Delayed granuloma formation in a patient with vanishing bile duct syndrome 7 years post-liver transplantation.

A patient was found to have numerous granulomata 7 years after orthotopic liver transplantation for primary sclerosing cholangitis (PSC) on a recent liver biopsy specimen. This histopathologic finding prompted a review of the literature to determine the commonality of this feature in the absence of the usual causes of granulomatous liver disease, none of which were found to be the cause of this patient's liver histopathologic state. The presence of posttransplantation granulomata is rare, and although previously reported to occur shortly after liver transplantation, this finding has not been reported previously with either PSC or vanishing bile duct syndrome. We are not aware of another case of granulomata associated with recurrent PSC or vanishing bile duct syndrome 7 years after liver transplantation.

Control of the epidermal growth factor receptor and its ligands during renal injury.

AIM: We studied control of the epidermal growth factor (EGF) receptor and its ligands during kidney injury, since they may be importantly involved in repair. METHODS: The folic acid model of renal injury was used in these studies. Messenger RNA (mRNA) was evaluated by solution hybridization. Immunohistochemistry of transforming growth factor alpha (TGF-alpha) was also performed. RESULTS: Twenty-four hours after folic acid induced acute renal injury, creatinine increased from 0.3 +/- 0.03 mg/dl in controls to 2.0 +/- 0.8 mg/dl in folic acid injured kidneys (n = 4, p < 0.03). mRNA for the EGF receptor was increased nearly sevenfold by 24 h, and mRNA for the receptor was increased as early as 1 h following folic acid treatment. EGF receptor ligand caused a profound downregulation of the receptors in proximal tubule basolateral membranes, but receptors returned rapidly to the membrane surface in injured kidneys. The mRNA levels for heparin-binding EGF and TGF-alpha, two EGF receptor ligands, increased within 1 h of injury. TGF-alpha mRNA increased from 1.0 +/- 0.09 (relative densitometry units) in control animals to 2.9 +/- 0.13 in folic acid treated rats at 24 h (n = 4, p < 0.01), and immunohistochemical staining for TGF-alpha increased in injured kidneys at distal nephron sites. CONCLUSIONS: These studies indicate that upregulation of the EGF receptor is related to an increase in mRNA. The rapid return of receptors to the membrane surface following ligand stimulation may be useful in maintaining a mitogenic stimulus. Multiple EGF-like ligands may be important in activating the upregulated EGF receptor during repair from renal injury.

Mrna expression of transforming growth factor-alpha and the EGF receptor following nephrotoxic renal injury.

We studied gene expression for transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), heparin binding (HB) EGF, and the EGF receptor following acute renal failure induced by mercuric chloride administration to gain insight into potential mechanisms of renal repair. Twenty four hours after HgCl2, 2 mg/kg, creatinine increased from 0.3+/-0.01 mg/dl in controls to 2.2+/-0.26 mg/dl in injured rats (n = 5, p < 0.01). Similar changes were observed after 3 days. Messenger RNA expression for EGF was decreased at 24 hours in HgCl2 treated rats and remained depressed for at least 3 days. On the other hand steady state mRNA for TGF-alpha increased nearly 2 fold at day 3 in HgCl2 treated rats 4 mg/kg. Heparin binding EGF was increased early, by day one in injured kidneys and gene expression for the EGF receptor was increased as well. Immunohistochemistry documented an increase in expression of TGF-alpha in injured kidneys at distal nephron sites. These studies suggest that TGF-alpha along with HB EGF may be important ligands for the EGF receptor during repair from renal injury.

Regulation of the epithelial cell-specific integrin, CD103, by human CD8+ cytolytic T lymphocytes.

BACKGROUND: The destruction of the graft epithelium by CD8+ cytolytic T lymphocytes (CTL) is an important aspect of organ allograft rejection. Our recent finding in a mouse model that the epithelial cell-specific integrin, CD103, defines a subset of CD8+ CTL potentially sheds new light onto such interactions. The goal of the present study was to assess the relevance of these data to the human system. METHODS: CD103 expression by human T-cell populations generated in mixed lymphocyte cultures or isolated from transplant nephrectomy specimens was quantitated using multiparameter FACS analyses. RESULTS: CD103 defined a major subset (26-76%) of CD8+ CTL generated in human mixed lymphocyte cultures; cell sorting experiments confirmed that the CD103+ and CD103- subsets both possess allospecific lytic activity. Anti-transforming growth factor (TGF)-beta blocked the appearance of the CD103+ CTL subset, and persistent expression of CD103 by CD8+ CTL was dependent on bioactive TGF-beta. Isolated CD103+ and CD103- CD8 subsets maintained their phenotypic integrity during in vitro expansion, although optimal CD103 expression on the former was TGF-beta dependent. Although CD103+ cells were rare among activated CD8 cells in peripheral lymphoid compartments (< 10%), analyses of transplant nephrectomy specimens revealed that a major subset (21-61%) of CD8 memory/effector cells that infiltrate rejecting renal allografts express high levels of CD103. CONCLUSIONS: We conclude that CD103 defines a discrete and stable subset of human CD8+ CTL and that CD103 expression by such cells is initiated and maintained by bioactive TGF-beta. These data point to the existence of a human effector subset that is uniquely specialized for the destruction of the graft epithelium.

