Allergic fungal sinusitis. A report of two cases with diagnosis by intraoperative aspiration cytology.

BACKGROUND: Allergic fungal sinusitis (AFS) is a newly recognized form of sinusitis characterized by opacification of the paranasal sinuses by "allergic mucin" (AM) admixed with scattered fungal organisms. AM consists of necrotic, or partially necrotic, eosinophils and Charcot-Leyden crystals suspended in lakes of laminated, mucinous material. AFS is characterized by the absence of bone or soft tissue invasion, purulent exudate or granulomatous inflammation. Clinically, it is important to differentiate AFS from both acute invasive fungal sinusitis and noninvasive mycetoma because the three diseases are treated with different modalities and have different prognoses. Although the radiologic features of AFS are often characteristic, occasionally it may be difficult to exclude neoplasia. CASES: Two cases of AFS, in which intraoperative diagnosis was made on the basis of the presence of both AM and fungal organisms, are reported. CONCLUSION: Cytologic diagnosis of AFS can be made from intraoperative sinus aspirates from the presence of AM and fungal elements. AM and fungi provide presumptive evidence for a noninvasive, allergic fungal disease and can help reassure clinicians intraoperatively and guide clinical management.

Comparison of biopsy and serological methods of diagnosis of Helicobacter pylori infection and the potential role of antibiotics.

OBJECTIVE: Endoscopic biopsy and serological methods were compared for their ability to detect Helicobacter pylori infection in patients undergoing upper gastrointestinal endoscopy at a state university hospital. METHODS: Subjects were characterized on the basis of gastrointestinal symptoms, endoscopic findings, socioeconomic and demographic features, and the use of certain medications, tobacco, and alcohol. Current infection was detected in gastric antral specimens by rapid urease testing, histopathology, and bacterial culture. Serum levels of IgG to H. pylori were measured by ELISA. RESULTS: Of 240 subjects, 115 (47.9%) were currently infected as determined by rapid urease testing, histopathology, and/or culture results, whereas 63.3% had elevated anti-H. pylori IgG levels (p < 0.001). This difference in the prevalence of current infection and seropositivity was preserved when the study population was analyzed according to age, race, gender, and other characteristics. Prior use of antibiotics was associated with a significant reduction in the frequency of H. pylori infection. CONCLUSIONS: Serological evidence of H. pylori infection was consistently greater than the prevalence of infection documented by biopsy methods in this study, suggesting suppression or recent clearance of infection. Further studies are needed to examine the factors that may affect the detection of H. pylori infection.

The effect of class II major histocompatibility complex expression on adherence of Helicobacter pylori and induction of apoptosis in gastric epithelial cells: a mechanism for T helper cell type 1-mediated damage.

Helicobacter pylori infection is associated with gastric epithelial damage, including apoptosis, ulceration, and cancer. Although bacterial factors and the host response are believed to contribute to gastric disease, no receptor has been identified that explains how the bacteria attach and signal the host cell to undergo apoptosis. Using H. pylori as "bait" to capture receptor proteins in solubilized membranes of gastric epithelial cells, class II major histocompatibility complex (MHC) molecules were identified as a possible receptor. Signaling through class II MHC molecules leading to the induction of apoptosis was confirmed using cross-linking IgM antibodies to surface class II MHC molecules. Moreover, binding of H. pylori and the induction of apoptosis were inhibited by antibodies recognizing class II MHC. Since type 1 T helper cells are present during infection and produce interferon (IFN)-gamma, which increases class II MHC expression, gastric epithelial cell lines were exposed to H. pylori in the presence or absence of IFN-gamma. IFN-gamma increased the attachment of the bacteria as well as the induction of apoptosis in gastric epithelial cells. In contrast to MHC II-negative cell lines, H. pylori induced apoptosis in cells expressing class II MHC molecules constitutively or after gene transfection. These data describe a novel receptor for H. pylori and provide a mechanism by which bacteria and the host response interact in the pathogenesis of gastric epithelial cell damage.

Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype.

BACKGROUND & AIMS: Studies have shown that gastric T cells are increased during Helicobacter pylori infection. The purpose of this study was to characterize the human gastric T-cell responses in the presence or absence of H. pylori. METHODS: T-cell surface antigens were examined by immunohistochemistry or after isolation for evaluation of surface antigens and cytoplasmic cytokines using flow cytometry. RESULTS: CD4+ and CD8+ T cells were increased in situ during infection with H. pylori. Freshly isolated gastric T cells expressed cytoplasmic interferon gamma (IFN-gamma) and interleukin (IL)-2 after a brief stimulation. Simultaneous four-color flow cytometry demonstrated that both CD8+ and CD4+ T cells expressed IFN-gamma. Because stimulation through CD30 favors the induction of IL-5 and Th2 cells, gastric and colonic T cells were examined for CD30 expression. Consistent with the notion that Th2 cells are found in the intestine, CD30 was evident throughout the lamina propria of the colon but was virtually absent in the stomach. Furthermore, freshly isolated gastric T cells produced little IL-4 and virtually no IL-5 or tumor necrosis factor beta. CONCLUSIONS: These observations show that gastric T cells resemble the Th1 type, which may explain their failure to induce immunity to H. pylori and their ability to contribute to the pathogenesis of gastric disease.

Elevated expression of Bcl-2 and Bcl-x by intestinal intraepithelial lymphocytes: resistance to apoptosis by glucocorticoids and irradiation.

Administration of glucocorticoids or exposure to ionizing radiation in vivo results in a rapid cell death of thymocytes. We report that murine small intestinal intraepithelial lymphocytes (IEL) are resistant to both steroid- and radiation-induced deletion. This is due to resistance to apoptosis, as evidenced by the absence of detectable apoptotic IEL nuclei in situ after in vivo glucocorticoid treatment. IEL express normal levels of glucocorticoid receptors and these receptors bind [3H]dexamethasone to equivalent levels as other lymphocyte populations. Thus, their survival is due to post-receptor signaling mechanisms. Many IEL express high levels of Bcl-2 and that of these Bcl-2high IEL are largely TCR gamma delta +. Those IEL that do express high levels of Bcl-2 are CD8 alpha + beta - CD4-. In addition, IEL express Bcl-x, another protein shown to be involved in the protection of cells from apoptotic signals. IEL represent the first lymphocyte population in vivo shown to have high levels of expression of both molecules, that otherwise occur only in activated lymphocytes in vitro. These data suggest that the Bcl-2+Bcl-x+ IEL are activated cells and not an effete population of cells necessarily destined to die. Also, the high levels of Bcl-2 and Bcl-x in this in vivo activated population supports the in vitro correlate of protection from activation-induced cell death.

Photosensitization of experimental hepatocellular carcinoma with protoporphyrin synthesized from administered delta-aminolevulinic acid: studies with cultured cells and implanted tumors.

BACKGROUND/AIMS: Photodynamic therapy using porphyrins or related compounds and laser light is an investigational treatment for neoplasms. The aim of this study was to establish whether this might be applicable for hepatocellular carcinoma using protoporphyrin synthesized in the tissue from administered delta-aminolevulinic acid. METHODS: We measured porphyrin accumulation in normal rat hepatocytes and Morris hepatoma cells in culture, and in subcutaneously implanted hepatomas and other tissues of the rat after administration of delta-aminolevulinic acid, and assessed cell and tissue damage after application of laser light. RESULTS: Porphyrin accumulation after delta-aminolevulinic acid was added to the medium was greater and continued to increase for a longer period of time in hepatoma cells than in hepatocytes (1337+/-42 vs 513+/-31 fluorescence units/cell at 8 h, means+/-SE, p<0.001). After intraperitoneal injection of delta-aminolevulinic acid to rats with subcutaneously growing hepatomas, porphyrin content in tumor and liver was similar at 4 h but was higher in tumor at 6 h. Laser light caused necrosis of normal and malignant liver cells in culture and subcutaneous hepatomas in vivo. CONCLUSIONS: We conclude from these in vitro and in vivo studies that porphyrin accumulation after administration of delta-aminolevulinic acid in this hepatoma is substantial and time dependent, and delivery of laser light locally can cause tumor photosensitization and necrosis.

