Role of mesenchymal cell death in lung remodeling after injury.

Repair after acute lung injury requires elimination of granulation tissue from the alveolar airspace. We hypothesized that during lung repair, signals capable of inducing the death of the two principal cellular elements of granulation tissue, fibroblasts and endothelial cells, would be present at the air-lung interface. Bronchoalveolar lavage fluid obtained from patients during lung repair induced both fibroblast and endothelial cell death, while fluid obtained at the time of injury or from patient controls did not. The mode of cell death for endothelial cells was apoptosis. Fibroblast death, while morphologically distinct from necrosis, also differed from typical apoptosis. Only proliferating cells were susceptible to the bioactivities in lavage fluid, which were trypsin sensitive and lipid insoluble. Histological examination of lung tissue from patients after lung injury revealed evidence of apoptotic cells within airspace granulation tissue. Our results suggest that cell death induced by peptide(s) present at the air-lung interface may participate in the remodeling process that accompanies tissue repair after injury.

Radiotherapy in mice with yttrium-90-labeled anti-Ly1 monoclonal antibody: therapy of established graft-versus-host disease induced across the major histocompatibility barrier.

A monoclonal antibody recognizing Ly1, the murine homologue of CD5, was labeled with 90Y. In vivo biodistribution studies showed that 90Y-anti-Ly1 selectively localized in lymphoid tissue. Groups of B10,BR mice (H-2k) were lethally irradiated and given major histocompatibility complex-disparate C57BL/6 (H-2b) bone marrow and spleen cells to induce graft-versus-host disease (GVHD). Eight days later, mice with active GVHD were administered a single i.p. injection of 50 microCi90Y-anti-Ly1. Fifty % of these mice were alive 2 months after treatment. Long term (greater than 4-month) survival was significantly higher than in phosphate-buffered saline-treated mice. Survival was slightly improved in groups of mice receiving control irrelevant antibody labeled with 90Y or mice receiving free 90Y. However, survival in these groups was not significantly different from the phosphate-buffered saline-treated control group. The improved survival was supported by data showing improved mean animal weight. An anti-GVHD effect was confirmed by histopathological analysis. Unlabeled anti-Ly1 monoclonal antibody at comparable doses to 90Y-anti-Ly1 was not effective. Animals that died following 50-microCi treatment did not die of radiation toxicity, since all mice receiving 50 microCi 90Y-anti-Ly1 plus syngeneic bone marrow survived. The window of therapy was narrow in our studies, since 100 microCi 90Y-anti-Ly1 did not confer any survival advantage. Animals that did survive long term were studied for evidence of alloengraftment and found to have high levels of circulating donor mononuclear cells. 90Y-Anti-Ly1 localized in the spleen, thymus, liver, kidney and bone marrow but not in the bowel, lung, muscle, or skin. Animals given similar doses of free 90Y, 90Y-anti-Ly1, or labeled irrelevant antibody eliminated free 90Y fastest, followed by 90Y-anti-Ly1 and then labeled irrelevant antibody. Hematological analysis of peripheral blood from 90Y-anti-Ly1-treated mice showed reduction in total WBC counts, absolute lymphocyte numbers, and absolute neutrophil numbers on day 24 after treatment. Myelosuppression recovered by day 38. These findings indicate that Ly1-positive cells are involved in the effector phase of GVHD and that radiolabeled antibodies may be useful as cell-specific probes for studying the GVHD network. 90Y-Anti-Ly1 protected recipients long term from lethal GVHD, and the fact that it had a rather remarkable inhibitory and selective effect on the lymphoid system of mice suggests that these agents may have broader application in the field of transplantation.

Respiratory syncytial virus-induced acute lung injury in adult patients with bone marrow transplants: a clinical approach and review of the literature.

