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Biomedical subjects

K Shirabe

Publications and source records attributed to K Shirabe.

At least 19 recordsLinked to original sources

Evaluation of a hybrid artificial liver using a polyurethane foam packed-Bed culture system in dogs.

BACKGROUND AND AIMS: We developed a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver (PUF-HAL), which was effective for recovery from liver failure in rat experiments. In this report, the design of a scaled-up PUF-HAL for dogs is described and evaluated using a dog acute liver failure model. METHODS: Warm ischemic liver failure was induced with a portocaval shunt in each dog. The dogs were divided into two groups: (1) a control group (N = 4), in which each dog was attached to a PUF-HAL without hepatocytes for 9 h, and (2) a HAL group (N = 5), in which each dog was attached to a PUF-HAL with hepatocytes. Blood pressure, blood ammonia, blood glucose, serum creatinine, and other parameters related to liver function were compared between the two groups. RESULTS: In the HAL group, blood ammonia and serum creatinine levels were significantly lower, and blood pressure and blood glucose levels significantly higher, than those in the control group. CONCLUSIONS: The scaled-up PUF-HAL developed for large animals is useful as a liver support system in the dog acute liver failure model.

Ammonia

Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume.

BACKGROUND: Postoperative liver failure is a life-threatening complication after hepatic resection. Because of recent advances in liver surgery technique and a more stringent patient selection, mortality after hepatic resection has steadily decreased, but its incidence still ranges from 10% to 20%. The factors linked to postoperative liver failure in major hepatic resection in the modern era should be reevaluated. STUDY DESIGN: Of 80 patients with viral markers (hepatitis C viral antibody or hepatitis B surface antigen) who underwent major hepatic resections (no less than bisegmentectomies) for hepatocellular carcinoma between 1990 and 1996, 7 patients (8.8%) died of postoperative liver failure within 6 months after hepatectomy. The cause of liver failure was analyzed based on both the preoperative data and the intraoperative findings. In addition, since all the patients who died of liver failure underwent a right hepatic lobectomy, a further data analysis was also done in 47 patients who underwent a right lobectomy of the liver. A volumetric analysis by CT was then done to evaluate the remnant liver volume. RESULTS: Between the patients with liver failure and those without liver failure who underwent a right lobectomy, there were no significant differences in preoperative data or intraoperative findings. Volumetric analysis revealed that the remnant liver volume of patients who died of liver failure was significantly smaller than that of patients who lived (p = 0.008). The incidence of liver failure in patients with a remnant liver volume of less than 250 mL/m2 was 7 of 20 (38%), while it was 0 of 27 in patients with a liver volume of no less than 250 mL/m2 (p = 0.0012). The only significant risk factor for liver failure in patients with a remnant liver volume of less than 250 mL/m2 was diabetes mellitus (p = 0.0072). CONCLUSIONS: The expected remnant liver volume appears to be a good predictor for liver failure in patients who undergo a right lobectomy of the liver. In patients with diabetes mellitus and an expected remnant liver volume of less than 250 mL/m2, a major hepatectomy should be avoided. Careful patient selection based on volumetric analysis in major hepatectomy cases could help prevent the occurrence of postoperative liver failure.

Aged

[Factors linked to 5-year survival after hepatectomy for hepatocellular carcinoma: univariate and multivariate analyses of 312 patients].

The purpose of this study was to clarify the factors linked to 5-year survival after hepatectomy for hepatocellular carcinoma (HCC). Three hundreds and twelve patients who underwent hepatectomy for HCC between 1985 and 1994 were observed for at least 5 years. These patients were divided into 2 groups: 160 patients who died within 5 years after hepatectomy and 152 patients who did not die within 5 years. Statistical analysis by chi 2 test showed that the favorable factors linked to 5-year survival were (a) diabetes mellitus (-), (b) albumin > 3.7 g/dl, (c) hepaplastin test > 61%, (d) indocyanine green retention test at 15 minutes < 16%, (e) curative resection (+), (f) alpha-fetoprotein < or = 32 ng/ml, (g) portal vein invasion (-), (h) intrahepatic metastasis (-), and (i) stage I and II. Statistical analysis by stepwise regression test showed that the favorable factors linked to 5-year survival were (a) intrahepatic metastasis (-), (b) diabetes mellitus, (c) indocyanine green retention test at 15 minutes < 16%, (d) curative resection (+) and (e) alpha-fetoprotein < or = 32 ng/ml. When patients diagnosed with HCC, patients selection for hepatectomy should be done, based on the total estimation, such as tumor invasiveness, liver functions, and diabetes mellitus.

