Increased expression of major histocompatibility antigens in the liver as a result of cholestasis.

Increased expression of major histocompatibility complex (MHC) antigens may occur following liver transplantation. The mechanism by which this occurs is unclear. Postoperative complications may result in cholestasis. We have investigated the possibility that cholestasis may cause increased expression of MHC antigens in the liver. Cholestasis was induced in rat livers by bile duct ligation and transection. Total serum bilirubin rose markedly postoperatively and remained elevated over a period of 21 days. Samples of bile taken from rats were shown to remain sterile during the study period and there was no evidence of viral infection. Liver tissue taken 1, 3, 7, and 21 days postobstruction showed a marked increase in the expression of rat class I MHC antigens but not class II antigens. We suggest that cholestasis itself can induce increased MHC class I antigens in the liver. Therefore, if cholestasis occurs postoperatively in the human liver transplant recipient this might lead to increased expression of human class I MHC antigens and add to the overall cellular immune activity in a rejection reaction, although cholestasis probably cannot initiate rejection.

Macrophages and neutrophils infiltrating into the liver are responsible for tissue factor expression in a rabbit model of acute obstructive cholangitis.

Acute obstructive cholangitis (AOC) is one of the most fatal outcomes in sepsis, and frequently complicates disseminated intravascular coagulation (DIC). Recently we found that the plasma tissue factor (TF) level increased and changed in parallel with plasma markers of DIC in patients with AOC. To elucidate the role of TF in the pathogenesis of coagulopathy in AOC, we investigated the plasma levels of TF and its localization by immunohistochemical staining in rabbit models of AOC. Plasma TF activity significantly increased 3 h after the insult (0.63 +/- 0.1¿9 U/ml; p < 0.01) compared with that beforehand (0.05 +/- 0.02 U/ml), then reached a maximum level at 6 h (0.94 +/- 0.16 U/ml). The fluctuations in plasma TF activity correlated with those of the coagulation parameters including platelet count, fibrinogen, prothrombin time, and antithrombin III activity. Immunohistochemically, enhanced expression of TF was mainly detected in macrophages and neutrophils that had infiltrated into the liver sinusoids and around the bile duct, but not in the sinusoidal endothelial cells. A double immunofluorescence study revealed the concomitant presence of TF and fibrin at sites where macrophages and neutrophils had conglomerated. However, we could not detect an apparent change in TF expression in the lung or kidney. These data suggest that macrophages and neutrophils infiltrating into the liver sinusoids and around the bile duct play a pivotal role in TF expression, leading to coagulopathy in the acute phase of obstructive cholangitis in rabbits.

Renal papillary necrosis associated with Wegener's granulomatosis.

Review of the kidneys from 23 cases of Wegener's granulomatosis revealed necrosis of the renal papillae in five (21.7 per cent). These cases took a fulminant course of the disease consistent with the classic description of Wegener's granulomatosis, prevalence in the older age group, and rapid deterioration of renal function. Morphologic examination of the kidneys uniformly disclosed a variety of lesions in the blood vessels supplying the renal papilla. The most conspicuous was the widely distributed glomerular lesion represented by thrombotic and necrotic occlusion of capillary loops and crescent formation. A medullary interstitial lesion characterized by fibrinoid necrosis of the vasa recta was invariably found in the outer portion of the necrotic papilla. In addition, acute segmental and diffuse necrosis and occlusion by thrombosis were identified in the branches of spiral arteries in the adjoining papilla. The results provide an anatomic basis for the assumption that papillary ischemia due to impairment of the dual blood supply from the vasa recta and the calyceal arteries is the essential factor in papillary necrosis.

Renal amyloidosis with crescents.

An unusual case of renal amyloidosis associated with extensive crescents is reported. Light and electron microscopic examination revealed that deposits of amyloid were almost invariably involved in the locations in which proliferations of epithelial cells in the capsular spaces had merged with the glomerular tufts. Gaps or fractures of the capillary walls were present at such sites, in which amyloid fibrils were mingled with thrombic material containing fibrin. It is highly conceivable that the gaps apparently induced by amyloid deposition, with leakage of fibrin-fibrinogen into the capsular space, play a crucial role in the development of the extracapillary proliferation.

A traumatic neuroma associated with obstructive jaundice after laparoscopic cholecystectomy.