Acute lung injury induced by respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in patients who have undergone bone marrow transplantation. Twenty-nine of the 74 patients who received bone marrow transplants at the University of Minnesota during a 1-year period developed evidence of acute lung injury, and RSV was identified as the cause in 8. We discuss the clinical course of these 8 patients and offer a clinical approach to RSV infection occurring after bone marrow transplantation. We also review the immune response to infection with RSV and relate this information to the nature and degree of immunosuppression present in patients undergoing this type of transplantation. We found bronchoalveolar lavage with rapid antigen detection to be particularly useful for the prompt diagnosis of this serious infection. The virus was obtained from the lower respiratory tract of each patient and was identified in lavage effluent by culture and by antigen detection (ELISA). The mean time to a positive culture was 6 days, while detection of antigens of respiratory syncytial virus by ELISA was completed within 18 hours in all cases. The clinical progression of the illness in immunocompromised patients appears to be the same as in non-immunocompromised persons: upper respiratory tract infection and illness precede lower respiratory tract infection and acute lung injury. Seven of our 8 patients had upper respiratory tract symptoms or abnormal sinus radiographs, and upper respiratory specimens (cultures and ELISA from nasopharynx, throat, and sputum) were positive in 5 of 8 patients. Six patients developed RSV-induced lung injury before marrow engraftment; 4 of them had respiratory failure requiring mechanical ventilation and died, including 3 in whom RSV was eliminated from the lower respiratory tract following treatment with ribavirin aerosol. Two additional pre-engraftment patients had only relatively mild lung injury 4 days after beginning treatment with ribavirin for RSV infection in the upper respiratory tract. Their recovery suggests that early treatment may ameliorate RSV-induced lung injury. The remaining 2 patients developed lung injury after marrow engraftment. Both of these patients had clear chest radiographs, responded clinically to ribavirin, and survived. RSV is a potentially treatable cause of life-threatening lung injury, if the physician is aggressive in identifying the virus in the upper respiratory tract before evidence of lung injury appears. Rapid detection methods are essential when bone marrow transplant patients have fever along with signs, symptoms, or radiographic indications of nasal or sinus disorders.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical and laboratory evaluation of cytomegalovirus-induced mononucleosis in previously healthy individuals. Report of 82 cases.

The present report describes the clinical and laboratory profile of 82 previously healthy individuals who developed cytomegalovirus (CMV)-induced mononucleosis. Many of these patients posed initial diagnostic problems and were hospitalized with diagnoses such as fever of undetermined origin, active viral hepatitis, acute leukemia, probable systemic lupus erythematosus, autoimmune hemolytic anemia, and severe pancytopenia. These patients underwent a variety of diagnostic biopsies, including liver biopsies (6) and bone marrow aspirations (9). Four patients had exploratory laparotomies, 1 for a ruptured spleen, and another had a splenectomy following an erroneous initial diagnosis of agnogenic myeloid metaplasia. There was no apparent clinical response to a short course of steroid therapy in 3 of 5 cases and acyclovir in another. The vast majority of these patients demonstrated infectious mononucleosis-type reactive blood smears, negative heterophil antibody studies, mildly or moderately elevated aspartate aminotransferase activity, and evidence for subclinical hemolysis on serial specimens. The peak serum bilirubin levels were above 2.0 mg/dl in only 2 of 71 cases tested, both of the latter patients having significant hemolysis (hemoglobin values 8.6-9.3 g/dl). The CMV-IgM test had a high sensitivity for detection of CMV macroglobulins (positive in 81 of 82 cases). In contrast, complement-fixing antibodies to CMV showed diagnostic four-fold titer changes in only 39/82 cases (47.6%). Despite its great sensitivity, the CMV-IgM test is limited by a one-way crossreaction of acute Epstein-Barr virus (EBV)-IM sera and spurious positive reactions in some sera due to the presence of rheumatoid factors. Based on EBV-specific serologic studies, the 82 patients with CMV-IM could be divided into 4 groups: 3 patients without antibodies to EBV; 2) 69 patients with uncomplicated serologic data indicative of long-past EBV infections; (3) 6 patients with unusual antibody profiles, e.g., anti-D responses; and (4) 5 patients, including 1 originally susceptible to EBV, with apparent dual CMV/EBV infections. At the conclusion of our study, final diagnoses and initial hematologic data were correlated in 750 cases in which CMV macroglobulins were searched for. The vast majority of patients with active CMV infections initially demonstrated either markedly or moderately reactive peripheral blood smears. These data support our impression that diagnostic tests for CMV, as well as for EBV, are seldom indicated in symptomatic previously healthy patients whose blood smears during the acute phase (first several weeks) of their illnesses are either nonreactive or minimally reactive.

Invasive Scopulariopsis in the immunocompromised host.

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Long-term complications of arteriohepatic dysplasia.

