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It has been hypothesized that abdominal trauma may be one of the factors involved in membranous obstruction of the inferior vena cava. We present two cases of membranous obstruction of the inferior vena cava associated with trauma. One asymptomatic case, associated with an occult myeloproliferative disorder, developed within 3 years of a violent abdominal trauma. The other case, associated with familial plasminogen deficiency, was discovered at surgery 3 days after a road accident with obvious abdominal trauma, since superimposed extensive thrombosis of the inferior vena cava caused acute Budd-Chiari syndrome. We conclude that underlying prothrombotic conditions are probably necessary for the development of membranous obstruction of the inferior vena cava and that minor trauma may contribute to the development of thrombosis through indirect mechanisms.

Serum apolipoprotein A-I measurement was compared in alcoholic patients according to presence or absence of chronic pancreatitis and liver fibrosis. Among alcoholic patients without liver disease, apolipoprotein A-I was significantly lower in patients with chronic pancreatitis (157 +/- 70 mg/dl) than in patients without pancreatitis (209 +/- 74 mg/dl, p less than 0.001). In cirrhotic patients, apolipoprotein A-I was lower in patients with chronic pancreatitis (82 +/- 35 mg/dl) than in patients without pancreatitis (102 +/- 45 mg/dl), but this difference was not significant. The decrease of serum apolipoprotein A-I was independent of nutritional parameters whether or not there was cirrhosis. Immunohistochemical study of pancreatic samples with chronic pancreatitis showed that apolipoprotein A-I was located in the pancreatic fibrosis whereas lobules were unstained. This study suggests that apolipoprotein A-I is trapped by the pancreatic extracellular matrix and that this sequestration might explain, in part, the decrease of the serum apolipoprotein A-I.

Summary In an attempt to study the mechanisms leading to fibrosis in chronic pancreatitis, an in situ immunohistochemical investigation of lymphocytes and of class II major histocompatibility complex expression (HLA-DR) by epithelial cells has been designed. Samples of normal pancreas (n = 8), chronic calcifying pancreatitis (n = 4), chronic obstructive pancreatitis (n = 6), and diffuse fibrosing pancreatitis (n = 6) have been studied. In normal pancreas, T-lymphocytes were rare and were located in the epithelial layer of pancreatic ducts and in the penductal connective tissue. Duct cells were constantly HLADR negative. In chronic calcifying pancreatitis and chronic obstructive pancreatitis, T cells were numerous and were located around ducts and in the spreading areas of fibrous septa. In chronic obstructive pancreatitis, the duct cells strongly expressed the HLA-DR antigen. In diffuse fibrosing pancreatitis, fibrous tissue was devoid of lymphocytes and duct cells never expressed the HLA class II antigen. These results suggest that lymphocytes are involved in the fibrosing process occurring in chronic calcifying pancreatitis and chronic obstructive pancreatitis but not in diffuse fibrosing pancreatitis. The significance of de novo expression of HLA-DR antigen by duct cells is discussed.

Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administration of docetaxel. In experiment (Exp) 1, the drug was given once a week (wk) for 6 wks (20 mg/kg/wk) or for 5 wks (30 mg/kg/wk) at one of six circadian times, during light when mice were resting [3, 7, or 11 hours after light onset (HALO)], or during darkness, when mice were active (15, 19, or 23 HALO). Endpoints were survival and body weight change. In Exp 2 and 3, docetaxel (30 mg/kg/wk) was administered twice, 1 wk apart, at one of four circadian stages (7, 11, 19, or 23 HALO). Endpoints were hematological and intestinal toxicities. In Exp 4, circadian changes in cell cycle phase distribution and BCL-2 immunofluorescence were investigated in bone marrow as possible mechanisms of docetaxel tolerability rhythm. In Exp 5 to 7, docetaxel was administered to mice bearing measurable P03 pancreatic adenocarcinoma (270-370 mg), with tumor weight and survival as endpoints. Mice from Exp 5 and 6 received a weekly schedule of docetaxel at one of six circadian stages (20 or 30 mg/kg/wk at 3, 7, 11, 15, 19, or 23 HALO). In Exp 7, docetaxel (30 mg/kg) was given every 2 days (day 1, 3, 5 schedule) at 7, 11, 19, or 23 HALO. Docetaxel dosing in the second half of darkness (19 or 23 HALO) resulted in significantly worse toxicity than its administration during the light span (3, 7, or 11 HALO). The survival rate ranged from 56.3% in the mice treated at 23 HALO to 93.8 or 87.5% in those injected at 3 or 11 HALO, respectively (Exp 1, P0.01). Granulocytopenia at nadir was -49 +/- 14% at 7 HALO compared with -84 +/- 3% at 19 HALO (Exp 2 and 3, P0.029), and severe jejunal mucosa necrosis occurred in 5 of 8 mice treated at 23 HALO as opposed to 2 of 18 receiving docetaxel at 7, 11, or 19 HALO (Exp 2 and 3, P0.02). The time of least docetaxel toxicity corresponded to the circadian nadir in S or G2-M phase and to the circadian maximum in BCL-2 immunofluorescence in bone marrow. Docetaxel increased the median survival of tumor-bearing mice in a dose-dependent manner (controls: 24 days; 20 mg/kg weekly, 33 days; 30 mg/kg weekly or day 1, 3, 5 schedule, 44 or 46 days, respectively; Exp 5-7). Survival curves of treated mice differed significantly according to dosing time for each dose and schedule (P from log rank0.003 to P0.03). In Exp 5 and 6, the percentage of increase in life span was largest if docetaxel was administered weekly at 7 HALO (20 mg/kg, 220%; 30 mg/kg, 372%) and lowest after docetaxel dosing at 19 HALO (80% with 20 mg/kg) or at 15 HALO (78% with 30 mg/kg). In Exp 7, (day 1, 3, 5 schedule), docetaxel was most active at 11 HALO (percentage increase in life span, 390%) and least active at 23 HALO (210%). Docetaxel tolerability and antitumor efficacy were simultaneously enhanced by drug dosing in the light span, when mice were resting. Mechanisms underlying the tolerability rhythm likely involved the circadian organization of cell cycle regulation. Docetaxel therapeutic index may be improved with an administration at night in cancer patients, when fewest bone marrow cells are in S or G2-M phase.

We report a case of primary lymphoma of the liver successfully treated by major liver resection. The tumor exhibited the immunohistological features of a B-cell low-grade lymphoma of the lymphoplasmacytic type. Tumoral plasmacytic cells showed cytoplasmic-positive staining for IgG and kappa light chains. In addition, we detected a serum monoclonal peak of IgG kappa, a finding that has not been reported previously. Clinical, pathological, and immunohistochemical data from the literature are reviewed.

In a semiquantitative assessment of the expression of transforming growth factor (TGF) beta 1 in liver biopsy specimens from patients with chronic hepatitis C, treatment with interferon alfa-2b (3 million units (MU) three times weekly) decreased the expression of TGF beta 1 in six of seven patients. The reduction in TGF beta 1 correlated significantly with the scores for inflammation (p < 0.05) and necrosis (p < 0.05), but not with the alanine aminotransferase activities (p = 0.36) or the score for fibrosis (p = 0.86).

HLA-DR expression, lymphocyte subsets, and the distribution of proliferating cells were studied in hyperplastic polyps from the colorectum. The density of T-cells (CD5+) (mean of cells/mm2 of tissue +/- SEM) was higher in the lamina propria of hyperplastic polyps (64.2 +/- 4.2) than in normal colonic mucosa (36.7 +/- 2.6, P less than .001). The CD4/CD8 ratio was higher in hyperplastic polyps (6.3 +/- 0.9, P less than .0001) and in colonic adenomas (5.9 +/- 0.9, P less than .001) compared with normal mucosa (2.3 +/- 0.2). Lymphocytes of the lamina propria were never Ki-67 positive either in normal mucosa or in hyperplastic polyps or adenomas. The epithelial layer of hyperplastic polyps and of normal mucosa did not express the HLA-DR antigen, whereas pericryptal fibroblasts and most of the leukocytes of the lamina propria were strongly positive for this antigen. In the epithelial layer proliferating cells were localized exclusively in the lower part of epithelial crypts, as was the case in normal mucosa, whereas in adenomas Ki-67-positive cells were present throughout the entire height of the mucosa. Thus, in hyperplastic polyps lymphocytes are increased in the lamina propria, with a predominance of the CD4 subset in close contact with HLA-DR positive pericryptal fibroblasts.