A traumatic neuroma of the biliary tract is rarely associated with biliary obstruction. The authors describe a case of obstructive jaundice that occurred after laparoscopic cholecystectomy. Obstructive jaundice developed in a 39-year-old woman 8 months after laparoscopic cholecystectomy. The stricture was resected and a Rouxen-Y hepaticojejunostomy was performed. Histological examination revealed a traumatic neuroma and a fibrous scar around the biliary duct. To our knowledge, a traumatic neuroma of the biliary tract after laparoscopic cholecystectomy has not been reported previously. Thermal injury may cause the late onset of a fibrous scar and traumatic neuroma. Therefore, traumatic neuroma should be included in the differential diagnosis when late-onset biliary tract obstruction develops after laparoscopic cholecystectomy.

Separate histogenesis of combined hepatocellular and cholangiocellular carcinoma in two patients.

Double primary liver carcinomas, i.e. hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) are rare. Two patients in whom double primary liver carcinomas were surgically resected are described herein. Case 1: A 51-year-old Japanese man with chronic type B hepatitis underwent hepatectomy for primary HCC with intrahepatic metastasis. Case 2: A 67-year-old Japanese man with a history of rectal cancer and CCC underwent lateral hepatic segmentectomy for a suspected recurrence of intrahepatic CCC. Lack of direct contact between tumors, no evidence of histological transition and clearly different immunohistochemical staining for cytokeratin support a distinct histogenesis of the tumors in these two patients. The findings indicate that combined HCC and CCC can arise synchronously or metachronously as an intrahepatic double cancer.

Traumatic pancreatic duct rupture in a child diagnosed by endoscopic retrograde pancreatography.

We report on a child who sustained blunt abdominal trauma with pancreatic duct rupture diagnosed by preoperative endoscopic retrograde pancreatography (ERP). Duct laceration remained undiagnosed by computerized tomography or ultrasonography. Preoperative ERP is the only known method for the accurate diagnosis of injury to main pancreatic duct. Even in children with pancreatic trauma we recommend ERP before any surgery is attempted to help in decisions on operative strategy.

[Estrogen receptors in human gastric, hepatocellular, and gallbladder carcinomas and normal liver tissues].

Steroid binding assay using the dextran coated charcoal (DCC) method was applied to human tissues including tumors of the digestive organs, and the results were compared with those of enzymeimmunoassay (EIA) and immunocytochemical assay (ICA) with monoclonal antibody against human estrogen receptor of MCF-7 breast cancer cells. Using the DCC method, estrogen receptor activity was detected in 6 of 26 cases (23.1%) with gastric carcinoma, 3 of 16 hepatocellular carcinoma cases (18.8%), 1 of 3 gallbladder carcinoma cases (33.3%), and both of the 2 cases (100%) with normal liver tissue. However, using EIA, no ER activity was detected in any case. Moreover, ER positive cells were not found by immunohistochemical staining in the gastric carcinoma cases or in normal liver tissue, both of which showed ER activity by the DCC method. These results suggest that the estrogen receptor like material exists in cytosol of the human digestive tumors and normal liver tissue, but that the specificity of the antibodies against estrogen receptor molecules in these tumors may be different from that of the breast tumors.

[Therapeutic value of hepatectomy and transcatheter arterial embolization (TAE) for hepatocellular carcinoma].

Therapeutic value of hepatectomy and TAE was evaluated retrospectively in 150 hepatectomized and 117 non-hepatectomized patients of hepatocellular carcinoma (HCC). Operative death was seen in 5 patients. Cumulative 5 years survival rate and disease free cumulative 5 years survival rate of the 145 hepatectomized patients were 35.4 per cent and 23.6 per cent respectively. These survival rates were significantly affected by tumor size, intrahepatic metastasis (IM) and vascular invasion (Vp). But the influences of tumor margin (TW) and curative resection (relative curative or relative non-curative) were slight. Ninety-two patients (69:dead, 23:alive) had tumor recurrences. TAE was performed in 56 out of 92 patients effectively and 2 years survival rate was 31.5 per cent. Overall cumulative 5 years survival rate of non-hepatectomized patients was 6.6 per cent, but this group showed a more reduced hepatic reserve and more advanced tumor stage. Six patients treated by TAE survived more than 4 years. Hepatectomy is a first option for the treatment of HCC since complete cure may be estimated. However, because of operative risk and higher recurrence rate, use of current multidisciplinary treatment including TAE is necessary for the prognostic improvement of HCC with or without hepatectomy.

