Pretreatment effects on the uptake/retention kinetics of L-dopa in Harding-Passey melanoma.

Malignant melanoma cells possess a unique biochemical pathway that converts L-3,4-dihydroxyphenylalanine (L-dopa) to the biopigment melanin. Selective cytotoxic incorporation of exogenous L-dopa into melanoma cells in vivo may provide a means of designing specific chemotherapeutic agents useful in the treatment of this disease. Using the Harding-Passey murine melanotic tumor model, a preferential uptake of [3H]L-dopa by the tumor was characterized. Following pretreatment of the tumor-bearing mice with nonradioactive L-dopa, a significant enhancement (p less than 0.01) of [3H]L-dopa incorporation and retention into melanoma for a period of 24 h was observed, when compared with the concomitant tissue distribution and clearance of radioactivity in the control animals. This finding suggests that by initial pretreatment of melanoma with nonradioactive L-dopa, the subsequent selective accumulation of [3H]L-dopa in tumor may provide a useful tool in testing new modalities of therapy in malignant melanoma.

Characterization of a new primary human pancreatic tumor line.

A primary human pancreatic tumor line (BxPC-3) has been established from a biopsy specimen of a histologically confirmed adenocarcinoma of the body of the pancreas. Tumorigenicity was proven by xenograft in athymic nude mice. Upon re-establishment of tumor xenografts in tissue culture, the epithelial tumor cells retained their original morphology. Histopathologically, the tumors grown in nude mice exhibited the original characteristics of the primary adenocarcinoma in the patient, producing traceable mucin and displaying moderately well to poorly differentiated adenocarcinomas with occasional lymphocytic infiltrations at the tumor peripheries. Furthermore, the tumor xenografts differentially expressed carcinoembryonic antigen, human pancreas cancer-associated antigen, and human pancreas-specific antigen. Karyotyping and glucose-6-phosphate dehydrogenase isoenzyme characterization revealed that this tumor line was of human origin and devoid of HeLa cell contamination. The BxPC-3 tumor line has been maintained for more than four years in our laboratory and represents a valuable model for primary human pancreatic cancer.

Postoperative respiratory complications in patients with Hodgkin's disease: relationship to the size of the mediastinal tumor.

Postoperative respiratory complications were investigated in patients with Hodgkin's disease, stages I-III, presenting with a mediastinal mass. By measuring the ratio between the widest diameter of the mediastinal mass and the width of the thorax at T5-6 (mediastinal thoracic ratio, MTR) in a PA chest X-ray, patients were divided into three groups: I: MTR less than 0.35 (41 patients); II: MTR 0.35-0.49 (33 patients); and III: MTR greater than 0.50 (23 patients). Five patients of group II and eight of group III received preoperative radiation therapy (RT) to the mediastinum due to severe clinical or radiological findings associated with the mediastinal mass. No patient of group I received preoperative RT. Without preoperative RT, group III had a significantly higher incidence of respiratory complications (7/15) compared to groups I (7/41) and II (2/28). Respiratory complications were not significantly different after preoperative RT in group III (1/8) compared to that observed in groups I plus II without preoperative RT (9/69).

Simultaneous evaluation of a pancreas-specific antigen and a pancreatic cancer-associated antigen in pancreatic carcinoma.

A pancreas cancer-associated antigen (PCAA) and a pancreas-specific antigen (PaA) were simultaneously quantitated by enzyme-linked immunosorbent assays in serum specimens from 51 normal controls, 76 pancreatic cancers, 194 nonpancreatic cancers, and 22 benign pancreatic diseases. Primary immunological reagents used in the enzyme-linked immunosorbent assays were our polyclonal antibodies produced in rabbits against purified PCAA and PaA. Results revealed discordance of these two markers in pancreatic cancer, suggesting that the presence of these two biochemically and immunologically distinct pancreas proteins in patients' serum may reflect different biological aspects of cancer. The combination test resulted in a better sensitivity and specificity for pancreatic cancer, 90 and 85%, respectively, than either PCAA or PaA assay alone. This study demonstrated that the combination of serum PCAA and PaA tests yields an additive clinical value and may be a useful adjunctive aid for the immunodiagnosis of the pancreatic cancer.

Skin pressure measurements on various mattress surfaces in cancer patients.

