Hepatic giant cells in hepatitis C virus (HCV) mono-infection and HCV/HIV co-infection.

BACKGROUND: The clinical and biological significance of syncytial giant cell change of hepatocytes in hepatitis C viral (HCV) infection is poorly understood. AIM: To investigate the clinical and histological correlates of giant cell transformation in the setting of HCV mono-infection and co-infection with HCV and HIV. METHODS: The prevalence of hepatocyte giant cell transformation was determined and serological, biochemical and histological findings examined. RESULTS: Among 856 liver biopsy specimens, 22 cases (2.6%) showed giant cell transformation, representing 18 individuals. The median serum ALT was 37 IU/l, AST 49 IU/l, and alkaline phosphatase 97 IU/l. Eleven cases had HCV RNA loads available, with a median HCV RNA of 5.52 log IU/ml. Twelve of 17 individuals with available test results were also HIV positive (71%), compared to 46% of controls (p = 0.08). Giant cell transformation was found exclusively in zone 3 hepatocytes; the accompanying histological findings were otherwise typical of chronic HCV. The hepatic giant cells typically had a cytoplasmic appearance that resembled smooth endoplasmic reticulum proliferation. Most cases had only mild inflammation and fibrosis, with a median modified hepatic activity index (MHAI) grade of 3/18 and a median MHAI stage of 1/6. Three individuals had follow-up biopsies; all continued to have giant cell change. CONCLUSION: Giant cell transformation occurs most commonly in the setting of HCV/HIV co-infection, but can also be seen in chronic HCV infection alone. Histologically, giant cells were located in zone 3 hepatocytes, were persistent over time, and do not appear to be a marker of aggressive hepatitis.

Assessment of the morphology and significance of the lymph nodal and hepatic lesions produced in rats by the feeding of certain mineral oils and waxes. Proceedings of a pathology workshop held at the Fraunhofer Institute of Toxicology and Aerosol Research Hannover, Germany, May 7-9, 2001.

A Panel of medical and veterinary pathologists reviewed published and unpublished reports dealing with studies of various white mineral oils and waxes in F344 and Sprague-Dawley rats. They also had available and studied histologic slides from both subchronic and chronic studies of certain mineral hydrocarbons (90-day oral study of low melting point wax (LMPW) in female Fischer 344 and Sprague-Dawley rats; 90-day studies of P15H* and P70H white oil and high melting point wax (HMPW) in male and female F344 rats and 24 month study of P70H white oil in male and female F344 rats. The Panel also reviewed mineral oil-induced alterations in tissues of human patients (liver, hepatic lymph node and spleen). The Panel agreed that certain of the mineral hydrocarbons produced lesions in the mesenteric lymph nodes and liver of the F344 rat and these lesions were best described as microgranulomas/granulomas. The lesions were fundamentally similar in both organs, although varying in severity with dose and type of mineral hydrocarbons. The Panel agreed that hepatic lesions with inflammatory cell infiltration, necrosis, and fibrosis were produced only by feeding of LMPW and the lesions were confined to F344 rats and not found in Sprague-Dawley rats. The most severe granulomatous lesions in the mesenteric lymph nodes were found in high dose LMPW-fed F344 rats. The microgranulomas were similar in subchronic and chronic studies. Also, little difference existed between controls and treated F344 rats in the incidence and severity of the lesions after 2 years of feeding P70H white oil. The Panel agreed that some slight reversibility existed for these lesions, but also agreed that complete resolution was unlikely as regression of the lesions in the rat would likely be slow. The Panel agreed that a minimal severity infiltrate of mononuclear inflammatory cells occurred in the base of the mitral valve in a slightly increased incidence in F344 rats fed LMPW. The Panel concluded that these mitral valve alterations had little if any toxicologic significance as the focal infiltrate was minimal in severity, occurred in controls, occurred in association with murine cardiomyopathy, and were unlike the responses in the liver and mesenteric lymph nodes. The Panel agreed that the lesions observed in the liver and mesenteric lymph nodes of F344 rats exposed to MHCs, especially the LMPW, were different morphologically from changes observed in lymph node, liver, and spleen of humans that were mineral oil-users. These changes in humans are usually found incidentally in tissues taken at biopsy or autopsy. The MHC-induced lesions can be considered incidental and inconsequential in humans.

Local tumor recurrence following hepatic cryoablation: radiologic-histopathologic correlation in a rabbit model.

