Mononuclear phagocytes (Kupffer cells) and endothelial cells. Identification of two functional cell types in rat liver sinusoids by endogenous peroxidase activity.

The fine structural characteristics and phagocytic properties of peroxidase-positive and peroxidase-negative cells in rat hepatic sinusoids were investigated. Cells with a positive peroxidase reaction in the endoplasmic reticulum and the nuclear envelope make up approximately 40% of cells in rat hepatic sinusoids and have abundant cytoplasm containing numerous granules and vacuoles, and occasional tubular, vermiform invaginations. After intravenous injection of colloidal carbon, the luminal plasma membrane of these cells shows continuous sticking of carbon, and there is evidence of avid phagocytosis of colloidal carbon particles. Peroxidase-positive cells are the only cells in hepatic sinusoids which phagocytize large (0.8 micro in diameter) latex particles. In contrast, the peroxidase-negative endothelial cells, which make up 48% of cells, have scanty perinuclear cytoplasm and organelles, and their long cytoplasmic extensions that form the lining of the hepatic sinusoids have fenestrations; these cells ingest small amounts of colloidal carbon, principally by micropinocytosis, exhibit no sticking of carbon particles to their plasma membranes, and do not ingest the larger (latex) particles. The so-called fat-storing cells are peroxidase negative and totally nonphagocytic. The peroxidase reaction thus distinguishes the typical mononuclear phagocytes or Kupffer cells of rat liver from the endothelial-lining cells.

Recurrent febrile panniculitis and hepatitis in two patients with acquired complement deficiency and paraproteinemia.

Repeated episodes of febrile panniculitis and hepatitis were the main clinical features in two patients with an IgG1 kappa paraproteinemia and severe depletion of the early components of the classical pathway of complement (acquired C1 inhibitor deficiency). They did not have episodes of cutaneous angioedema or evidence of immune complex disease. In the more severely affected patient, the episodes responded to steroids. These features have not been described with acquired C1 inhibitor deficiency and may be related to complement activation.

Leukocyte myeloperoxidase deficiency and diabetes mellitus associated with Candida albicans liver abscess.

Reported here is a case of hereditary myeloperoxidase deficinecy in a diabetic patient suffering from a Candida albicans liver abscess. Peroxidase activity is completely absent from the neutrophils and monocytes although it is present in the eosinophils. The different forms of myeloperoxidase deficiency are discussed.

Studies of portal hemodynamics and hepatic oxygen consumption during acute liver allograft rejection.

Hemodynamics and oxygen variables, plasma cytokines, and histological features of a liver tissue sample obtained by transvenous biopsy were evaluated during 65 episodes of acute rejection. The hepatic venous pressure gradient was significantly higher in patients with acute rejection than in those without (5.1+/-0.3 vs. 3.1+/-0.2 mmHg, P<0.01). The increase in pressure gradient was related to the severity of rejection lesions. Hepatic blood flow was significantly lower in patients with than in those without acute graft rejection (1.28+/-0.11 vs. 1.75+/-0.13 L/min, P<0.05). Plasma interleukin-6 levels were significantly increased in patients with acute rejection and positively correlated with pressure gradient values. In patients with acute rejection, a significant decrease in hepatic venous oxygen content (-16%) was associated with a significant increase in hepatic oxygen consumption (+24%), whereas hepatic oxygen transport did not change significantly. In treated patients with a favorable response, the pressure gradient decreased significantly by 46%, but it remained elevated in patients who later developed chronic graft rejection. In conclusion, this study confirms that acute graft rejection may induce an increase in portal pressure, which is related to the severity of rejection lesions. It also shows that acute rejection decreases hepatic blood flow and increases hepatic oxygen consumption. In addition, it suggests that the hepatic venous pressure gradient might be useful to determine the outcome of rejection.

Intracavitary cardiac extension of hepatoma.

Acute right atrial obstruction in a 62-year-old man was demonstrated angiographically to be due to a tumor, which was later proved to be metastatic hepatoma. Resection of the tumor resulted in total symptomatic relief.

Increased frequency of DR3 antigen in alcoholic hepatitis and cirrhosis.

