Analysis of factors affecting outcome after hepatectomy of patients with liver cirrhosis and small hepatocellular carcinoma.

OBJECTIVE: To review our policy of screening patients at risk of developing hepatocellular carcinoma (HCC), and to present 10 years' experience of hepatic resection for small HCC (< 5 cm). DESIGN: Retrospective study. SETTING: Teaching hospital, Germany. SUBJECTS: 861 patients with hepatic cirrhosis and oesophageal varices of whom 151 (18%) had HCC confirmed histologically; 30 of these tumours (20%) were less than 5 cm in diameter and suitable for resection. INTERVENTIONS: Segmentectomy (n = 14) bisegmentectomy (n = 10), and oncologically defined wedge resection (n = 6). MAIN OUTCOME MEASURES: Mortality, morbidity, and survival. RESULTS: 4 patients died within 30 days of liver failure and sepsis (n = 20, liver failure (n = 1), and bronchopneumonia (n = 1). The main beneficial prognostic factors were Child classification, donation of autologous blood, and an encapsulated tumour. The main indicators of a poor prognosis were invasion of the liver, venous invasion, invasion of the resection margin, and the presence of microsatellite tumours and nodules. 12 of the 26 survivors developed recurrences during the first five years postoperatively (46%). Kaplan-Meier survival curves showed that survival at 1 year was 80%, at 3 years 65%, and 5 years 50%, and at 10 years 30%. CONCLUSION: Hepatic resection is a useful treatment for small HCC, but its success depends on early detection and careful selection of patients.

Primary chondrosarcoma of the left inferior lobar bronchus.

A primary chondrosarcoma arising in the left inferior lobar bronchus is described in a 67-year-old man. The symptoms upon admittance were dyspena, cough with purulent sputum and weight loss. The tumor was removed by pneumonectomy. Eight months later the patient died of massive mediastinal lymph node involvement. While tracheobronchially located primary pulmonary chondrosarcoma tends to remain localized, the peripheral variety tends toward mediastinal lymph node involvement and thoracic metastasis. The treatment of choice is resection in a radical manner, whenever possible.

Renal bile acid excretion as a cause of neoplastic lesions in the urinary tract after total portacaval shunt in the normal rat?

Rats with a total portacaval anastomosis (PCA, PC-SS) develop preneoplastic and neoplastic lesions in the urinary tract. In contrast to this, animals with a modified shunt (mPCA) do not develop these lesions. To evaluate the possible role of bile acids excreted with the urine for tumor development, total plasma bile acid concentration and 24 hours urinary bile acid excretion were measured radioimmunologically in rats with total and modified shunts. Additionally the renal 14C-glycocholic acid excretion into the urine was studied after oral administration. Total plasma BA increased from 4.89 +/- 1.0 mumol/l in sham-operated controls to 77.7 +/- 39 mumol/h in PCA and 52.9 +/- 36.7 mumol/l in mPCA rats (p less than 0.001 vs controls, PCA vs mPCA = n.s.). Urinary bile acid excretion rose from 0.2 +/- 0.29 mumol/24 hours in controls to 4.47 +/- 4.49 in PCA and 2.55 +/- 2.22 mumol/24 hours in mPCA rats (p less than 0.001 vs control; PCA vs mPCA = n.s.) 14C-glycocholic acid was excreted within 24 hours into the urine in 13.6 +/- 11.5% in PCA and 26.3 +/- 23.5% of the administered dose in mPCA-rats (controls; 2.98 +/- 0.67%, p less than 0.001; PCA vs mPCA = n.s.). Since renal BA-excretion is similar in both shunted groups, urinary BA does not seem to be of primary significance for cancer development in the urinary tract of totally shunted rats.

Cell fusion as a mechanism for the formation of giant cells (Langhans' type). Autoradiographic findings in autoimmune tubulo-interstitial nephritis of the rat.

The formation of multinuclear giant cells of the Langhans' type in tubulo-interstitial auto-immune nephritis in the rat has been investigated by means of autoradiography. While in the majority of giant cells all nuclei were radiolabeled, in a few both labeled and unlabeled nuclei were present. This latter finding represents strong evidence in favour of the hypothesis that giant cells do not form by endomitotic processes but rather through fusion of certain precursor cells. According to previous studies this precursor cell population consists mainly of epitheloid cells, i.e. modified monocytes.