Analysis of Variance

Expression of matrix metalloproteinase-9 in surgically resected intrahepatic cholangiocarcinoma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) has recently been reported to be related to cancer cell invasion. This study was performed to clarify the expression of MMP-9 in surgically resected intrahepatic cholangiocarcinoma (IHCC). METHODS: In 37 patients with IHCC who underwent a surgical resection, the expression of MMP-9 and the clinicopathologic characteristics of MMP-9-positive IHCC were investigated. The expression of MMP-9 was immunohistochemically detected in 16 (43%) of 37 IHCC. The patients were divided into MMP-9 (-) IHCC (n = 21), MMP-9 (+) IHCC (n = 12), and MMP-9 (++) IHCC (n = 4). RESULTS: The survival rate after surgical resection in patients with MMP-9 (-), (+), and (++) IHCC, was 66%, 39%, and 0% at one year, 50%, 32% and 0% at 3 years, respectively (P = .001). The incidence rate of lymph node metastasis was 6 (28%) of 21 in MMP-9 (-) patients, 7 (58%) of 12 in MMP-9 (+) patients and 4 (100%) of 4 in MMP-9 (++) patients. The incidence rate of lymph node metastasis increased in proportion to an increase in the expression of MMP-9 in IHCC (P = .02). Recurrence in the lymph node was more common in patients with MMP-9 (+) and (++) cancers than in those with MMP-9 (-) cancers. CONCLUSIONS: The expression of MMP-9 in IHCC was a prognostic factor related to lymph node metastasis.

Adult

Clinicopathologic features of patients with hepatocellular carcinoma surviving >10 years after hepatic resection.

BACKGROUND: This study was performed to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients surviving >10 years after hepatic resection. METHODS: Between January 1971 and April 1987, 142 patients underwent hepatic resection. Thirty-nine patients who died of surgical morbidity (surgical mortality rate: 27.5%) were excluded from this study. Among the 103 patients who survived and were observed for >10 years after surgery, 12 patients (11.7%) survived >10 years after hepatectomy. The surviving patients were divided into 2 groups: 10-year survivors (n = 12) and nonsurvivors (n = 91). A comparative study between the two groups was made. RESULTS: Preoperative liver function tests such as the indocyanine green retention test at 15 minutes and albumin levels showed that 10-year survivors had better liver function than nonsurvivors. With regard to virus markers, 5 of 12 patients (41.7%) were positive for hepatitis B surface antigen (HBs-Ag) and the incidence of hepatitis B virus-related HCC was significantly higher than in nonsurvivors (P = 0.020). The results also showed that 4 of 12 long term survivors had hepatitis C virus (HCV) antibody and 1 patient did not have any HCV antibody or HBs-Ag. In two other patients, the HCV antibody was not measured and HBs-Ag was negative. Among four patients with the HCV antibody, the serum HCV RNA concentration, measured by branched DNA probe assay, was <0.5 in 3 patients and 1.72 in 1 patient. Therefore, the HCV RNA concentration tended to be lower in 10-year survivors. Tumor recurrence occurred in 8 of the 10-year survivors. Solitary recurrence was observed in five patients whereas multiple recurrence was observed in three patients. All five patients with solitary recurrence underwent a second resection. CONCLUSIONS: Based on the results of the current study, good liver function, HBs-Ag positivity, and a low concentration of serum HCV RNA in HCV-related HCC should be considered potentially good predictors of a long term survival.

Adult

Natural killer cell activity in patients with hepatocellular carcinoma: a new prognostic indicator after hepatectomy.

BACKGROUND: Natural cytotoxicity mediated by natural killer (NK) cells is believed to play an important role in host anticancer defense mechanisms. The aim of this study was to examine the prognostic significance of NK cell activity after hepatectomy in patients with hepatocellular carcinoma. METHODS: The NK cell activity in 210 patients with hepatocellular carcinoma was measured and evaluated in relation to clinicopathologic variables using univariate and multivariate analyses. RESULTS: The NK cell activity was decreased significantly in hepatocellular carcinoma patients compared with the control groups (P < 0.001). No correlation was observed between NK cell activity and the clinicopathologic variables. Multivariate analyses indicated that NK cell activity as well as intrahepatic metastases, platelet count, and serum albumin level were independent prognostic factors. CONCLUSIONS: This study suggests that the preoperative NK cell activity will help predict recurrence and prognosis after hepatectomy in patients with hepatocellular carcinoma.

