Renal cell carcinoma metastatic to the pancreas: clinical and radiological features.

OBJECTIVE: To review the clinical features, computed tomographic (CT) appearance, and treatment outcomes in a case series of patients with renal cell carcinoma (RCC) metastatic to the pancreas. PATIENTS AND METHODS: We retrospectively reviewed the records of 23 patients (15 men and 8 women) with RCC metastatic to the pancreas, detected by CT examination between 1986 and 1996. All patients had undergone a previous nephrectomy for RCC. RESULTS: Isolated mild elevation in liver function test results (in 5 patients) or in serum amylase level (in 8 patients) was observed. New-onset diabetes was detected in 3 patients. The CT characteristics of the pancreatic metastases generally resembled those of primary RCC with well-defined margins and greater enhancement than normal pancreas with a central area of low attenuation. The mean interval between resection of the primary RCC and detection of the pancreatic metastases was 116 months (range, 1-295 months). In 18 patients (78%), the pancreatic metastases were diagnosed more than 5 years after nephrectomy. The pancreas was the initial metastatic site in 12 patients (52%). Survival was shortened with higher tumor grade (mean survival time of 41 months and 10 months in patients with grade 2 and 3, respectively). Surgical resection was carried out in 11 patients (7 distal and 3 total pancreatectomies and 1 distal pancreatectomy followed 4 years later by total pancreatectomy), with 8 patients alive at a mean follow-up of 4 years, 6 of whom remained free of recurrence. Overall, 12 patients (52%) were alive at a mean of 42 months after diagnosis of metastatic disease. CONCLUSIONS: The appearance of metastatic RCC lesions in the pancreas closely resembles the appearance of primary RCC on CT images. Pancreatic metastases from RCC are frequently detected many years after nephrectomy. Patient survival correlates with tumor grade. Histologic analysis of pancreatic masses in patients with a history of resected primary RCC is important since the prognosis for RCC metastatic to the pancreas is much better than that for primary pancreatic adenocarcinoma.

CT characteristics of metastatic disease of the pancreas.

Contrast material-enhanced computed tomographic (CT) scans obtained over a 10-year period in 66 patients with metastases to the pancreas were retrospectively reviewed. The primary tumors most commonly responsible for these metastases were renal cell carcinoma (30.3%) and bronchogenic carcinoma (22.7%). Metastases showed no predilection for any particular part of the pancreas. The majority (75.8%) of metastases appeared as tumors with discrete margins, and most of these tumors were round or ovoid with smooth borders. Over three-fourths of the lesions demonstrated enhancement (usually heterogeneous). Vascular involvement was uncommon. In those patients in whom pancreatic metastases were discovered some time after the primary tumor was identified, the interval ranged from 2 to 295 months, with the longest mean interval (120.2 months) being associated with metastatic tumors from renal cell carcinoma. The appearance of these tumors at CT--predominantly hyperattenuating masses, often with nonenhancing internal components--was similar to that of primary renal cell carcinoma. In most pancreatic metastases, however, clinical information in conjunction with CT characteristics such as multiplicity of tumors or hypervascularity permit differentiation of metastases from primary neoplasm. When diagnosis of a pancreatic neoplasm is uncertain, percutaneous biopsy often permits histologic confirmation of the tumor type.

Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice.

Prostate cancer mortality results from metastasis to bone and hormone-independent tumor growth. Models to study these progressive changes are lacking. Here we describe the propagation of advanced human prostate cancer by direct transfer of surgical samples from patients into immune-deficient male SCID mice. Explants from six of eight patients formed prostate tumors and two showed unique cytogenetic, biologic and molecular features that were retained through six or more passages. One grew in an androgen-independent fashion, whereas the second formed tumors that regressed following castration then regrew. Micrometastatic disease was detected in the hematopoietic tissues of half of the recipient mice. Thus selected specimens of advanced human prostate cancer can be propagated in SCID mice in a manner that recapitulates the clinical transition from androgen-sensitive to androgen-independent growth, accompanied by micrometastasis.

Chaetogaster limnaei (annelida: oligochaeta) as a parasite of the zebra mussel Dreissena polymorpha, and the quagga mussel Dreissena bugensis (mollusca: bivalvia).

Dreissenid mussels, Dreissena polymorpha and D. bugensis, were found to be infected by the naidid oligochaete Chaetogaster limnaei at four sites in the St. Lawrence River. This is the first report of this species infecting dreissenids anywhere in the world. Most worms inhabited the mantle cavity, where they caused erosion of the mantle and gill epithelia as determined by histopathological examination. Others penetrated various tissues; one had invaded the ovary and was feeding on oocytes and ovarian tissues. Of 606 mussels examined, 166 (27.4%) harbored at least 1 C. limnaei. The prevalence varied between 1% and 80%, depending on the collection site and date. The worms were slightly but significantly more prevalent in D. bugensis than in D. polymorpha. The intensity ranged from 1 to 18 worms per infected host. Variations in prevalence and intensity were not related to the size or sex of the host, but the data did suggest some seasonality.

