Phosphoglyceride crystal deposition disease presenting as multiple paragastric masses.
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Connective Tissue↗
Biomedical subjects
Michiie Sakamoto
Publications and source records attributed to Michiie Sakamoto.
Hepatic nodules with early enhancement during computed tomography portography: report of six cases.
AIM: To study the clinicopathologic characteristics of hepatic nodular lesions with high attenuation (increased portal blood flow) compared with surrounding hepatic parenchyma on computed tomography (CT) during arterial portography (CTAP). METHODS: For six lesions found in six patients demonstrated as a high-attenuated mass by CTAP, CT during hepatic arteriography (CTHA; n = 3 patients), digital subtraction hepatic arteriography (n = 6) and conventional helical CT (n = 6) were evaluated retrospectively and compared with histopathologic findings (n = 4). Pathologic diagnosis was atypical adenomatous hyperplasia, nodule-in-nodule hepatocellular carcinoma (HCC) in one resected lesion each and overt HCC in two biopsied lesions. Two patients did not undergo any therapy and were followed up. RESULTS: The average size of lesions was 2.2 cm (range 1.2-3.5 cm). The CTAP revealed high attenuation in all six lesions; entirely within the lesion (n = 4 lesions) or peripherally with a central low attenuation (n = 2). In contrast, CTHA showed low attenuated lesions; entirely within the mass (n = 2) or peripherally with a central high-attenuated spot (n = 1). Hepatic arteriogram revealed only two hypervascular lesions; entirely and partially in one each. In the arterial phase of helical CT, all but one lesion were iso- or hypo-attenuated. In two patients who were followed up to 39 and 55 months without therapy, neither tumor growth nor hemodynamic change of the lesion was recognized on CT. CONCLUSIONS: Even though the incidence of hepatic nodular lesions demonstrated as high attenuating on CTAP is low, all but one lesion in the current series showed iso- or hypo-attenuation on CTHA and/or helical CT, suggesting the hemodynamics are reciprocal between CTAP and CTHA. One exceptional lesion that showed high attenuation on both CTAP and conventional CT was pathologically advanced HCC. Based on the follow-up study of two untreated patients, this kind of lesion with high attenuation on CTAP seems to grow slowly.
Aged↗
Overexpression of osteopontin in hepatocellular carcinoma.
Human hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies. In order to identify genes involved in HCC progression, we conducted a differential display analysis and found osteopontin (OPN) to be overexpressed in HCC. OPN is known to be a secreted adhesive glycoprotein, associated with tumorigenesis and metastasis in several cancers. Quantitative polymerase chain reaction analysis of 30 HCC cases revealed the average ratio of OPN to glyceraldehyde-3-phosphate dehydrogenase in tumors to be significantly higher than that in the surrounding non-cancerous liver (4.7 +/- 1.6 vs 0.18 +/- 0.04, P = 0.0072). Immunohistochemistry confirmed the OPN protein was expressed mainly on cancer cells, and was positive in 12 of 30 HCC, most of which showed transcript overexpression. Both OPN transcript and OPN protein were significantly overexpressed in HCC with capsular infiltration, compared with HCC without capsular infiltration. Moreover, OPN-positive cancer cells were often dispersed in the periphery of cancer nodules and were adjacent to stromal cells. Although OPN overexpression was not related to vascular invasion or intrahepatic metastasis, OPN was suggested to play a role in HCC, especially in cancer-stromal interactions.
Adult↗
Less aggressive features of colorectal cancer with liver metastases showing macroscopic intrabiliary extension.
We have previously reported the frequent occurrence of bile duct invasion by liver metastases from colorectal cancer. We found that patients with macroscopic intrabiliary cancer growth survive longer after hepatectomy than those without this feature. In the present study, we analyzed the clinicopathological features of primary colorectal cancer showing macroscopic intrabiliary extension of liver metastases. We reviewed 217 patients who underwent initial hepatic resection for colorectal liver metastasis between 1992 and 1998, and analyzed the corresponding primary colorectal cancers clinicopathologically. Microscopic bile duct invasion was found in 89 of 217 cases (40.6%) and, of these cases, 23 (10.6%) had macroscopic intrabiliary extension. Histological sections of the corresponding primary colorectal cancer were available in eight (group A) of these 23 cases. These were compared with 20 cases, selected randomly, of colorectal cancer that did not show bile duct invasion and were diagnosed as liver metastases. These patients underwent hepatectomy during the same period as group A and were used as a control (group B). The histology of the primary tumors revealed well-differentiated adenocarcinoma in 100% of group A and in 25% of group B. The average maximum diameter of the primary tumor was 5.32 cm in group A and 3.61 cm in group B. Venous invasion was detected in 25% of group A and in 90% of group B (P < 0.01), while the incidences of lymphatic vessel invasion and lymph node metastases were similar between the groups. These data suggest that macroscopic intrabiliary extension could be a good indicator of a unique subgroup of colorectal cancers showing less aggressive features even though they develop liver metastases. Careful histological evaluation is important even for metastatic tumors.