PURPOSE: It has been stated that arteriohepatic dysplasia is a form of biliary paucity with a good prognosis. We wished to determine the long-term morbidity and mortality associated with arteriohepatic dysplasia. PATIENTS AND METHODS: The charts of all patients with arteriohepatic dysplasia followed by the pediatric gastroenterologists of the University of Minnesota into adulthood were reviewed. RESULTS: Over the last 33 years, the pediatric gastroenterologists have followed 16 children with syndromic paucity, six of whom are now beyond age 18 years. Although five of six patients responded to medical therapy with improvement in their cholestasis and appeared stable clinically through childhood, five of six patients had complications of arteriohepatic dysplasia after age 16 years that resulted in severe morbidity (three) or death (two). These complications included hepatic failure (two), renal failure (one), cerebellar herniation (one), and hepatocellular carcinoma (one). In only one patient were symptoms of the complications present prior to the age of 18 years. CONCLUSION: As more patients with arteriohepatic dysplasia reach adulthood, it appears that this syndrome may be accompanied by long-term manifestations extending beyond childhood. It is important that physicians assuming management of these patients from pediatricians be aware that new abnormalities may appear without warning and that the hepatic disease may deteriorate despite apparent stability through childhood.

Invasive Fusarium infections in bone marrow transplant recipients.

From November 1982 to September 1983, three cases of invasive infection due to Fusarium species were documented in bone marrow transplant recipients. Fusarium was cultured from discrete skin nodules (one patient), maxillary sinus (one patient), or from the blood and surgically excised nasal septum (one patient). All three isolates were resistant to 5-fluorocytosine, whereas only one isolate was resistant to amphotericin B. Although all three patients died, two of the patients had clearing of their Fusarium infection. From this experience and from a review of the literature, it is concluded that despite the dismal prognosis for immunocompromised patients with Fusarium, beneficial therapies would include systemic amphotericin B, local surgical resection, and possibly leukocyte transfusions.

Graft-versus-host disease of the gastrointestinal tract.

Gastrointestinal tract disease (GIT) is relatively common following bone marrow transplantation (BMT). Infections, particularly with viral agents, are similar to those affecting any immunosuppressed transplant recipient. However, two unique aspects of BMT are (a) cytotoxic damage caused by the chemotherapy and irradiation used to eradicate the patient's native marrow and (b) gastrointestinal involvement with graft-versus-host disease (GVHD). GVHD may affect any portion of the GIT; therefore, both upper and lower GIT biopsies may provide diagnostic information not evident in biopsy from a single site. The upper GI tract has a higher yield of positive biopsy specimens, but it is more difficult to biopsy. The basic histopathological feature of acute GIT GVHD, which occurs in the first 100 days posttransplant, is necrosis of individual cells in the regenerating compartment of the mucosa. Severe disease may lead to loss of crypts and eventual sloughing of the mucosa. The histology of acute GVHD may be simulated by cytoreductive agents and viral infections, particularly with cytomegalovirus (CMV). Therefore, an absolute biopsy diagnosis of acute GVHD cannot be made in the first 21 days posttransplant or in any mucosa containing CMV inclusions. The GIT is less often involved in chronic than in acute GVHD. The basic pathology of chronic GIT GVHD is fibrosis of the submucosa and subserosa. Therefore, mucosal biopsy is of limited usefulness in the diagnosis of chronic GVHD.

Problems in the interpretation of liver biopsies after liver transplantation.

As more liver transplants are performed and we realize that biopsy is the best means to diagnose rejection, the surgical pathologist has gained prominence as part of the transplant team. The surgical pathologist now plays a pivotal role in the day-to-day management of liver transplant patients. Diagnosis of rejection is a major task; however, other processes, particularly infectious ones, are also important causes of liver dysfunction that must be distinguished from rejection. Rapid and accurate diagnosis of acute rejection is possible if attention is paid to diagnostic criteria. The biopsy is also valuable to assess efficacy of therapy and provide prognostic information. The histological diagnosis of chronic rejection remains difficult, if not impossible. In all cases, and especially in the assessment of chronic rejection, close cooperation with the clinical staff is essential for proper patient management.

Adenomas in glycogen storage disease type 1. Two cases with unusual histologic features.

