Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy.

AIM: This study aimed to investigate the clinicopathological predictors of survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC-MF), following curative intent hepatectomy. METHODS: Clinical characteristics and outcomes were analyzed in a series of 42 patients who underwent curative hepatectomy for ICC-MF between February 1987 and December 2012. The relationship between immunohistochemical expression profiles of mucin (MUC) core proteins (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. RESULTS: The overall median follow-up period was 2.6 years (0.2-17.9). Bile duct reconstruction (p = 0.017), lymph node metastasis (p = 0.049), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse predictors of overall survival by univariate analysis. Bile duct reconstruction (p = 0.048), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.005) were found to be independent predictors of poor prognosis by multivariate analysis. Maximal mass diameter ≥5.0 cm (p = 0.011) was found to be an independent predictor for the tumor recurrence. There was a strong correlation between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression was more frequent in patients with concurrent MUC5AC expression (p = 0.019). CONCLUSIONS: MUC5AC expression was significantly related to long-term prognosis and aggressive tumor development, and may be a useful prognostic marker.

Regression of rectal MALT lymphoma after antibiotic treatment in a patient negative for Helicobacter pylori.

A 53-year-old man was referred to our hospital with bloody stool. Barium enema study and colonoscopy revealed multiple small nodules on the anterior wall of the lower rectum. Biopsy specimens showed proliferation of atypical lymphoid cells forming the nodules. Mucosa-associated lymphoid tissue lymphoma was diagnosed on the basis of histologic and immunohistochemical examinations. No metastasis was detected in lymph nodes or distant organs, indicative of clinical stage I disease. Although the test results were negative for Helicobacter pylori, eradication therapy was performed. The lesion disappeared completely within 9 months after the triple antibiotic therapy. H. pylori eradication therapy may be a useful treatment option regardless of H. pylori status.

Quantitative measurement of hepatic portal perfusion by multidetector row CT with compensation for respiratory misregistration.

Our purpose was to determine whether hepatic portal perfusion assessed by multidetector row CT using compensation for respiratory misregistration can predict the severity of chronic liver disease. We carried out dynamic CT in 43 patients (chronic hepatitis: n=9; cirrhosis: n=24; normal liver: n=10). In this series, 20 patients had liver tumours. The CT protocol was designed to avoid respiratory artefacts and included two interscan breathing periods during the study. To compensate for respiratory misregistration, image sets in the same z-axis position were acquired from four-slice data on each scan, and the portal perfusion calculations were made according to the maximum slope method. Portal perfusion was compared with and without compensation for respiratory misregistration, and the different types of hepatic disease. In the liver tumour patients in particular, portal perfusion was compared with the degree of hepatic fibrosis in the liver sections. Portal perfusion in the patients without compensation for respiratory misregistration (1.10 ml min(-1)ml(-1)) was higher than that of those with compensation (0.99 ml min(-1)ml(-1); p=0.036). Hepatic portal perfusion of patients with chronic hepatitis (0.97 ml min(-1)ml(-1)) and liver cirrhosis (0.88 ml min(-1)ml(-1)) was less than that of patients with normal liver (1.32 ml min(-1)ml(-1); p=0.03, 0.001). Moderate correlation was seen between portal perfusion and the percentage of fibrosis in patients with liver tumours (r=0.55). Hepatic portal perfusion obtained by multidetector row dynamic CT using compensation for respiratory misregistration has the potential to improve non-invasive assessment of the degree of chronic liver disease.

Necessity of multiple gastric biopsies from different sites for detection of clarithromycin-resistant Helicobacter pylori strains.