Antibacterial effects of niridazole. I. Effect on infection of mice with Salmonella typhimurium.

Niridazole was shown to be an effective chemotherapeutic agent for mice infected intravenously with a niridazole-sensitive strain of Salmonella typhimurium. Death rates as well as bacterial counts per spleen were reduced, even in compromised animals. Histologic examination of spleens proved the reduction of inflammatory reaction due to Salmonella infection. A suppressive effect of niridazole treatment on immunity to challenge infection with S. typhimurium was not found, as demonstrated by infection with a niridazole-resistant strain of S. typhimurium.

Wound closure with a fibrin tissue adhesive.

In an animal experiment performed on 25 rabbits, normal suture of dermal incisions was compared with wound closure by means of a new adhesive system. This system consisted of a fibrinogen cryoprecipitate and a thrombin solution, which were mixed. After 2, 4, 6, 9, 14 and 21 days, macroscopical and histological studies were performed. The bonded wounds showed less scar formation. In the clinical cases, the new method was used for the closure of incisions at the lateral and inferior orbital rim after osteosynthesis of Le Fort II and III midface fractures. Bonding was combined with a subcutaneous suture to avoid stress and yield good adaptation of deeper wound layers. Improved functional and esthetic results were demonstrated.

[Problems of hepatoportal encephalopathy after portacaval anastomosis in the rat (author's transl)]. / Zum Problem der hepatoportalen Enzephalopathie nach portokavaler End-zu-Seit-Anastomose der Ratte.

Necrosis and injury of ganglia cells as well as alterations of the glia represent the morphological changes in portal-systemic encephalopathy. This is a frequent complication of a spontaneous or surgical porta-caval collateral circulation. Such changes can also be observed when porta-caval end-to-side anastomosis (PCA) was constructed in otherwise healthy rats. Increased incorporation rates of 3H-thymidine into the glia were indication for enhanced proliferating activity. Efforts done to maintain the pancreatic venous blood flow to the liver beside PCA resulted in significant diminuation of brain pathology and function. The latter measured by EEG. This happened although the grade of hyperammonemia was virtually identical in both settings. The interpretation is offered that access of the liver to hepatotrophic substances (i. e. insulin) from the pancreas prevents portal-systemic encephalopathy in PCA which is in agreement with data of the literature. The observation implies that in clinical action exclusively those surgical techniques should be used by which the venous blood supply from the pancreas to the liver is maintained.

[The effects of flavonoids on rat liver during chronic palloidin intoxication/Morphological and biochemical studies (author's transl)]. / Zur Wirkung von Flavonoiden an der Rattenleber bei chronischer Phalloidin-Vergiftung. Morphologische und klinisch-chemische Untersuchungen.

Continuous intraperitoneal administration of phalloidin (0.5 mg/kg body weight/day) leads to an alteration of intracellular contractile acto-myosinfilaments in rat liver. The hepatocytes show an accumulation of fibrillar material with some loss of contractile function of the pericanalicular web. Biochemically an increase of serum transaminases and alkaline phosphatase occurs. Histochemically the liver exhibitis changes in the distribution of some hepatocellular enzymes. The influence of the flavonoid (+)-cyanidanol-3 on these phalloidin-induced lesions was studied by histochemical, immunofluorescence and biochemical methods. The results imply, that (+)-cyanidanol-3 is probably protecting the plasma membrane of hepatocytes and therefore reduces the entrance of phalloidin into the cytoplasm. In addition an increased activity of the reticuloendothelial system was observed, perhaps resulting from the flavonoid administration. Both effects could be discussed as mechanisms of flavonoid action in the liver.

The regeneration of the cells of the macula densa after subtotal nephrectomy in the rat.

An autoradiographic study of the proliferative response of the cells of the Macula Densa days or months after the removal of 5/6 of the rat's kidney has shown that these cells are capable of division. The index of labelling of these cells is considerably lower than that of the other cells of the distal tubules. This applies of the kidney of normal controls and to the remnant after partial nephrectomy, shortly after operation as well as several months later. The cells of the Macula Densa therefore seem to represent a more stable population in the nephron. They therefore differ from the other cells of the distal tubules not only in appearance and function, but also in the pattern of cell proliferation.

On the pathogenesis of galactosamine hepatitis. Indications of extrahepatocellular mechanisms responsible for liver cell death.