Hepatic beta 2-microglobulin distribution in primary biliary cirrhosis.

The distribution of beta 2-microglobulin (beta 2-m) was studied by immunoperoxidase in paraffin sections of 30 liver biopsies from 28 patients with primary biliary cirrhosis (PBC). In 24 of the patients beta 2-m was demonstrable on the membranes of hepatocytes, whereas normal hepatocytes were usually negative. This increased display of beta 2-m probably parallels increased display of class I HLA antigens. The affected hepatocytes may be more susceptible to T cell-mediated immune attack. A greater number of beta 2-m displaying hepatocytes was seen in the later stages of PBC, in keeping with the hypothesis that in this disease hepatocyte involvement is a secondary phenomenon. Bile duct epithelium continued to display beta 2-m at all stages of the disease.

Expression of beta 2-microglobulin on hepatocytes in acute and chronic type B hepatitis.

beta 2-Microglobulin display was examined in 131 liver biopsies from patients with acute and chronic type B hepatitis, using an indirect immunoperoxidase method. Enhanced expression of beta 2-microglobulin on hepatocyte membranes was observed in patients with acute hepatitis, chronic active hepatitis with moderate to severe activity and cirrhosis, when compared with normal liver. In acute hepatitis, beta 2-microglobulin-positive hepatocytes were mainly observed in perivenular areas in association with bridging necrosis. In chronic hepatitis, beta 2-microglobulin-positive hepatocytes were observed mainly in periportal zones and in some areas of lobular activity. Diffuse-enhanced display of beta 2-microglobulin on hepatocytes was observed in 5 of 6 patients treated with lymphoblastoid interferon as part of a trial of antiviral therapy. The mechanism by which beta 2-microglobulin display is enhanced on hepatocytes in patients not treated with interferon is uncertain. However, display of beta 2-microglobulin on hepatocytes probably reflects display of HLA-A, B and C antigens and may influence the course of hepatitis B virus infection by increasing susceptibility of the affected cells to T cell-mediated immune attack.

Hyalinized hemangioma of the liver.

We report the case of a 65-yr-old woman with hyalinized hemangioma of the liver which, on radiological examination, resembled primary or metastatic carcinoma of the liver. She had undergone a partial colectomy for a sigmoid adenocarcinoma, followed by the diagnosis of a hepatic tumor with ultrasonic echogram 5 months later. The tumor was depicted as a low-density mass on plain computed tomography (CT), and an enhancement at the peripheral portion was noted by contrast CT. Hepatic angiography disclosed a faint pooling of contrast medium in segment 8. A subsementectomy of the liver was performed under the diagnosis of metastatic adenocarcinoma or hepatocellular carcinoma. Histologically, the tumor was composed of dense collagenous tissues with marked hyalinization and scattered sclerotic vessels. Elastic fibers were distributed concentrically around the vessels. Totally hyalinized sclerosis of hemangioma is uncommon, and can be erroneously diagnosed as carcinoma by radiologic examination. This unusual hemangioma is reported, with pertinent literature.

A 10-year survivor with unresectable hepatic metastases from sigmoid colon carcinoma treated with regional chemotherapy.

We treated a man with unresectable hepatic metastases from sigmoid colon carcinoma who has since survived for more than 10 years. A sigmoidectomy with lymph node dissection was performed and a continuous hepatic arterial infusion of 5-fluorouracil (5-FU) with intermittent infusion of mitomycin C (MMC) was administered for about 3 months after this operation. The total doses of 5-FU and MMC were 16 g and 84 mg, respectively. Tegafur also was administered orally at a dose of 600 mg/day for about 8 months. The carcinoembryonic antigen (CEA) level (which had reached 4,409 ng/ml preoperatively) normalized 4 months after surgery, and still remains normal. Very few patients with unresectable hepatic metastases survive for 5 or more years. However, regional chemotherapy can be effective in some patients.

Role of macrophages in atherosclerosis. Sequential observations of cholesterol-induced rabbit aortic lesion by the immunoperoxidase technique using monoclonal antimacrophage antibody.

