Kazuhiko Hatano

Prognostic impact of cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study.

The expression of Cathepsin B (CB) and matrix metalloproteinase-9 (MMP-9) in extirpated tissues of adenocarcinomas in non-small cell lung cancer from 90 cases was investigated immunohistologically, and the correlations between the extent of the expression and the clinicopathological features were assessed for investigating the process of tumor metastasis. It is important to reveal the mechanisms of destruction of the basal membrane and infiltration of tumor cells at the primary lesion. Sections were obtained from 10%-formalin-fixed and paraffin-embedded tissues. They were reacted with an anti-human CB polyclonal antibody or an anti-human MMP-9 polyclonal antibody. Of 90 patients, 58 (64.4%) and 39 (48.3) cases were found to be positive for CB and MMP-9 expression, respectively. A significantly higher extent of the CB expression was observed in the tissues of patients who showed postoperative recurrence of the tumor (P = 0.013). Especially, a similar observation was obtained among early cases of T1N0 (P = 0.023). In contrast, no such tendency was demonstrated in the expression profile of MMP-9. Furthermore, the enzyme expressions were compared among different types of metastases. Patients with higher extents of CB expression tended to show significantly higher rates of hematogenous and intrapulmonary metastases (P = 0.023 and P = 0.010, respectively). However, there was no significant correlation between MMP-9 expression and the prognostic factor of the patients. Therefore, we suggested that evaluation of CB expression in the tumor tissue might be useful as a postoperative prognostic factor of pulmonary adenocarcinoma. Especially, early cancer of T1N0 cases showing higher expression of CB may need postoperative adjuvant chemotherapy.

Relationship of Hepatic Functional Parameters with Changes of Functional Liver Volume Using Technetium-99m Galactosyl Serum Albumin Scintigraphy in Patients Undergoing Preoperative Portal Vein Embolization: A Follow-Up Report

BACKGROUND To identify predictors of changes in functional hepatic volumes after portal vein embolization (PVE) before hepatectomy, we examined the relationship between hepatic functional parameters and changes in functional volume of the embolized and non-embolized liver based on a previous volumetric analysis. MATERIAL AND METHODS Subjects were 24 patients who underwent PVE, which was performed through the trans-ileocolic vein (n = 4) or by percutaneous transhepatic puncture (n = 20). The RI liver volume parameter was measured by liver scintigraphy with technetium-(99m) galactosyl human serum albumin ((99m)Tc-GSA). Computed tomography (CT) volume parameter was also measured. RESULTS Significant atrophy of the embolized liver and hypertrophy of the non-embolized liver (change of 72 ± 108 cm(3) and 111 ± 91 cm(3), respectively) (change of 7.8%) was observed after PVE. The change in these RI volume parameters (change of 173 ± 175 cm(3) and 145 ± 137 cm(3) , respectively) (16.5%) was significantly greater than CT volume parameters (P < 0.01). CT vol and RI vol in the embolized and non-embolized liver were well correlated (r = 0.75 and 0.69, respectively). However, the correlation between CT and RI volume parameters in the embolized and non-embolized liver after PVE was very weak (r = 0.17 and 0.03, respectively). Only alkaline phosphatase level correlated negatively with atrophic CT volume parameter of the embolized liver (r = -0.455, P < 0.05). When compared with CT volume parameter, more parameters were significantly correlated with changes of RI volume parameter in the embolized liver: pre-PVE pressure; ICGR15; and serum levels of hyaluronate, total bilirubin, albumin, and alkaline phosphatase. Only platelet count was significantly correlated with hypertrophy of the non-embolized liver. CONCLUSION RI volume parameter might more accurately reflect functional changes in the embolized liver and non-embolized liver than CT volume parameter. Correlated parameters might allow us to predict the functional effect of PVE.

Relationship between morphological diversity and AgNORs or cathepsin B expression in colorectal cancers

The biological characteristics associated with the morphological diversity of colorectal cancers were investigated to elucidate the causes of this diversity. We examined the proliferative and infiltrating activity of tumor cells, indicated by the mean number of Ag nucleolar organizer region associated proteins (NORs) per nucleus (MNA) and the immunohistochemical response to cathepsin B(CB), in various morphological types of early and advanced colorectal cancers. We examined 73 colorectal cancers obtained by endoscopic and surgical resection. MNA values for sessile and flat-elevated cancers were greater than the values for pedunculate, subpedunculate, and flat-or-depressed early cancers (sessile,P<0.05). In advanced cancers invading the muscularis propria, protruding cancers showed significantly higher MNA values than small ulcerative cancers (P<0.01). CB expression increased significantly with the progression of colorectal cancers (P<0.01), but was not related to morphological diversity in early and advanced cancers. In both sessile and flat cancers, CB expression was higher in moderately differentiatiated than in well differentiated adenocarcinomas. These results indicate that, in colorectal cancers, protruding early cancers without stalks and protruding advanced cancers have higher proliferative activity than pedunculate or flat early cancers and small ulcerative advanced cancers, respectively, and that CB expression is not associated with morphological diversity, but with depth of invasion and histological differentiation.