Allergic fungal sinusitis.

Allergic fungal sinusitis is a non-invasive disease, first described in the early 1980s. We review our experience with 25 patients treated at the University of Texas Medical Branch, Galveston. All patients were treated surgically, using endoscopic techniques in 17, and combined endoscopic and external procedures in eight. Histological evidence of tissue invasion was absent in all 25 patients, in spite of extensive destruction of the skull base in four. Dematiaceous fungi were the most common cultural isolate. Fifteen patients were available for more than 6 months post-operative follow-up. None of the eight patients who developed recurrent disease had been treated with post-operative systemic steroids. Four of the seven patients who remained disease-free had received steroids. Clinical trials to test the efficacy of systemic steroids in the prevention of disease recurrence are clearly warranted.

Allergic fungal sinusitis with cranial base erosion.

BACKGROUND: Allergic fungal sinusitis (AFS) usually follows a slow, nonaggressive course. However, massive bone destruction can occur, with extension of the disease process outside of the confines of the sinuses. METHODS: Our series of 28 cases of AFS was reviewed. We identified 6 cases of AFS with definite radiographic evidence of skull base erosion. RESULTS: Histologic diagnostic criteria for AFS were present in all 6 cases. All patients were managed with surgery, most recently conservative endoscopic surgery. An earlier patient underwent dural resection. Antibiotics were used in all patients, but no antifungal agents were administered. No patient has had a permanent neurologic complication, although one was seen with abducens palsy. There have been no cerebrospinal fluid (CSF) leaks. All 6 cases also had orbital bone erosion, but none has had permanent ophthalmologic sequelae. All patients were initially suspected to have a neoplastic disease. CONCLUSIONS: We propose a new diagnostic entity, "skull base allergic fungal sinusitis" (SBAFS), which incorporates the histologic diagnostic criteria of AFS with the computed tomographic (CT) criteria of bone erosion. Biopsy is necessary to rule out invasive fungus or tumor. Otolaryngologists, ophthalmologists, and neurosurgeons should be familiar with SBAFS so that systemic antifungal agents, craniotomy, and dural resection-which might initially appear necessary-can be avoided. Endoscopic surgical debridement and drainage combined with topical steroids can lead to resolution of disease, even in the presence of marked bone erosion and cranial neuropathy.

Skull base allergic fungal sinusitis with abducens palsy in the third trimester.

Allergic fungal sinusitis (AFS) usually follows a slow course, but bone erosion including that of the skull base can be seen. Patients may present with intracranial extension mimicking a cranial base neoplasm. We describe a 21-year-old pregnant female initially seen at 27 weeks gestation with a complete right sixth nerve paralysis. MR imaging showed an apparent nasopharyngeal neoplasm invading both temporal lobes. Further evaluation revealed typical findings of fungal sinusitis on both CT and MR images. Biopsy results fulfilled the diagnostic criteria of AFS, and after endoscopic treatment the sixth nerve palsy quickly resolved. Although abducens palsy has been reported with acute bacterial sinusitis and with mucocele, and limitation of eye motility has been described with orbital involvement by AFS, we are unaware of any prior reports of true cranial nerve palsy associated with proven AFS. Our patient had no evidence of mucocele or of bacterial infection. The palsy in this case was presumably the result of compression of the cavernous sinus. The patient's pregnancy made decision making regarding imaging and surgical intervention complex. Mother and child are alive and well 31 months after surgery.

Endoscopically removed malignant colorectal polyps: clinicopathologic correlations.

