for invasive carcinoma. A main duct type IPMN should be resected. Surgical treatment is indicated for a branch duct IPMN with suspected malignancy (tumor diameter ≥ 30 mm, mural nodules, dilated main pancreatic duct, or positive cytology) or positive symptoms. Malignant IPMNs necessitate lymph node dissection (D1). IPMNs are associated with a high incidence of extrapancreatic malignancies and pancreatic ductal carcinoma.

Possible contribution of CD44 variant 6 and nuclear β‐catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinoma

In an earlier study, the authors demonstrated that tumor budding was useful for predicting lymph node metastasis in patients with early invasive (T1) colorectal carcinoma. This study was undertaken to clarify the associations between tumor budding, E‐cadherin‐catenin complex, and CD44 variant 6 abnormalities.

Predictive factors for lymph node metastasis of differentiated submucosally invasive gastric cancer

BACKGROUND For early gastric cancer, submucosal invasion may be unrecognized until histopathologic examination of the specimen obtained by EMR. Gastrectomy with lymphadenectomy is the standard treatment for such submucosal cancers. However, approximately 80% of submucosal cancers do not have lymph node metastasis. Unnecessary surgery could be avoided if a subgroup of patients with submucosal cancer with negligible risk of lymph node metastasis can be defined. This study was conducted to define such a subgroup. METHODS Data from 104 patients surgically treated for differentiated submucosal cancers were retrospectively collected. A multivariate analysis of clinicopathologic factors was performed to identify predictive factors for lymph node metastasis. RESULTS Three independent risk factors, namely, female gender (p=0.0174), deep invasion (> or =500 microm) into the submucosal layer (p=0.001), and presence of lymphatic involvement (p < 0.0001) were associated with lymph node metastasis. Lymph node metastasis was not observed in any patient who had limited submucosal invasion and absence of lymphatic involvement. The rate of lymph node metastasis was calculated to be 80% in patients who had both deep submucosal invasion and lymphatic involvement. CONCLUSIONS If endoscopic resection specimens exhibit no deep penetration (<500 microm) into the submucosal layer and lymphatic involvement is absent, EMR may be sufficient treatment for submucosal well-differentiated early gastric cancers. A long-term follow-up study of patients with such lesions treated by EMR alone is required.

Coexpression of Matrilysin and Laminin-5 γ2 Chain May Contribute to Tumor Cell Migration in Colorectal Carcinomas

We attempted to examine the correlation between matrilysin and laminin-5 γ2 chain expression with reference to the number of dedifferentiation units along the entire invasive front (tumor budding). Immunostaining for hMMP-7 and laminin-5 γ2 chain was performed in 50 T1 colorectal carcinomas, and immunoreactivity was evaluated at the invasive front of the tumor. On hematoxylin–eosin sections, the number of tumor budding was counted. The localization of matrilysin tended to be widespread compared with that of laminin-5 γ2 chain. Matrilysin and laminin-5 γ2 chain expression were positive in 28 (56%) and 15 (30%) tumors respectively. There was a significant correlation between matrilysin and laminin-5 γ2 chain expression (P = 0.02). Matrilysin(+)/laminin-5 γ2 chain(+) tumors had a significantly greater amount of tumor budding than matrilysin(−)/laminin-5 γ2 chain(−) tumors (P = 0.003) or matrilysin(+)/laminin-5 γ2 chain(−) tumors (P = 0.03). In conclusions, coexpression of matrilysin and laminin-5 γ2 chain may contribute to tumor cell migration in colorectal carcinomas.

Recent developments in gastric endoscopic submucosal dissection: Towards the era of endoscopic resection of layers deeper than the submucosa

With technical advances in endoscopic submucosal dissection (ESD), several variations of endoscopic procedure derived from ESD and fusion procedures of endoscopy and laparoscopy for upper gastrointestinal submucosal tumor and cancer have recently been developed. The former includes endoscopic muscularis dissection (EMD), submucosal endoscopic tumor resection (SET), endoscopic submucosal tunnel dissection (ESTD) and endoscopic full‐thickness resection (EFTR), and the latter includes laparoscopic and endoscopic cooperative surgery (LECS), laparoscopy‐assisted endoscopic full‐thickness resection (LAEFR), and laparoscopic lymphadenectomy without gastrectomy following ESD. In the present article, recent developments in gastric ESD and advanced procedures derived from ESD are discussed.