BACKGROUND: It has been reported that approximately 10% of patients infected with Helicobacter pylori have both clarithromycin-susceptible and clathromycin-resistant strains. However, there have been no reports indicating whether only one gastric biopsy is sufficient to detect clarithromycin-resistant strains. METHODS: Sixty-five H. pylori-infected patients were selected for this study, and 40 of them were given clarithromycin-based eradication therapy. Four gastric biopsies, 2 from the antrum and 2 from the corpus, were obtained from each of the 65 patients. Susceptibility of H. pylori strains to clarithromycin was examined by detecting mutations of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: The clarithromycin-resistant strains were detected in 16 of the 65 (25%) patients. Only 5 of the 16 (31%) patients had the resistant strains in both the antrum and corpus. When only 1 or the other biopsy from the antrum was used, the resistant strains were detected in 8 (50%) or 9 (56%) of the 16 patients. CONCLUSIONS: These data indicate that multiple gastric biopsies from both the antrum and the corpus should be used to detect clarithromycin-resistant H. pylori strains.

Human telomerase reverse transcriptase, p53 and Ki-67 expression and apoptosis in colorectal serrated adenoma.

BACKGROUND: Serrated adenoma (SA) has recently been proposed as a distinct histological lesion of the colorectum. However, no definite histopathologic criteria for SA have been established, and its histogenesis and natural history remain unclear. METHODS: We analysed 25 hyperplastic polyps (HPs), 26 low-grade SAs (LG-SAs), 32 high-grade SAs (HG-SAs), 18 low-grade tubular adenomas (LG-TAs), 16 high-grade TAs (HG-TAs) and 20 carcinoma in situ (CIS). To clarify molecular features of SA, we used in situ hybridization to examine the expression of human telomerase reverse transcriptase (hTERT), immunohistochemistry to examine the expressions of p53 and Ki-67, and in situ DNA nick end labeling to detect apoptotic cells. RESULTS: The incidence of hTERT expression was 1 (4.0%) of 25 for HP, 12 (46.2%) of 26 for LG-SA, 18 (56.3%) of 32 for HG-SA, 6 (33.3%) of 18 for LG-TA, 7 (43.8%) of 16 for HG-TA, 12 (80.0%) of 15 for CIS, respectively. The incidence of hTERT expression in SA was significantly higher than that in HP. Seventeen (29%) of the 58 SAs were regarded as positive for p53 protein, but none of the HPs showed p53 immunoreactivity. Ki-67 labeling index in SA, TA and CIS was significantly higher than that in HP. The apoptototic index was not significantly different between HP, SA, TA and CIS. In HG-SA, the incidence of hTERT expression in p53-positive lesions was significantly higher than that in p53-negative lesions. CONCLUSIONS: These results suggest that hTERT and p53 expression increase in the early stages of carcinogenesis in SA and that SA has a malignant transformation similar to that of TA. It may be useful to investigate hTERT and p53 expression for differential diagnosis of SA from HP.

Microsatellite instability is a genetic marker for the development of multiple gastric cancers.

Multiple gastric cancers are found in 5-15% of all patients with gastric cancer. However, no molecular markers have yet been shown to be clinically useful for predicting which patient will or will not have multiple gastric cancers. Recently, microsatellite instability (MSI) has been identified as a molecular marker for multiple colorectal cancers. To elucidate whether MSI could be used as a molecular marker for multiple gastric cancers, we examined MSI in 38 patients with a single gastric cancer, in 26 patients with synchronous multiple gastric cancers and in 14 patients with metachronous multiple gastric cancers. In the patients with synchronous multiple gastric cancers, 1 of the larger tumors was examined. In the patients with metachronous multiple gastric cancers, the first gastric cancer was examined. Five microsatellite loci, including D17S855, D18S58, D18S61, BAT25 and BAT40, were examined with microsatellite assay. MSI was divided into low frequency of MSI (MSI-L) and high frequency of MSI (MSI-H) by the number of affected loci. MSI-L was detected in 3 of the 38 (8%) patients with a single gastric cancer, in 7 of the 26 (27%) patients with synchronous multiple gastric cancers and in 6 of the 14 (43%) patients with metachronous multiple gastric cancers. MSI-H was detected only in 1 of the 38 (3%) patients with a single gastric cancer. The frequency of MSI-L was significantly higher in patients with multiple gastric cancers, both synchronous and metachronous, than in those with a single gastric cancer (p < 0.05 and p < 0.01, respectively). Patients with MSI(+) gastric cancer developed a significantly higher frequency of secondary gastric cancer, when compared with patients with MSI(-) gastric cancer (p < 0.05). These data suggest that MSI may play an important role in the development of multiple gastric cancers, and it may be used clinically as a molecular marker for the prediction of multiple gastric cancers.