Twenty-eight patients with histologically proven carcinoma were studied on two dynamic and six static mattress surfaces to determine which mattress surface would provide the least skin surface pressure at the sacrum, dorsal spine, trochanter and heels. Measurements were taken with an especially designed inflatable bladder, and the mean of the maximum skin surface pressures was determined for the static and dynamic surfaces in the inflated and deflated state. Using less than or equal to 32 mm Hg as the skin surface pressure at which the arteriolarcapillary blood flow is interrupted, we concluded that the mud gel bed generally tended to record the lowest skin surface pressure for all of the sites. Although some of the static surfaces recorded pressures less than or equal to 32 mm Hg at the sacrum and dorsal spine, the deflated dynamic surfaces were superior to the remaining static surfaces in reducing the skin surface pressures.

Human pancreatic adenocarcinoma: in vitro and in vivo morphology of a new tumor line established from ascites.

A human pancreatic tumor cell line has been established from the ascites of a patient with histopathologically confirmed adenocarcinoma of the head of the pancreas and maintained for more than 12 months in the laboratory. Epithelioid tumor cell colonies, which resulted from primary tissue cultures of the ascitic cell component, were mechanically isolated by needle micromanipulation. Tumorigenicity was proven in athymic nude mice. Morphologically the pancreatic tumor epithelial cells grew to confluency with moderately tight adhesion to the culture plastic surface and with free-floating cells in the medium. Upon re-establishment of the tumoral xenograft in tissue culture, the epithelial cells retained their original morphology. Histologically the tumor grown in nude mice exhibited prototypic characteristics of the primary adenocarcinoma in the patient, producing abundant mucin and displaying a broad spectrum of glandular differentiation, which ranged from well to poorly differentiated adenocarcinomas with occasionally localized lymphocytic infiltrations. Furthermore, the tumor expressed carcinoembryonic antigen and human pancreas cancer associated antigen. This tumor line, designated AsPC-1, has been cultured for at least 10 passages in vitro and 3 in vivo. It represents a new model for human pancreatic cancer.

Evaluation of a human pancreas-specific antigen by enzyme-linked immunosorbent assay.

A sensitive sandwich-type enzyme immunosorbent assay has been developed for quantitation of a new human pancreas-specific antigen (PaA). With this method, PaA at a concentration as low as 0.8 ng/ml can be detected. The assay was reproducible as shown by the coefficients of variation for within (4.8%) and between (6.1%) assays. Serum PaA levels from 51 healthy persons ranged from less than 4 to 34 ng/ml. Using 21.5 ng/ml (the upper 97.5 percentile of normal controls) as an upper limit, 42 of 60 pancreatic cancer (70%), 3 of 14 pancreatitis (21%) and 2 of 6 cholelithiasis (33%) had an elevated PaA. Very few patients with other cancers were shown to have an elevated PaA: 3/40 (8%) of lung cancer, 2/43 (5%) of colorectal cancer, 3/40 (8%) of prostate cancer and 1/39 (3%) of breast cancer. The sensitivity and specificity of the serum PaA test for the detection of pancreatic cancer were calculated to be 70% and 95%, respectively. These results indicate that PaA may be useful as an adjunctive tool in immunodiagnosis of pancreatic cancer.

Isolation, characterization and clinical evaluation of a pancreas cancer-associated antigen.

A pancreas cancer-associated antigen (PCAA) was identified and isolated from ascites fluid of human pancreatic cancer. Purified PCAA was homogeneous as determined by polyacrylamide gel electrophoresis. PCAA was a glycoprotein with a molecular weight of approximately 1,000,000 and consisted of 20% carbohydrates and 80% peptides, had an isoelectric point of 4.7, and migrated to alpha 2-beta region. It possessed a sedimentation coefficient of 14S and appeared to be a fibrous or fibroglobular protein. Immunoreactivity of PCAA was sensitive to proteolytic enzymes, perchloric acid, KSCN, glycine-HCl at pH 2.5, urea and lithium diiodosalicylate; and insensitive to neuraminidase or beta-glucosidase. Immunohistochemical technique revealed that PCAA was located in the cytoplasm of ductal epithelial cells of malignant pancreas. Using heteroantiserum raised against purified PCAA, horseradish peroxidase and CNBr-activated Sepharose 4B, an enzyme-immunoassay (EIA) for circulating PCAA has been developed. From a group of 40 healthy blood donors, an upper limit of 16.2 micrograms of PCAA/ml of serum has been tentatively determined. An elevated PCAA was shown in 67% (29/43) of patients with pancreas cancer, as well as in 30% (11/36) of lung cancer patients, 27% (10/37) of colonic cancer patients, and in 16% (6/36) of breast cancer patients. The reactive antigen in sera of these cancers was shown to be immunologically identical. PCAA also was detected in extracts of various human tissues, particularly pancreatic tumors, colonic tumors, and in a normal colon. Further, PCAA exhibited heterogeneity in molecular weight, isoelectric point, and electrophoretic mobility.

