Shinichi Mikami

Additional Hepatocellular Carcinomas Undetectable before Surgery

The presence of small additional hepatocellular carcinomas (HCCs) undetectable before hepatic resection is a crucial topic for hepatic surgeons. We assessed the incidence of pathologically diagnosed multiple HCCs in 267 patients who underwent hepatic resection for HCC. Ninety-five additional HCC nodules were detected in 72 of the patients (27%). The survival rate of these 72 patients was significant worse than for the 195 with single nodular HCC (p= 0.0013). Twenty-one (22%) were detected before surgery, 29 (31%) during surgery, and 45 (47%) on pathologic examination after surgery. The mean nodule diameters for each group were 2.1, 1.0, and 0.9 cm, respectively (p < 0.0001). None of the 21 nodules detected before surgery was well differentiated, whereas 30 of the 74 nodules in the other two groups were well-differentiated. Although the mean nodule diameter of the well-differentiated HCC group was the smallest, there was no significant difference among the three groups assigned according to tumor differentiation (p= 0.2355). Altogether, 9 of 16 patients with additional nodules detected before surgery (56%) and 49 of 59 with additional nodules detected during or after surgery (88%) had cirrhosis of the liver. The odds ratio for detecting a new HCC nodule during or after surgery in the presence of cirrhosis was 5.444 (p= 0.0087). Improvement in the detection of small additional HCC nodules before and during surgery and meticulous follow-up after surgery are necessary for patients with cirrhosis. For patients without cirrhosis, surgical treatment may be performed according to the results of preoperative imaging studies.

Immunohistologic Attempt to Find Carcinogenesis from Hepatic Progenitor Cell in Hepatocellular Carcinoma

Aim: To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens. Methods: Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene. Results: CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation. Conclusion: These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis.

Immunohistochemistry and angiography in adenomatous hyperplasia and small hepatocellular carcinomas

The sinusoidal structure and blood supply of 38 liver nodules less than 2 cm In diameter were Investigated. There were 18 cases of adenomatous hyperplasia (AH) and 20 cases of hepatocetlular carcinoma (HCC). Growth pattern, encapsulation and vascularity were examined, and Immunohistochemistry performed for factor VIII related antigen (factor VIII), type IV collagen (collagen IV), lamlnln and CD68. There were significant differences between AH and small HCC, except for the expression of CD68. There were differences In tumor size, vasculartty and the components of the basement membrane between AH and small, well differentiated HCC. The cases of AH were supplied by the portal system and maintained the sinusoidal structure, but small well‐differentiated HCC were supplied by a mixture of portal and arterial vessels. In spite of their small size, moderately and poorly differentiated HCC had capillary and were supplied by branches of the hepatic artery.

Relationship of the Microvascular Type to the Tumor Size, Arterialization and Dedifferentiation of Human Hepatocellular Carcinoma

Unlike normal liver with the sinusoids, hepatocellular carcinomas (HCCs) possess capillaries. Whether these capillaries derive from the sinusoids remains unclear in human HCCs. This study aimed to examine sinusoidal capillarization in human HCCs and its relationship to the tumor size, arterialization and dedifferentiation. Thirty‐eight HCCs with a diameter of 10–140 mm were pathologically and angiographically examined. By electron microscopy, the microvasculature of tumors was classified into sinusoidal, intermediate and capillary types, which were all negative, partially positive and all positive, respectively, for four parameters, i.e., endothelial defenestration, continuous basement membrane, lack of Kupffer cells, and lack of lipid‐containing hepatic stellate cells. Well‐, moderately and poorly differentiated HCCs displayed sinusoidal/intermediate/capillary types, intermediate/capillary types and only capillary type, respectively, suggesting the transition from the sinusoids to capillaries in well‐differentiated (and probably moderately differentiated) HCCs. Furthermore, well‐differentiated HCCs with a diameter of less than 30 mm often received preferential portal venous blood, while moderately and poorly differentiated ones were all supplied with arterial blood, indicating a relationship between dedifferentiation and arterialization. In contrast, the microvascular type displayed no significant relationship with tumor size or arterialization in well‐differentiated HCCs. The present study has demonstrated that sinusoidal capillarization occurs in human well‐differentiated HCCs and seems to be related to dedifferentiation of parenchymal tumor cells, but not to tumor size or arterialization.

Computed Tomography during Arteriography and Arterial Portography in Small Hepatocellular Carcinoma and Dysplastic Nodule: A Prospective Study

We studied the relationship between the findings of computed tomography during arteriography (CTA) and computed tomography during arterial portography (CTAP), and pathologic findings of 81 small nodular lesions (3 cm or less in diameter) in resected liver specimens. The 81 lesions consisted of 8 dysplastic nodule (DN) lesions, 23 well‐differentiated hepatocellular carcinomas (early HCCs) and 50 moderately or poorly differentiated HCCs (advanced HCCs). We also performed standard computed tomography (CT), digital subtraction angiography (DSA), magnetic resonance imaging (MRI), and ultrasonography, and compared sensitivities with CTA, CTAP, or combination of CTA and CTAP with other imaging methods. Forty‐four of the 50 advanced HCCs, 12 of the 23 early HCCs, and none of 8 DNs hyperattenuated with CTA and hypoattenuated with CTAP. The sensitivity for the early HCCs was significantly higher for CTA and CTAP in combination as compared with DSA or standard CT. The sensitivity for the advanced HCCs was significantly higher for CTA and CTAP in combination than with DSA. The sequential changes of the blood supply from the portal vein to the hepatic artery during the development of the HCCs were observed. Although CTA and CTAP in combination were useful for the distinction of advanced HCC from early HCC or DN, CTA and CTAP used in combination were not superior to CTA alone in the detection of such lesions.