In order to evaluate the pathogenesis of galactosamine hepatitis, the action of galactosamine on mast cells, and alteration in the complement system suring the course of this experimental injury were studied. It has been previously demonstrated that rat livers after colectomy are refractory to galactosamine-induced liver cell necrosis and inflammation. For this reason colectomized animals were used to see whether the biochemical alterations produced by this aminosugar and thought to be responsible for cell death developed. Results showed: 1. galactosamine potently degranulates mast cells in vivo and in vitro, 2. the complement system is a) activated during the course of galactosamine hepatitis, probably by circulating endotoxins, and b) is essential for liver cell death in galactosamine hepatitis, and 3. colectomy does not prevent biochemical changes known to occur during galactosamine metabolism. It is concluded that death of galactosamine-injured liver cells is triggered by extrahepatocellular mechanisms, which lead ultimately to an activated complement system by endotoxins. It is postulated that related mechanism may also occur in viral hepatitis and in fulminant hepatic failure in man.

[The histological changes in cartilage (incus) in the middle ear after conservation--an animal study (author's transl)]. / Uber das histologische Verhalten von Knorpel (Ambossgelenkpfanne) im Mittelohrraum nach unterschiedlicher Konservierung. Eine tierexperimentelle Studie.

This study demonstrates the histological changes of incus cartilage after transplantation into the middle ear space of rabbits. Conservation was performed by deep-freezing, lyophilisation in connection with gamma-irradiation, or with Cialit in differing dilutions. Controlled deep-freezing at about -196 degrees C and uncontrolled deep-freezing at about -20 degrees C guarantee after transplantion the survival of some vital chondrocytes. The other methods of conservation cause death of all chondroxytes. Cartilage prepared by these methods demonstrates potential for new bone formation. Only the xenogenetic cartilage loses its osteogenic potential after treatment by lyophilisation in connection with gamma-irradiation. The histological value of the transplant differs according to the method of conservation. No special tendency for resorption or inflamatory reactions could be seen.

[Implantation of ossicles (A histological study in animals) (author's transl)]. / Zur Ubertragung von Gehörknöchelchen (Eine tierexperimentelle Studie mit vergleichender Histologie).

Autogenetic and allogenetic incuses as well as xenogenetic malleus were implanted into the middle-ear of rabbits after different procedures of conservation. The process of healing was studied by histological examination. The different conservation methods are leading to different antigenic qualities of the donor material. A different reorganization along the wurse of the donor vessels is resulting. Accordingly a different extent of osteoneogenesis of the intercellular substance is induced. The vascular tissue showed a revascularization in the case of autogenetic transplantation and in the case of implantation after cialit conservation of 1:5000. Whereas deep-freezing led to swelling, cialit conservation 1:500 to temporary fibrosis of the sides of vessels. Hyalinosis of the vessels was observed after lyophilization and gamma-sterilization of the xenogenetic malleus. The different effects on the healing process are discussed.

[Incus, controlled deepfrozen or in cialit conserved, after allogenetic implantation. An animal-experimental study with comparing histology (author's transl)]. / Der kontrolliert tiefgefrorene und der in Cialit konservierte Amboss nach allogenetischer Implantation. Eine tierexperimentelle Studie mit vergleichender Histologie.

The histological reactions to the implantation of allogenetic incus after conservation in Cialit or after controlled deepfreezing are described. After 5 months the incusses of both conservation technics show the same good tendency of revitalisation. Therefore the controlled deep-freezing technic does not offer an advantage compared to the Cialit conservation method at least for the present state of knowledge.

[The implantation of lyophilized and gamma-sterilized allogenetic incus and of lyophilized and gamma-sterilized xenogenetic malleus (calf) in rabbits and humans (author's transl)]. / Die Implantation des lyophilisierten und gamma-sterilen allogenetischen Amboss und des lyophilisierten und gamma-sterilen xenogenetischen Hammer (Kalb) bei Kaninchen und Mensch.

The histological reactions to the implantation of allogenetic and xenogenetic lyophilized and gamma-sterilized material into the middle ear of rabbits and men is described. In contrary to the behaviour of allogenetic material the xenogenetic shows a clear minor tendency of revitalisation. The reason is the antigen-antibody-reaction which takes place at the capillary network of the donor and leads to a hylinosis with following obliteration of the vascular rete. Therefore the angiogenetic osteogenesis cannot develop. The clinical usuability of such material is discussed.