Adenocarcinoma↗
Minute pancreatic adenocarcinoma presenting with stenosis of the main pancreatic duct.
We describe a case of minute pancreatic ductal adenocarcinoma featuring stenosis of the main pancreatic duct (MPD) and associated with histological findings of periductal elastosis and fibroblast proliferation. A 53-year-old Japanese man with preoperative radiological evidence of MPD stricture and dilation of the distal MPD, and suspected of having pancreatic cancer, underwent successful resection. Neither radiological nor macroscopic examination directly disclosed any tumorous lesions, and a small focus of carcinoma (8 x 8 mm) was only revealed on microscopic examination. The tumor was a poorly differentiated, invasive ductal adenocarcinoma that had invaded the intrapancreatic nerves and veins. Interestingly, the MPD located at the edges of the tumor had not been destroyed by the carcinoma, but its wall had been thickened by elastic tissue and fibroblast proliferation, resulting in stenosis. The peripheral pancreas exhibited secondary obstructive pancreatitis. To date, the detection of small pancreatic tumor masses using imaging procedures remains difficult, and most patients are diagnosed on the basis of pancreatic ductal changes. However, the published work on small pancreatic cancers contains little information about the histological features of the affected MPD. The present findings suggest that MPD strictures are not always provoked by destruction or filling with cancer cells, and that they can be caused by periductal elastosis and fibroblast proliferation in a minute carcinoma. Such changes in the MPD may therefore be of clinical importance in the detection of early stage cancers.
Adenocarcinoma↗
Pancreatic metastasis from renal cell carcinoma extending into the main pancreatic duct: a case report.
While metastasis to the pancreas is uncommon, it may occur from renal cell carcinomas (RCCs). We here present a case of pancreatic metastasis from RCC extending into the main pancreatic duct (MPD) in a 66-year-old Japanese man. The patient had a history of RCC treated with a radical nephrectomy 17 years previously and was found to have a mass approximately 2 cm in diameter in the body of the pancreas on radiological images. The patient was suspected of having pancreatic metastasis from RCC and underwent a distal pancreatectomy with splenectomy. Histologically, the tumor consisted of cells arranged in trabecular and alveolar structures with clear or eosinophilic granular cytoplasm, compatible with a metastatic RCC. The pancreatic tumor extended into the MPD with the stream of pancreatic juice. This condition is similar to RCC extension into the renal vein and the inferior vena cava. In conclusion, although extension into the MPD may be rare, such a growth pattern may be characteristic of metastases from RCCs.
Aged↗
Ras farnesylation inhibitor FTI-277 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis.
The E-cadherin/catenin cell adhesion system is often down-regulated in epithelial tumors. This is thought to play an important role in cancer invasion and metastasis, and restoration of this system may suppress metastatic spread of cancer. In this study, the effects of a Ras farnesylation inhibitor (FTI-277) on E-cadherin-mediated cell-cell adhesion and metastatic potential were examined. In cell aggregation assays, FTI-277 stimulated aggregation of colon, liver and breast cancer cells. In vitro cultures of cancer cells showed that FTI-277 induced strong cell-cell contact. Immunoblotting analysis showed that FTI-277 increased E-cadherin/catenin (alpha, beta and gamma) expression and strongly stabilized E-cadherin/catenin with the actin cytoskeleton. Northern blotting studies indicated that the observed increase in the E-cadherin/catenin protein content was due to increased expression of their genes. After inoculation of the spleens of mice with severe combined immunodeficiency (SCID) with cancer cells, FTI-277 treatment for 3 weeks markedly reduced splenic primary tumor growth and the rate of liver metastasis compared with control counterparts. Our data demonstrate that FTI-277 can activate functioning of the E-cadherin-mediated cell adhesion system, which is associated with suppression of cancer cell metastasis. Therefore, selective inhibition of Ras activation may be useful for preventing cancer metastasis.
Cadherins↗
Correlation between laminin-5 gamma2 chain expression and epidermal growth factor receptor expression and its clinicopathological significance in squamous cell carcinoma of the tongue.