BACKGROUND/AIMS: Treatment options for patients with endoscopically removed malignant colorectal polyps are polypectomy alone vs. polypectomy followed by surgery. The aim of this study was to define histopathologic parameters that can be used for clinically relevant treatment decisions. METHODS: Five pathologists evaluated 140 polyps for the presence or absence of unfavorable histology. Unfavorable histology was tumor at or near (< or = 1.0 mm) the margin and/or grade III and/or lymphatic and/or venous invasion. Adverse outcome was recurrent and/or local cancer and/or lymph node metastasis. RESULTS: Adverse outcome was 19.7% (14 of 71), 8.6% (2 of 23), and 0% (0 of 46) when unfavorable histology was present, indefinite (lack of agreement), and absent, respectively (P < 0.0005, present vs. absent). Four patients with cancer > 1.0 mm from the margin had an adverse outcome (2 with lymphatic invasion and 2 indefinite for lymphatic invasion). Four patients with negative resections later developed distant metastases. Eight patients (6.3%) died of disease, and 2 of 69 without unfavorable histology (both indefinite for lymphatic invasion) had an adverse outcome. Interobserver strength of agreement was substantial to almost perfect for margin, grade, and venous invasion and fair to substantial for lymphatic invasion. CONCLUSIONS: This system is usable clinically. Patients with unfavorable histology are probably best managed by resection postpolypectomy, whereas in the absence of unfavorable histology, they probably can be treated by polypectomy only.

Sporotrichosis as a presenting manifestation of hairy cell leukemia.

An infectious episode is the presenting manifestation of hairy cell leukemia (HCL) in approximately 30% of cases. Most often this is bacterial and only rare cases of opportunistic fungal infection are described. We report a patient who presented with sporotrichal involvement of multiple cutaneous sites and lymph nodes. The lesions resolved following antifungal therapy, but persisting pancytopenia and splenomegaly necessitated further hematological evaluation. A diagnosis of HCL was suspected based on morphologically characteristic hairy cells in the peripheral blood that contained tartrate resistant acid phosphatase. A bone marrow biopsy specimen had a normocellular marrow with an increase in interstitial lymphoid cells that stained with L26, MB2, and LN2 antibodies. On flow cytometry these cells were positive for the leukocyte common antigen, B cell markers, and the CD11c antigen confirming the diagnosis of HCL. We believe that this is the first report of sporotrichosis infection as a presenting manifestation of HCL.

Hepatic function during short-term total parenteral nutrition: effect of exposure of parenteral nutrients to light.

Total parenteral nutrition (TPN) solutions either exposed to light (+L) or protected from light (-L) were infused for 5 days through jugular cannulas in freely moving rats placed in metabolic cages. At the end of the 5 day period, bile flow, biliary inorganic phosphate and biliary gamma-glutamyl transferase activity, as well as biliary concentrations of several essential and branch chain amino acids were significantly lower in the -L animals compared to +L animals. In addition, biliary glutathione was significantly lower in the +L animals. In both groups of animals, plasma tyrosine decreased significantly from pre-TPN values despite a doubling of plasma phenylalanine concentrations suggesting that tyrosine may become a conditionally essential amino acid in rats provided TPN. Our findings indicate that short-term parenteral infusion of light exposed TPN solutions alters hepatobiliary function as well as amino acid homeostasis and that the changes are minimized by light protection of the infusates. The exact mechanisms of the contribution of light exposure in the induction of hepatic dysfunction remain to elucidated.

Cystadenoma and cystadenocarcinoma with mesenchymal stroma of the liver. Immunohistochemical analysis.

Cystadenoma with mesenchymal stroma is a rare neoplasm of the liver that occurs exclusively in young women and has a potential for malignant transformation. A light microscopic and immunohistochemical study of a case of biliary cystadenoma and another of biliary cystadenocarcinoma revealed a range of differentiation of the lining epithelial cells. The lining cells in the cystadenoma resembled the cells of the normal intrahepatic bile ducts. In contrast, the epithelial lining in the case of cystadenocarcinoma had features of intestinal mucosa, including goblet, Paneth, and endocrine cells similar to those found in other mucinous cystic neoplasms of the foregut area. The compact "ovarianlike" mesenchymal stromal cells had immunohistochemical characteristics of myofibroblasts. These are reactive contractile cells that may proliferate in response to the expanding cysts and female hormones, and they differ immunohistochemically from ovarian stromal cells.