Role for the stem cell factor/KIT complex in Schwann cell neoplasia and mast cell proliferation associated with neurofibromatosis.

Schwann cells are the primary cell type in the disfiguring lesions associated with neurofibromatosis type 1 (NF-1). These lesions also contain abnormally high numbers of mast cells, a cell type which develops in response to stem cell factor. We report here that neonatal and adult rat and human Schwann cells, as well as a transfected rat Schwann cell line and a human Schwannoma line derived from an NF-1 patient, all produced stem cell factor mRNA and protein. In coculture experiments, surface expression of stem cell factor by neonatal rat Schwann cells was profoundly downregulated by contact with dorsal root ganglion neurites. The receptor for stem cell factor, KIT, was not expressed in normal Schwann cells but was expressed in the human Schwannoma line, suggesting that aberrant KIT expression may form an autocrine loop in certain Schwann cell neoplasias.

Systemic lupus erythematosus is not genetically linked to the beta chain of the T cell receptor.

The genomic DNA polymorphism of the beta chain of the T cell receptor was examined. The restriction fragment length polymorphism distribution was similar in systemic lupus erythematosus patients, their relatives, and normal controls. Our observations suggest that these genes are not coinherited with genes responsible for systemic lupus erythematosus.

A novel mechanism of somatic rearrangement predicted by a human T-cell antigen receptor beta-chain complementary DNA.

The T-cell antigen receptor is a cell surface molecule vital in mediating the cellular immune response. The arrangement and rearrangement of the gene segments encoding the beta-chain polypeptide of the receptor are similar to those of immunoglobulin gene segments. The two constant region genes of the human T-cell antigen receptor are 8 kilobases apart with a cluster of joining segments located 5' of each constant region gene. Although most beta-chain gene rearrangements involve the variable, diversity, and joining segments, analysis of a beta-chain complementary DNA clone suggests the occasional occurrence of another type of rearrangement.

Nucleotide sequences of the human and mouse atrial natriuretic factor genes.

Mouse and human atrial natriuretic factor (ANF) genes have been cloned and their nucleotide sequences determined. Each ANF gene consists of three coding blocks separated by two intervening sequences. The 5' flanking sequences and those encoding proANF are highly conserved between the two species, while the intervening sequences and 3' untranslated regions are not. The conserved sequences 5' of the gene may play an important role in the regulation of ANF gene expression.

Specific class II histocompatibility gene polymorphism in BB rats.

The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune etiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat major histocompatibility complex. To better define the BB rat's RT1-linked diabetogenic gene (RT1-DM), we have used restriction endonucleases BamH1 and EcoR1 in conjunction with an I-A alpha (class II mouse major histocompatibility complex) gene probe to study RT1 class II gene polymorphisms among diabetes-prone BB rats and the related non-diabetes-prone BBN rats. Both BB and BBN rats are indistinguishable RT1u by serologic methods. Four polymorphic chromosome types (la, lb, lla, and llb) were recognized among the control BBN rats. In contrast, all BB rats were homozygous (lla/lla). From the multiple breeding programs involved, we hypothesize that the BB rat's RT1-linked diabetogenic gene is linked to an l-A alpha-defined gene of the type lla chromosome. The ability to split the RT1u of BB rats will provide a powerful tool to localize and characterize RT1-DM.

Class I, II and III major histocompatibility complex gene polymorphisms in BB rats.

The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune aetiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat's major histocompatibility complex. To study further the RT1 linked diabetogenic gene of the BB rat, we have studied restriction fragment length polymorphism using 32P-labelled DNA probes of the major histocompatibility complex genes. As we have previously reported, an I-A alpha probe (mouse class II gene) defines four chromosome types in the control BBN population, only one of which is found among diabetes prone BB rats. All BB rats we have studied are homozygous for the type IIa chromosome. Here we examine restriction fragment length polymorphisms using three other DNA probes. Using a DC beta-probe (human class II), the same pattern of polymorphisms (though different molecular weights) is found as with the I-A alpha probe. An H-2d C4 (fourth component of complement, mouse class III) defines no polymorphisms among or between BB and BBN rats. Using H-2 LdC-2 domain probe (mouse class I) many polymorphisms are apparent and in a limited series distinguishes I-A alpha defined IIa/IIa BBN rats from IIa/IIa BB rats. These studies provide the basis to subtype the RT1u identical BB and BBN animals and should aid in the localization and characterization of the RT1 linked diabetogenic gene of the BB rat.