HLA-A, B and DR antigens were determined in 33 patients suffering from confirmed alcoholic hepatitis, with or without cirrhosis. Past alcohol consumption and plasma immunoglobulins were also determined in 21 cases. An increased frequency of the DR-3 antigen was found in patients as compared with the control group (a sample of the Geneva population (31% v. 11%, p less than 0.05)). Although past alcohol consumption tended to be less in DR-3 positive patients in comparison with the other patients, the difference was not significant. No other differentiating clinical, immunological or histological features were observed among DR-3 positive patients. Our findings that there appears to be an increased frequency of DR-3 antigens in patients with alcoholic hepatitis, together with the previous work showing an increased frequency of HLA-B8 in the same condition, is particularly interesting in the light of the known association of both these antigens with autoimmune disease. These results would suggest that liver damage in chronic alcoholism is genetically predisposed, and that autoimmune mechanisms could be involved in the pathogenesis of alcoholic liver disease.

[Acute Budd-Chiari's syndrome after surgical treatment of polycystic liver disease]. / Syndrome aigu de Budd-Chiari après traitement chirurgical d'une polykystose hépatique.

A case of acute Budd-Chiari syndrome after surgical treatment of polycystic liver disease is described. This complication, presently unreported in the literature, was secondary to the operative interruption of two hepatic veins, while the third was already obstructed by pericystic fibrosis. Preoperative radiologic vascular mapping should be performed in case of voluminous polycystic liver disease when associated liver resection appears likely.

[Histologic and immunohistochemical profiles of benign granular cell tumors. Report of 41 cases]. / Profils histologique et immunohistochimique des tumeurs bénignes à cellules granuleuses. A propos de 41 cas.

Since the descriptions of << myoblastomas >>, later denominated granular cell tumours, many immunohistological and ultrastructural studies have been undertaken with the aim of establishing their histogenesis. Now the hypothesis of a neurogenic origin appears clear. From the large number of cases (53) diagnosed in Geneva over a period of 10 years, we decided to do a retrospective study of these tumours with regard to their immunohistological phenotypes, using the following markers: S100 protein (S100), Neuron specific enolase (NSE), Vimentin, Chromogranin, Glial fibrillary acidic protein (GFAP), Keratin, Epithelial membrane antigen (EMA), Desmin, Smooth muscle alpha actin. 100% of tumours were positive for S100, and 90% for NSE, which confirms the neurogenic origin. 70% were Vimentin positive, with however a variable intensity. All the other markers were negative. Immunohistological staining for S100 and NSE may be useful tool in the diagnosis of these tumours.

[Positron emission tomography (PET) in the preoperative evaluation of cervical lymph node metastasis of ORL cancer]. / La tomographie par émission de positrons (PET) dans l'évaluation préopératoire des métastases ganglionnaires cervicales des cancers ORL.

The distribution of specific radiolabeled biological compounds in tumor tissues can be imaged by positron emission tomography (PET). The substance used is fluorodeoxyglucose, labeled with the positron emitter fluorine-18. This substance is partly trapped in tumor cells with increased glucose metabolism. This noninvasive imaging technique allows to assess quantitatively and in three dimensions the extent of metastatic disease in ENT cancer. The case presented illustrates the important value we foresee for this new imaging modality in the presurgical staging of cervical metastatic disease of ENT tumors. Sensitivity and specificity of the PET-FDG imaging technique for the loco-regional staging of ENT cancer are, according to preliminary results of an ongoing, prospective clinical study, very high.

Proliferation of mononuclear phagocytes (Kupffer cells) and endothelial cells in regenerating rat liver. A light and electron microscopic cytochemical study.

