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.

Lumpectomy for mammary carcinoma. A retrospective analysis of 40 presumptive candidates from a surgical series.

This presumptive study concerns the value of lumpectomy as a curative procedure for minimal breast carcinoma, defined as an operable cancer no larger than 2 cm in diameter, with no palpable axillary lymph nodes, and, in peripherally located lesions, no Paget's disease. From 199 surgically treated mammary cancer patients, 40 cases met the minimal criteria. Thirty-eight of the minimal breast carcinoma patients had a radical mastectomy and two had a supraradical procedure. The pathology findings and survival data were analyzed in these minimal carcinoma cases, and it was calculated that lumpectomy alone would have left cancer cells in 48% of the patients because of regional lymph node involvement by cancer, extension of cells from a peripheral cancer to the nipple ducts, or presence of a second carcinoma in the breast. However, the estimated 30-year cure rate in these radical surgically treated patients was 86%.

Effect of sodium meclofenamate on ultraviolet radiation induced carcinogenesis.

Sodium meclofenamate (Meclomen), an antiprostaglandin antileukotriene agent, was found in previous studies to protect primates against x-ray induced brain edema, esophagitis and cystitis. In the present study, it appeared to protect hairless mice against the carcinogenic effect of ultraviolet B-radiation.

Central nervous system metastasis from breast carcinoma. Autopsy study.

Central nervous system (CNS) metastasis was noted in 309 patients of 1044 autopsy cases of breast carcinoma. The brain was involved in 193 cases, and cranial dura in 167 cases. In 82 cases, the cranial dura was the sole site of CNS involvement. Metastasis to the leptomeninges was found in 59 cases, and to the spinal cord and dura in 32 cases. Metastases to the infratentorial portion of the brain was almost as frequent as to the cerebrum. Forty-two percent of the brain metastasis were single lesions, which is similar to the frequency of solitary metastasis to the brain from malignant tumors as a whole. CNS metastasis occurred more frequently in younger patients than older patients, and the clinical course of these patients was shorter than for those patients without CNS metastasis. CNS metastasis developed in the late stage of the disease, and often was not recognized clinically. Only 31% of the cases were clinically diagnosed or suspected before death. A median survival of these patients after clinical diagnosis of CNS metastasis was 33 days. However, a significant improvement was noted in the clinical diagnosis and median survival in the latter half of the study period. Eleven patients lived for more than 1 year after diagnosis of CNS metastasis. Only 14% of the 309 patients died from CNS failure.

Protection of normal tissues with 2-aminoethylisothiouronium during local pelvic radiation in monkeys.

Intestinal and bladder injury are the main limiting factors to radiation therapy in patients with pelvic neoplasms. 2-Amino-ethylisothiouronium (AET) is a radiation-protective agent when given systemically but absorbs poorly from the intestines. Accordingly, it was explored for the local protection of the bowel and bladder during radiation to the pelvis. Radiation localized to the pelvis in various high fractionated doses and various schedules was applied to pairs of stumptailed monkeys (Macaca arctoides): one was always a control; and the other was treated with AET. AET was applied to the bladder through a catheter and to the rectum with a cotton tampon during the time of radiation. After radiation, AET was removed by repeated washings. Control animals developed hemorrhage, diarrhea, and emaciation and died at various times after completion of the radiation course; biopsy of rectal mucosa showed severe radiation damage. AET-treated animals had only occult blood in the stools and suffered slight weight loss; rectal biopsies showed normal tissues 2 weeks after radiation.

Metastatic basal cell carcinoma of the skin. Metastasis to the skeletal system producing myelophthisic anemia.

In the typical patient with a metastasizing basal cell carcinoma, the tumor is large, ulcerated, and has been neglected. Recurrences are common, and the tumor is usually refractory to all modalities of treatment. Our patient neglected to seek medical help for 10 years, at which time metastases were already present. Our case is unique because the metastases to the skeletal system produced a myelophthisic anemia.

Axillary lymph node metastasis from an occult breast cancer.

Twenty-nine cases were reviewed in which carcinoma manifested first as the enlargement of an axillary node from an occult breast carcinoma. A small hidden breast cancer was identified in 16 patients. In the remaining 13, the breast tumor was never discovered. Regardless of whether the primary tumors were discovered, the metastasis-free survival rates were comparable to those of patients with breast carcinoma with axillary nodal metastasis. The authors recommend that carcinoma found in an axillary node should be treated as a breast cancer, even in the absence of the breast tumor. Extensive investigative procedures in an attempt to uncover an extramammary primary site were largely unproductive and should either be omitted or performed selectively. Mammography, if positive or suspicious, can lead to the primary tumor in 75% of the patients, but, when negative, it does not necessarily exclude the breast as the source of the carcinoma. A carcinoma of the breast was found by pathologic examination in 44% of the patients with negative mammograms.

The influence of histologic type on survival in non-Hodgkin's lymphoma.