Adult

Role of carboxyl residues surrounding heme of human cytochrome b5 in the electrostatic interaction with NADH-cytochrome b5 reductase.

To identify the cytochrome b5 residues responsible for the electrostatic interaction with NADH-cytochrome b5 reductase (b5R), we prepared and characterized the cytochrome b5 mutants in which Glu41, Glu42, Glu63, Asp70, and Glu73 were replaced by Ala, utilizing site-directed mutagenesis and the expression system for cytochrome b5 in Escherichia coli. Apparent Km values of the wild type b5R for Glu42Ala cytochrome b5 and Asp70Ala cytochrome b5 were approximately three-fold and six-fold higher than that for the wild type cytochrome b5, respectively, while the kcat values for those mutants were not remarkably affected. In contrast, Glu41Ala, Glu63Ala, and Glu73Ala cytochrome b5 showed almost the same kinetic properties as the wild type cytochrome b5. Furthermore, kinetic studies on combinations of the cytochrome b5 and b5R mutants suggested the interaction between Glu42 and Asp70 of cytochrome b5 and Lys125 and Lys41 of b5R, respectively, in the reaction.

Amino Acid Substitution

Electrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5 studied by site-directed mutagenesis.

Electrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5 was studied by site-directed mutagenesis. The target residues for mutagenesis were selected on the basis of the previously reported chemical cross-linking study of these two proteins, which implicated possible charge-pair interactions between Lys-41, Lys-125, Lys-162, and Lys-163 of the enzyme, and Glu-47, Glu-48, Glu-52, Glu-60, Asp-64 (group A), and heme propionate of cytochrome b5. Mutant reductases that lost one of the above-listed Lys residues showed higher K(m) values for cytochrome b5 and lower kcat values than those of the wild type, suggesting that all of the examined Lys residues participate in binding with cytochrome b5 as reported previously. In contrast, a removal of one of (or even all of) the group A residues from cytochrome b5 by mutagenesis caused no significant effect on the catalytic properties of cytochrome b5. Additional elimination of another set of negative residues (Glu-41, Glu-42, Asp-57, and Glu-63 (Group B)), which are also located close to heme, elevated the K(m) value by more than five folds. These results suggest that there should be other acidic residue(s) than group A in cytochrome b5 which participate in binding with NADH-cytochrome b5 reductase.

Binding Sites

A thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for patients with cirrhosis and hepatocellular carcinoma.

OBJECTIVE: To evaluate the results of a thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for hepatocellular carcinoma in patients with impaired liver function. DESIGN: Retrospective study. SETTING: A university hospital in Japan. PATIENTS: Twenty-seven patients who from 1991 to 1996 underwent a thoracoabdominal hepatectomy for hepatocellular carcinoma located mainly in the superior portion of the liver and 20 patients who underwent a transdiaphragmatic hepatectomy for hepatocellular carcinoma located near the diaphragm. MAIN OUTCOME MEASURES: Morbidity, survival, and disease-free survival after each operation. Comparisons were then made with 183 patients who had undergone an ordinary transabdominal hepatectomy during the same period. RESULTS: In the thoracoabdominal hepatectomy group, 17 patients underwent a partial resection, 4 patients underwent a subsegmentectomy, and another 6 patients underwent either a segmentectomy or a procedure that was greater in size than a segmentectomy, whereas all of the patients in the transdiaphragmatic group underwent a partial resection. The morbidities in the thoracoabdominal group included pleural effusion in 6 patients (22%); intra-abdominal infection in 5 patients (19%); and hepatic failure in 3 patients (11%), of whom 1 died (mortality rate, 4%). In the transdiaphragmatic group, only 2 patients (10%) had non-life-threatening complications. The cumulative survival rates and the disease-free survival rates of the patients at 3 years were 51% and 24% in the thoracoabdominal hepatectomy group and 62% and 30% in the transdiaphragmatic hepatectomy group; no significant differences were observed when these findings were compared with those of patients who had undergone a transabdominal hepatectomy. CONCLUSION: The outcomes of the patients undergoing thoracoabdominal hepatectomy and those undergoing a transdiaphragmatic hepatectomy were generally satisfactory in spite of the fact that these procedures were performed on patients with cirrhosis and impaired liver function.