The proliferation of littoral cells in regenerating rat liver after partial hepatectomy has been investigated using endogenous peroxidase and uptake of large (0.8-mu) latex particles as markers of Kupffer cells. Female rats were subjected to 2/3 partial hepatectomy and sacrificed at intervals up to 11 days. Prior to sacrifice, animals were injected with latex and their livers were fixed by perfusion and were processed for cytochemical localization of peroxidase. The sinusoidal cells exhibited a marked regenerative response after partial hepatectomy. Peroxidase activity persisted in endoplasmic reticulum of Kupffer cells during mitosis. Furthermore, latex particles were exclusively localized in such peroxidase-positive cells, thus confirming their identity as Kupffer cells. Quantitative counts revealed that the peak mitotic activity of Kupffer cells occurred at 48 hours, whereas that of endothelial cells was at 96 hours after partial hepatectomy. Our findings indicate that Kupffer cells are capable of dividing locally in the liver; no morphologic evidence of transformation of endothelial cells or monocytes to Kupffer cells was found. The significance of these observations concerning the origin of Kupffer cells is discussed, and it is concluded that in the model of liver regeneration after partial hepatectomy the Kupffer cells are formed predominantly by local cell division.

Proliferation of endothelial cells in estrogen-stimulated rat liver. A light and electron microscopic cytochemical study.

The mononuclear phagocytes (Kupffer cells) in the normal rat liver can be distinguished from the endothelial cells on the basis of their endogenous peroxidase activity in the endoplasmic reticulum and their exclusive ability to phagocytose large (0.81 mum.) latex particles. Using these cellular markers we have investigated the effects of an estrogen upon the mitotic activity and the ultrastructure of individual types of littoral cells in the rat liver. Adult female rats received a single 10-mg. injection of diethylstilbestrol, and at daily intervals up to 6 days their livers were fixed by perfusion and processed for localization of peroxidase. Mitotic figures were rare in untreated control animals, but dividing littoral cells with both positive and negative peroxidase reaction could be identified. The exclusive localization of injected latex particles in dividing peroxidase-positive cells indicated that peroxidase reaction identified the Kupffer cells not only in the interphase but also during the mitotic division. In estrogen-treated animals there was a sharp rise in the mitotic activity of littoral cells; the activity reached its peak on the 3rd day and returned to normal levels on the 6th day after the initial injection. A breakdown of the dividing cells on the basis of their peroxidase reactivity revealed that nearly the entire population of dividing cells consisted of peroxidase-negative endothelial cells. In addition, numerous hyperactive Kupffer cells containing large phagolysosomes with phagocytosed peripheral blood cells and latex particles were seen. Intermediate cell-types with cytochemical features between Kupffer cells and endothelial cells or between monocytes and Kupffer cells were not encountered. Because of the limited phagocytic capacity of hepatic endothelial cells, our observations would provide morphologic evidence in support of previous physiologic studies, indicating that estrogen treatment has little or no effect upon the particle clearing function of the reticuloendothelial system in rats. The rare but clear demonstration of dividing Kupffer cells in liver sinusoids would indicate that these cells are capable of self-replication in situ. Finally, our observations suggest that estrogens may play an important role in the pathophysiology of endothelial cells.

[Adenocarcinoma of the appendix. 6 cases and review of the literature]. / Adénocarcinome de l'appendice. A propos de 6 cas et revue de la littérature.

The adenocarcinoma of the vermiform appendix is most frequently discovered at the pathological examination, which causes the problem of a second operation. Our study was done on 145 patients and compares survival according to the attitude taken by the surgeon. It seems that the most favorite treatment is a precocious right hemicolectomy.

[Long-term tumor-free surviving patients with anaplastic small cell bronchial cancer]. / Langfristig tumorfrei überlegende Patienten mit anaplastischem kleinzelligen Bronchuskarzinom.

Report on 12 patients with small cell lung cancer who achieved disease-free survival for over 24 months after initial therapy. All the cases were classified as limited disease. Median age was 62 years and median performance status 0. Only 2 patients had weight loss of more than 5% in the six months prior to the diagnosis. Four patients were treated by local therapy alone (surgery in 3, radiotherapy in 1). Eight patients received systemic treatment (chemotherapy in 4, chemotherapy plus radiotherapy in 4). Median duration of cytostatic treatment was 17 months, with 3 of 8 patients receiving chemotherapy for less than 6 months. Three patients relapsed 27, 34 and 54 months after initial treatment. Median survival is 52 + months. It is concluded that long term disease-free survival can be achieved in patients with limited disease small cell lung cancer, even where initial treatment is relatively short.

