Donald S. Ross

Incidentally discovered adrenal masses

It is becoming increasingly common to discover adrenal masses incidentally on radiologic imaging studies. Adrenal masses are also occasionally found unexpectedly during operation. Herein, we review 10 cases of incidentally discovered adrenal masses which illustrate the experience with the treatment of these lesions in the past 8 years. A management plan based on this experience and a review of previously published data are discussed.

Circulating immune complexes in patients with colorectal cancer

We have attempted to better define host humoral immune response in neoplasia by quantitating serial circulating immune complex values before and after surgery in patients with primary or metastatic colorectal cancer. Circulating immune complex levels were correlated with serial carcinoembryonic antigen values and tumor courses in patients with primary resectable colorectal cancer (four patients), resectable liver metastases (three patients), diffuse liver metastases treated with regional chemotherapy (three patients), and untreated intrahepatic (one patient) and extrahepatic metastases (one patient). Circulating immune complex levels, as measured by an antigen-nonspecific assay, which utilized 4 percent polyethylene glycol insolubilization, were increased in all patients at presentation (734 delta OD450 +/- 381) when compared with normal human control sera (202 +/- 4, p less than 0.05). No particular relation was found between presenting circulating immune complex levels and tumor burden. Progressive circulating immune complex increases were demonstrated only in patients whose tumors were either completely removed or dramatically responded to regional therapy (that is, when the tumor antigen load, as reflected by the carcinoembryonic antigen value, rapidly diminished). Serum samples obtained at times of presumed antibody excess in the patients with gastrointestinal cancers were found to contain unexpectedly high concentrations of IgA. We believe these data demonstrate the kinetics of circulating immune complex change during tumor course and they have allowed us to begin to identify circulating immune complex components in patients with colorectal cancer. The results confirm our earlier findings in patients with gestational tumors and differ from accepted relations between immune complexes and tumor growth.

Effects of tumor growth on interleukins and circulating immune complexes. Mechanisms of immune unresponsiveness

This study delineates the temporal relationship between immune complex formation and tumor growth, and provides one possible explanation for host immunosuppression during tumor growth. The authors have studied serial circulating immune complex (CIC) levels and interleukin (IL) elaboration by peripheral blood cells (IL‐1 production by adherent mononuclear cells [AMC]; and IL‐2 generation by peripheral blood mononuclear cells [PBMC]) during the growth of syngeneic tumor isografts in an inbred rat model. Male Wistar/Furth (W/Fu) rats were injected, subcutaneously (SC) with 2 × 106 W163 (a dimethylhydrazine [DMH]‐induced colon adenocarcinoma) cells into their hind limbs. Serial CIC levels, (measured by the antigen nonspecific polyethylene glycol turbidity assay) and IL‐1 and IL‐2 production were measured before isografting and weekly thereafter. Progressive local tumor growth occurred for 3 weeks followed by regional lymph node metastases during the fourth week. During local tumor growth, there was a progressive rise in CIC levels (123% rise compared with baseline value; P < 0.05) which correlated with a fall in both IL‐1 and IL‐2 generation (r = −0.768). At the time of regional metastasis, the mean CIC levels declined, and there was a further significant decrease in IL production (IL‐1 = 0.9% and IL‐2 = 10% of controls in tumor bearers). These results show that progressive tumor growth results in decreased IL production by host PBC, and suggest that CIC may be involved in regulating IL generation. Cancer 53:1373‐1378, 1984.

Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia.

The authors have studied serial circulating immune complex (CIC) levels in 15 patients with gestational trophoblastic neoplasia (GTN) for several reasons. Gestational trophoblastic neoplasia can easily be followed from presentation to remission, and CIC changes can be compared with changes in human chorionic gonadotropin (HCG) which is a specific and quantitative marker of trophoblastic tumor load. Twelve patients with hydatidiform molar pregnancy presented with normal CIC levels (255 δ OD450 ± 97, mean SE [standard error]) as measured by our antigen nonspecific polyethylene glycol (PEG) turbidity assay. Only after reduction in tumor load as monitored by a fall in HCG did CIC rise. In contrast, three patients with choriocarcinoma presented with significantly elevated CIC levels (513 δ OD450 ± 147, P < 0.05 compared to normals) which slowly declined in parallel with HCG levels following evacuation and chemotherapy. Sera at peak PEG‐CIC from three patients with molar pregnancy or choriocarcinoma were precipitated with 3.75% polyethylene glycol to concentrate circulating immune complexes. Circulating immune complex levels were fractionated on Sephadex G‐200 in an acid buffer (pH = 2.8). An identifiable antigenic component of the CIC in both diseases was found to be paternal HLA antigen. This was demonstrated by the ability of the latest eluting CIC fraction to inhibit paternal lymphocyte lysis using anti‐HLA antisera against the husbands HLA tissue type. In each case, this fraction contained no immunoglobulin or beta‐2 microglobulin and was antigenically crossreactive with only one of the husbands HLA haplotypes. The authors believe the PEG‐CIC assay has allowed them to define the kinetics of host humoral response in GTN, and has provided a method for recovering immunogenic tumor‐associated antigens from these complexes which may apply to other solid tumors. Cancer 53:1316‐1321, 1984.

Tumor Growth, Interleukins, and Immune Complexes

Using an antigen-nonspecific assay for circulating immune complexes (PEG-CIC) that detects immune complexes in regions of both antigen and antibody excess, we have shown in our recent studies that changes in serial PEG-CIC levels correlate with changes in tumor volume in a variety of human and animal tumors (Jerry et al., 1976; Rodrick et al., 1983). Furthermore, the elevations in CIC levels were shown to precede decreases in T-cell mitogenic responses to PHA. The precise mechanism of immune modulation in tumor-bearing hosts still remains unclear although regulatory interactions between host immunocytes are undoubtedly involved. As interleukins (IL) play a central role in the mediation and amplification of immune response, and as our earlier data pointed to a temporal relationship between changes in PEG-CIC and tumor growth, we postulated that immune complexes by perturbing intercellular interactions might decrease IL generation.