Angiogenesis at the site of deepest penetration predicts lymph node metastasis of submucosal colorectal cancer.

PURPOSE: Intratumor microvessel count has been reported as a useful prognostic factor in patients with cancer of various organs. This study was undertaken to clarify the relation between microvessel count and lymph node metastasis in submucosal colorectal cancer. METHODS: Microvessel count was estimated in 254 invasive tumors that had been resected from patients with submucosal colorectal cancer. Immunohistochemistry with antibodies against CD34 was performed on archival specimens, and microvessel counts were estimated based on the average count of three fields (original magnification, x400) in the most vascular area at the site of deepest submucosal penetration. RESULTS: Microvessel count ranged from 10 to 98, with a median of 40. Lesions with high microvessel counts (> or =40) had a significantly higher incidence of lymph node metastasis than those with low microvessel counts (<40; 21.8 percent vs. 6.2 percent). None of the 79 lesions with low microvessel counts and submucosal invasion up to a depth of 1,500 microm had metastasized to the lymph nodes. In multivariate analysis, microvessel count was an independent risk factor for lymph node metastasis in submucosal colorectal cancer (P = 0.0026). CONCLUSION: Microvessel count at the site of deepest submucosal penetration can be one of the most useful predictors for lymph node metastasis. Analysis that combines microvessel count and depth of submucosal invasion may predict the occurrence of lesions without lymph node metastasis.

MUC1 and cathepsin D expression in early colorectal carcinoma showing V type pit pattern.

The relation between MUC1, cathepsin D expression, and histologic features in early colorectal carcinomas (CRCs) with V type pit pattern was examined in 78 patients. We classified V type pit pattern into two grades (VA, VN) and we subclassified the VN type pit pattern into three subtypes (Grade A, B, and C) according to the degree of appearance of VN type pit pattern. At the tumor surface, the status of desmoplastic reaction and pit disorder or destruction were subclassified histologically into three grades (-, +, ++). MUC1 and cathepsin D expression were examined immunohistochemically at a superficial level and at the deepest part of the tumor invasion. MUC1 expression showed a significant correlation with high grade carcinoma, desmoplastic reaction (+) levels in VA type pit pattern (P<0.05), and high grade carcinoma, sm2 and sm3 lesions, desmoplastic reaction (+) and (++) levels, pit disorder or destruction (+) and (++) levels in VN type pit pattern (P<0.05). Cathepsin D expression had a significant correlation with m and sm1 lesions and desmoplastic reaction (-) levels in VN type pit pattern (P<0.05). In VA type pit pattern, a significant correlation between cathepsin D expression and histologic findings was absent. The incidence of MUC1 expression in VN.Grade B and C type pit pattern was significantly higher than that in VA and VN.Grade A type pit pattern (P<0.05). The incidence of cathepsin D expression in VA, VN.Grade A and B type pit pattern was significantly higher than that in VN.Grade C type pit pattern (P<0.05). MUC1 expression (+) or (++) levels at the deepest part of a tumor was identical to that (+) or (++) levels at the superficial part except for one case. Cathepsin D expression at the deepest part of a tumor differed from that at the superficial part. Desmoplastic reaction may be related to MUC1 and cathepsin D expression; however, pit disorder or destruction may be related to only MUC1 expression in V type pit pattern. MUC1 expression at the superficial part of a tumor may be related to expression at the deepest part; however, cathepsin D expression at the superficial part may not be related to expression at the deepest part in submucosal CRCs with V type lesions.