We compared the effects of different fixatives and enzymatic-digestion procedures on the immunohistochemical visualization of type-I, -III and -IV collagen in paraffin-embedded normal human liver sections. None of the fixatives tested allowed the staining of these antigens without prior enzymatic digestion. The best results i.e. strong staining intensity and well-defined localization, were obtained when liver tissue was fixed in Bouin's fluid or in other solutions containing picric acid. Several other fixatives, including Carnoy's fluid, Lillie's AAF, 10% neutral formalin and 96% ethanol, gave unsatisfactory results. Pepsin was ineffective for unmasking type-I and -III collagen antigens, and was only partially effective for visualizing the type-IV collagen antigen. The best results were obtained when material fixed in Bouin's fluid was embedded in paraffin and digested with trypsin. Using this procedure, the results were comparable to those obtained in unfixed frozen sections with respect to the staining intensity, specificity and non-specific staining.

A longitudinal study of intra and extrahepatic bile duct injuries was performed in an animal model of secondary sclerosing cholangitis induced by formalin injection into the common bile duct. Lymphocytic infiltration inside and around the bile ducts occurred seven days after injection. The disease later evolved to a fibrous cholangitis of the small bile ducts. Septal intrahepatic and extrahepatic bile duct involvement became evident three months after formalin injection. The ductular proliferation led to a progressive biliary cirrhosis with portal to portal fibrous septa. After formalin injection, bile duct cells expressed the Ia antigen in the cytoplasm and/or on the membrane of bile duct cells. The intensity of staining did not correlate with the duration or severity of the disease. Lymphocytes infiltrating into and around the bile duct were mainly T-cells. This study suggests that a local cell-mediated immune response to the injection of a toxic agent induces pathological features similar to those of sclerosing cholangitis in man.

One-hundred and forty eight patients operated upon for chronic pancreatitis were reviewed retrospectively in 5-20 year followup. Treatment was by drainage of the duct of Wirsung to adefunctionalized jejunal loop, distal pancreatectomy, pancreato-duodenectomy, splanchnicectomy with an operative mortality of 5%. Influence of clinical and anatomical data upon long term survival and symptomatic results was studied. Among Wirsungo-jejunostomy, distal or cephalic pancreatic resections, survival rates were highest with drainage of the duct of Wirsung and lowest with the pancreatoduodenectomy. Retrospectively, post-operative alcoholism appeared as the alone factor affecting long-term survival. Pancreatic insufficiency and liver cirrhosis were main causes of death. Among the survivors, the percentage of good symptomatic results ranged from (1/3) with splanchnicectomy to 6 of 8 after duodeno-pancreatic resection. Alcohol abstinence affected sypmptomatic results but at a lesser degree than for survival. It was observed that when left pancreatectomy was performed, drainage of the remaining duct of Wirsung into the jejunum significantly improved the good results from 40% to 75%. In the group of wirsungo-jejunostomies without pancreatic resection, it was found that pancreatic calcifications and a large diameter of the duct of Wirsung at the time of operation were favorable prognostic factors.

Light and transmission electron microscopic study as well as immunohistochemical investigation were performed on three cases of light chain deposition disease (LCDD) with severe liver dysfunction. In two cases, the amount of light chain deposits in the liver was moderate and did not correlate with the severity of clinical and biological symptoms. Ultrastructural study demonstrated a collagenization of the Disse's space, with basement membrane-like material in association with light chain deposits. Immunohistochemical investigation showed a marked increase of collagen types I, III, and IV, as well as fibronectin and laminin in perisinusoidal space. This study suggests that collagenization of the Disse's space has a minor role in liver dysfunction. The analogy between kidney and liver lesions in diabetes and in LCDD is stressed, but the mechanism of this abnormal accumulation of matrix proteins remains unknown.

Excerpt To the editor: Sprengers and associates (1) report the first two cases of obstructive jaundice related to primary bile duct carcinoma in patients with von Recklinghausen disease. Carcinomas...