PURPOSE: To use radiologic-histopathologic correlation in an animal model to distinguish normal postoperative findings from evidence of residual tumor after cryoablation of malignant hepatic tumors. MATERIALS AND METHODS: Hepatic cryoablation was performed in 12 rabbits with VX2 tumors and in two healthy rabbits. Nonenhanced and dynamic contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging and power and color Doppler flow ultrasonography (US) were performed 7-8 days after cryoablation. Histopathologic findings were correlated with imaging findings. RESULTS: Twenty tumors of 5-20 mm (mean, 10 mm) and seven areas of normal liver were treated with cryolesions of 11-21 mm (mean, 15 mm). All cryolesions exhibited arterial phase rim enhancement at CT and MR imaging, and 13 (57%) of 23 lesions demonstrated peripheral flow at US because of granulation tissue. There was macroscopic recurrence in 15 (75%) of 20 treated tumors; 14 (93%) appeared as peripheral nodularity with low-grade enhancement. Necrotic tissue did not enhance. Intact vessels extended up to 6 mm inside cryolesion margins and caused focal internal enhancement and Doppler flow. Areas of high signal intensity on T2-weighted MR images correlated with liquefaction necrosis, granulation tissue, and tumor. CONCLUSION: In this animal model, recurrent tumor typically appeared as focal nodules at the cryolesion periphery. Rim and central foci of enhancement, Doppler flow, and increased signal intensity on T2-weighted MR images can be normal findings after hepatic cryoablation.

High viral load and mild liver injury in children with hemophilia compared with other children with chronic hepatitis C virus infection.

BACKGROUND: In adults with hepatitis C virus (HCV) infection, the severity of liver disease may be influenced by the mode of transmission. The purpose of this study was to evaluate whether the mode of transmission affects liver injury and viral load in children with chronic HCV infection, independent of duration of infection and/or HCV genotype. METHODS: Thirty-nine anti-HCV (EIA-2) positive patients, were divided into three groups: group 1, children with a history of blood transfusion (n = 9; age, 13.3+/-1.3 years), group 2, children with hemophilia (n = 19; age, 11.6+/-0.8 years); and group 3, children with maternal-fetal transmitted disease (n = 10; age, 4.7+/-1.1 years). Serum alanine aminotransferase, HCV viral load, HCV genotype, and liver histology were assessed. RESULTS: Serum HCV viral load was higher in group 2 (4.27+/-1.0x10(6) copies/ml; p = 0.006) than in group 1 (0.73+/-0.3x10(6) copies/ml) and in group 3 (0.83+/-0.2x10(6) copies/ml). Conversely, group 2 had less severe liver injury compared with children of similar age in group 1 (p = 0.022). Despite a shorter duration of infection, group 3 had liver injury similar to that in group 1. Hepatitis C virus genotype did not influence the level of viremia or liver injury. CONCLUSIONS: Although children with hemophilia exhibited a high HCV viral load, liver histopathology was less severe than in children who had acquired HCV by blood transfusion or maternal-fetal transmission. These observations support the need to investigate the role of host immune response rather than the virus per se in the pathogenesis of HCV infection in children.

Serum concentrations of cardiac troponin I in sudden death: a pilot study.

Sudden cardiac death due to lethal arrhythmia may be the initial presenting symptom of ischemic heart disease. In many cases, in the absence of trauma, a majority of these deaths will be visually inspected by a medical examiner and released with death being ascribed to atherosclerotic cardiovascular disease, coronary artery disease, arrhythmia, myocardial infarction, or a similar diagnosis. When an autopsy is performed, there may be significant cardiovascular disease but no gross or histologic evidence of an acute myocardial infarct unless the patient survived for several hours following the event. Biochemical assays of creatine kinase MB fraction (CKMB) performed on serum have been used to document myocardial injury in the absence of morphologic changes. Newly developed assays for cardiac troponin I (cTnI) may detect myocardial injury with a greater sensitivity than CKMB. A prospective study was performed on 28 autopsied patients at the Office of the Chief Medical Examiner of the state of Maryland. Subclavian blood was sampled for subsequent analysis of serum CKMB and cTnI. In 3 cases of cardiac-related death, there was insufficient plasma for analysis of both CKMB and cTnI, and only CKMB was quantitated. In 12 cases, hemolysis rendered interpretation questionable. Of the remaining 16 cases, the mean serum CKMB level was 857.9 ng/ml (n = 7) and the cTnI level was 93.4 ng/ml (n = 4) for cardiac-related deaths, compared with mean CKMB levels of 116.4 ng/ml (n = 9) and mean cTnI levels of 16.6 ng/ml (n = 9) for non-cardiac-related deaths. The differences in serum elevation of both CKMB and cTnI noted between the cardiac- and non-cardiac-related deaths were statistically significant. Serum cTnI concentrations >40 ng/ml were only noted in cardiac-related deaths. These data suggest that an elevated postmortem serum concentration of cTnI reflects ischemic heart disease and supports its use in determining cause of death. Quantitation of this analyte may prove useful when death may be due to an arrhythmia following a morphologically undetectable microinfarct.