Hepatic resection for intrahepatic cholangiocarcinoma: relation to gross tumor morphology.

BACKGROUND/AIMS: The aim of this study was to investigate the clinicopathologic features and biological behaviors related to the gross appearance of intrahepatic cholangiocarcinoma. METHODOLOGY: Fourteen patients with intrahepatic cholangiocarcinoma who underwent hepatic resection between 1986 and 1998 were divided into four groups according to the gross appearance of the tumor: ID (intraductal growth) type (n = 1), PD (periductal-infiltrating) type (n = 4), MF (mass-forming) type (n = 5), MF-with-PD type (n = 4). RESULTS: Overall survival at 1, 5, and 10 years was 50.0%, 35.7%, and 35.7%, respectively. All three long-term survivors without recurrence had tumors unassociated with vascular invasion, intrahepatic metastasis, or lymph node metastasis. The MF and MF-with-PD tumors were more frequently associated with vascular invasion and/or lymph node metastasis than the ID or PD type. The Ki-67-positive grade of the cancer cells was clearly higher in the MF and MF-with-PD tumors than in the ID or PD type. All of the cases of MF-with-PD tumors were stage IV-A and had a poor outcome. CONCLUSIONS: Extended hepatic resection with a sufficient surgical margin yielded good results in intrahepatic cholangiocarcinoma patients without vascular invasion, intrahepatic metastasis, or lymph node metastasis. However, it is necessary to develop a new effective strategy for advanced intrahepatic cholangiocarcinomas, such as the MF-with-PD type.

Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: a comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component.

BACKGROUND AND AIMS: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). METHODS: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. RESULTS: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. CONCLUSIONS: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.

Clinicopathologic features and endoscopic treatment of superficially spreading colorectal neoplasms larger than 20 mm.

BACKGROUND: A colorectal neoplasm that spreads superficially over the mucosa is known as a laterally spreading tumor. The clinicopathologic features of these large lesions and the efficacy and safety of endoscopic mucosal resection (EMR) were studied retrospectively. METHODS: Surgically or endoscopically resected laterally spreading tumors larger than 20 mm in diameter were studied. Lesions were divided into 2 macroscopic subtypes: F-type, composed of superficially spreading lesions with a flat and smooth surface, and G-type, composed of superficially spreading aggregates of nodules that form relatively flat, broad-based lesions with granulonodular and uneven surfaces. RESULTS: Thirty-three lesions were of the F-type and 87 the G-type. G-type (mean +/- SD, 35.3 +/- 11.4 mm) lesions were significantly larger (p < 0.01) than F-type (26.0 +/- 7.2 mm) lesions. F-type lesions had a significantly higher frequency of invasive cancer (27.2%) than G-types (10.3%)(p < 0.05). Of the 120 lesions, 81 (67.5%) were resected endoscopically. Patients with 78 of these lesions were followed postoperatively for 60.8 +/- 20.1 months. The rate of local recurrence of endoscopically treated tumors as determined at colonoscopy was 7.4% (6/78). These lesions were completely resected endoscopically. Distant metastases were not detected. Thirteen (16.0%) patients had local bleeding after EMR that was stopped endoscopically. Microperforation of the colonic wall as a result of EMR was diagnosed in 1 (1.2%) of 81 cases. CONCLUSIONS: Laterally spreading tumors larger than 20 mm, especially those of the G-type, have a low rate of invasion despite their relatively large size. The F-type lesion has a higher malignant potential than the G-type. EMR is an effective and safe treatment for the large laterally spreading tumor.

Helicobacter pylori eradication therapy for high-grade mucosa-associated lymphoid tissue lymphomas of the stomach with analysis of p53 and K-ras alteration and microsatellite instability.