Recent investigations have revealed that growth factors may influence the invasive activity of tumor cells. Expression of laminin-5 gamma2 chain (LN-5 gamma2) and epidermal growth factor receptor (EGFR) in squamous cell carcinomas of the tongue in 104 patients with stage II, III, and IVA, B (excluding the cases with distant metastasis) was examined immunohistochemically to determine the correlation between the two molecules and the associations with the clinicopathological features of each tumor. LN-5 gamma2 expression was clearly demonstrated in the cytoplasm and EGFR in the cell membranes of cancer cells. A significant increase in positivity for LN-5 gamma2 was observed in tumors showing poor differentiation (p < 0.001), infiltrative growth (p < 0.001), and deep invasion (p = 0.038). In a multivariate analysis, increased positivity for LN-5 gamma2 was an independent predictor of an unfavorable outcome (p < 0.001). A significant increase in positivity for EGFR was observed in tumors showing infiltrative growth (p = 0.032) and poor prognosis (p = 0.008). The LN-5 gamma2 expression was correlated significantly with EGFR expression (p < 0.001). Patients with tumor positivity for both molecules showed the worst prognosis (p < 0.001). LN-5 gamma2 overexpression and EGFR overexpression is evident in tumors showing infiltrative growth, suggesting that EGFR may influence the invasive activity of tumor cells through overexpression of LN-5 gamma2.
Adult↗
Src family kinase inhibitor PP2 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis.
The E-cadherin/catenin cell adhesion system is often down-regulatedin epithelial tumors. This is thought to play an important role in cancer invasion and metastasis. Restoring this system may enable suppression of the metastatic spread of cancer. This study examined the effect of Src family kinase inhibitor PP2 on E-cadherin-mediated cell-cell adhesion and metastatic potentials. In cell aggregation assays, PP2 stimulated the aggregation of colon, liver, and breast cancer cells. In vitro cultures of cancer cells showed that PP2 induced strong cell-cell contact. Immunoblot analysis showed that PP2 enhanced E-cadherin/catenin expression and that increased E-cadherin/catenin proteins were strongly associated with the actin cytoskeleton. Northern blot studies indicated that the observed increase of E-cadherin/catenin protein content was due to their increased gene expression. After the spleens of severe combined immunodeficient mice were inoculated with cancer cells, treatment with PP2 for 3 weeks markedly reduced the rate of liver metastasis, compared with the control counterparts. Our data demonstrate that PP2 can activate the functioning of the E-cadherin-mediated cell adhesion system, which is associated with the suppression of metastasis in cancer cells. Thus, selective inhibition of Src activation may be potentially useful in the prevention of cancer metastasis.
Animals↗
Clinicopathological significance of galectin-3 expression in ductal adenocarcinoma of the pancreas.
PURPOSE: Galectin-3, a member of the beta-galactoside-binding lectin family, has multiple biological functions including cell-cell interactions and cell-extracellular matrix adhesion, cellular proliferation, cellular differentiation, and apoptosis. The aim of this study was to determine the relationship of galectin-3 expression to clinicopathological findings and patient prognosis in ductal adenocarcinoma of the pancreas. EXPERIMENTAL DESIGN: We examined galectin-3 expression in 104 surgically resected pancreatic ductal adenocarcinoma cases with stages I through IV using immunohistochemistry and investigated the relationship of it to overall survival. RESULTS: Patients were divided into two groups: a low expression group, where <60% of tumor cells were positive; and a high expression group, where > or =60% of tumor cells were positive. Cases in the low expression group had a significant tendency to be at later stages, to have distant metastasis, and to have less differentiated tumors, compared with cases in the high expression group (P = 0.001 for stage, P = 0.001 for metastasis, and P = 0.006 for differentiation). Postoperative overall survival was worse in the low galectin-3 expression group than in the high galectin-3 expression group (P = 0.004). Multivariate analysis showed that the risk ratio of prognosis was 2.06 among patients in the low galectin-3 expression group compared with the high galectin-3 expression group (P = 0.006). CONCLUSIONS: Decreased expression of galectin-3 was associated with advanced stage, tumor de-differentiation, and metastasis in ductal adenocarcinoma of the pancreas. Galectin-3 expression might be a useful prognostic marker for survival in ductal adenocarcinoma of the pancreas.
Aged↗
Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis.
We report the cloning and characterization of a cancer-associated cell membrane glycoprotein recognized by mAb NCC-3G10. The antibody showed strong reactivity to a wide variety of cancer cells, but only to a limited number of normal cells including lymphocytes, endothelial cells, and basal cells of stratified squamous epithelium. The cDNA for the antigen encodes 178 aa, which includes a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Transfection of the cDNA into PLC/PRF/5 liver cancer cells resulted in reduced cell-cell adhesiveness, based on both morphology and results of Ca(2+)-dependent cell aggregation assay. In transfected cells, E-cadherin was markedly decreased at the protein level in inverse proportion to the expression level of the antigen recognized by NCC-3G10, but not at the mRNA level. Aggregation of the antigen by NCC-3G10-coated beads triggered accumulation of actin, suggesting some interplay between this antigen and E-cadherin through actin. When metastatic ability was examined in severe combined immunodeficient mice by injecting PLC/PRF/5 cells into the spleen, the transfectants formed a markedly higher number of metastatic nodules in comparison with controls. We have named this cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis, dysadherin.
