Sumio Inoue

Hepatic resection for hepatocellular carcinoma. Clinical features and long-term prognosis.

Ninety-eight hepatic resections for hepatocellular carcinoma were performed on 94 patients from 1963-1985. HBs antigen was positive in 17% of patients, preoperative serum alpha-fetoprotein was more than 20 ng/mL in 70% of patients, and liver cirrhosis was present in 75% of patients. Hospital mortality rate was 19%, and the volume of operative blood loss was the most decisive factor that affected the short-term prognosis. Excluding the 19 hospital deaths, the long-term survival rates of 75 patients were 73%, 42%, and 25% for 1, 3, and 5 years, respectively. Prognostic factors that influenced the long-term prognosis were investigated by comparing the survival curves. Significant differences of survival patterns were noted when analyzed on the basis of preoperative alpha-fetoprotein level (less than or equal to 200 vs. greater than 200 ng/mL), tumor size (less than or equal to 5 vs. greater than 5 cm), and tumor capsule. The recurrence of carcinoma was the main cause of death in 56% (42 patients) who died after discharge from the hospital. The development of effective prevention and treatment against recurrent tumors is necessary to improve long-term prognosis.

Postoperative recurrence of hepatocellular carcinoma.

Sixty-nine patients with hepatocellular carcinoma underwent curative hepatic resections as primary cases from 1981 to 1986. Seven patients died in the hospital after operation. The other 62 patients left the hospital and were closely followed for 25 to 78 months. Recurrence of carcinoma became obvious in 41 (66%) of 62 patients. The clinical and pathologic features of these 41 patients were not significantly different from those of the other patients. Recurrent tumors were found in the residual liver in 38 patients (93%), in the bone in 2 (5%), and in the lung in 1 (2%). Recurrence was diagnosed within 1 year, between 1 and 2 years, and more than 2 years after the operation in 22 (56%), 10 (26%), and 7 (18%) patients, respectively. It was difficult to determine the exact time of recurrence in two patients. There was a significant negative correlation between the size of primary tumor and time until recurrence; the larger the primary tumor, the shorter the time until recurrence. Among the 29 patients who underwent local excisions for their primary tumors, 19 recurrences were observed. Eighteen were found in the residual liver, in the same segment as the primary tumor, or in one near it. Larger hepatic resection for primary tumors is thus advocated to prevent recurrence.

Pure red cell aplasia caused by parvovirus B19 infection in a renal transplant recipient

To the Editor: Human parvovirus B 19, which is the etiologic agent of transient aplastic crisis in hemolytic anemia, is known to cause chronic bone marrow failure in immunocompromised hosts (1-4). To our knowledge, there have been 2 previous case reports describing parvovirus B 19 infection in renal transplant recipients (5 ,6 ) . We report here another case of severe anemia caused by parvovirus B 19 infection in a renal transplant recipient. Although humoral immune response to the virus was absent for a while due to immunosuppressive therapy, treatment with a regimen of intravenous commercial immunoglobulin resulted in rapid elevation of the reticulocyte count and resolution of the anemia. A 48-year-old man with chronic renal failure secondary to diabetic nephropathy, who had been undergoing chronic hemodialysis and administration of recombinant human erythropoietin (rhEPO) for the treatment of renal anemia, was hospitalized to receive a cadaveric kidney transplant. On the 1st hospital day (d 0), he underwent cadaver donor kidney transplantation, and immunosuppressive therapy with cyclosporin (3 mg/kg/d), prednisolone (70 mg/d), mizoribine (200 mg/d), and antilymphocyte globulin (1000 mg/d) was started. The donor was a 52-year-old man who had died of subarachnoid hemorrhage. Laboratory examination of the recipient on admission showed a white blood cell count of 5300/mm3, a hemoglobin level of 10.6 g/dl, and a platelet count of 204 000/mm3. After transplantation, his anemia began to progress without improvement after rhEPO treatment. On d 18, his hemoglobin level dropped to 5.0 g/dl, reticulocyte count was 0.08 %, white blood cell count was 2500/mm3, and platelet count was 172000/mm3. Bone marrow aspiration revealed severe erythroid hypoplasia with the appearance of many giant proerythroblasts, suggesting the presence of parvovirus B 19 infection. Thereafter, rhEPO was discontinued and the patient was treated with a 7-d course of intravenous commercial immunoglobulin preparations ( 5 g/d) and red cell transfusion. Thereafter, the reticulocyte count increased and his anemia improved. Normal hematopoiesis was observed on bone marrow examination on d 38. The serial serum specimens during the course of illness were subjected to enzyme-linked immunosorbent assay (ELISA) for detection of virus antigen, and polymerase chain reaction (PCR) for detection of virus DNA. B19 antigen became positive on d 2, reached a peak on d 5 , and lasted 18 d. However, viral DNA was detected by PCR in the serum specimen taken just before transplantation, and was negative or faintly positive on d 48. Interestingly, the amount of viral DNA was transiently elevated on d 153 (Fig. 1). The presence of a replicative form of B 19 virus was demonstrated by Southern blot analysis in the bone marrow specimen (Fig. 2) (7). In the serum specimen from the donor, viral DNA was not detected. The assay of virusspecific antibody revealed that IgM and IgG response was not observed until d 153 while the appearance of IgG response was detected in the sample

