Junichi Uchino

Predictive factors for long term prognosis after partial hepatectomy for patients with hepatocellular carcinoma in Japan. The liver cancer study group of japan

Background. Great progress in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) has led to an increased number of resectable cases. Much attention has been paid to the factors affecting long term survival of patients with HCC after partial hepatectomy.

Efficacy and safety of preoperative percutaneous transhepatic portal embolization with absolute ethanol: A clinical study

BACKGROUND Preoperative portal embolization has been performed by using various thrombogenic substances to increase the safety and resectability of liver surgery. We evaluated the clinical safety and efficacy of using absolute ethanol in preoperative portal embolization. METHODS Our study included 19 patients who had undergone right hepatic lobectomy. According to our criteria for right lobectomy of the liver, seven patients were not appropriate for the operation because of a high risk in each of postoperative liver failure. Those patients received preoperative right portal embolization with 11 to 32 ml absolute ethanol. The remaining 12 patients satisfied our criteria and received no preoperative embolization. RESULTS Although alanine aminotransferase concentrations increased dramatically after the embolization, all serologic changes reverted within 3 weeks. The mean volume of the nonembolized lobe increased from 320 cm3 to 619 cm3 and 667 cm3 2 and 4 weeks, respectively, after embolization. The mean regeneration rate of this lobe was 21.3 cm3 per day for the first 2 weeks and 11.4 cm3 per day for the first 4 weeks after embolization. All patients underwent right lobectomy of the liver and survived; none of the patients had severe complications associated with embolization or surgery. The postoperative survival periods were not statistically significant between the patients with and without preoperative portal embolization. CONCLUSIONS According to our criteria for liver surgery, the seven patients should not have undergone major surgery, but each underwent right lobectomy of the liver and all survived, showing that portal embolization with absolute ethanol brings about compensatory hepatic hypertrophy for major surgery and that its extreme effect on liver regeneration could widen the range of patients appropriate for liver surgery.

Detection of tyrosine hydroxylase mRNA and minimal neuroblastoma cells by the reverse transcription-polymerase chain reaction

To facilitate the diagnosis of bone marrow metastasis in neuroblastoma, we have developed a method of amplifying and detecting the tyrosine hydroxylase (TH) mRNA sequence in bone marrow cells using a combination of reverse transcription and the polymerase chain reaction (RT/PCR). By this method, the sequence of TH was detected clearly in the neuroblastoma tissues of all 6 patients and not detected in the bone marrow cells of any of the 9 negative control children. In a reconstitution experiment, 1 neuroblastoma cell per 100,000 normal bone marrow cells could be detected, thus indicating the great sensitivity of this method. Based on these results, this technique may be of value in the diagnosis and treatment follow-up of bone marrow metastasis of neuroblastoma.

Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy. A report from the study group of Japan

One hundred nine newly treated patients with advanced neuroblastoma were entered in this study between January 1985 and May 1989. The eligible patients included infants younger than 12 months of age with Stage IVA disease (bone cortex, distant lymph node, and/or remote organ metastases) and patients aged 12 months or older with Stage III or IV disease (IVA plus IVB with tumor crossing the mid‐line and with metastases confined to bone marrow, liver, and skin). The patients first received six cyclic course of intensive chemotherapy (regimen A1), consisting of cyclophosphamide (1200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (pyrarubicin; 40 mg/m2), and cisplatin (90 mg/m2). Original tumors and the regional lymph node metastases were removed some time during these first six cycles of chemotherapy. The patients were further divided into three groups. Patients in course 1 received alternating treatment by regimen B (cyclophosphamide and ACNU) and intensified regimen A1, and those in course 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in course 3 were treated with bone marrow transplantation (BMT) preceded by high‐dose preconditioning chemotherapy. Survival rates were 77% in Stage III and 54% in Stage IV at 2 years, and 70% in Stage III and 45% in Stage IV at 3 years. The major toxicities encountered were bone marrow suppression with leukocyte counts down to 100/mm3, mild cystitis, and hearing impairment. The 2‐year survival rate was 78% in 21 patients who underwent BMT when complete remission was achieved. We concluded that our intensive induction chemotherapy is of significant value in increasing the rate of complete response, and in widening the indications for and achieving improved results of treatment with BMT.