Apoptosis and hepatic allograft reperfusion injury.

Necrosis and apoptosis are distinct, but nonexclusive mechanisms of cell death. Until recently, investigators have focused upon necrosis as the sine qua non of lethal cell injury. Specifically, within the realm of liver transplantation, preservation strategies dealing with ischemia/reperfusion injury have concentrated upon minimizing the biochemical and histologic correlates associated with necrosis. Little is known of the role of apoptosis in reperfusion injury in human liver transplantation. Post-reperfusion liver biopsies from 35 patients were retrospectively analyzed for histologic evidence of necrosis. Apoptosis was identified histologically and using a chromogenic technique of in situ labeling of fragmented DNA. The number of apoptotic cells increased in parallel with the necrosis reperfusion score in a significant fashion (p = 0.003 by ANOVA). There was not a Zone 1, 2 or 3 predominance to the histologic distribution of apoptotic cells. The recipient peak serum transaminase values were also noted to increase with the reperfusion score (p = 0.001 by ANOVA). These results suggest that: 1) apoptosis occurs in the setting of reperfusion injury during human orthotopic liver transplantation (OLT); and 2) the extent of apoptosis increases in parallel with pathologic and biochemical parameters of reperfusion injury. Given the distinct nature of apoptosis and the highly regulated and conserved pathway for its initiation, inhibition of apoptosis with specific molecular targets, may serve to decrease allograft reperfusion injury.

Primary hepatic low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) associated with primary biliary cirrhosis.

We describe a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the liver of a patient with early-stage primary biliary cirrhosis (PBC). The patient, a 62-year old woman, presented with abnormal liver function tests, a positive antimitochondrial antibody titer (1:160), and a liver mass. The resected mass, 6.0 x 5.0 x 4.0 cm, had the features of MALT-type lymphoma. The neoplastic cells were small lymphoid cells of B-cell lineage that surrounded reactive lymphoid follicles and infiltrated bile ductules to form lymphoepithelial lesions. The uninvolved liver had histologic evidence of early stage PBC, characterized by segmental duct destruction with granulomata and an inflammatory infiltrate in the portal triads composed of lymphocytes, plasma cells, and occasional eosinophils. A periportal lymph node showed histologic features of the hyaline-vascular type of Castleman's disease, without evidence of malignant lymphoma. Low-grade B-cell lymphomas of the MALT type rarely arise in the liver and, to our knowledge, have not been reported previously in association with PBC. The association in this case suggests that chronic antigenic stimulation as a result of PBC induced the accumulation of acquired MALT, which subsequently transformed to low-grade B-cell lymphoma.

End stage renal transplant failure: allograft appearances on CT.

INTRODUCTION: Failed renal allografts often are left in situ in patients who revert to chronic dialysis therapy or who undergo retransplantation. These patients may be investigated with computed tomography (CT) imaging for allograft-related or other abdominopelvic disease. This study describes the appearances of failed renal transplants on CT. METHODS: A retrospective study was made of the clinical records and CT findings on 25 studies in 14 patients, 5-156 months (average, 44 months) following allograft failure. CT studies were reviewed for allograft position, size, shape, attenuation value, calcification, cyst formation, related abdominopelvic findings and the presence of other allografts. Correlation was made with clinical findings in all patients and with pathological findings in six. RESULTS: Global shrinkage was noted in eight failed allografts, all of which were asymptomatic. Enlargement of two failed allografts was due to symptomatic acute infarction of the allograft in one patient and subacute haemorrhagic infarction simulating a tumour mass in another. CT attenuation values in individual allografts varied markedly due to fatty replacement, hydronephrosis, haemorrhage or dense calcification. Both a failed longstanding and a functioning more recently placed renal allograft were present in seven patients, four of whom had acute complications related to the more recently transplanted kidney. Two of six calcified allografts were mistaken for opacified bowel on CT. CONCLUSION: A wide spectrum in size, shape and attenuation values may be detected in failed renal allografts by CT. These organs may be the site of acute disease despite their lack of physiological function or may be diagnostically confusing findings in patients with acute disease related to more recently transplanted organs.