Recent studies have shown that 70-80% of low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress in response to eradication of Helicobacter pylori (H. pylori). However, there are no reports on whether gastric high-grade MALT lymphomas regress after H. pylori eradication. We performed H. pylori eradication therapy in 4 patients with stage I, high-grade MALT lymphoma after obtaining their informed consent. H. pylori infection was observed in all 4 patients. The patients were treated with proton-pump inhibitor-based eradication therapy for 1 or 2 weeks, and then underwent endoscopic examination and biopsy sampling. H. pylori eradication was achieved in all 4 patients. Six months after eradication treatment, 2 patients showed complete regression of the lymphoma and 2 patients showed no change. The 2 patients with non-responding lymphoma were then treated with an additional chemotherapy (CHOP regimen), whereupon the tumors completely regressed. These patients, followed-up at least 18 months after eradication treatment, showed no recurrence. We also examined genetic alteration of the p53 and K-ras genes and microsatellite instability in these high-grade MALT lymphomas. One patient with a tumor that showed no change after H. pylori eradication, had a loss of heterozygosity of the p53 gene. No other genetic alterations were detected among the patients. Our results indicate that the eradication of H. pylori may be effective not only for patients with low-grade MALT lymphoma but also for patients with high-grade MALT lymphoma. The treatment may be efficacious as a first-line therapy for patients with high-grade MALT lymphoma. However, our sample size was limited and further studies are needed to clarify the issue.

B-cell monoclonality in Helicobacter pylori-associated chronic atrophic gastritis.

B-cell monoclonality has been reported not only in gastric lymphoma, but also in 1.3-21% of Helicobacter pylori-associated chronic gastritis (Hp-CG) cases. The aim of this study was to determine the significance of B-cell monoclonality in Hp-CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The density of Hp, polymorphonuclear neutrophil activity, chronic inflammation, glandular atrophy, and intestinal metaplasia (IM) were scored according to the updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy chain gene rearrangement using polymerase chain reaction amplification. B-cell monoclonality was detected in 6% of informative samples. B-cell monoclonality was found in 18% of the samples from Hp-CG patients with marked glandular atrophy but in none of the samples from Hp-CG patients with none to moderate glandular atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG patients with marked IM, in 11% of the samples from Hp-CG patients with moderate IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell monoclonality was significantly more frequent in Hp-CG patients with marked glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was also more significantly frequent in Hp-CG patients with moderate or marked IM than in Hp-CG patients without IM (P < 0.05). Of 35 Hp-CG patients, 26 (74%) had identical B-cell populations in the antrum and the corpus, and all were polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B-cell populations in at least one gastric biopsy specimen. There were no patients with monoclonal B-cell populations in both the antrum and the corpus. These data suggest that glandular atrophy and IM in gastric biopsy specimens may be markers for gastric mucosa-associated lymphoid tissue (MALT) lymphoma-genesis and that multiple gastric biopsy specimens from both the antrum and the corpus may be needed to assess the risk of gastric MALT lymphoma.

Clinical significance of human erythrocyte glucose transporter 1 expression at the deepest invasive site of advanced colorectal carcinoma.

OBJECTIVE: Malignant cells exhibit increased glucose uptake and utilization in vitro and in vivo. This process is thought to be mediated by the glucose transporter (Glut) family. The aim of this study was to elucidate the clinical significance of Glut1 expression at the site of deepest invasion as a predictor of the invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). METHODS: One hundred and fifty-two patients who had undergone surgical resection for advanced CRC were entered in this study. Histologic subclassifications at the deepest invasive site included well-differentiated (W), moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp), poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression was examined immunohistochemically with a labeled streptavidin-biotin kit using anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67 expression was also examined. All immunoreactivity was analyzed at the deepest invasive site, central portion and superficial part. The immunohistochemical expression of Glut1 was defined as positive if distinct staining of the membrane or cytoplasm was observed in at least 30% of tumor cells. RESULTS: Glut1 expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive site. The incidence of Glut1 expression at the deepest invasive site correlated significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%), depth of invasion (invasion of muscularis propria/invasion of subserosa or subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs. presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke's stage (Duke's

c-myc gene mutation in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma.