Actins↗
Beta-catenin mutations in sporadic fundic gland polyps.
Fundic gland polyp (FGP) is the most common gastric polyp. It occurs sporadically or in association with familial adenomatous polyposis (FAP). FAP patients carry germline mutations of the adenomatous polyposis coli (APC) gene, and previous studies have revealed frequent somatic mutations of the APC gene in FGPs associated with FAP. Although inactivation of the APC gene contributes to histogenesis of FGPs associated with FAP, this rarely happens in sporadic cases. Loss of the APC gene promotes abnormal accumulation of beta-catenin, and mutation of GSK-3 beta phosphorylation sites in the beta-catenin gene can have a similar effect. To elucidate the contribution of beta-catenin gene mutation to the histogenesis of sporadic FGP, we analyzed beta-catenin gene mutation in exon 3 in 45 FGP lesions obtained from 35 patients. Somatic mutations were found in 29 lesions: 28 were missense mutations and one was an in-frame deletion. All of the missense mutations were confined to the former two serine residues of the GSK-3 beta phosphorylation sites and their flanking residues (codons 32, 33, 34, 37). Analysis in cases with multiple FGPs revealed a different mutation in each lesion, indicating their multicentric origin. Therefore, a significant proportion of sporadic FGPs have genetic alterations involving beta-catenin stabilization, as did FAP-associated FGPs.
Adult↗
Successful outcome after resection of pancreatic cancer with a solitary hepatic metastasis.
The presence of hepatic metastasis in pancreatic cancer has generally been considered to be a contraindication for surgery. However, the present case survived seven years after concomitant resection of pancreatic cancer and hepatic metastasis. This shows that hepatic metastasis may be a strong predictor of poor survival, but not a determinant of noncurability. Surgical resection may be an option for highly selected patients with pancreatic cancer complicated with hepatic metastasis.
Adult↗
Endoscopic ultrasonography of nonfunctioning pancreatic islet cell tumors with histologic correlation.
BACKGROUND/AIMS: Preoperative differentiation of benign and malignant pancreatic nonfunctioning islet cell tumors remains problematic. The present study aimed to evaluate endoscopic ultrasonography (EUS) features of benign and malignant tumors with histologic correlation. METHODOLOGY: Ten patients with surgically resected nonfunctioning pancreatic islet cell tumors were retrospectively reviewed. RESULTS: EUS demonstrated a homogenous hypoechoic (n=2) or hyperechoic (n=1) mass in the 3 benign tumors. EUS showed a hypoechoic mass with an irregular central hyperechoic portion (n=4), a hyperechoic mass with an irregular central hypoechoic portion (n=1), a cystic mass with a large irregular internal hypoechoic portion (n=1), or a hypoechoic mass within the entire lumen of the main pancreatic duct (MPD) (n=1) in the 7 malignant tumors. Histologically, the irregular central portions of the malignant tumors corresponded to necrosis, hemorrhage, fibrosis with hyalinosis, cystic degeneration, and/or calcification. Complete obstruction of the main pancreatic duct on EUS was observed in the 2 malignant tumors. The echogenicity of the tumors was closely associated with arrangement of tumor cells and quantity of fibrous stroma. CONCLUSIONS: Heterogeneous internal structures and complete obstruction of the main pancreatic duct are considered as important EUS features that are suggestive of malignancy in nonfunctioning pancreatic islet cell tumors.
Adult↗
Long-term survival of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement.
We report the case of a very rare 6-year disease-free survivor of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement. A 76-year-old female with liver dysfunction was referred to our institution. Contrast-enhanced computed tomography showed a 5-cm low-density tumor with irregular marginal enhancement in the left and caudate lobes of the liver. Cholangiography revealed complete obstruction of the left hepatic bile duct. Angiography showed obstruction of the left branch of the portal vein. Metastasis to the hilar lymph nodes was disclosed at surgery. The patient underwent left hepatectomy with caudate lobectomy, resection of the extrahepatic bile duct, and lymphadenectomy. The total vascular exclusion of the liver was used for hepatectomy and reconstruction of the portal vein. Microscopically, the tumor was a poorly differentiated adenocarcinoma with many infiltrating lymphocytes, and extensive necrosis was present within the tumor. The experience gained in the present case suggests that aggressive surgery may be a potential approach to provide a hope of long-term survival for patients with intrahepatic cholangiocarcinoma despite the presence of regional lymph node metastasis and vascular invasion.
Aged↗