Efficacy of preoperative portal vein embolization prior to major hepatectomy for patients with impaired liver function: A retrospective study

Hepatocellular carcinoma (HCC) is often associated with chronic liver disease, such as hepatitis or cirrhosis, and this association may limit the use of surgery as a therapy, and if surgery is pursued, may give rise to postoperative hepatic failure. We evaluated the outcome in patients with HCC given preoperative portal vein embolization (PVE) before they underwent major hepatectomy. After PVE, portal pressure increased significantly. Two weeks after PVE, both the volume of the non-embolized lobe and the 15-min indocyamine green retention rate (ICG R15) were significantly increased. The prognostic score, calculated on the basis of age, ICG R15, and the resection rate, was significantly decreased. The operative mortality rate was significantly lower in patients who underwent PVE before surgery than in patients who did not receive PVE. The cumulative survival rate of the PVE patients, even those with cirrhosis of the liver, was significantly higher. Prior PVE appears to allow more extensive major hepatectomy and to lessen the risk of this invasive surgery. However, patients in whom the portal pressure immediately after PVE was more than 30cm H2O and/or whose prognostic score exceeded 50 points developed postoperative hepatic failure. These features should be kept in mind when it is decided whether surgery is indicated. Nevertheless, preoperative PVE appears to be a beneficial procedure for patients undergoing major hepatectomy, particularly those with chronic liver disease.

Course before and after percutaneous transhepatic portal vein embolization of a patient with cholangiocarcinoma monitored by scintigraphy with Tc-99m galactosyl human serum albumin

Percutaneous transhepatic portal vein embolization (PTPE) causes atrophy of the embolized lobe and compensatory hypertrophy of the nonembolized lobe, and improves the safety of hepatectomy. We report a patient with cholangiocarcinoma who underwent embolization of both anterior and posterior branches of the right portal vein before hepatectomy. Scintigraphy with Tc-99m galactosyl human serum albumin was performed before and 4 weeks after PTPE. After PTPE, the right lobe of the liver was atrophied and the left lobe of the liver was enlarged, compared with before PTPE. The receptor index of the entire liver was almost unchanged before and after PTPE, but the right lobe receptor index after PTPE was 23% less than the pre-PTPE value, whereas the left lobe receptor index had increased 37%. Scintigraphy with Tc-99m galactosyl human serum albumin is useful for evaluating segmental functional reserve before and after PTPE.

Follow-up for hepatic nodules detected only by angio-CT in noncancerous regions of the liver with hepatocellular carcinoma.

1997年3月末までにCT during arterioportographyとCT during arteriography (CTA) を併用した血管造影下CT (angio-CT) を施行後に開腹した肝細胞癌 (肝癌) 103例中, angio-CT単独陽性結節は9例 (10結節, 9%) にみられた. 男女比は8: 1, 平均年齢は63歳. 8例にHCV抗体, 1例にHBs抗原を認めた. 臨床病期I期6例, II期3例で, 5例には肝硬変を認めた. 単独陽性結節径は平均1cm. 全例主病巣は別に存在し, CTAでhigh density areaを呈しangio-CT以外の画像診断法で描出されなかった. 術後平均観察期間は608日で, 5例に残肝再発がみられたが, angio-CT単独陽性結節からの残肝再発は肝深部に存在していた2結節 (20%) にみられた.angio-CT単独陽性結節のうち少なくとも20%は真の肝癌結節であるが, 肝辺縁部の結節は偽陽性結節の可能性が高い.

Selection of Scale of Hepatic Resection for Small Hepatocellular Carcinoma Evaluated on the Basis of Recurrences Examined Retrospectively.

1993年末までの主腫瘍径2cm以下の小肝細胞癌 (肝癌) 切除82例を対象に, 術式と肝機能評価法, 予後との関係を検討した. 施行術式はHr2: 8例, Hr1: 11例, HrS: 20例, Hr0: 43例であり, 広範囲切除例の肝機能は良好であったが, 術式決定には術中の肝肉眼所見が最も重視されていた. 82例中39例が残肝再発したが, Hr2の予後は他の肝切除術式より良好であった. そこでHr2可能条件をICGR1515%以下, CS1, Z1以下と仮定すると, Hr2未満切除74例中12例がHr2可能例であったが, 再発は2例にすぎなかった. 逆にHr2未満施行で再発をきたした37例のうちHr2を行えば切除領域に再発病巣が含まれた症例は7例であったが, Hr2可能例は1例に過ぎなかった. 小肝癌に対する切除術式は再発からみると, 術前の肝機能成績および術中所見を考慮した現行の基準が適切であると考えられた.