Pancreatic acinar cell carcinoma with endocrine differentiation: immunohistochemical and ultrastructural analyses.

The majority of pancreatic malignant tumors are adenocarcinomas of the ductal type (ductal cell carcinomas) and combined tumors consisting of different tumor components are very rare. We present here a rare case of acinar cell carcinoma with apparent foci of endocrine differentiation. A 46-year-old man underwent pylorus-preserving pancreatoduodenectomy under the diagnosis of pancreatic tumor. The pancreatic tumor was mainly composed of typical acinar cell carcinoma, but some tumor cells were positive for both acinar and endocrine cell markers such as pancreatic amylase, trypsin, lipase and chromogranin A. At the electron-microscopic level, the tumor cells were seen to have numerous electron-dense neuroendocrine, as well as a few zymogen-like, granules. The tumor part positive for both acinar and endocrine cell markers originated from a subclone (dis-differentiated tumor cells) of the typical acinar cell carcinoma tissue of the pancreas.

Small-for-size grafts in living-related liver transplantation.

BACKGROUND: The problems associated with small-for-size grafts in living-related liver transplantation are not fully understood. STUDY DESIGN: A consecutive series of 79 patients underwent 80 living-related liver transplantation procedures, including one retransplant, at the University of Tokyo from January 1996 to January 2000. They were divided into two groups by graft size: graft weight/recipient standard liver volume ratios of 40% or less (n = 24), and more than 40% (n = 56). Preoperative status, mortality, morbidity, duration of hospital stay, and postoperative graft function were examined and compared between the groups. RESULTS: The rate of patients who were restricted to the intensive care unit preoperatively was comparable between the groups (33% versus 21%, p = 0.27). The mean standard liver volume ratios were 37% in the small graft group and 84% in the large group. Survival rates were 80% (5 of 24) for the small graft group, which was significantly lower than that for the large group (96%, 54 of 56, p = 0.02). The rate of acute rejection was comparable between the groups (33% versus 43%, p = 0.47). Vascular complication was observed in 17% of the small graft group patients and 23% of the large group (p = 0.77). No difference was observed in the frequency of bile leakage or bile duct stenosis (25% versus 21%, p=0.77). Hyper-bilirubinemia and elongation of prothrombin time persisted longer in the small graft group than in the large group (p < 0.0001 for both). CONCLUSIONS: Our surgical results may suggest that a graft weight ratio of 40% or less provides a lower chance of survival after living-related liver transplantation.

MUC1 and MUC2 expression in human gallbladder carcinoma: a clinicopathological study and relationship with prognosis.

Mucins are a group of high molecular weight glycoproteins consisting of a mucin core protein and O-linked carbohydrates. To date, nine apomucins (MUC1-8, and MUC5B) have been identified. Recent studies have demonstrated that MUC1 is expressed in tumors of various human organs, and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. MUC2 is a major secreted mucin of colon and is known to be expressed in cells showing intestinal metaplasia in the stomach and other organs. MUC2 expression in the mucosal epithelia is an apparently abnormal phenomenon related to the neoplastic process. In this study, we examined MUC1 and MUC2 expression in human gallbladder adenocarcinoma and its clinicopathological significance and relationship with the prognosis of the patients. MUC1 immunoreactivity was detected not only in the cancer cells but also in the cancer stroma. Cytoplasmic MUC1 expression was significantly relation to lymphatic invasion and lymph node metastasis (p < 0.001), and was associated with a poor outcome. In contrast, MUC2 was rarely expressed in gallbladder carcinomas, and its immunoreactivity was detected only in the cancer goblet cells. Overexpression of MUC2 was not significantly related to lymphatic invasion or lymph node metastasis, or prognosis of patients. These observations suggested that MUC1 expression plays a more important role than MUC2 expression in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

Stromal sialyl Le(a) expression is correlated with vascular invasion of human gallbladder adenocarcinoma.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Lea is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human gallbladder carcinomas. In this study, we examined sialyl Le(a) expression in human gallbladder adenocarcinoma and its clinicopathological significance. Sialyl Le(a) immunoreactivity was detected not only in cancer cells (cytoplasmic type; 68.5%, 37/54) but also in cancer stroma (stromal type; 46.3%, 24/54). According to TNM classification, stromal sialyl Le(a) expression was detected in 60. 0% (24/40) and 7.1% (1/14) of the T2-4 and T1 cancers, respectively (p<0.01). Stromal sialyl Le(a)-positive gallbladder cancers frequently showed lymphatic invasion, venous invasion and lymph node metastasis (62.9%, 62.5% and 70.0%, respectively) (p<0.01). These observations suggested that sialyl Le(a) expression plays important roles in vascular invasion and metastasis of human gallbladder adenocarcinomas.

DF3 expression in human gallbladder carcinoma: significance for lymphatic invasion.

DF3 (MUC 1) is a member of a family of high molecular weight glycoproteins. Recent studies have demonstrated that DF3 is expressed in tumors of various human organs, and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. However, expression patterns of DF3 have not yet been established in human gallbladder carcinomas. In this study, we examined DF3 expression in human gallbladder adenocarcinoma and its clinicopathological significance. DF3 immunoreactivity was detected not only in the cancer cells (cytoplasmic type; 50.0%, 27/54) but also in the cancer stroma (stromal type; 46.3%, 25/54). According to TNM classification, 65.0% (26/40) of T2-4 gallbladder cancers showed cytoplasmic DF3, while 7.1% (1/14) of the T1 cancers were cytoplasmic DF3-positive (p<0.001). Stromal DF3 expression was detected in 62.5% (25/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.001). Lymph node metastasis was frequently found in the cytoplasmic DF3- and stromal DF3-positive gallbladder cancers (59.3% and 60.0%, respectively). These observations suggested that DF3 expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

CEA immunohistochemical localization is correlated with growth and metastasis of human gallbladder carcinoma.

Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e., modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human gallbladder carcinomas. In this study, we examined CEA expression in human gallbladder adenocarcinomas and its clinicopathological significance. CEA immunoreactivity was detected not only in the cancer cells (cytoplasmic type: 63.0%, 34/54) but also in the cancer stroma (stromal type: 29.6%, 16/54). According to TNM classification, 75.0% (30/40) of T2-4 gallbladder cancers showed cytoplasmic CEA, while 28.6% (4/14) of the T1 cancers were cytoplasmic CEA-positive (p<0.05). Stromal CEA expression was detected in 40.0% (16/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.05). Lymph node metastasis was frequently found in the cytoplasmic CEA- and stromal CEA-positive gallbladder cancers (44.1% and 62.5%, respectively). These observations suggested that CEA expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

Stromal expression of thrombospondin-1 is correlated with growth and metastasis of human gallbladder carcinoma.

Thrombospondin-1 (TSP1) is one of the extracellular matrix glycoproteins that affect cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we examined TSP1 expression in human gallbladder adenocarcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 74.5% (29/39) of the T2 and T3 gallbladder cancers were TSP1-positive, while none (0/14) of the T1 cancers showed TSP1 expression (p<0.001). Lymph node metastasis and venous involvement were frequently found in the TSP1-positive cases (90.0% and 87.1%, respectively) of gallbladder adenocarcinoma (p<0.001). These observations suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human gallbladder adenocarcinomas, and that stromal TSP1 immunoreactivity is a good predictor of vascular involvement and lymph node metastasis.