Role of nitric oxide in porcine liver circulation under normal and endotoxemic conditions.

The role of nitric oxide (NO) in the liver vasculature during baseline and endotoxic shock states was evaluated in 17 anesthetized pigs. Mean systemic arterial pressure, pulmonary arterial pressure, and portal venous pressure and flow, hepatic arterial pressure and flow, and cardiac output were measured. Pressure-flow (P-Q) relationships defined resistances as a back pressure and a slope. Inhibition of nitric oxide synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) at baseline increased mean arterial pressure, pulmonary arterial pressure, hepatic arterial pressure, and the slopes of their P-Q relationships (P < 0.05) but had no effect on portal venous pressure or its P-Q relationship. After endotoxin (10 micrograms/kg iv), NO induced arterial dilation and attenuated increases in portal venous and pulmonary arterial resistances (P < 0.05) that were reversed by L-NAME. NOS inhibition was stereospecifically reversed by L-arginine. Local control of liver blood flow at baseline via the hepatic arterial buffer response and hepatic arterial autoregulation were increased in gain after L-NAME. Endotoxic shock ablated the hepatic arterial buffer response and autoregulation independent of either NO or an alpha-adrenergic-receptor agonist (P < 0.05). Under baseline conditions, NO modulates pulmonary, systemic, and hepatic arterial but not portal venous resistances. NO production during endotoxic shock induces arterial hypotension and hepatic arterial vasodilation and attenuates increases in both portal and pulmonary resistances. NOS inhibition in endotoxic shock could increase morbidity due to a loss of local control of liver blood flow and marked increases in resistance to venous return across both the liver and lungs.

Alternations in liver hemodynamics in an intact porcine model of endotoxin shock.

Septic shock decreases preload, increases splanchnic blood pooling and edema formation, and induces hepatic dysfunction. We hypothesized that the hemodynamic effects of endotoxemic shock on the portal venous (PV) and hepatic arterial (HA) vascular beds contribute to this picture. Multipoint pressure-flow relationships were generated to evaluate the slope (resistance or conductance) and effective back pressure (Pback) in each bed in an intact porcine model of endotoxemia. Slope and Pback were determined during endotoxemia over 300 min (n = 8) and compared with sham-treated control studies (n = 5). At time (t) = 60 min, HA slope significantly decreased (P < 0.05) without a change in Pback. The HA buffer response (HABR), defined as a decrease in HA resistance produced by reduction in PV flow (Qpv), was abolished at t = 90 min. The PV Pback significantly increased without a change in PV slope. At t = 300 min, HA slope returned to baseline, and the HABR was present while PV slope and Pback increased (P < 0.05). Fractional flow (flow relative to cardiac output) was constant except for a transient increase in HA fractional flow at t = 60 min. Histological studies showed focal necrosis and hemorrhage without evidence of vasoconstriction or thrombosis. In conclusion, endotoxic shock leads to time-dependent impairment of Qpv with increased PV resistance, causing an increase in splanchnic blood pooling and subsequent decrease in venous return. The HA bed is dilated early with an absent HABR. Later an HABR is present but defined by increased HA resistance for a given Qpv.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy.

PURPOSE: We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. PATIENTS AND METHODS: The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. RESULTS: In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. CONCLUSION: These findings suggest that IVL represents a high-grade non-Hodgkin's lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy.

Choledochal cyst disease. A changing pattern of presentation.

