Intrahepatic metastases in hepatocellular carcinoma: the role of the portal vein as an efferent vessel.

The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. Two hundred and thirty one tumors (< or = 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected at random from the 231 tumors. The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and the frequency of vascular invasion (correlation coefficient = 0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in six tumors. In all eight patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.

The role of oval cells in rat hepatocyte transplantation.

BACKGROUND: Oval cells are liver cells capable of differentiating into either hepatocytes or biliary epithelial cells. We compared growth of hepatocytes and biliary epithelial cells between spleens transplanted with oval cell-free and oval cell-enriched rat liver cells. METHODS: Oval cell-enriched liver cells were obtained from livers of adult rats that had undergone treatment with acetylaminofluorene and partial hepatectomy, although oval cell-free liver cells were obtained from livers of untreated rats. Hepatocyte and biliary epithelial cell growth in the spleen was evaluated by counting periodic acid-Schiff-positive cells and cytokeratin 19-positive cells respectively in sections from transplanted spleens. RESULTS: Spleens transplanted with oval cell-free liver cells and spleens transplanted with oval cell-enriched liver cells contained similar numbers of hepatocytes after 2 weeks. Numbers of hepatocytes in spleens transplanted with oval cell-free liver cells decreased markedly at 4 and 8 weeks, then increasing slightly until 32 weeks. In spleens transplanted with oval cell-enriched liver cells, numbers of hepatocytes decreased only slightly at 4 weeks and then increased markedly. At 4, 8, 12, 16, 24, and 32 weeks, numbers of hepatocytes in spleens transplanted with oval cell-enriched liver cells respectively were 2.3, 3.5, 4.5, 6.7, 6.3, and 15.1 times hepatocyte numbers in spleens transplanted with oval cell-free liver cells. Numbers of biliary epithelial cells in spleens receiving oval cell-enriched liver cells showed changes similar to those in spleens transplanted with oval cell-free liver cells, increasing markedly at 4 weeks and then markedly and rapidly decreasing. CONCLUSIONS: Intrasplenic transplantation of oval cell-enriched liver cells enhanced growth of hepatocytes compared with transplantation of oval cell-free liver cells; this was not true for biliary epithelial cells.

Increase in muscarinic acetylcholine receptors in mouse intestine by hexamethonium treatment.

The effects of hexamethonium (C6) administration on muscarinic acetylcholine receptors (mACh-R) in the intestine and brain of mice were investigated. Mice were treated with C6 with an osmotic mini-pump (330 mg/kg/day) for one week and then the binding of 3H-quinuclidinylbenzilate (3H-QNB) in the intestine and brain were assayed. This treatment increased the maximum specific binding (Bmax) of 3H-QNB from 160 to 320 fmoles/mg protein in the ileum and from 190 to 340 fmoles/mg protein in the rectum, without affecting the KD values in these regions. On the contrary, C6 treatment did not change the Bmax or KD value in brain tissues. This C6 treatment increased the sensitivity of the contractile response of the intestine to muscarinic agonists, possibly by increasing mACh-R.

Aneurysmal intrahepatic porto-capsular vein anastomosis.

Two cases of intrahepatic porto-capsular vein anastomosis are described, both of which were complicated by liver cirrhosis and hepatocellular carcinoma. In both cases a branch of the portal vein in the posterior segment of the liver was markedly dilated and directly anastomosed at its periphery with the liver's capsular vein, then connected with the inferior vena cava. One of the two cases underwent partial hepatectomy. Histopathological examination of the resected specimen did not reveal any direct relation between the shunt and the carcinoma. The shunting in both cases appeared to have resulted from portal hypertension complicated by liver cirrhosis.

Plasma exchange therapy for endotoxin shock in puppies.