Phaeohyphomycosis caused by Bipolaris spicifera: an informative case.

A case of phaeohyphomycosis caused by Bipolaris spicifera involving the brain and sinuses is presented. The patient survived following surgery and ketoconazole therapy, which successfully treated both the sinus and the brain infections.

"Reverse-figure 3" sign in duodenal adenocarcinoma arising in a villous adenoma: radiographic demonstration.

The radiographic "reverse-figure 3" sign is a well-known indicator of pancreatic head enlargement. We present a case in which this characteristic sign was produced by an invasive adenocarcinoma of the duodenum that arose in a periampullary villous adenoma.

Identification of Campylobacter pylori by endoscopic brush cytology.

To investigate the value of Papanicolaou-stained endoscopic brush samples in the diagnosis of Campylobacter pylori infection of the upper gastrointestinal tract, 138 brush and biopsy samples from the esophagus, stomach, and duodenum, taken concomitantly, were reviewed retrospectively. In 35 cases, Campylobacter-like organisms (CLOs) were found in both cytology and biopsy samples. In 15 cases, CLOs were seen in biopsy material only, and in 8 cases, CLOs were found in cytology material only. CLOs were found in 49% of the gastric specimens and 33% of the Barrett's esophagus specimens by histologic or cytologic examination or by both methods. CLOs were found by at least one method in 64% of the gastric samples with active gastritis 40% with borderline gastritis, 15% without gastritis, and in 64% with adenocarcinoma. Cytologic examination of endoscopic brush samples is a valuable technique for the diagnosis of gastric Campylobacter infections and can be performed easily in cytopathology laboratories.

Aluminum-associated hepatobiliary dysfunction in rats: relationships to dosage and duration of exposure.

Aluminum may contaminate parenteral nutrition solutions and accumulate in bone and liver of patients receiving this therapy. Although aluminum exposure is associated with low-turnover osteomalacia, there are few studies of hepatotoxicity. We therefore studied the effects of aluminum given to rats on total serum bile acid concentration and bile flow to determine if aluminum administration could produce abnormalities. Aluminum was given intravenously as follows: 5 mg/kg daily for 7 or 14 days and 1 mg/kg for 14 days. Hepatic aluminum was high in treated rats and undetectable in controls. Total serum bile acid concentrations were significantly higher in treated rats than in pair-fed controls with higher concentrations after 14 days than after 7 days. Bile flow was reduced by 33% in rats given 5 mg/kg but not in rats given 1 mg/kg. Hepatic aluminum correlated inversely with bile flow but not with serum bile acid concentration. Aluminum exposure in rats is associated with elevated serum bile acid concentration and diminished bile flow and may play a role in the pathogenesis of parenteral nutrition-induced hepatobiliary dysfunction.

Treatment of intestinal ischemia with oxygenated intraluminal perfluorocarbons.

Liquid perfluorocarbons are biologically inert compounds capable of dissolving up to 40 percent oxygen by volume. This remarkable and reversible oxygen solubility has encouraged investigations into therapeutic application in situations where tissue oxygen delivery is impaired. One such setting is intestinal ischemia. Identically prepared devascularized segments of rat intestine were treated with either intraluminal oxygenated perfluorocarbon (perfluorotributylamine) or physiologic saline solution. After timed sacrifice, blinded quantitative histologic evaluation for ischemic injury was performed. The perfluorotributylamine treatment groups had histologic scores indicative of less severe injury between 1 and 4 hours. These scores achieved statistical significance (p less than 0.05). We conclude that intraluminal oxygenated perfluorocarbons have a significant protective effect in this model of intestinal ischemia. This quantitative analysis is unique and is an important aspect of the preclinical evaluation of the perfluorocarbon preparations.