Histologic groups in 231 cases of malignant lymphoma were correlated with survival data at 100 months from the time of initiation of the study. Patients in the first two decades of life fared comparably with adults, but those over 60 years of age showed a poorer survival trend. Seven favorable and four unfavorable histopathologic groups were found with collective median survivals of 83 and 16 months, respectively (P less than 0.001). The favorable group included three follicular classes (cleaved, mixed, and large noncleaved) and four diffuse classes (small lymphocytic, cleaved, Burkitt non-cleaved, and convoluted lymphocytic). The unfavorable group consisted of four diffuse classes (plasmacytoid lymphocytic, mixed, and small and large non-cleaved). The group of 88 patients with follicular lymphoma had significantly longer overall survival than the group of 143 patients with diffuse lymphomas. No significant differences in survival were noted within three grades of follicular involvement. The favorable and unfavorable diffuse lymphomas had collective median survivals of 82 and 16 months, respectively (P = 0.01). Significant survival differences due to pattern of nodal involvement (P = 0.01) were found in patients with mixed and large non-cleaved cell lymphomas, but not in those with cleaved cell lymphomas. The group with large cleaved cells had significantly longer survival than those with large non-cleaved cells. Patients with mixed and large non-cleaved cell lymphomas of the same nodal pattern had similar survival data.

Metastatic patterns and target organ arterial blood flow.

The frequency of metastatic involvement of eight 'target' organs from primary adenocarcinomas of the rectum and squamous cell carcinomas of the esophagus correlates significantly with target organ arterial blood flow (ml/min/g) when the primary cancers were in the upper third of the rectum or lower third of the esophagus, where the initial main venous drainage was into the portal system. When the primary cancers were located in other regions of these two organs where the initial main venous drainage was into the systemic venous system, this correlation was not seen. The results confirm that the 'hemodynamic' or 'mechanical' theory holds for two types of primary cancers in specific anatomic locations. In addition, they support the hypothesis that as yet unspecified interactions of cancer cells with the portal system, when this represents the initial main route for venous drainage, produce conformation with the 'hemodynamic' theory.

Organ vascularity and metastatic frequency.

The "hemodynamic" or "mechanical" theory proposes that the frequency of metastases in different organs is primarily determined by the numbers of cancer cells delivered to them in their arterial blood. This theory has not yet been adequately tested in man because reproducible, noninvasive measurements of organ blood flow have only recently become available. Correlation between these data and the metastatic frequency in 10 organs, in groups of patients with primary cancers in 15 anatomic sites, has therefore been sought. No correlation was obtained between metastatic frequency and organ weights, blood volumes, blood volumes per gram, "transit times," or blood flow. However, correlations significant at the 4-8% level were obtained between organ blood flow per gram and metastatic frequency in 4 of 5 groups of primary cancers with initial venous drainage into the portal system, compared with 1 of 10 draining into the caval system. At present, no definitive explanation can be offered for the apparent compliance of one set of primary cancers with the "hemodynamic" theory of metastasis, but not the others.

The histology of liver tumors in oral contraceptive users observed during a national survey by the American College of Surgeons Commission on Cancer.

As part of the national survey on the tumorigenesis of oral contraceptive drugs conducted by the American College of Surgeons' Commission on Cancer, a histologic study was made of 94 cases of liver tumors in users and non-users of oral contraceptives. Pathologic criteria were established and then the slides were studied; the results were tabulated to determine the significance of each of the criteria as related to the use of contraceptives. These criteria included tumor size, peliosis hepatis, hemorrhage, necrosis, fibrosis, thrombosis, and vascular alterations of the intima and media. Cases of focal nodular hyperplasia in pill users exhibited greater vascular alterations, fibrosis, peliosis, and tumor size as compared to focal nodular hyperplasia observed in non-pill users. In addition, hemorrhage, necrosis, and peliosis were much more common in hepatic cell adenoma than in focal nodular hyperplasia. In the material reported in this series there were no hepatic cell adenoma cases observed in non-pill users. Focal nodular hyperplasia cases exhibited an overwhelmingly greater degree of vascular intimal and medial alterations than hepatic cell adenoma. The results suggest that the effects of oral contraceptives on the liver may be primarily upon the vasculature.

Metastases from carcinoma of mammary gland: an autopsy study.

Information on metastases from carcinoma of the mammary gland in an autopsy study of 707 cases occurring in white women over a 15-year period are presented and tabulated. Multiple primary cancers occurred in 19% of the cases. Of the 137 cases that exhibit more than one neoplastic malignancy, 31 (23%) were present in the contralateral mammary gland. Seventy patients had no metastasis from the mammary cancer at the time of death, and 55 of these patients had another cancer. Additional information has been added concerning the frequency of metastasis in parathyroid and thymus. When a parathyroid contains a metastasis, extensive metastases were noted in many organs and thus represents a late stage of the cancer.