OBJECTIVE: The authors compared the presentation, treatment, and long-term outcome of children and adults with choledochal cysts. SUMMARY BACKGROUND DATA: The typical patient with choledochal cyst disease has been the female infant with the triad of jaundice, an abdominal mass, and pain. However, the recent experience of the authors suggested that the disease currently is recognized more commonly in adults. METHODS: Forty-two patients (11 children, 32 adults) with choledochal cyst disease were treated primarily at this institution between 1976 and 1993. Patients presentation, clinical evaluation, and operative treatment were obtained from existing records. Long-term follow-up was obtained by records, physician, or direct patient contact. RESULTS: One child--but no adults--had the classic triad of jaundice, abdominal mass, and pain. Children were more likely to have two of the three signs or symptoms (82% vs. 25%; p = < 0.05). Adult patients most commonly had abdominal pain and were thought to have pancreatitis (23%) or acute biliary tract symptoms, prompting cholecystectomy (50%). The type of choledochal cyst seen in children and adults was similar; the fusiform extrahepatic (Type I) was most common (50%), and the combined intrahepatic and extrahepatic (Type IVA) was the next most prominent (33%). For both children and adults, treatment consisted of excision of the cyst and biliary reconstruction with a hepaticojejunostomy. There was no surgical mortality. Gallbladder or cholangiocarcinoma was identified in three adults (9.7%), two of which were manifest on presentation. Long-term follow-up revealed one patient with a biliary stricture and three patients with Type IVA cysts who had intrahepatic stones. CONCLUSIONS: Children and adults differ in presentation of choledochal cysts, with adults commonly having acute biliary tract or pancreatic symptoms. Surgical treatment with cysts excision and biliary bypass is safe and effective in children and adults with excellent long-term results that minimize the development of malignancy.

Carcinoma of the body and tail of the pancreas.

Recently, several institutions have reported improved results in the treatment of patients with carcinoma of the head of the pancreas. In an attempt to determine whether similar trends could be demonstrated for patients with carcinoma of the body and tail of the pancreas, the records of all 113 patients with an adenocarcinoma of the body or tail of the pancreas treated at The Johns Hopkins Hospital between 1972 and 1989 were reviewed. The patients were divided into two groups: those diagnosed between 1972 and 1982 (41 patients) and those between 1983 and 1989 (72 patients). No significant differences in tumor stage were observed between the two groups. The proportion of patients who underwent surgery decreased from 68% to 47% (p = 0.02). The number of patients who had bypass operations (15% versus 17%) or pancreatic resection (5% versus 10%) was similar in the two groups, but the proportion of patients who underwent exploratory laparotomy with biopsy only decreased from 49% to 21% (p = 0.002). The postoperative 30-day mortality (7% versus 3%), postoperative morbidity (18% versus 21%), median survival (4 months versus 3 months), and the 1-year survival (8% versus 9%) did not differ significantly between the two groups. One patient survived for 6 years after resection, and another patient is still alive 3 years after resection. Thus, unlike adenocarcinoma of the head of the pancreas, it appears that treatment results for patients with adenocarcinoma of the body or tail of the pancreas have not improved in recent years, the only change being a decreased need for exploratory laparotomy with biopsy only.

Spectrum of cystic tumors of the pancreas.

The pathologic and clinical classification, as well as the behavior, of cystic tumors of the pancreas has been the subject of controversy. We retrospectively reviewed 50 patients with a diagnosis of cystic tumor of the pancreas observed at The Johns Hopkins Hospital from 1984 to 1991. These tumors were classified into three broad groups: I, cystadenoma; II, cystadenocarcinoma; and III, adenocarcinoma with mucin production or an associated cyst. The three groups did not differ with respect to age or sex. The most common clinical presentation was abdominal pain. Symptoms and signs among the three groups were similar except that patients with cystadenomas were less likely (p less than 0.05) to be jaundiced and more likely (p less than 0.05) to be asymptomatic. Radiologic findings on computerized tomography, cholangiography, and arteriography also overlapped, making precise preoperative determination of tumor type difficult. Operative classification was also often not possible. The resectability rate (Group I, 91%; Group II, 67%; Group III, 53%) and 5-year survival rate (Group I, 90%; Group II, 72%; Group III, 14%) correlated with careful pathologic determination. Cystic tumors of the pancreas represent a spectrum of disease ranging from benign cystadenoma to adenocarcinoma masquerading as cystadenocarcinoma. We recommend resection whenever possible, even when preoperative evaluation suggests benign disease.

Pancreatic cancer cell DNA content correlates with long-term survival after pancreatoduodenectomy.