Morphine augmentation increases gallbladder visualization in patients pretreated with cholecystokinin.

UNLABELLED: The purpose of this study was to determine if a combination of cholecystokinin (CCK) pretreatment followed by morphine augmentation improved the detection of cystic duct patency compared with CCK pretreatment only. METHODS: One hundred fifty-five patients with suspected acute cholecystitis had scintigraphy performed with 185-481 MBq (5-13 mCi) 99mTc-mebrofenin adjusted to the patients' total bilirubin levels. All patients were pretreated with 0.02 microgram/kg sincalide injected intravenously over 3-5 min. Sequential imaging was performed until gallbladder activity was identified or up to 90 min postinjection of mebrofenin. If no gallbladder was identified, a second dose of mebrofenin was given as necessary to have tracer in the biliary system. Then, 0.04 mg/kg intravenous morphine sulfate was administered, followed by imaging for up to 30 min or until gallbladder visualization. RESULTS: Twenty-eight percent (43/155) of the patients pretreated with CCK had nonvisualization of the gallbladder at 90 min postinjection of radiotracer. After intravenous morphine, the gallbladder was identified in 42% (18/43) of these patients (p = 0.0001). CONCLUSION: Hepatobiliary imaging with CCK pretreatment and imaging for 90 min was insufficient to identify all patent cystic ducts. Morphine augmentation significantly increased the frequency of gallbladder visualization in patients pretreated with CCK.

Bacillary angiomatosis associated with extensive esophageal polyposis: a new mucocutaneous manifestation of acquired immunodeficiency disease (AIDS).

Bacillary angiomatosis is a rare infection that has been associated with human immunodeficiency virus infection. The causative organism is Rochalimaea henselae and contact with cats is a risk factor. We present a case of a 37-yr-old man who had recent prolonged exposure to a cat and presented with fever, iron deficiency anemia, and guaiac-positive stools who had biopsy-proven bacillary angiomatosis skin lesions and on esophagogastroduodenoscopy had multiple, diffuse, friable, polypoid lesions in the esophagus. The histology of the esophageal polyps was identical to the skin lesions, and the polyps disappeared after treatment with erythromycin. Bacillary angiomatosis should be included in the differential diagnosis of infectious upper gastrointestinal manifestations associated with AIDS.

Transforming growth factor-alpha expression in human renal cell carcinoma: TGF-alpha expression in renal cell carcinoma.

OBJECTIVES: To characterize the expression of transforming growth factor-alpha (TGF-alpha) in various histologic types of renal cell carcinomas. METHODS: Immunohistochemistry of renal cell carcinoma and adjacent normal tissue was performed on formalin-fixed tissue using a specific monoclonal antibody to TGF-alpha. RESULTS: Clear and distinct staining was present in normal distal convoluted tubules and collecting ducts. The growth factor was not observed in the glomerulus or the proximal tubule. In tumors composed of clear cells, staining was evident only in endothelial cells but not in the tumor cells themselves. In granular cell type tumors, the tumor cells as well as endothelial cells stained for TGF-alpha. When mixed cell type tumors were studied, a heterogenous pattern of growth factor expression was found. Endothelial cells and granular cells but not clear cells demonstrated positive staining. CONCLUSIONS: These studies suggest that TGF-alpha is likely to play a major role in neovascularization of clear cell carcinomas and that the growth factor may be more important in supporting proliferation of granular cell type tumors.

Role of radiation therapy in the management of malignant chondroid syringoma.

BACKGROUND: Malignant sweat gland neoplasms are exceedingly rare tumors. Malignant chondroid syringoma (MCS) is one of the rarest subtypes, and as such, still poorly understood. It lacks distinctive clinical features, often delaying initial diagnosis and therapeutic management. OBJECTIVE: A current case and the available literature are reviewed to determine the overall clinical course of the MCS and the potential role of adjuvant therapy. METHODS: A case of MCS was studied by light microscope, immunohistochemistry, and electron microscopy. The clinical data of this case and of other reported cases are summarized and compared. RESULTS: This tumor recurred locally after initial local excision. Subsequent re-excision and radiation therapy rendered the patient without evidence of disease. This case study and the literature review of the 20 reported cases indicate that MCS is highly recurrent with tendency toward metastasis. CONCLUSION: MCS appears to behave in an aggressive manner. An initial treatment modality is aggressive surgery. Adjuvant radiation therapy with or without chemotherapy should be tried in future cases.