The efficacy of plasma exchange (PE) therapy for endotoxin (ET) shock has not been evaluated. The following experimental study was designed to evaluate the feasibility of PE in infants and children and determine the efficacy as a therapeutic modality for ET shock. A compact circuit for PE designed for this experiment consists of two pumps and a membrane plasma separator for a venovenous extracorporeal circulation with the limited prime volume of 100 mL. The capacity of this device for PE was tested. When a membrane separator of 0.3 m2 in surface area was used, a plasma flux of 5 to 13 mL/min was satisfactorily obtained with the blood flow rate of 25 to 40 mL/min, which was taken through centrally placed catheters of 18 gauge or larger. Transmembrane pressure was maintained in a safe range (0 to 50 mm Hg) in the first 90 minutes, during which time a PE of 100 mL/kg was completed with a sieving coefficient greater than 0.8. In 14 puppies (1.8 to 3.5 kg), a shock state was produced by infusion of ET (Escherichia coli, 055:B5). Eight puppies were resuscitated simply with lactated Ringer's solution and bicarbonate. Six puppies were treated with PE using 100 mL/kg of fresh-frozen plasma prepared from adult dogs. A significant decrease in the mean blood pressure, platelet and leukocyte counts, total protein, and CH50 was documented in all animals after ET administration. Seven of eight control animals died within 24 hours of post-ET infusion. All of the six PE-treated animals survived for 48 hours or longer.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of 21 patients with biliary atresia living more than 10 years.

The outcome of 21 survivors (8 males, 13 females; age range, 11 to 29 years) followed for > 10 years after surgery for biliary atresia are discussed. Of the 21 patients, 18 with type III disease had hepatic portoenterostomy (Kasai operation), and 3 with type I disease had hepaticoenterostomy. Twenty patients are alive leading almost normal lives; however, 13 (61.9%) patients did have a history of complications, including hemorrhage from esophageal varices in 10, from a gastric ulcer or erosion in 3, and from a duodenal ulcer in 2; biliary reobstruction in 3; and multiple pulmonary arteriovenous fistulae in 2. Of those with complications, 7 required surgery. One died suddenly at the age of 19 years of a bleeding gastric ulcer. Liver function is normal in 9 (45.0%) of the 20 alive patients, 2 (10.0%) have slight hepatic dysfunction, and 9 (45.0%) have mild-to-moderate hepatic dysfunction. Liver function is almost normal in 3 patients who had a history of variceal hemorrhage.

Successful Kasai operation for biliary atresia in a 9 month old.

A rare case of a successful Kasai operation for biliary atresia in a 9 month old is described. For infants over 6 months of age, there had been no reports of long-term survival after this procedure.

Extensive dissection at the porta hepatis for biliary atresia.

Dissection at the porta hepatis is the crucial step in surgery for biliary atresia. The authors describe their procedure for extensively dissecting the porta hepatis. The technique is based on an anatomic cast corrosion of the human liver, and the portal vein serves as the landmark for dissection. Lateral dissection at the hepatic hilus is critical to the procedure. On the right side, the anterior portal branches are dissected to the bifurcation of the S5 and S7 segmental portal branches, over the bifurcation of the anterior and posterior portal branches. On the left side, the liver parenchyma, which bridges the umbilical point, is sectioned, and the left portal branch is dissected to the umbilical point over the pars transversalis and taped. The fibrous mass that lies within the confines of the portal branches, including the dorsal aspect, is transected completely. This procedure was performed in 16 infants; the jaundice cleared in 93.7%.

Inhibition by an angiogenesis inhibitor, TNP-470, of the growth of a human hepatoblastoma heterotransplanted into nude mice.

BACKGROUND/PURPOSE: The effect of TNP-470, an angiogenesis inhibitor, on the growth of a hepatoblastoma transplanted into nude mice was examined. METHODS: A hepatoblastoma obtained from a 3-year-old girl was serially transplanted into nude mice subcutaneously, and the transplant tumors of the seventh and eighth generations were used for experiments. Expression of various markers in the tumors was examined immunohistochemically. TNP-470 was injected subcutaneously every other day into tumor-bearing mice from 3 weeks after tumor transplantation. The proliferation of tumor cells and endothelial cells was estimated by means of the bromodeoxyuridine labeling index. RESULTS: The original hepatoblastoma showed the histology of the epithelial type, consisting of both the fetal and embryonal subtypes and was positively stained with anti-alpha-fetoprotein (AFP), anti-cytokeratin-19 and polyclonal anticarcinoembryonic antigen antibodies, and an antihuman hepatocyte antibody (hepatocyte paraffin 1). The transplant tumors consisted of solid nests of tumor cells with numerous vascular lakes of various sizes, and showed positive staining with all antibodies that reacted positively with the original hepatoblastoma. Injections of TNP-470 at the doses of 15 mg and 30 mg/kg body weight suppressed the tumor growth and the increase in the serum level of AFP dose dependently. Injections of TNP-470 also suppressed the proliferation of tumor cells and endothelial cells in the tumors. CONCLUSIONS: Hepatoblastomas maintained in nude mice retained the immunohistochemical characteristics of the original hepatoblastoma, and TNP-470 suppressed the growth of hepatoblastomas transplanted into nude mice. TNP-470 may be worth investigating further as to its usefulness as a therapy for hepatoblastomas.