Successful resection of a large hepatoblastoma in a young adult: Report of a case

Hepatoblastoma (HB) rarely occurs in adults, and very few cases of successful resection have been documented. We report herein the unusual case of a 22-year-old, otherwise healthy woman with no history of liver disease who presented with upper abdominal pain and hepatomegaly. Tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative, but the AFP was mildly elevated at 77 ng/ml, the normal being <20. There was no evidence of liver cirrhosis on either the laboratory or histologic examinations. A well-demarcated solid mass of 14cm in diameter, which was lobulated and partly necrotic, was detected in the liver by computed tomography (CT). The lesion was echogenic on ultrasound, slightly hypodense on CT, and mildly hyper-vascular on arteriogram. The entire tumor was resected by extensive hepatectomy preserving only the lateral segment and part of the posterior segment of the liver. Histologically, the neoplasm was diagnosed as a pure epithelial HB of the fetal type. Following the operation, the patient has been well and free of recurrence for 38 months, maintaining low alpha-fetoprotein (AFP) levels at around 5 ng/ml. To our knowledge, this is the longest reported survival of an adult following surgical resection of an epithelial HB.

Long-term prognosis of surgical patients with hepatocellular carcinoma

SummaryWe reviewed 139 resected patients with hepatocellular carcinoma at our clinic between 1963 and 1987, and using the 118 cases for the period between 1963 and 1986, we analyzed the prognostic factors that influenced the long-term prognosis by comparing the survival curves. Significant differences in the survival patterns were noted when analysed on the basis of the preoperative indocyanine green maximal removal rate (>0.4 mg kg−1 min−1 versus <0.4 mg kg−1 min−1), tumor size (>5 cm versus <5 cm, etc.) and the existence of tumor capsule. The recurrence of carcinoma was the main cause of death of 32 patients (56%), who died after being discharged from hospital. To improve the prognosis of patients with surgically treated hepatocellular carcinoma, postoperative multidisciplinary treatment is mandatory.

Spontaneous rupture of hepatocellular carcinoma: An approach with delayed hepatectomy

Two cirrhotic patients with ruptured hepatocellular carcinoma (HCC), presenting with hemoperitoneum, were successfully treated by elective hepatectomy. Both of these patients, a 67-year-old female and a 76-year-old male, had first been taken to other primary hospitals by ambulance due to hypovolemic shock. They were then found to have a mass of approximately 5 cm in the cirrhotic liver. In the initial management, however, neither any direct hemostasis by surgery nor indirect measures such as transcatheter hepatic arterial embolization were performed in either case. Instead, conservative treatment consisting mainly of fresh blood and plasma transfusions were continued for more than a month until the liver function stabilized. In both hepatectomies, the use of a microwave tissue coagulator resulted in minimal intra-operative blood loss and an appreciably excellent post-operative course. These cases point to the effectiveness of a “wait and see” policy for selected patients with ruptured HCC.