Aged

Treatment strategy for patients with cystic lesions mimicking a liver tumor: a recent 10-year surgical experience in Japan.

OBJECTIVE: To clarify some of the difficulties in determining the appropriate surgical indications for cystic lesions mimicking a neoplasm in the liver. DESIGN: A retrospective review of hepatic resections for cystic lesions mimicking a neoplasm in the liver between August 1, 1986, and July 31, 1996. SETTING: A university hospital with a long history of hepatic resection for cystic lesions mimicking a neoplasm in the liver. PATIENTS: Ten patients with such cystic lesions in the liver, who underwent a hepatectomy during a recent 10-year period, were included in this study. MAIN OUTCOME MEASURES: Detailed clinicopathologic data were analyzed, and comparisons were made between the preoperative and postoperative diagnoses. RESULTS: The postoperative diagnoses consisted of cysts, including cysts complicated by an infection or hemorrhage in 7 patients, localized cystic dilation of the bile duct due to hepatolithiasis in 1, cystadenoma in 1, and mucin-producing cholangiocarcinoma in 1. In only one case was postoperative diagnosis identical to the preoperative diagnosis. In one case, an intraoperative pathological examination showed the tumor to be a mucin-producing cholangiocarcinoma instead of a cystadenocarcinoma. A tumor-marker analysis of the fluid in the cystic lesions also did not contribute to a definite diagnosis. Furthermore, cytological examination of the fluid could not completely exclude malignancy. Neither mortality nor morbidity occurred in any of the patients, and their mean length of hospitalization after hepatectomy was only 13.7 days. CONCLUSIONS: The accurate diagnosis of cystic lesions mimicking a tumor remains problematic; however, the results of hepatectomy for such cases are normally satisfactory. Such cystic lesions of the liver should be indicated for hepatectomy whenever the possibility of a cancerous neoplasm cannot be completely ruled out.

Adult

Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection.

We evaluated the effect of diabetes mellitus on the prognosis of hepatocellular carcinoma after an elective hepatic resection. Of the 342 patients who underwent a hepatic resection between April 1985 and March 1995, 87 (25.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (36.0% vs. 22.5%, P = .0239). The postoperative survival rate and the cancer-free survival rate were also better in patients without diabetes than in those with diabetes (P = .0333, P = .0149). The results of a multivariate analysis show diabetes mellitus to be an independent and prognostic indicator after a hepatic resection with hepatocellular carcinoma. According to the above findings, diabetes mellitus is thus considered to be a risk factor for prognosis after hepatic resection in patients with hepatocellular carcinoma.

Adult

Perioperative change in albumin messenger RNA levels in patients with hepatocellular carcinoma.

A quantitative assay of albumin messenger RNA (mRNA) in blood samples was designed using the competitive reverse-transcription polymerase chain reaction, and the significance of measuring albumin mRNA levels in the blood of patients with hepatocellular carcinoma (HCC) in hepatic resection was evaluated. Albumin mRNA levels were measured in the following: (1) peripheral blood in 11 patients with HCC and 20 control subjects without liver disease, (2) blood in the portal and hepatic veins in five patients with HCC immediately after laparotomy, and (3) a perioperative series of peripheral blood in eight patients with HCC. Two patients with HCC whose albumin mRNA level in peripheral blood was markedly high were both at stage IVa. On the other hand, 20 control subjects showed negative or <5 x 10(3) transcripts/microgram RNA of albumin mRNA expression. Immediately after laparotomy, the albumin mRNA levels in the tumor-draining hepatic vein were greater than in the portal and non-tumor-draining hepatic veins in four of five patients with HCC. Albumin mRNA levels in peripheral blood showed a marked increase after mobilization and/or resection of the liver and, thereafter, gradually decreased at postoperative day 7 in all eight patients with HCC. A new method to measure the albumin mRNA levels in blood samples was developed, and high albumin mRNA levels in the peripheral blood of patients with advanced-stage HCC suggest the presence of HCC cells in the circulation. Increased levels in the tumor-draining hepatic vein could indicate the spontaneous release of tumor cells or nontumorous hepatocytes or an increased albumin transcription in activated blood mononuclear cells. An increase in the levels in peripheral blood during an operation is intermittent. Therefore, an increased albumin mRNA level in the tumor-draining vein suggests, but does not prove, that the increased albumin mRNA level reflects tumor cells entering the systemic circulation. This alone does not prove that the prognosis is worsened.