To elucidate the role of macrophages in atherosclerosis, sequential observations were carried out on cholesterol-induced aortic lesions of the rabbit with the immunoperoxidase technique by use of monoclonal antimacrophage antibody. Animals on cholesterol diets for 8 weeks or longer showed increased accumulations of lipid-filled macrophages in the intima. At a very early stage, when no grossly visible alterations were observed, macrophages were seen clinging to the endothelial surface with apparent penetration of the endothelium. A single line of three or four vacuolated macrophages were found in otherwise normal subendothelial spaces. In flat lesions consisting of a few layers of foam cells, lipid-laden macrophages were the cells that predominated. In advanced plaque lesions, negatively staining, most presumably, smooth muscle foam cells became noticeable and increased in number. At this stage, macrophage foam cells predominated in the superficial layer of the lesion, whereas negatively staining foam cells were prevalent in deeper areas. Macrophages were also spotted within areas of necrosis, and they were occasionally observed near the necrotic core of the atheroma. During 24 to 74 weeks after termination of the cholesterol diet, the number of cells with specific macrophage staining markedly diminished. The results support the concept that circulating monocytes are the prime source of foam cells in the initial phase of atherogenesis. It seems likely that the major role of macrophages in atherogenesis is to remove lipids from areas of lesion formation. The failure of macrophages to perform their scavenger role successfully may be a major factor in the accumulation of lipid-rich debris in advanced lesions. Relative paucity of macrophages may also be an important factor explaining why regression of atherosclerosis occurs rarely in the rabbits.

Expression of beta-2-microglobulin on hepatocytes after liver transplantation.

The distribution of beta 2-microglobulin was studied by an immunoperoxidase method in paraffin sections from sixteen serial graft liver biopsy samples taken after liver transplantation from four patients who had received transplants for advanced primary biliary cirrhosis. Mild to moderate acute rejection was diagnosed in three of the patients. Expression of beta 2-microglobulin on hepatocyte membranes was greater during rejection, and tended to fall after the rejection episode. However, a few hepatocytes continued to display beta 2-microglobulin on their cell membranes. Rejection was characterised histologically by infiltration of portal tracts with lymphoid cells, and cholestasis. Enhanced display of beta 2-microglobulin on hepatocytes probably reflects display of HLA A, B, and C antigens and may be associated with increased susceptibility of the affected cells to T-lymphocyte-mediated immune attack.

Hepatobiliary fibropolycystic diseases. A clinical and histological review of 51 patients.

The clinical, radiological and hepatic histological features of 51 patients with hepatobiliary fibropolycystic disease were reviewed. Many of the patients had more than one of the diseases; the combination of both congenital hepatic fibrosis (CHF) and Caroli's disease was most striking. Twelve patients with CHF (50% male) presented at 6 +/- 2 years of age (mean +/- SEM) with hepatosplenomegaly or variceal bleeding. Their main problems were recurrent variceal bleeds and renal disease. Polycystic kidneys and renal stones were present in 79% and chronic renal failure in 30%. Six of the 8 patients with Caroli's disease were male (75%) and presented later (aged 37 +/- 8 years) with hepatomegaly or cholangitis. Recurrent cholangitis developed in most (7/8) and 2 had polycystic kidneys. Twelve patients had a combination of CHF and Caroli's disease presenting with hepatosplenomegaly, bleeding or cholangitis. As in Caroli's disease, most (83%) were male, but the age of presentation (15 +/- 4 years), and the incidence of polycystic kidneys (42%) and renal failure (8%) was intermediate between CHF and Caroli's disease. In these patients, bleeds always predated cholangitis. Histologically, acute cholangitis was superimposed on the changes of CHF. Adult polycystic liver disease (10 patients) presented later (43 +/- 3 years) in females (90%) with pain, a mass or incidentally; polycystic kidneys were present in 33%. Microhamartomas (10 patients), which were usually incidental findings, were diagnosed latest (50 +/- 6 years). Three choledochal cysts were seen. The hazard of cancer in these diseases was reflected by 2 bile duct cancers and 1 pancreatic cancer (incidence 6%). This study has confirmed that hepatobiliary fibropolycystic diseases form part of a family and are often associated together. However, the diseases are of greatly differing severity and the prognosis in an individual patient is determined by the fibropolycystic diseases present.

Benign schwannoma in the hepatoduodenal ligament: report of a case.

A 62-year-old woman with a large mass in the hepatic hilus underwent surgery. Histologically the tumor was predominantly composed of spindle-shaped cells with nuclear palisading and cells that stained positively for S-100 protein. The diagnosis was benign schwannoma (neurilemoma). The presence of lymphoid cuffing with lymphoid follicles in the capsule and xanthomatous change differed from conventional soft parts schwannoma and closely resembled benign schwannoma in the gastrointestinal tract.