Kazutaka Furukawa

Prognostic factors after hepatectomy for hepatocellular carcinomas. A univariate and multivariate analysis

The current study determines the prognostic factors after hepatectomy for hepatocellular carcinomas. The 295 patients who underwent hepatectomy from 1973 through 1987 were included for a univariate and a Cox multivariate analysis. The favoring conditions were determined as follows. The essential requirements are (1) the absence of tumor thrombi; (2) no intrahepatic metastasis, but even when present, it should be close to the main tumor and removed with a massive resection; and (3) retention rate of indocyanine green dye (ICG) at 15 minutes should be within 14 ± 4.2% (M ± SD) to allow that resection. The desired requirement is that the tumor size should preferably be less than 5 cm; a wider free margin from tumors (⩾ 1 cm) is recommended, but not determining factor. The eligible patients, having no thrombi, no intrahepatic metastasis, a tumor size of 5 cm or less, negative surgical margin (⩾ 1 cm), had achieved a 5‐year survival of 78%. In conclusion, resection therapy is the first option for patients with those requirements.

A prediction scoring system to select the surgical treatment of liver cancer. Further refinement based on 10 years of use.

ObjectiveThis study reports further refinement of a prediction scoring system, which was established in 1980 as a guide to determine a safe limit for hepatectomy, based on 10 years of use. Summary Background DataIn the past, whether major resection was safe was judged empiricially from the net resection volume or the residual hepatic volume combined with the patients liver function. However, such judgment was not based on objectively defined criteria. MethodsPatients with hepatocellular carcinoma (HCC; n=376) and metastatic cancer (n=58) who had hepatectomy at some time from 1981 through 1990 were entered into this study. A prediction score (PS) was computed using a multiple regression equation that consists of computed tomographic scan-estimated resection rate, indocyanine green retention rate, and the patients age. A PS greater than 55 was classified as a risky zone, a PS of 45 to 55 was considered borderline, and a PS less than 45 was a safe zone. ResultsWith HCC and chronic liver disease, all patients in the risky zone died, whereas 33% in the borderline zone died and 7.3% died who were in the safe zone. With metastatic cancer with normal liver, all patients in the risky zone died, whereas no patient in either the borderline or safe zones died. The major cause of death in the risky zone was liver failure due to excessive resection. In the borderline and safe zones, liver failure developed primarily after abdominal sepsis or pulmonary infection, particularly for those with adverse prognostic factors such as disturbed glucose tolerance, lower platelet count, and higher indocyanine green retention rate. ConclusionPrediction scores can eliminate deaths related to excessive resection for patients with normal or injured livers. When patients have adverse prognostic factors, careful surgery and postoperative

Microwave Coagulonecrotic Therapy for Hepatocellular Carcinoma

Abstract. The present study reports on the usefulness of microwave coagulonecrotic therapy (MCT) as a treatment option for hepatocellular carcinoma (HCC) with poor hepatic reserve. From June 1992 to March 1995, MCT using a microwave electrode was employed on 8 patients using laparoscopic control and 19 with the open method, and wedge resection (Hx) was applied to the 23 patients. All patients had HCC with poor hepatic reserve. Radiation output was 100 watts with a mean radiation duration of about 30 minutes. The severity of liver dysfunction and the regional characteristics of the tumor (tumor size, multiplicity, portal invasion, tumor depth) were comparable between the MCT and Hx groups. The operative time was significantly shorter for the MCT group than the Hx group. The mean blood loss was 1570 ml in the Hx group but negligible in the MCT group. There was no operative mortality in the MCT group in contrast to 4.3% (1 of 23) in the Hx group. Complications were observed in 11.1% (3 of 27) and 34.8% (8 of 23), respectively, for the MCT and Hx groups. The postoperative total bilirubin had lower values and the start of diet was earlier in the MCT group than the Hx group. The 3-year crude and disease-free survival rates were 86% and 44%, respectively, for patients who underwent MCT, which were comparable to 75% and 14% for those with Hx. MCT can achieve long-term results equivalent to those obtained by wedge resections, but it is less invasive and technically easier. Therefore it can be an alternative option in place of limited resection for HCC with poor hepatic reserve.

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.

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.