Coccidioidomycosis in a patient with lymphoma. Spherulation in human pleural fluid medium.

In a Caucasian woman who had had a giant follicular lymphoma for 21 months a small lesion developed in the upper lobe of the left lung. Excision, histologic study, and culture of the lesion were performed. Of the many stained sections, only one revealed endospore-containing spherules within the caseous necrosis of a granuloma, and only four spherules were identified. On agar medium the same tissue yielded a fast-growing fungus that produced arthrospores alternating with empty cells, typical of Coccidioides immitis. The arthrospore suspension was inoculated intraperitoneally into a mouse and into a medium of human pleural fluid at 40 C. Spherules containing endospores developed in the internal organs of the mouse and in the pleural fluid medium. The phylogeny of C. immitis is briefly discussed.

Inflammatory fibrous histiocytoma: case report.

This report concerns a patient with inflammatory fibrous histiocytoma, who in contrast to previous reported cases, has had a long survival (20 years), without evidence of recurrent disease following treatment. An interesting but nonreproducible study was the development of leukemia in 2 of 3 Swiss strain mice following the intraperitoneal injection of a saline extract of the patient's tumor.

Squamous-cell carcinoma of the floor of the mouth.

This study was based on the analysis of 100 cases of squamous-cell carcinoma of the floor of the mouth. The male/female ratio was 4.25:1. The peak incidence in women was in the 50 to 59 year age group; in men there was equal frequency in each age group above 50. The five-year survival rate decreased from 86 per cent to 0 as the stage of disease progressed from I to IV. The five-year survival for all stages of disease was 52.7 per cent. Thirty-three per cent developed new primary malignancies; 22 per cent were of the upper alimentary and respiratory tracts. Distant metastases were present in 21 per cent. Fifty per cent were heavy smokers, 33 per cent were heavy drinkers, 28 per cent were both heavy smokers and heavy drinkers, and 21 per cent were nonsmokers and nondrinkers.

An autopsy study of the metastatic patterns of human leukemias.

This paper analyses the distribution of metastases at every site of the human body in acute lymphoblastic, chronic lymphocytic, acute myeblastic and chronic myelocytic leukemias in patients that come to autopsy. It appeared that the 4 types of leukemia had a similar seeding frequency of the skin, breast, trachea, diaphragm and all other muscles. The highest incidence of metastases was found in the lymphatic system (i.e. all lymph-nodes and spleen). Acute lymphoblastic leukemia showed an excess of metastases in the major blood vessels, pleura, large intestines, extrahepatic biliary tract, ureters, prostate, cervix uteri, central nervous system, thymus, ovaries and pituitary. The excess of metastases at specific sites did not cluster either in topographical areas or in anatomical systems, with the exception of metastases in the central nervous and endocrine systems (acute lymphoblastic leukemia). Chronic lymphocytic leukemia showed an excess of metastases in all lymph nodes, kidney, adrenals and heart. A lymphatic route of dissemination, as opposed to a blood-borne spread of malignant cells, was hypothesised to account for the excess of metastases in the above mentioned organs in patients affected with chronic lymphocytic leukemia. Soil specificity with the degree of anaplasia of leukemic cells may account for the higher than expected occurrence of metastases in a given organ, for a specific leukemia. This remark holds true particularly for acute lymphoblastic leukemia.

Ths significance of metastases to the adrenal glands in adenocarcinoma of the colon and rectum.

A study to determine the frequency of metastases to the adrenal glands following carcinoma of the colon and rectum was undertaken. Patients with, or without, adrenal spread were compared regarding age, sex, race and survival time. The over-all metastatic pattern was analyzed to determine its usefulness for predicting the presence of metastases to the adrenal glands. Autopsy reports and clinical records of patients with adrenal spread were reviewed regarding the extent of tumor involvement in the glands and possible adrenal insufficiency. Of 457 patients with adenocarcinoma of the colon and rectum who underwent autopsy, 63 or 14% had metastasis to the adrenal glands. Of these, 29 had bilateral involvement. Patients with bilateral metastases had a lower median age than did those without adrenal spread. No correlation was found between adrenal metastatic status and sex or race. Although survival time was found to be shorter for patients with bilateral metastases of the adrenal glands, adrenal insufficiency did not seem to be the reason for this shorter survival time. In retrospect, however, the presence of adrenal insufficiency could not be ruled out in several of these patients. Eight sites were studied with regard to whether or not metastatic involvement in a specific site might indicate a higher risk for simultaneous metastases to the adrenal glands. It was found for all sites that, when involved, there was a higher frequency of metastases to the adrenals than if free of tumor. Metastases especially above the diaphragm indicated a considerable risk for adrenal involvement. Different sites were combined in groups and studied in the same way. It was found that the more sites involved, the higher the relative chance of metastases to the adrenals. It was suggested that the results presented may be useful in predicting the relative chance of adrenal metastases in patients with advanced carcinoma of the colon and rectum.