[TNM classification--pediatric tumors].

The clinical and postsurgical TNM classifications (cTNM and pTNM) for neuroblastoma (NB), nephroblastoma (WT) and soft tissue sarcomas were presented in 1982 by the TNM Committee in UICC in collaboration with SIOP. The Japanese TNM Committee proposed new pTNM systems (J-pTNM) for NB and WT, and new cTNM and pTNM system for primary liver carcinoma in infants and children (HT). These pTNMs were based on the staging systems developed by the Malignant Tumor Committee of the Japanese Society of Pediatric Surgeons. The proposal of subdivision of M category in NB was presented for testing the new telescopic ramifications of TNM. The TNM for HT was added as a new classification recommended for testing. The effectiveness of these TNM systems was assessed using NB, WT and hepatoblastoma (HB) cases which were registered in collaborating institutes. The analyses suggested that pTNM, especially the J-pTNM system in NB, WT and HT were effective for the assessment of prognoses, although cTNM systems were not enough to assess the extent of the disease.

[Pathohistological evaluation of hepatic artery ligation (HAL) or transcatheter arterial embolization (TAE) on primary carcinoma of the liver].

Ischemic effect of interruption of hepatic artery upon the expansively growing primary carcinoma of the liver was studied on six resected specimens obtained by hepatectomy having been carried out 10 to 35 days after HAL or TAE. Both HAL and TAE were found to bring about an extensive coagulative necrosis in the main tumor. No substantial difference was observed between the two in the degree or the mode of necrosis produced. Complete necrosis of the tumor was observed in a case of a nodular type hepatoma in the visceral aspect of the right posterior segment. An incomplete necrosis was obtained in the main tumor of remaining 5 cases. The necrotized region was clearly demarcated from the viable portion in the tumor by the septal formation which was probably used to be the part of the capsule around the tumor. This suggested that the compartment in the tumor separated by these septa is supplied by the different artery independently. Therefore, if the interruption therapy is chosen as the sole procedure, it is stressed that complete hepatic dearterialization is mandatory for the treatment of liver cancer.

[The significance of hepatic lobectomy as the surgical treatment for primary hepatocellular carcinoma].

Since most patients with primary hepatocellular carcinoma (HCC) in Japan have cirrhosis, indication of hepatectomy is now tending to be limited to a single segment or subsegment for small HCC. However, pathologic examinations on the resected specimens have revealed that intrahepatic metastases were associated in more than 50% of HCC smaller than 5 cm, indicating that hepatic resection is required in these patients to be as extensive as possible within the limit of hepatic reserve. Our multiple regression equation provided for the preoperative prediction of an early prognosis of hepatectomized patient has successfully reduced the incidence of postoperative fatal liver failure from 17% before 1980 to 6% after 1981. The sequential volumetric CT measurements of the remaining liver after hepatectomy in humans has revealed an ability of the cirrhotic liver to regenerate nearly as normal liver in patient who has well tolerated hepatic resection. Ligation or embolization of the portal vein of an affected side in patients with unresectable HCC has rapidly induced a compensatory hypertrophy in the contralateral lobe to be remained, indicating the potential usefulness of this procedure to relatively reduce the loss of functioning liver mass by the proposed lobectomy.

[Late complications after successful Kasai's operation for biliary atresia].

