Nobutaka Ichikawa

Progression of hepatocellular carcinoma as reflected by nuclear DNA ploidy and cellular differentiation

BACKGROUND/AIMS Intratumor heterogeneity of DNA ploidy within a single hepatocellular carcinoma is not well understood. The present study was designed to examine the histologic distribution of intratumor DNA ploidy in hepatocellular carcinomas of different growth types in relation to cell differentiation. METHODS Twenty patients (16 men and four women; mean age, 60.2 years) with hepatocellular carcinoma (mean diameter, 4.3 cm) were studied. One hundred and twenty-seven samples from different sites of each tumor were analyzed by determination of the nuclear DNA content and histological examination. RESULTS The DNA ploidy was heterogeneous in nine (45%) of the 20 tumors. Five tumors had a mixture of diploid and aneuploid regions, and the remaining four consisted of aneuploid regions with different DNA indices. There was no significant difference in patient characteristics between the heterogeneous and homogeneous groups. A significant correlation was found between tumor growth type and the incidence of heterogeneity. Only 16% of single nodular carcinomas without intratumor septal formation exhibited heterogeneity, while single nodular tumors with septal formation or confluent multinodular tumors were associated with high incidences of different DNA ploidy patterns or DNA indices. There was no aneuploidy in well-differentiated foci, while aneuploidy was frequently found in moderately or poorly differentiated foci (incidences of 67% and 74%, respectively). CONCLUSIONS Heterogeneity of DNA ploidy may develop along with changes in growth pattern and cell dedifferentiation or by confluence of nodules originating from different tumor cell clones.

Contribution of the portal flow on hepatic tissue perfusion increases in reduced hepatic vascular bed

Background: A hepatic artery-portal vein reciprocal response and hepatic hemodynamics have well been investigated under normal condition, but not under pathologic condition with decreased vascular bed. This study was designed to determine the hemodynamic changes in the hepatic blood flow, tissue perfusion and interrelationship between portal venous flow (PVF) and hepatic arterial flow (HAF) after inflow interruption in the various size of hepatic vascular bed. Methods: Anesthetized dogs were used to measure PVF and HAF using a transit time flow meter and hepatic tissue flow (HTF) using a laser Doppler flow meter before and after portal venous (PVO) or hepatic arterial occlusion (HAO) under various range of portal triad occlusion (PTO). Results: The ratio of HAF/TLF (total liver flow) was 38+/-14% under the basal condition. This ratio did not change under the 30% PTO where there was a similar decrease in PVF and HAF, but reduced to 25+/-12% under the 70% PTO where there was more selective reduction in HAF than PVF. Although a reciprocal HAF increase was observed under any conditions after PVO, the TLF and HTF decreases after PVO were largest under the 70% PTO with the highest PVF/TLF ratio. On the other hand, there was no reciprocal PVF increase in any conditions after HAO, and the TLF and HTF decreases after HAO were minimal under the 70% PTO with the lowest HAF/TLF ratio. Conclusions: With decreasing hepatic vascular bed, dependency of the remnant hepatic hemodynamics and tissue perfusion on the portal blood flow increased. These findings suggest that an integrity of portal venous flow becomes crucial in the remnant hepatic tissue perfusion after extensive hepatic resection.

Cellular DNA content and histopathological analysis in hepatocellular carcinoma with multiple nodules

Multiple tumors within the liver are a characteristic feature of hepatocellular carcinoma (HCC). This study investigated alterations in the histologic type and DNA content of multiple nodules of HCC. Both a pathologic examination and flow cytometric DNA analysis were performed on 49 resected specimens of multinodular HCC. The results showed that 35 cases had multiple metastatic satellite nodules around the main tumor (group 1), while 14 had two solitary nodules in different segments without satellite nodules (group 2). In group 1, 28 out of 35 (80.0%) showed a single DNA index while 7 (20.0%) revealed two different DNA contents in the main tumor. The histological type, cytological grade, and DNA index were equivalent between the main and satellite tumors in 100%, 88.6%, and 97.1% of the cases, respectively. In group 2, all tumors showed a single histological type, cytological grade, and DNA index in each nodule. The histological type was identical in 85.7% of the pairs of nodules, but the cytological grade and DNA index were different in 42.9% and 85.7%, respectively. The patients in group 2 showed a significantly higher 5-year survival rate than that in group I (64.8%vs 27.2%,P<0.05). This study thus indicates that the cytological grade and DNA content are useful in distinguishing multicentric occurrence from intrahepatic metastasis in HCC.

A report of resected mesenchymal hamartoma of the liver in adult.

我々は,検診にてCA19-9の軽度上昇を指摘され,超音波にて偶然発見された成人の肝間葉性過誤腫を経験したので報告する.症例は47歳の女性である.超音波やCTにて肝のS6より肝外性に発育する大きさ7cmの腫瘍を認め,腫瘍は充実性の部分と嚢胞性の部分にて構成されていた.血管造影では腫瘍全体に濃染像が見られた,良性腫瘍を最も疑ったが,悪性腫瘍も否定できず手術を施行した.切除標本では大きさ7.5cm×7.5cmの境界明瞭で光沢のある充実性腫瘍で,内部に大小の嚢胞を認めた.組織像では主に豊富な線維結合織よりなり,その間に大小の血管あるいはリンパ管や,小胆管の増生を認めた.現在,術後3年であるが,再発兆候はない.肝間葉性過誤腫の本邦報告例は64例であり,このうち15歳以下の小児例が52例と大部分を占め,成人例はわずか12例に過ぎない.小児例では腫瘍の発育速度は早く,成人例では発育速度は緩慢であるも悪性腫瘍との鑑別も困難で,共に切除が第一選択の治療である.悪性化や転移例はなく予後良好であるが,3例の再発例があり注意を要する.

Laparoscopic Resection of an Epithelial Cyst in an Intrapancreatic Accessory Spleen

An epithelial cyst in an intrapancreatic accessory spleen (ECIAS) is rare. We herein report a case of a patient with ECIAS who underwent laparoscopic surgery. A 57-year-old woman was referred to our hospital because of a pancreatic tail tumor. She was asymptomatic, and a physical examination revealed no remarkable abnormalities. The levels of the tumor marker carbohydrate antigen 19-9 (CA19-9) and s-pancreas-1 antigen (SPan-1) were elevated. Ultrasonography showed a well-defined homogeneous cystic tumor. Computed tomography showed a well-demarcated cystic tumor in the pancreatic tail. Magnetic resonance imaging showed that the cystic tumor exhibited low intensity on T1-weighted images and high intensity on T2-weighted images. The cystic tumor was diagnosed as mucinous cystic neoplasm preoperatively. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. A histopathological examination revealed the cyst wall to be lined by stratified squamous epithelium within splenic parenchyma, and the ultimate diagnosis was ECIAS. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. ECIAS is very difficult to diagnose preoperatively. Laparoscopic surgery is a safe and minimally invasive procedure for patients with difficult-to-diagnose pancreatic tail tumor suspected of having low-grade malignancy.

Intratumor Pressure in Hepatocellular Carcinoma

Intratumor pressure and hepatic tissue pressure were measured intraoperatively in 50 patients with hepatocellular carcinoma. Changes in these pressure were monitored before and after individual occlusion of the proper hepatic artery and the portal vein. Our result indicated that intratumor pressure was regulated predominantly by hepatic arterial blood flow, and increased with tumor capsular formation. In contrast, hepatic tissue pressure was regulated predominantly by portal blood flow, and increased with portal vein pressure.