Treatment results of advanced neuroblastoma with the First Japanese Study Group protocol

PURPOSE To elucidate the efficacy of intensive induction and consolidation chemotherapy regimens (Study Group of Japan for Advanced Neuroblastoma [JANB] 85) for patients with advanced neuroblastoma aged 1 year or older. PATIENT AND METHODS One hundred fifty-seven patients with newly diagnosed advanced neuroblastoma were entered into this study between January 1985 and December 1990. Eligible patients were 12 months old or older with stage III or IV disease. The patients first received six cyclic courses of intensive induction chemotherapy (designated regimen A1) consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydro-pyranyl Adriamycin (pirarubicin; 40 mg/m2), and cisplatin (90 mg/m2). The patients were further treated with three different consolidation protocols: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea, dacarbazine, and bone marrow transplantation. RESULTS Overall survival rates for patients with stage III disease without reference to the consolidation protocols were 80.8%, 76.9%, and 66.3% at 2, 5, and 10 years, respectively. The overall survival rates for patients with stage IV disease were 58.8%, 34.4%, and 28.9% at 2, 5, and 10 years, respectively. There were no statistically significant differences between the three consolidation treatment groups. Patients who did not achieve complete remission (CR) with induction chemotherapy and surgery all died, suggesting that CR is essential for the cure of advanced neuroblastoma. The overall 5-year survival rate of the 24 patients with N-myc amplified stage III and IV disease was 33.3%, and the longest survival time of a relapse-free patient was 103 months. CONCLUSION The intensive induction chemotherapy regimen used in this study may be of significant value in increasing the CR rate and survival for patients with N-myc amplified and nonamplified advanced neuroblastoma.

The significance of measuring liver volume using computed tomographic images before and after hepatectomy

The authors have developed a system to measure the volume of the liver parenchyma and tumors using computed tomographic images printed on film. The present study was carried out to clarify the usefulness of this method to assess both liver volume and the relationship between the volume increase and the functional recovery. We investigated 55 patients who underwent a hepatic resection of more than one segment. We calculated the effective resection ratio and the liver volume increase at the 4th postoperative week to evaluate postoperative hepatic insufficiency. The liver volume increase 4 weeks after surgery correlated significantly with the effective resection ratio and also showed an inverse correlation with the severity of chronic changes in the liver. The liver volume increase also inversely correlated with the preoperative retention of indocyanine green at 15 min. Patients with postoperative hepatic insufficiency tended to show a smaller liver volume increase than expected for their resection ratio. In contrast, noncirrhotic patients had no such particular tendency. In conclusion, measurement of the liver volume using this technique appears to be a simple and useful method to evaluate liver volume after resection; as such, it may also be used to evaluate hepatic regeneration after resection.

Therapeutic significance of surgery in advanced neuroblastoma: A report from the study group of Japan

The role of surgery was evaluated in 19 stage III and 102 stage IV neuroblastoma patients, all of whom were treated with intensive induction chemotherapy by the Study Group of Japan between January 1985 and March 1990. For stage III neuroblastoma, surgical intervention at the primary site was performed in 18 of the 19 patients, 9 during and 9 after the first three cycles of A1 regimen, consisting of high-dose cyclophosphamide, vincristine, THP-adriamycin, and cis-platinum. Gross complete resection of primary tumor and regional lymph nodes was feasible in 17 of the 19 patients (89%), and the survival rate for the 17 patients were 79%, 70%, and 70% at 2 years, 3 years, and 4 years, respectively. For stage IV, surgical intervention at the primary site was performed in 92 of the 102 patients (90%): 30 cases during the first 3 cycles of A1 chemotherapy and 62 cases after that, with gross complete resection accomplished in 81 of the 102 patients (79%). The 81 patients with gross complete resection achieved had a better prognosis than those 11 patients with partial resection (P less than .05). Overall survival rate was 62% at 2 years for 27 patients who underwent complete resection after 3 cycles of A1 when resolution of all metastases was obtained, whereas the survival was 52% at 2 years for 31 patients who similarly underwent complete resection but when evidence of persistent metastases was present. Patients in whom the ipsilateral kidney was preserved at surgery had an outcome superior to that of those with associated nephrectomy (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a liver metastatic variant of murine colon 26 carcinoma cells