Aged

Role of adhesion molecule expression and soluble fractions in hepatic resection.

BACKGROUND: Little has so far been documented about the relationship between liver injury and adhesion molecules. The aim of this study is to clarify the role of adhesion molecules in hepatic resection by studying both the expression of such adhesion molecules and the measurement of their soluble fractions in the blood. STUDY DESIGN: To study adhesion molecule expression in the liver, liver biopsies were obtained before and after hepatectomy in 14 patients. Using frozen sections, immunochemical staining for intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was then performed. To study the soluble fractions of adhesion molecules in the hepatic venous blood, the serum soluble fractions of ICAM-1 and VCAM-1 from another 17 patients were measured using an enzyme-linked immunosorbent assay. The plasma levels of polymorphonuclear leukocyte (PMN) elastase were also measured using an enzyme immunoassay. Both the preoperative and postoperative values of the serum soluble fractions of ICAM-1, VCAM-1, and PMN elastase were then compared. The correlation between their values and the perioperative variables was also investigated. RESULTS: Either ICAM-1 or VCAM-1 was stained on the sinusoidal endothelial cells and Kupffer cells or circulating PMNs in the sinusoid. The positive rate of either ICAM-1 or VCAM-1 staining in livers with more than 40 minutes of total ischemic time (80%) was significantly higher than that in livers with less than 40 minutes of total ischemic time (0%; p < 0.05). The incidence of postoperative complications in the ICAM-1 positive staining group tended to be higher than that in the ICAM-1 negative group. Both soluble fractions of ICAM-1 and VCAM-1 in patients with cirrhotic liver disease were also significantly higher than those in patients with a normal liver. The soluble VCAM-1 level in patients with a chronic active hepatitic liver tended to be higher than that in those with a nonactive hepatitic liver. The preoperative level of soluble ICAM-1 correlated with that ofVCAM- 1, PMN elastase, albumin, aspartate aminotransferease (AST), and the indocyanine green dye retention test at 15 minutes (ICG R15), while the preoperative level of VCAM-1 correlated with albumin, the hepaplastin test, AST, and ICG R15. Both the serum soluble ICAM-1 and VCAM-1 levels after hepatectomy were significantly lower than those before hepatectomy. By contrast, the posthepatectomy level of PMN elastase was significantly higher than its prehepatectomy level. The difference between the postoperative and preoperative values of soluble ICAM-1 correlated with the postoperative AST level, postoperative alanine aminotransferase level, and total ischemic time. CONCLUSIONS: Adhesion molecules were expressed in the liver after hepatic resection, and such expression correlated with a total ischemic time during hepatectomy. In addition, judging from the soluble forms of such molecules, these adhesion molecules play an important role in hepatic resection.

Aged

Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to clarify the risk factors for morbidity as well as to establish an optimum surgical strategy for hepatocellular carcinoma (HCC). METHODS: The risk factors linked to postoperative complications were analysed in 388 patients over a 10-year period, according to the kind of operative procedure. RESULTS: Stepwise regression analysis revealed that the most important factors related to postoperative morbidity were: age, creatinine level and the histological grade of fibrosis for the bisegmentectomy; the presence of diabetes mellitus, blood urea nitrogen level, the indocyanine green dye retention rate at 15 min and blood loss for the segmentectomy; the presence of diabetes mellitus and blood loss for subsegmentectomy; the presence of diabetes mellitus, the aspartate aminotransferase level, and the total operating time for resection less than subsegmentectomy. CONCLUSION: The most important risk factors were not always related to liver function tests, but instead to other coexisting conditions such as diabetes mellitus and operation stress including operating time and blood loss. Therefore, any future treatment strategy of hepatic resection for HCC should make every effort both to evaluate coexisting conditions carefully and to reduce operative stress as far as possible.

Age Factors

Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma.