The DNA content of 47 adenocarcinomas arising in the head of the pancreas from patients who had undergone successful pancreatoduodenectomy was measured. The DNA measurements of each tumor were made without knowledge of the clinical course by absorption cytometry performed on Feulgen-stained nuclei that had been disaggregated from pancreatic cancer tissue blocks. Forty-seven evaluable DNA distributions were obtained from specimens taken between 1975 and 1988. Of the 47 tumors, 19 (40%) were diploid and 28 (60%) were aneuploid cancers. The 19 patients with diploid cancers had a median survival time of 25 months. Median survival of the 28 patients with aneuploid cancers was 10.5 months. This difference was statistically significant (p = 0.003). A multivariate life table regression analysis demonstrated that the ploidy and proliferative index as determined by absorption cytometry were independent prognostic factors, as strong as or stronger than the number of positive nodes and tumor size. Thus cellular DNA content appears to be one of the most important predictors of survival in patients with adenocarcinoma of the head of the pancreas who have successfully undergone a pancreaticoduodenectomy.

Prominent mononuclear cell infiltrate is characteristic of herpes esophagitis.

Diagnosis of herpes esophagitis is often difficult since the characteristic nuclear inclusions and/or multinucleate giant cells of herpes virus infection may be absent in endoscopic biopsy specimens. We have noted aggregates of large mononuclear cells with convoluted nuclei adjacent to infected epithelium in the exudates of herpetic esophagitis, and postulate that this is a characteristic inflammatory response to the virus. To test this hypothesis, we reviewed biopsies from 22 cases of ulcerative herpetic esophagitis and from 44 control cases of nonherpetic esophageal ulcers (including nine cases of candidal and five cases of bacterial esophagitis) that contained a quantifiable amount of exudate. The estimated percentage of mononuclear cells present in the specimens was ranked independently by two reviewers using coded photomicrographs of exudate. Wilcoxon's rank sum analysis demonstrated significant correlation between presence of herpes and increased mononuclear cells (P less than .0001). Only one of the 22 herpes cases did not show a prominent mononuclear cell infiltrate. Immunoperoxidase studies performed on Hollande-Bouin's-fixed paraffin-embedded material from 11 herpes cases showed strong staining of the mononuclear cells for KP-1 (CD68), indicating that the majority of these cells are macrophages. These findings suggest strongly that aggregates of macrophages are characteristic of the inflammatory response in ulcerative herpetic esophagitis. The presence of these mononuclear cells in a biopsy specimen that initially does not show herpetic inclusions warrants additional studies to rule out herpes virus infection.

Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer.

Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months. The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival. Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival. The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05). Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05). The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion). However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival.

Fatal thrombocytopenia and liver failure associated with carboplatin therapy.

A patient with fatal severe thrombocytopenia and acute hepatic necrosis complicating carboplatin (JM8, CBDCA, NSC 241240) therapy is described. The patient, an 18-year-old man with acute lymphocytic leukemia, was given high-dose carboplatin as a part of a phase I trial of this agent for the treatment of leukemia. Carboplatin (270 mg/m2/day) was administered as an intravenous infusion on five consecutive days, and the patient died 10 days after his last dose of carboplatin from complications of thrombocytopenia and acute liver necrosis. Autopsy revealed hemorrhage into the substance of the myocardium and hemorrhagic centrilobular liver necrosis. The temporal relationship between the initial rise in this patient's liver function tests and treatment with carboplatin suggests that this patient's liver failure was in part due to carboplatin. The autopsy findings of hemorrhage into the substance of the myocardium and centrolobular liver necrosis suggest that, in addition to its direct effects, carboplatin may have also contributed indirectly to this patient's liver failure through the complications of thrombocytopenia.

Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy.

The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had greater than 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders.

Reversal by antrectomy of endocrine cell hyperplasia in the gastric body in pernicious anemia: a morphometric study.

Multifocal gastric carcinoid tumors occasionally develop in patients with pernicious anemia, associated with hyperplasia of endocrine cells in the atrophic and metaplastic gastric body mucosa. This constellation of findings probably requires a trophic drive from hypergastrinemia associated with antral G cell hyperplasia, a consequence of achlorhydria in these patients. We report a case in which antrectomy was performed on such a patient in order to abrogate the trophic stimulus. Antrectomy was followed by resolution of hypergastrinemia and a decrease in the size of polyps endoscopically. Nine months later, the gastric remnant was resected. Using morphometric techniques, endocrine cells in the initial antrectomy specimen (which included body mucosa at the resection line) were compared with those in the subsequently removed gastric body. Antrectomy resulted in striking decreases in number (137 versus 34/mm2; P = 0.0001) and size (93 versus 56 microns2; P = 0.0001) of endocrine cells of body mucosa. The findings suggest that antrectomy may be useful in the management of endocrine cell hyperplasia, and possibly also associated carcinoid tumors, in pernicious anemia.