Intraportal vein injection of highly metastatic L5 cells consistently resulted in liver metastases (increases in the number of tumor colonies in the liver), whereas inoculation of P cells rarely did. L5 cells invaded the basement membrane Matrigel in greater numbers than did P cells, suggesting that the metastatic potential of L5 cells is partly related to enhanced invasive properties. The enhanced adhesion of L5 cells to fibronectin-, laminin- and Matrigel-coated substrates, as well as their haptotactic migration to fribronectin, may be associated with the preferential expression of VLA-2 and VLA-4 integrins on the surface of these cells detected by flow cytometry. Gelatin zymograms showed that the degradative activity of 72-kD gelatinases was greater in L5 cells than P cells. These results indicate that, in addition to adhesiveness and motility, the invasive ability of L5 cells may also be attributed to enhanced gelatinolytic activity. L5 cells grew more rapidly than P cells in vitro. Thus, an experimental model using highly metastatic colon 26 L5 cells would be useful for analyzing the molecular mechanism of liver metastasis and for evaluating the efficacy of treatment of occult micrometastases which may already have been disseminated at the time of surgery.

Adjuvant chemoimmunotherapy for hepatocellular carcinoma patients. Adriamycin, interleukin-2, and lymphokine-activated killer cells versus adriamycin alone.

To determine improved postresection survival in patients with hepatocellular carcinoma, two postoperative protocols were compared: adoptive Chemoimmunotherapy versus chemotherapy. Following resection, 24 patients were allocated at random to receive (1) arterial infusion of Adriamycin. re-combinant interlcukin-2 and lymphokine-activated killer cells or (2) arterial infusion of Adriamycin alone. The spleen was removed at operation and used to prepare lymphokine-activated killer cells. Each group had 12 patients. They were followed until signs of recurrence appeared. The overall survival rates of the patients were 91.7%, 82.9%, and 72.5% at 1, 2, and 3 years, respectively, and slightly higher than would be expected with surgery alone. No statistically significant difference was found between the two groups either in the survival rate (generalized Wilcoxon test, P = .936) or in the cumulative disease free rate (P = .182). However, when patients who had had hepatic resection with negative margin (≥1 cm) were separated, the 2-year cumulative disease-free rate in the adoptive Chemoimmunotherapy was higher (83.3%, n = 6) than that in chemotherapy (37.5%, n = 8). Toxicity to adoptive Chemoimmunotherapy was moderate; no severe side effects were observed. Totally no statistical difference between the two groups was found. Although only one of six patients in adoptive Chemoimmunotherapy experienced recurrence after hepatic resection with negative margin, it was not feasible to determine the role of interleukin-2 and lymphokine-activated killer cells. We conclude that the adoptive Chemoimmunotherapy in this study is not an ideal adjuvant protocol after hepatic resection.

Liver resection in children, using a water-jet

The water-jet method has been used during hepatic resection in children. The instrument cuts the hepatic tissue by means of a high-pressure fine water-jet, while the exposed intrahepatic vessels are spared injury. Physiological saline was used for the jet water, and pressure of 12 to 15 kilograms of force per square centimeter (kgf/cm2) through a 0.15-mm-diameter nozzle was found to be optimal for cutting the liver parenchyma. The authors evaluated the usefulness of the water-jet dissector (n = 8) during bisegmentectomy or trisegmentectomy in comparison to the Cavitron Ultrasonic Surgical Aspirator (CUSA) (n = 5). The mean operation time was 4.08 +/- 0.87 hours for the water-jet group and 5.08 +/- 1.33 hours for the CUSA group. The mean blood loss was 602 +/- 659 mL for the water-jet group and 1,036 +/- 521 mL for the CUSA group. Although there were no significant differences with respect to operation time, blood loss, or postoperative complications, the liver parenchyma was dissected more easily using the water-jet. The authors believe that the mechanical simplicity and safety of the water-jet method will lead to its more widespread use in liver resection in children.