Two cases of hepatic adenomas arising in patients with glycogen storage disease type I are presented. In both cases, the adenomas showed unusual histological features including marked fatty change, a polymorphonuclear infiltrate, Mallory hyalin, and lamellar fibrosis. In addition, one case was associated with amyloidosis. Such features have only recently been described in adenomas and have not been reported previously in association with glycogen storage disease type I.

Colorectal polyps in Cowden's disease (multiple hamartoma syndrome).

Colorectal polyps are described in five patients with Cowden's disease. A brother-sister kindred and two unrelated patients had multiple colonic polyps 0.1-0.4 cm in diameter. Microscopical examination of seven polyps removed from these four patients showed distinctive lesions which were probably hamartomatous, and characterized by disorganization and proliferation of the muscularis mucosae with minimally abnormal overlying mucosa. The fifth patient had a solitary 2-cm epitheloid leiomyoma resected from the rectum. Review of all cases of Cowden's disease in the English literature suggests that gastrointestinal polyposis may be a frequent finding if it is specifically searched for. It does not appear that the previously reported association of Cowden's disease with gastrointestinal cancer is valid. The discovery of multiple colonic polyps 0.1-0.4 cm is diameter with a rectosigmoid distribution and a hamartomatous microscopical appearance is characteristic of Cowden's disease. Cowden's disease should be included in the differential diagnosis of gastrointestinal polyposis states.

Thymic carcinoma. Five distinctive histological variants.

Five histologically distinct variants of thymic carcinoma are described: mixed small cell undifferentiated squamous cell carcinoma (three cases), basaloid carcinoma (two cases), mucoepidermoid carcinoma (one case), clear cell carcinoma (one case), and sarcomatoid carcinoma (one case). While forming a heterogeneous group, these tumors bear the common features of an anterior mediastinal location and lack of evidence of a primary tumor elsewhere, marking them as primary thymic neoplasms. All except the sarcomatoid variant are morphologically related to similar malignant neoplasms of other organs. These tumors should be recognized as morphological variants of primary thymic carcinoma and demonstrate the ability of thymic epithelium to differentiate toward a variety of different cell types.

Neuromas of the appendix. A light-microscopic, immunohistochemical and electron-microscopic study of 20 cases.

The neural origin and even the existence of appendiceal neuromas have been questioned. We have studied 20 examples, 7 discovered during a prospective examination of 26 consecutive routine appendectomy specimens (for an incidence of 27%), 2 selected from random cases, and 11 discovered in a retrospective review of 11 randomly selected cases of appendices diagnosed as "fibrous obliteration." By light-microscopy, appendiceal neuromas appear as a loose proliferation of spindle cells usually in a myxoid background, frequently with entrapped fat and connective tissue and infiltrated by eosinophils. Seventeen were located centrally in the appendix without nodule formation. One was central with nodularity and two were confined to the mucosa. The spindle cells were positive for S-100 protein and neuron-specific enolase in all cases. In 12, serotonin positive cells entrapped in the proliferation were present. In 5 of 11 cases with apparent uninvolved appendix present in the specimen, the number of serotonin cells in the crypts was greater than in normal appendix controls. Two appendiceal neuromas contained somatostatin positive cells. Stains for vasoactive intestinal polypeptide, substance P, neurotensin, bombesin and gastrin were negative. Ultrastructural examination of one case confirmed the presence of a mixture of Schwann cells and cells containing neurosecretory granules. We conclude that appendiceal neuroma is a rather common entity, and that most cases of so-called fibrous obliteration actually represent appendiceal neuroma.

Liver allograft rejection. An analysis of the use of biopsy in determining outcome of rejection.

Two-hundred-seventy biopsy specimens from 47 patients undergoing liver transplants at the University of Minnesota were analyzed to determine if histological features could predict the eventual outcome of rejection episodes. Thirty-six patients (76.6%) rejected the transplant. Of these, five either suffered acute liver failure due to rejection (two cases) or developed chronic rejection (three cases). Features of significance in predicting such a bad outcome were arteritis, bile duct paucity, or simultaneous hepatocellular ballooning and hepatocellular dropout and necrosis. Other features, such as type and intensity of infiltrate, degree of bile duct damage, or simple presence of hepatocellular necrosis, were not predictive of outcome. Our conclusion is that biopsy is useful in predicting outcome. Since many of the histologic findings of predictive value were not present in initial pretreatment biopsy specimens, follow-up biopsies of patients being treated for rejection are recommended to assess efficacy of therapy.