OBJECTIVE: The aims of this study were to identify prognostic factors in patients who developed recurrent hepatocellular carcinoma (HCC) after repeat hepatectomy and to elucidate the role of multicentric occurrence in the second tumor after a first hepatectomy. SUMMARY BACKGROUND DATA: A repeat hepatectomy for recurrent HCC has been established as the most effective treatment modality, whenever it is possible. However, the prognostic factors for recurrent HCC after repeat hepatectomy have yet to be clarified. METHODS: Forty-one patients who underwent a curative repeat hepatectomy were retrospectively studied. Patient survival and disease-free survival after recurrence were univariately and multivariately analyzed using 38 clinicopathologic variables. The histologic grade of HCC at repeat hepatectomy was also compared with that at first hepatectomy. RESULTS: Patient survival after repeat hepatectomy did not differ substantially from that in 312 patients undergoing primary hepatectomy. However, the disease-free survival after repeat hepatectomy was significantly lower than that in patients with only a primary hepatectomy (p < 0.05). Multivariate analysis revealed only portal vein invasion in the first hepatectomy to be an independent and significantly poor prognostic factor. Regarding multicentric occurrence at repeat hepatectomy, only 6 of 40 patients (15%) whose specimens could be evaluated histologically were determined to be Edmondson and Steiner's Grade 1. CONCLUSIONS: The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.

Algorithms

Nm23-H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma.

AIMS/BACKGROUND: Decreased expression of nm23, a putative metastasis suppressor gene, has been reported to be related to either intrahepatic metastasis or a poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the true role of nm23-H1 expression in both intrahepatic and distant metastases of HCC. METHODS: Thirteen patients with single-nodule HCC, seven patients with HCC having satellite nodules and seven patients with HCCs having extrahepatic metastases were included in this study. The expression of nm23-H1 protein was immunohistochemically examined in both primary and metastatic nodules. RESULTS: Ten of 13 single-nodule HCCs were found to overexpress nm23-H1 protein. All main tumors, having satellite nodules, were found to overexpress nm23-H protein, except for two HCCs, which only partially expressed nm23-H1 protein. Regarding the nm23-H1 expression in intrahepatic metastases, most nodules overexpressed the protein. The expression of nm23-H1 was found to be low in only one intrahepatic metastasis specimen, while its primary tumor was also found to show a low expression of nm23-H1 protein. Microscopic portal vein invasion was found in three of the five patients studied, and all cancer cells in portal invasion overexpressed nm23-H1 protein. Nm23-H1 protein was expressed in all distant metastatic tumors and the staining intensity of most metastatic nodules was similar to that of the primary tumors. CONCLUSIONS: Our study demonstrated that nm23-H1 expression did not always decrease but instead tended to increase at both intrahepatic and extrahepatic metastatic sites. Based on these findings, nm23-H1 expression is not considered to be a reliable indicator of either intrahepatic or distant metastasis in HCC.

Adrenal Gland Neoplasms

Adenosquamous carcinoma of the liver: clinicopathologic characteristics and cytokeratin profile.

BACKGROUND: The clinicopathologic characteristics, biologic behavior, and histogenesis of primary adenosquamous carcinoma (ASC) of the liver have yet to be fully clarified. METHODS: Eight cases of ASC of the liver were analyzed both clinicopathologically and immunohistochemically using antibodies of cytokeratin (CK) 7, CK 8, CK 18, CK 19, and CK 903 (CK 5, CK 10, CK 11, and CK 14). The survival curve of the 6 patients with surgically resected ASC was compared with that of the 32 patients with common cholangiocarcinoma (CC). RESULTS: Most ASCs had invasive pathologic features, including venous invasion, lymphatic permeation, and intrahepatic metastases. There were lymph node metastases from 7 tumors (88%), and most of the metastases were adenocarcinoma. All adenocarcinoma (AC) components were positive for both CK 7 and CK 19. The squamous cell carcinoma (SCC) components were positive for CK 7 in all cases but were positive for CK 19 in only 5 cases (62.5%). The ACs were positive for CK 903 in only 3 cases (37.5%), whereas all SCCs were positive for CK 903. Almost all ACs were positive for both CK 8 and CK 18, whereas the SCCs were positive for CK 8 in only 3 cases (37.5%) and for CK 18 in no cases. All 6 patients with surgically resected ASC died of the disease within 1 year postoperatively. Their survival curve was significantly worse than that of the 32 patients with common CC (P < 0.001). The two patients on whom autopsy was performed also died within 1 year after diagnosis. CONCLUSIONS: ASC tended to have more aggressive biologic behavior and a poorer prognosis than common CC. The authors' immunohistochemical analysis of CK expression indicated that most of the ASCs of the liver that were studied developed from a squamous transformation of the preexisting CC.

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