Liver glycerokinase deficiency in man with hyperglycerolaemia and hypertriglyceridaemia.

Hyperglycerolaemia and glyceroluria is described in a patient who presented transient dietary-induced hypertriglyceridaemia. The increased glycerol in blood and urine was related to glycerokinase deficiency as evidenced by a hepatic tissue glycerokinase activity of one tenth (4.8 X 10(-5) mmol g-1 min-1) of that of normoglycerolaemic subjects (5.9 X 10(-4) ). As triglycerides are routinely determined by an enzymatic method after hydrolysis to glycerol, the differential diagnosis between true hypertriglyceridaemia and hyperglycerolaemia may prove difficult. Persisting "hypertriglyceridaemia' despite adequate dietary and drug treatment should suggest the existence of undiagnosed hyperglycerolaemia .

[The role of ultrasonography in the diagnosis of diffuse liver disease]. / L'apport de l'ultrasonographie dans le diagnostic des hépatopathies diffuses.

131 patients thought to have diffuse liver disease underwent ultrasonography and percutaneous liver biopsy. The ultrasonographic criteria examined were hepatic echogenicity compared to that of the renal cortex, homogeneity of hepatic parenchyma, and regularity of hepatic outline. On the basis of histologic examination of liver biopsies, several groups of pathologic lesions (not diagnostic entities) were established. Evaluation of ultrasound and histology was double blind. When the lobular architecture of the liver was respected histologically (normal liver, granulomatosis, siderosis, hepatitis), the ultrasound was normal in 86% of cases. The sensitivity of ultrasound was 0.9 for detection of fatty liver and 0.6 for cirrhosis. An abnormal ultrasound predicted structural modifications or a fatty liver in 93% of cases. Ultrasound proved incapable of differentiating between fatty liver and cirrhosis.

Hepatitis C: a possible etiology for cryoglobulinaemia type II.

Out of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa/IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II.

[Hereditary myeloperoxidase deficiency. Clinical, biological and genetic study]. / Déficience héréditaire en myéloperoxydase.

A case is reported of hereditary myeloperoxidase deficiency in a diabetic patient suffering from a Candida albicans hepatic abscess. Myeloperoxidase (MPO) is completely absent from the neutrophils and monocytes, although it is present in the eosinophils. Functional granulocyte studies have revealed normalchemotactic and phagocytic activity, although the bacterial activity is partially diminished with regard to Staphylococcus aureus and is almost nil with regard to Candida albicans. The granulocytic metabolism, when stimulated by zymosan, is characterized by greatly increased oxygen consumption. Genetic investigations have been conducted in 28 members of the patient's family. Cyto- and biochemical determination of MPO is clearly diminished in close relatives of the patient. Genetic analysis indicates recessive autosomal transmission with variable expressivity of the gene for the heterozygote state.

[Liver transplantation for primary biliary cirrhosis]. / Transplantation hépatique pour cirrhose biliaire primitive.

Primary biliary cirrhosis (PBC) is regarded as one of the optimal indications for orthotopic liver transplantation (OLT) in adults. Between July 1987 and August 1991, 7 patients had PBC as the indication for OLT. 6 were transplanted and one patient is still on the waiting list. The patients' mean age was 47 years (range: 39 to 59) and the time from diagnosis to indication for OLT was 4, 7, 8, 10, 12, 15 and 17 years. Variceal hemorrhage episodes treated by sclerotherapy (plus porta-caval shunt in one patient) occurred in 3 patients before OLT. All suffered from jaundice (mean bilirubin 232 mumol/l, range 116 to 536), weakness, anorexia and pruritus. There were no deaths in this series during a mean follow-up time of 26 months (range 6 to 43). With the exception of osteopenia, all complications of chronic liver disease were reversed by OLT. Despite numerous postoperative problems (e.g. reoperations, intense rejection episodes, cytomegalovirus infections and lumbar column fractures), the quality of life is excellent for these 6 patients. Mean bilirubin at time of last follow-up was 18 mumol/l (range 8 to 26). No evidence of PBC recurrence was found. Based on international experience confirmed by this series, we support the notion that no patient suffering from advanced PBC should be denied OLT whenever possible.