Hepatic angiomyolipoma: a clinicopathologic study of 30 cases and delineation of unusual morphologic variants.

Hepatic angiomyolipoma (AML) is frequently misdiagnosed. HMB-45 is a promising immunomarker for this tumor that leads to recognition of some AMLs with unusual morphology. The purpose of this collaborative study is to better define the morphologic variations of AML. Thirty AMLs were examined, including four biopsy specimens and two fine-needle aspirates. The diagnosis was confirmed by the presence of HMB-45-positive myoid cells. Almost half the cases were originally misdiagnosed as carcinomas or sarcomas. There was marked female predominance (25:5), and the mean age was 48.7 years (range 29-68). Three patients (10%) had evidence of tuberous sclerosis and all had renal AML. According to the line of differentiation and predominance of tissue components, the tumors was subcategorized into mixed, lipomatous (> or = 70% fat), myomatous (< or = 10% fat), and angiomatous type. The mixed type was the most common (11 resected cases), comprising sheets of epithelioid muscle cells admixed with islands of adipocytes, abnormal vessels, and frequently, hematopoietic cells. Six tumors (including three from biopsy specimens) were heavily fatty and showed predominantly adipocytes with epithelioid and short spindle myoid cells webbed between fat cells. Of 10 myomatous AMLs, five tumors showed a pure sinusoidal trabecular pattern and comprised mainly epithelioid cells. Typically, mature adipocytes were absent or scanty, but fat was seen as fine droplets within cytoplasm or as occasional large globules in sinusoids. Pelioid and inflammatory pseudotumor-like patterns were identified focally. Regarding cellular features of the myoid cells, most of the epithelioid cells were either eosinophilic or clear with spiderweb cell morphology. Three AMLs showed an almost purely oncocytic appearance with scanty fat. Large pleomorphic epithelioid cells existed as small foci. Spindle cells arranged in long fascicles were uncommon. D-PAS-positive globules were common around pelioid areas. Brown pigments with staining characteristics of hemosiderin and/or melanin were noted. In conclusion, we propose HMB-45-positive myoid cells as the defining criterion of hepatic AML, which is a tumor capable of dual myomatous and lipomatous differentiation and melanogenesis. Because of its protean morphologic appearance, recognition of the various variant patterns and cell types is important for a correct diagnosis, assisted by immunohistochemical confirmation with HMB-45. Trabecular and oncocytic cell tumors appear to stand out as distinctive subtypes.

Immunopathology of graft-versus-host disease in the upper gastrointestinal tract.

Class I and class II (HLA-DR, DP and DQ) MHC antigen expression and the phenotypic nature of the inflammatory infiltrate in gastric and duodenal biopsies in bone marrow transplantation patients with and without graft-versus-host disease were investigated. Increased expression of class I (P less than 0.016) and class II (HLA-DR, DP) antigens (P less than 0.002) was associated with GVHD. The epithelium in two GVHD-positive biopsies was HLA-DP-positive and HLA-DR-negative. None of the tissues expressed HLA-DQ. Association between MHC antigen expression and phenotype of infiltrating cell was then examined. The majority of GVHD biopsies showed an infiltrate composed of CD4+ cells and CD8+ cells. However, the two DP+, DR- biopsies were associated exclusively with CD8+ intraepithelial cells, suggesting sequential events in GVHD, with CD8+ cells infiltrating tissue first associated with HLA-DP expressions, followed by accumulation of CD4+ as well as CD8+ cells in association with expression of HLA-DR.

Simultaneous upper and lower endoscopic biopsy in the diagnosis of intestinal graft-versus-host disease.