The c-myc gene is involved in important cellular processes, including cell proliferation, differentiation, and apoptosis. We analyzed mutation of the c-myc gene in 51 patients with gastric lymphoma [27 patients with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 11 with high-grade MALT lymphoma, and 13 with diffuse large B-cell lymphoma (DLL)], by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. We also evaluated the relationship between mutation of the c-myc gene and regression of low-grade MALT lymphoma after Helicobacter pylori (H. pylori) eradication. Mutation in exon 2 of the c-myc gene was present in 2 of 20 (10%) patients with low-grade MALT lymphoma, in 1 of 7 (14%) patients with high-grade MALT lymphoma, and none of 10 patients with DLL. The 3 patients who had mutations of the gene, showed different patterns of mobility shift, suggesting different mutations. In addition, 15 patients with low-grade MALT lymphoma received anti-H. pylori therapy. All the patients achieved eradication. Nine of the 15 (60%) patients with low-grade MALT lymphoma showed complete regression (CR), 3 (20%) showed partial regression (PR), and 3 (20%) showed no change (NC). One of the 9 (11%) CR patients had a mutation of the c-myc gene. None of the 3 PR and 3 NC patients had mutation of the gene. There was no significant difference between the frequencies among the c-myc gene mutation in CR, in PR and in NC patients. These data suggest that mutation of the c-myc gene may not be commonly associated with development of gastric MALT lymphoma and DLL, and may not be associated with regression of low-grade MALT lymphoma after H. pylori eradication.

Microsatellite instability at D18S61 is associated with no regression of gastric mucosa-associated lymphoid tissue lymphoma after Helicobacter pylori eradication.

Recent studies have shown 70-80% of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regressing in response to eradication of Helicobacter pylori (H. pylori). Genetic mechanism of regression of gastric MALT lymphoma after H. pylori eradication remains unclear. To clarify the issue, we evaluated microsatellite instability (MSI) at 12 microsatellite loci in 15 patients with gastric low-grade MALT lymphoma, who received eradication therapy of H. pylori. H. pylori infection was observed in all the patients. After eradication therapy of H. pylori, patients were observed for a median of 21 months (range, 6-49 months). Eradication was achieved in all the patients. Nine of the 15 (60%) patients showed complete regression (CR), 3 (20%) partial regression (PR), and 3 (20%) no change (NC). MSI was detected in 3 of the 15 (20%) patients with low-grade MALT lymphoma. Compared with response to eradication therapy of H. pylori, MSI was detected in 1 of the 12 (8%) CR and PR patients, and in 2 of the 3 (67%) NC patients. Especially, MSI at D18S61 was detected in 2 of the 3 (67%) NC patients but in none of the 12 CR and PR patients. There was a significant difference between frequency of MSI at D18S61 in NC patients and that in CR and PR patients (p<0.05). These data suggest that MSI at D18S61 may be associated with lack of regression of gastric MALT lymphoma after H. pylori eradication.

Cathepsin D expression as a possible predictor of lymph node metastasis in submucosal colorectal cancer.

The aim of this study was to clarify the usefulness of cathepsin D expression as a predictor of lymph node metastasis in submucosal colorectal cancer (CRC). Cathepsin D expression was examined immunohistochemically in cancer and stromal cells located at the deepest portion of 254 invasive tumours that had been resected from patients with submucosal CRC. In cancer cells, the expression was classified according to differences in intracellular localisation: polarity positive, apical type (PA); polarity positive, basal type (PB); polarity negative (PN); or no expression (NE). Lesions with PN or NE expression showed a significantly higher incidence of lymph node metastasis than those with PA or PB expression. Alternatively, lesions with positive expression in stromal cells showed a significantly higher incidence of lymph node metastasis than that of those with negative expression. None of the lesions with PA or PB expression and negative expression in stromal cells had metastasised to the lymph node. In conclusion, analysis combining cathepsin D expression in cancer and stromal cells may be a quite useful predictor for lymph node metastasis and may broaden the indications for curative endoscopic treatment of submucosal CRC.