Taxol toxicity. Epithelial necrosis in the gastrointestinal tract associated with polymerized microtubule accumulation and mitotic arrest.

Taxol, an antineoplastic agent with a novel mechanism of action, is currently undergoing Phase I trials at The Johns Hopkins Hospital, Baltimore. The authors recently observed striking mitotic arrest associated with epithelial necrosis and ulceration in an esophageal biopsy specimen. The biopsy specimen was taken from a patient who received taxol the day before endoscopy. Review of our autopsy files revealed four other cases in which taxol had been administered. Sections of esophagus, stomach, small intestine, colon, liver, skin, bone marrow, and testes were examined for evidence of mitotic arrest. Mitotic arrest was seen in the two patients who underwent autopsy who received taxol less than 11 days before death, whereas the two autopsy patients who received taxol more than 2 weeks before death did not show these changes. Although mitotic arrest was most prominent in the esophagus, it was also found in the stomach, small intestine, colon, liver, and bone marrow. The mitotic arrest was associated with bundling of intermediate filaments and appeared to be secondary to accumulation of polymerized microtubules. These results suggest that taxol induces a transient mitotic arrest associated with cell necrosis.

Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma.

Hepatocellular carcinoma may share histologic features with a wide variety of epithelial tumors. To facilitate its pathologic diagnosis, clinical and pathologic material was reviewed from 62 patients with hepatocellular carcinoma and immunostaining was performed with polyclonal anti-carcinoembryonic antigen (pCEA), monoclonal anti-carcinoembryonic antigen (mCEA), anti-epithelial membrane antigen (EMA), and an antikeratin (KER AE1/AE3). Clinical information and follow-up were available for all patients from several sources. Cases with ambiguous clinical data or findings suggestive of metastatic carcinoma to the liver were excluded. In addition, the following tumors were immunostained and compared to hepatocellular carcinoma: 10 cholangiocarcinomas; 14 pancreatic adenocarcinomas; 4 gastric adenocarcinomas; 3 breast carcinomas; 5 renal carcinomas; 3 combined germ cell tumors of the testis; 3 adrenal cortical carcinomas; and 4 melanomas. The pCEA stained bile canaliculi in normal liver and in 39 of 62 (63%) hepatocellular carcinomas. This canalicular staining pattern of pCEA was unique to hepatocellular carcinoma. The mCEA (1 of 62, 1.6%) was almost always negative, and KER AE1/AE3 (9 of 59, 15.3%) was occasionally positive. The EMA stained 25 of 62 (40.3%). The adrenal cortical carcinomas and melanomas were negative for all antigens except rare pCEA and focal EMA staining in an adrenal tumor. Other carcinomas showed cytoplasmic pCEA (36 of 44, 81.8%), mCEA (40 of 46, 87.7%), EMA (41 of 43, 95.4%), and KER AE1/AE3 (42 of 44, 95.5%). Canalicular staining with pCEA is specific for hepatocellular carcinoma, while negativity with mCEA and KER AE1/AE3 is suggestive of hepatocellular differentiation.

Pseudo-graft-versus-host disease in heart and heart-lung recipients.

Autopsies from nine patients who had received a cardiac allograft transplant and one with a combined heart-lung transplant were assessed for histologic evidence of pseudo-graft-versus-host disease (pseudo-GVHD). Five of the ten patients had GVHD-like changes in two or more tissues, including prominent lymphocyte-associated bile duct injury consistent with marked hepatic pseudo-GVHD and mild cutaneous changes resembling GVHD. A sixth recipient had marked changes in the liver, but autopsy restrictions prevented examination of the skin. A seventh recipient had only mild pseudo-GVHD changes limited to the skin. In contrast, a series of six patients who were candidates for cardiac transplant had no specific pathologic changes suggesting pseudo-GVHD. The majority of those with pseudo-GVHD had received nonirradiated blood product transfusions, raising the possibility of posttransfusion engraftment and GVHD. Unlike the posttransfusion GVHD, however, two of the six developed GVHD-related complications late with a latent period of five and 9.5 months, and two recipients received no transfusions. All were receiving only modest doses of immunosuppressive agents at the time they developed liver function abnormalities, including low or tapering doses of cyclosporine (CsA). In some of these recipients, therefore, the pseudo-GVHD changes may well represent an autoimmune reaction resembling the post-CsA model of autoimmune disease.