Determinants of long-term survival following hepatectomy for hepatocellular carcinoma, with special reference to patients surviving more than 10 years

To elucidate the determinants of survival and the clinicopathologic features of long-term survivors of resections for HCC, we reviewed 539 patients who had had hepatectomy alone or hepatectomy together with hepatic arterial ligation or ethanol injection for the treatment of hepatocellular carcinoma (HCC) at our department between 1973 and December 1992. Of these patients, 30% (79/264) survived for more than 5 years and 11% (10/87) for more than 10 years. All the long-term survivors had received curative resections. The 5- and 10-year survivors accounted for 58% (79/136) and 29% (10/35) of those with curative resections, respectively. Crucial determinants for long-term survival were the absence of portal invasion and satellite nodules, a diploid pattern of DNA content, and a curative resection. A curative resection for diploid HCCs led to much better survival rates (73%) at 5 years than such a resection for aneuploid HCCs (35%), and than for non-curative resections for aneuploid HCCs (0%). The history and tumor background of the ten patients who survived for more than 10 years were characterized by good reserve liver function, warranting a wider resection, predominance of female sex, single nodular growth, and the absence of poorly differentiated cells, in addition to the favorable conditions described above. Three of the ten patients developed a new lesion; these were successfully treated by re-resection or repeated arterial embolization, since they were confined to the remnant liver and showed single nodular growth without extranodular spread. This analysis indicates that hepatectomy is the option of first choice for HCC patients with the potential for cure and good reserve liver function.

In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury

Background: No data are available concerning the in vivo subcellular dynamics of elements in liver grafts and the effect of endothelin receptor antagonist, TAK-044, against graft injury. Methods: Liver transplantation was performed in porcine under active veno-venous bypass. The grafts stored in chilled preservation solution were recirculated following reflush with lactated Ringers solution with or without TAK-044 (10 mg/kg). Cold and warm ischemic times of the grafts were comparable between the two groups. Elements (Na, K, Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitochondria and nucleus by electron probe X-ray microanalysis for the graft biopsy specimens obtained at various time from donor laparotomy to 1 week after liver grafting. Liver functions also were compared between the two groups. Results: In both groups, concentration of each element changed in parallel among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in cytoplasmic Na and Cl after portal reperfusion and in cytoplasmic and mitochondrial Ca after hepatic artery reperfusion. These were accompanied by K and mitochondrial S decreases without a statistical significance. In the TAK group, such postreperfusion elemental alterations were significantly suppressed and early deterioration of the liver functions was alleviated, as compared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular elements after reperfusion and better preservation of early graft function.

Dynamics of serum and tissue alkaline phosphatase activity after hepatectomy in normal and cirrhotic rat liver

Abstract To investigate the pathogenesis of bile stasis after partial hepatectomy in the cirrhotic liver, the activity of alkaline phosphatase in serum and liver tissue, as well as morphologic changes in the bile canaliculi, were compared between cirrhotic and normal rats. In the normal rats, and cirrhotic rats produced by intraperitoneal thioacetamide injection, blood and liver specimens were obtained before and 2, 7, and 14 days after 70% partial hepatectomy. Serum and liver tissue alkaline phosphatase (ALPase) activity, liver weight, and electron histochemical changes in the bile canaliculi and microvilli were assessed. The normal rats showed rapid regeneration and marked elevation in the serum hepatic and tissue ALPase with a peak on day 2. This was associated with the maximal bile canalicular dilation and increased pericanalicular lipid vesicles, but without the microvilli destruction. These changes were normalized by 14 days after hepatectomy. In contrast, in the cirrhotic rats, regeneration and elevation in the serum and tissue ALPase were delayed, and higher total bile acidemia persisted. The bile canaliculi with ectasia before hepatectomy underwent no further dilation, and was associated with marked destruction of the microvilli and weakened ALPase in the bile canalicular membrane. The pericanalicular lipid vesicles was sparse. Persistent cholestasis in the remnant cirrhotic liver after hepatectomy is closely linked to the morphologic derangement and ALPase activity in the intra- and peri-bile canalicular area, and serum ALPase is useful as an index monitoring bile secretory capacity of the remnant liver.

Indication Criteria of Hepatectomy for Hepatocellular Carcinoma Based on Long-Term Result

The current study reports what patients with hepatocellular carcinoma can get a potential cure and good quality of life from hepatectomy based on the long-term results. 504 hepatectomized patients from 1973 through 1992 were used. The survival rate of curative resections was 24% at 10 years in contrast to 0% at 7 years. Crucial factors determining curability and prognosis were degree of portal invasion (Vp) and intrahepatic metastasis (IM), and nuclear DNA content (diploidy vs. aneuploidy). No Vp and IM were found in 72% of 66 patients who survived more than 5 years, and diploidy HCCs accounted for 89% of them. Single nodular type of HCC less than 5 cm in size and well reserved liver functions allowing a wide resection, in whom are definite indication of hepatectomy.

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.