Graft-versus-host disease in the upper gastrointestinal tract presents with anorexia, vomiting, and abdominal discomfort. Because these symptoms are not specific, we have proposed that a diagnosis of upper GI GVHD requires histologic confirmation. However, the utility of upper endoscopy in the diagnosis of upper GI GVHD has not been examined. We report a retrospective analysis of 77 allogeneic bone marrow transplantation recipients who received simultaneous upper and lower GI tract biopsies. Upper GI GVHD was found in 44% of patients, of whom 59% also had a positive lower GI tract biopsy (P less than 0.001). Thirty-five percent of the patients with no clinical evidence of lower GI tract GVHD had symptomatic upper GI GVHD confirmed histologically. Patients with and without upper GI GVHD had no significant difference in their clinical symptoms or in their endoscopic findings. We found an association between upper GI and skin GVHD greater than stage I (P = 0.05), a trend to concordance between upper GI GVHD and clinical GVHD in the lower GI tract (P = 0.08), and with the overall clinical GVHD grade (P = 0.08) but no association with clinical liver involvement. Of these 77 patients, 16% had their treatment for acute GVHD changed to include systemic immunosuppression as a result of the upper GI endoscopic biopsy. In addition, 71% had other enteric pathology identified that required specific therapy. These data suggest that upper GI GVHD cannot be diagnosed accurately from its clinical presentation nor inferred from lower GI symptoms or from extraintestinal GVHD. Upper GI endoscopy with biopsy is an important tool in the diagnosis of intestinal GVHD.

Increased expression of class I major histocompatibility complex antigens on hepatocytes in rejecting human liver allografts.

We studied hepatocellular expression of major histocompatibility (MHC) antigens in 43 serial liver transplant biopsies from 22 patients (42 percutaneous, 1 autopsy specimen), 4 normal liver biopsies, and 8 percutaneous biopsies of diseased livers from non-liver-transplant patients. Frozen tissue sections were stained by an indirect immunofluorescence technique using monoclonal antibodies (MCAb) that recognize nonpolymorphic human class I or class II MHC determinants. Ethidium bromide was used to stain nuclei and rhodamine-conjugated anti-basement-membrane antibodies to delineate epithelial and vascular structures. HLA-DR antigens recognized by MCAb OKIa1 and I2 were not detected on hepatocytes but were detected on the bile duct epithelium in 7 of 27 transplant biopsies, including 5 with acute rejection and 1 with chronic liver disease that later progressed to chronic rejection. HLA-A, B, C antigens recognized by MCAb 34/28 intensely stained cells lining the liver sinusoids but were negative on hepatocytes in 4 normal liver biopsies and 7 of 8 non-transplant biopsies. Expression of class I MHC antigens on hepatocyte membranes was increased in 17 of 21 (81%) biopsies from patients with acute rejection, in 4 of 4 with chronic transplant liver disease, but in only 3 of 18 (17%) biopsies from patients with no rejection (chi square = 8.62, P less than 0.01). Our observations demonstrate increased expression of MHC class I antigens in association with acute rejection in human orthotopic liver transplantation. Histologic resolution of the rejection episode is generally followed by a decrease in hepatocyte class I antigen expression. Further analysis of this response may have value in assessing the severity of the rejection and effectiveness of treatment.

Use of alpha-1-antitrypsin staining in the diagnosis of nodular regenerative hyperplasia of the liver.

Nodular regenerative hyperplasia (NRH) is a disorder characterized by regenerative nodules scattered diffusely throughout the liver without associated fibrosis. It is most often recognized at autopsy when the entire liver is available for inspection. The diagnosis of NRH by needle biopsy is much more subtle. Since alpha-1-antitrypsin (AAT) expression by hepatocytes in a variety of liver diseases has suggested that it may represent a marker for regenerative or damaged hepatocytes, we elected to study the expression of AAT by immunohistochemical staining of paraffin-embedded tissue of biopsy material as a possible marker of this diagnosis. Seventeen biopsies of the liver showing histologic features consistent with NRH were selected and compared with 20 biopsies of the liver without features of NRH. Eight of the NRH cases showed periportal granular AAT staining as opposed to only one of the non-NRH biopsies (P less than .01; Fisher exact test). These results indicate that AAT expression is increased in the regenerating compartment (as opposed to the presumably damaged atrophic portion) of the liver in NRH and suggest that AAT staining may be useful in confirming the biopsy diagnosis of NRH.

Venoocclusive lesions of the central veins and portal vein radicles secondary to intraarterial 5-fluoro-2'-deoxyuridine infusion.

Venoocclusive disease is characterized by the occurrence of occlusive lesions of the central and subhepatic veins, usually involving the liver in a diffuse fashion. We report a case showing venoocclusive lesions of the central veins and the portal vein radicles affecting only a portion of the left lobe of the liver following intraarterial 5-fluoro-2'-deoxyuridine therapy for metastatic adenocarcinoma of the colon. Possible mechanisms and the significance of venoocclusive lesions of portal vein radicles are discussed.