Hepatic resection for minute hepatocellular carcinoma

Twenty-three patients with minute hepatocellular carcinoma, defined as a solitary lesion ≦2 cm, underwent hepatectomy at our institute during the 10 years between January, 1979 and December, 1988. Hepatitis B surface antigen was positive in 4 patients and the preoperative serum alpha-fetoprotein level was within the normal range in 7 patients and slightly elevated (20–200 ng/mL) in 14 patients. Liver cirrhosis was present in 16 patients and chronic hepatitis in 6 patients. The diagnosis was first suspected from the results of periodic examinations, including echography and the measurement of alpha-fetoprotein, in all except one patient. Minor hepatic resection was performed in 22 patients, and lobectomy in one patient in whom the tumor was located centrally in the liver. Three patients died of hepatic failure in hospital following surgery, and the survival rates of the other 20 patients at 1, 3, and 5 years were 90, 79, and 61 per cent, respectively. The prognostic factors that influenced long-term survival were investigated by comparing the survival curves. The only factor associated with a significant difference in survival was the severity of concomitant liver disease. Thus, severe cirrhosis is the main obstacle against the long-term survival of patients with minute hepatocellular carcinoma.

Surgical experience with nonparasitic cysts of the liver--the characteristics and constituents of cyst fluid.

Fifteen patients with nonparasitic hepatic cysts underwent surgery to relieve abdominal complaints, at the First Surgical Department, Tokyo University Hospital between 1966 and 1989. Total removal of the cyst was carried out in 14 of the patients, while puncture and aspiration only were performed in the other patient in whom a cyst had ruptured spontaneously, after which hemoperitoneum was observed at emergency laparotomy. The size of the cysts varied from 7–19 cm with a mean of 12.4 cm. Histological study revealed a congenital cyst in 14 patients and a cystadenoma in one. The epithelium lining of the internal surface of the congenital cysts was highly atrophic and desolated and often disappeared. Examination of the cyst fluid revealed the same concentration of electrolytes as in the serum. Hepatic enzyme levels were usually lower than in the serum, but lactic dehydrogenase and aminotransferase levels were elevated in a few cases. Tumor marker levels of the cyst fluid were higher than those in the serum in four of five patients examined.

Does H2-receptor antagonist alter the renal function of cyclosporine-treated kidney grafts?

Histamine-type 2 antagonists (H2-blockers) as represented by cimentidine have been shown to adversely affect renal allograft function, particularly when coadministered with cyclosporine, currently a major immunosuppressant. To determine whether or not a newer and more powerful H2-blocker, famotidine, would produce similar adverse effects, we assessed seven cyclosporine-treated renal allograft recipients with regard to changes in their renal function on or off the H2-blocker over a one-week period. Neither the administration nor withdrawal of famotidine (20–40 mg/day) resulted in any significant changes in serum creatine, BUN, urine output or cyclosporine trough levels, suggesting that famotidine can be safely administered as an H2-blocker to cyclosporine-treated renal allograft recipients.

Cyclosporine and partial liver allotransplants in a simplified rat model

We designed a simplified rat model to assess the effects of cyclosporine (CsA) on liver transplants. Auxiliary liver grafts consisting of 20 per cent of the whole liver were supplied with portal inflow and the bile was drained into the stomach. The cuff technique was used routinely for both end-to-end and end-to-side venous anastomoses. The host liver was totally deprived of portal inflow. Two inbred strains of rats, LEW and F344, were used for isograft (LEW→LEW) and allograft (F344→LEW). All survivors were killed at the end of the fourth week after transplantation. During four weeks, the isografts increased by 108 per cent in wet liver weight. Animals with allograft were treated with CsA given i.m., in a daily dose of 20 and 40 mg/kg for the rirst ten days post transplantation. The CsA-treated rats were free from parenchymal destruction of the allograft, as was characteristic of the allograft controls. The rats given CsA in the dose of 40 mg/kg showed a 173 per cent increase in the wet liver weight of the transplant, such being greater than allografts in rats on 20 mg/kg of CsA (100 per cent) and even than isografts. These results indicate that auxiliary partial liver grafts benifit from the use of CsA not only through suppression of allorejection but through a potential “hepatotrophic effect” of the agent.