Differences in spatial localization and chromatin pattern during different phases of cell cycle between normal and cancer cells

We studied differences in chromatin patterns and the spatial localization of centromeres of chromosome 11 during the cell cycle between normal peripheral blood lymphocytes (PBL) and human promyelocytic leukemia cells (HL-60) using fluorescence in situ hybridization. The pericentromeres in both cells were located at the periphery during Gq (quiescent) phase, but moved towards the nuclear center in G1 and mid-S phase. During G2, the pericentromeres of PBL continued to move towards the nuclear center whereas those of HL-60 returned to the periphery. The angle defining the spatial location of two pericentromeres, in reference to the center of the nucleus, increased in PBL cells from a mean of 67 degrees during Gq phase to 106 degrees during G1 phase (P < 0.01), and the two pericentromeres remained wide apart throughout the entire cell cycle. In HL-60, the angle also increased during G1, but then decreased during mid-S and G2 phases. Both cells exhibited pericentromeric signals during Gq that were round and compact, and the entire chromatin was loosely condensed. The signal became more loose and dispersed during the G1 and mid-S phases. The pericentromere signal varied during G2 and was generally rod-like or bipartite with condensation of the entire chromatin or chromosome-like. Our results suggest that subtle but important differences in spatial localization of pericentromeres are present during the interphase between normal PBL and HL-60 cells.

Evaluation of surgical resection for pancreatic carcinoma at a Japanese single cancer institute.

BACKGROUND/AIMS Surgical resection is a radical treatment option for pancreatic carcinoma (PC); however, it is still difficult to cure and patient prognosis is poor at this stage. METHODOLOGY We examined the demographics, surgical records and outcome in 64 patients with hilar PC undergoing surgical resection. RESULTS Pancreatoduodenectomy (PD) was carried out in 48 patients, distal pancreatectomy (DP) in 14 and total pancreatectomy in two. Postoperative complications were observed in 18 patients (28%) but no hospital deaths. All stage I patients showed carcinoma in situ of intraductal papillary mucinous carcinoma (IPMC). Postoperative adjuvant chemotherapy was performed in 15 patients (23%) using gemcitabine or S-1. Cancer recurrence was observed in 36 patients (56%) and 31 died of carcinoma. The 5-year cancer-free and overall survival rate was 12% and 14%, respectively. CA19-9 level, morphological type, T category, lymph node metastasis, extrapancreatic nerve plexus invasion, retropancreatic tissue invasion, distal bile duct invasion, duodenal invasion and arterial system invasion were significant poor prognostic factors; however, portal vein system invasion was not significantly associated with prognosis. Cancer infiltration at bile duct cut-end and dissected peripancreatic tissue margin and presence of residual tumor showed a poor prognosis. Surgical prognosis in only non-invasive IPMC was satisfactory. CONCLUSIONS Radically extended surgical resection is necessary and newly effective adjuvant chemotherapy is a promising modality to improve patient survival in PC patients.

A CASE OF HUGE CHOLANGIOCELLULAR CARCINOMA WITH EXTRAHEPATIC GROWTH

We experienced a case of huge cholangiocellular carcinoma with an extrahepatic growth. An 89-year-old woman was admitted to the hospital because of an abdominal mass and abdominal discomfort. The tumor markers showed marked increases, CEA and CA 19-9 were 1.275ng/ml and 4.950U/ml, respectively. Abdominal echo visualized a huge tumor with a well defined margin, which was growing expansively from the right lobe of the liver. Abdominal CT revealed that the tumor was so huge as to reach to the pelvic cavity. Angiography showed that the tumor was fed from a 5 and a 6 arteries of the liver and no parasitic vessels were detected. Curative operation was performed with limited resection of segment 5 and 6 of liver. The excised tumor was 15×10×8cm in size, and 1, 300g in weight. Histopathologically, the tumor was diagnosed as well differentiated tubullar adenocarcinoma with some papillary proliferation. This case is very rare, since the huge cholangiocellular carcinoma with an extrahepatic growth have been reported in only two cases in Japan.