Biliary cystadenocarcinoma: report of a case presenting with osseous metastasis and a review of the literature.

Biliary cystadenocarcinoma is a rare malignancy, and osseous metastasis resulting from this tumor have been recorded in only one of the 19 documented cases in the literature. The case report of this 59-year-old male is unusual in that the patient's initial clinical manifestations of the disease were that of osseous metastases, while the primary tumor eluded discovery for greater than 1 year. Although this is the first documented case in which radiation and chemotherapy were used to control the disease, the use of these agents may have contributed to the delay in establishing the primary site of the tumor. The clinical and pathologic features of this and the previously reported cases are reviewed with an emphasis on the newer diagnostic modalities being used in more recent cases to establish the diagnosis for this tumor.

The role of hepatic artery ligation and dearterialization with infusion chemotherapy in advanced malignancies in the liver.

Because of limited benefits derived with the use of systemic chemotherapy, 15 patients with metastatic malignancy of the liver or hepatoma were treated by hepatic artery ligation (6) or dearterialization (9) and regional infusion chemotherapy. There were two postoperative deaths and three patients required surgical drainage of hepatic tumor liquefaction necrosis. The median survival was 14 months with two patients still living. The longest survivors were those patients with visceral leiomyosarcoma or carcinoid tumor. Five of the patients had failed to respond to previous chemotherapy, all showed a favorable response to this therapy. Rigid criteria for proper case selection have been developed which should reduce the operative mortality. Hepatic artery ligation is a therapeutic modality that can be of benefit to patients for whom no other satisfactory treatment is available.

Significance of 99mTc-sulfur colloid splenic image in malignant melanoma.

To evaluate the clinical significance of 99mTc-sulfur-colloid (TsSC) spleen scan findings in patients with malignant melanoma, a retrospective study was undertaken. Eighty-one patients with histologically proven malignant melanoma who received treatment in Roswell Park during a five-year period were included in this study. The scans were analyzed for spleen size, differential uptake of the tracer in liver and spleen, and for the presence of metastases in these two organs. These data were compared with stage of disease, survival, and autopsy findings. Significant correlation was found between the splenic size as measured on the scintiscan and at autopsy examination. The spleen size was found to be normal in 92% of the patients in early melanoma. The median survival of patients who had a normal-sized spleen by scan criteria was found to be longer than those who had splenomegaly. No significant difference in survival was noted between the patients with and without augmented splenic uptake of TcSC. Only a small number (17.7%) of patients with augmented splenic uptake had splenic metastases; hence, the possible role of immunological factors was considered.

Extraosseous osteogenic sarcoma: case report.

Extraosseous osteogenic sarcoma is a highly malignant tumor, and in order to improve the chances of survival of those who have it, aggressive surgical treatment, including major amputations, should be performed. Based on the results obtained in the treatment of its osseous counterpart, the use of adjuvant chemotherapy is strongly recommended. Evaluation should not be done because it is usually followed by local recurrence.

Mesenteric fibromatosis in Gardner's syndrome.

Two patients with mesenteric fibromatosis in Gardner's syndrome were treated by us. These tumors are slow-growing and may remain quiescent for long periods. Review of similar cases in the literature discloses that less than half of these tumors have been removed, pointing to the difficulty of their resection. Dissection of the infraduodenal portion of superior mesenteric vessels may help define whether these tumors are resectable. Radiation therapy or treatment with antiestrogens may be helpful in the treatment of unresectable tumors.