The late complications in 25 patients more than 3 years after successful Kasai's operation for biliary atresia were presented. Nine (36%) of these 25 patients had episodes of variceal hemorrhage with portal hypertension, and biliary reobstruction in 3 (12%), bleeding from duodenal ulcer in 2, bleeding from gastric erosion in one, and diffuse pulmonary arterio-venous shunt in one were observed. Recently esophageal varices have been well controlled by endoscopic sclerotherapy, and the surgical treatment may be indicated in older children complicated with severe hypersplenism and marked splenomegaly, which are resistant for sclerotherapy. As a surgical procedure, splenectomy with periesophago-gastric devascularization (Hassab's operation) seems to be very useful for portal hypertension by biliary cirrhosis. The reoperation, hepaticoenterostomy, was performed in 3 patients with biliary reobstruction. All three patients are alive and well, and two of them are at 19 years (university student) and 24 years (married life) of age. Hepatic Rehepaticoenterostomy is well indicated rather than liver transplantation, if biliary reobstruction is incurable with conservative therapy. Many of the patients with complications were able to carry on an almost normal life, if suitable treatments for complications were taken.

[Nuclear DNA analysis of hepatocellular carcinoma].

Retrospective DNA ploidy studies of paraffin-embedded blocks were performed by flow cytometry on 212 surgically resected hepatocellular carcinoma. One hundred and sixty-four of 212 specimens yielded evaluable DNA histograms. Eighty-three cases showed a DNA diploid pattern and 81 a DNA non-diploid pattern. The incidence of non-diploid pattern increased with the tumor size. (2cm; 15.4%, 2-5; 42.3%, 5-10; 70.8% greater than 10; 73.3%). The DNA pattern correlated with the backgrounds, the degree of vascular invasion, intrahepatic metastasis and serum AFP levels. Survival of patients with non-diploid pattern was significantly less than those with diploid patients in any different stage. Of thirty who survived three years with disease free condition, 20 patients showed diploid patterns. Though remaining 10 patients were non-diploid patterns, 9 were high DNA index more than 1.5. It is concluded that flow cytometric DNA ploidy study had prognostic value for patients with surgically resected hepatocellular carcinoma.

[Treatment of patients with hepatoma and esophageal varices].

Fifty-nine patients with hepatoma associated with advanced esophageal varices who received a variety of therapeutic modalities in the past 10 years at our department were reviewed. Our therapeutic modalities are hepatic resection, hepatic artery ligation (HAL) and trans-arterial embolization (TAE) for those with hepatoma and non-shunting treatment (NST; esophageal transection or Hassab's procedure) and endoscopic sclerotherapy (ST) for those with esophageal varices. A patient selection was made by our own criterial developed by a multiple regression analysis for the hepatoma and KICG value for esophageal varices. Out of 59.16 underwent hepatic resection and NST. Eight survived more than 2 years. The longest survivor has been living for 4 yr and 4 months. Two-year survival rate is 69.8%. Another 16 underwent HAL and NST. Two-year survival was 14.6%. Another 7 underwent ST following hepatic resection or HAL. Five of the 7 received an emergency ST. Hemostasis was achieved in all of them. Two-year survival was 21.8%. The remaining 20 underwent ST and TAE; 13 received an emergency ST with 85% of hemostasis rate. None of them survived more than 2 years. From these data, it is suggested that a proper selection of patients for a proper therapeutic modality improves the prognosis even in those with hepatoma associated with advanced esophageal varices.

[Pathophysiology of defecatory disturbance in the patient with Hirschsprung's disease and chronically constipated patients with simple megarectum].

The disturbance of defecation in the patient with Hirschsprung's disease and the pathophysiology of constipation in the constipated patient with simple megarectum were investigated. In Hirschsprung's disease, an existence of aganglionosis and the sphincter achalasia are two main factors which cause clinical symptoms such as chronic constipation and megacolon. As a surgical treatment, we have routinely performed our modified Duhamel's operation. Postoperative followup study indicated that the most cases in our series have gained a satisfactory defecatory function 1 to 3 years after operation. In chronically constipated patient with simple megarectum, on the other hand, it was found manometrically that the most of them had significantly high anal canal pressure and incomplete anal relaxation after rectal stimulation. These findings indicate that those patients have hypertonic and achalasic sphincter. Therefore, the authors propose "high anal pressure syndrome (HAPS)" for such constipated patient with simple megarectum. As to the surgical treatment, 6 patients with simple megarectum had a complete posterior internal sphincterotomy and the postoperative results were excellent or good in our series.