Epithelial-myoepithelial carcinoma of the parotid gland with adenoid cystic carcinoma-like features: a case report with immunohistochemical study.

A 69-year-old japanese female with epithelial myoepithelial carcinoma (EMC) in the parotid gland is reported. The tumor, 3.5 x 4.0 x 1.5 cm in size, was located in the left parotid gland. Histopathological examination of the surgically removed tumor revealed that it was composed of double-layered, tubule-like structures formed by inner eosinophilic ductal cells and outer clear cells, as well as solid clear cell nests. The unique histological finding of this tumor was that it had a cribriform-like arrangement of myoepithelial cells resembling an adenoid cystic carcinoma. On the other hand, the typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of low molecular weight cytokeratins, CAM 5.2 and EMA in the ductal part, and smooth muscle actin, S-100 protein, and vimentin in the myoepithelial component.

Progression of primary biliary cirrhosis after proctocolectomy for ulcerative colitis.

We report a case of progression of primary biliary cirrhosis (PBC) after proctocolectomy for ulcerative colitis. A 43-year-old woman underwent a total proctocolectomy after being diagnosed with ulcerative colitis. In the course of the preoperative investigation, liver function test results were within the normal range. Four months after the proctocolectomy, the patient showed a high level of alkaline phosphatase (2398 IU/l) and a positive anti-mitochondrial antibody titer (>1:160). There were no associated symptoms. A liver biopsy demonstrated expansion of all portal areas by infiltrates of lymphocytes and histiocytes. These appearances indicated chronic biliary disease and were compatible with PBC. The association of PBC and ulcerative colitis is rare. However, a review of the recent literature suggests that PBC and ulcerative colitis may be associated; this combination should be kept in mind.

Growth characteristics of rectal carcinoid tumors.

PURPOSE: Tissue growth depends on both cell proliferation and cell death. This study was designed to examine the growth characteristics of rectal carcinoid tumors. METHODS: Fifty rectal carcinoid tumors were studied clinicopathologically and experimentally. Expression of Ki-67, TGF-alpha, p53, and bcl-2 was examined immunohistochemically, and apoptotic cells were identified by the in situ DNA nick end labeling method. EGF receptor expression was examined by a colorimetric in situ mRNA hybridization technique. RESULTS: The median Ki-67 labeling index (LI) in all lesions was 0.62 +/- 0.59%. Ki-67 LI was significantly (p < 0.01) higher in lesions larger than 5 mm than in lesions smaller than 5 mm. TGF-alpha was expressed more frequently (p < 0.01) in lesions larger than 5 mm (100%) than in lesions smaller than 5 mm (65.2%). Ki-67 LI was significantly (p < 0. 05) higher in lesions with TGF-alpha expression than in lesions without TGF-alpha expression. The in situ hybridization revealed EGF receptor expression in all 46 lesions with intact mRNA (100%), and coexpression of TGF-alpha and EGF receptor was found in 39 of the 46 (84.8%) lesions. The median apoptotic index (AI) in all lesions was 0.15 +/- 0.12%. AI has increased with tumor size and was significantly (p < 0.05) higher in lesions with a higher Ki-67 LI than in lesions with a lower Ki-67 LI. p53 protein was detected in only 1 patient who had liver metastases, and the gene mutation was confirmed by polymerase chain reaction and single-strand conformation polymorphism analysis. bcl-2 expression was absent in all lesions. CONCLUSIONS: The Ki-67 LI indicated a low cellular proliferative activity in rectal carcinoid tumors. AI was very low, and was significantly correlated with proliferative rate. Inhibition of apoptosis by mutated p53 or bcl-2 may not have occurred in most of these tumors. TGF-alpha/EGF receptor autocrine mechanisms may play a possible role in tumor growth, and the cellular proliferative activity may increase as tumors grow larger.