Effect of cholecystokinin on human cholangiocarcinoma xenografted into nude mice.

Gastrointestinal polypeptide hormones regulate growth of various normal gastrointestinal tissues as well as certain visceral cancers. Since cholecystokinin (CCK) promotes growth of normal biliary tract, we sought to determine whether CCK affects the growth and metabolism of human cholangiocarcinoma line SLU 132. Twenty-six nude mice with s.c. xenografts of this cancer received either CCK octapeptide (50 micrograms/kg/dose) or 0.9% NaCl solution (saline) twice a day i.p. for 14 days. Tumor volume was calculated from Vernier caliper measurements. At sacrifice on Day 15, tumors were excised, weighed, and examined histologically. DNA, RNA, and protein were measured in the xenografted carcinomas. Because this cholangiocarcinoma produces carcinoembryonic antigen (CEA), we obtained serum at sacrifice for CEA radioimmunoassay and also tumor tissue for CEA immunolabeling with murine anti-CEA monoclonal antibody. Serum CEA levels were 90% higher in the CCK-treated group. Tumor tissue in the CCK-treated group also contained more CEA than did the controls. Mean tumor volume increased significantly in the saline group during the 14-day treatment period, whereas mean tumor volume did not increase significantly in the CCK group. Exogenous high-dose CCK thus appears to increase production and release of CEA from SLU-132; it also appears to retard growth of this tumor line in the nude mouse.

Leiomyosarcoma of the broad ligament. A case report and literature review with follow-up.

A case of leiomyosarcoma arising in a preexisting leiomyoma of the broad ligament is presented with ultrastructural and Feulgen microspectrophotometric confirmation. This is the fourth reported case of leiomyosarcoma of the broad ligament and the second reported case to show evidence of a preexisting leiomyoma. Three of these patients died after intervals of 1, 7, and 19 months; one is alive and well with no evidence of disease after 12 years. The definitive evidence of malignant transformation of a leiomyoma has particular relevance to the controversy regarding the relationship of uterine leiomyosarcomas and leiomyomas.

Exfoliative dermatitis: presenting sign of fallopian tube carcinoma.

A woman presented with severe exfoliative dermatitis and a pelvic mass subsequently found to be fallopian tube carcinoma. After resection of the tumor and four courses of cisplatin, doxorubicin, and cyclophosphamide, the skin condition cleared.

Long-term outcome following testicular ischemia in the rat.

Male germ cells are quite sensitive to interruption in blood flow. Eight weeks after subjection to 45 minutes of testicular ischemia, the spermatogenic epithelium of the rat remains significantly damaged, though other cell types are well preserved. The authors evaluated the testicular recovery of the rats at 8 and 72 weeks after the 45-minute period of warm ischemia. Twenty-eight rats were studied: 14 underwent 45 minutes of total left testicular ischemia; 14 received no treatment. Four rats from each group were necropsied at 8 weeks to document the ischemic injury. At 72 weeks, the 18 surviving rats were necropsied to evaluate the long-term outcome of the treatment. At 8 weeks, significant left testicular injury was documented. However, at 72 weeks there was no difference in testicular weight or sperm head count between the groups: in all 36 testicles, the repopulation index was 1.00, the epididymal index was 3+, the modified Johnsen index was 14, and the spermatic cord score was 7 (all are maximum obtainable scores). Neither contralateral orchiopathy nor injury to spermatic cord structures was observed. Our work shows that ischemia-induced testicular injury is fully reversible with time in this model.

Response to exogenous cholecystokinin of six human gastrointestinal cancers xenografted in nude mice.

Gastrointestinal hormones regulate growth of cancers as well as normal tissues. We investigated whether long-term cholecystokinin (CCK) administration might affect growth or metabolism of human tumors xenografted in nude mice. In each experiment, approximately 20 nude mice bearing subcutaneous xenografts of the particular cancer line being studied were used. Half received CCK and half received saline solution intraperitoneally twice daily for 14 days. Tumor volume and body weight were measured every 3 days. If the tumors produced marker substances, these were measured in nude mouse serum and also in the xenografts. Tumor growth was significantly retarded by CCK in two of the six cancers studied. In each case, DNA, RNA, and protein reflected tumor volumes. In one of these tumors (SLU 077), serum carcinoembryonic antigen (CEA) levels paralleled the tumor volumes. In another tumor (SLU 132), serum CEA levels and tumor immunolabeling for CEA and pancreatic oncofetal antigen increased in response to CCK administration, whereas tumor volumes did not. These findings suggest that exogenous highdose CCK altered the growth and metabolism in two of six human cancers studied.

Magnetic resonance imaging in planning limb-salvage surgery for primary malignant tumors of bone.

In defining the linear extent of a malignant tumor in a long bone, radiographs, computerized tomography, and scintigraphy are routinely employed, especially when non-ablative surgery is being considered. The drawbacks of these modalities in defining the true intracompartmental extent of disease within a bone can largely be overcome with the use of magnetic resonance imaging. We did a prospective analysis of magnetic resonance imaging in sixteen consecutive patients with a primary malignant tumor of a long bone, and it showed that this modality has clinical promise of being more precise than the other modalities in defining the true proximal and distal extent of a tumor in a long bone. Coronal images permit easier planning of surgical techniques for salvage of a limb using an allograft than do a multiplicity of transverse images.

Magnetic resonance imaging of soft tissue masses: an evaluation of fifty-three histologically proven tumors.

Fifty-three histologically confirmed soft tissue masses in 48 patients were evaluated by magnetic resonance imaging (MR) and computerized tomography (CT). Twenty-three of these were malignant, twenty-three benign and seven of intermediate malignancy (all aggressive fibromatosis). The two procedures were compared for sensitivity and delineation of masses, their relationship to important neurovascular structures, their potential for histological diagnoses, their relative roles in influencing the surgical approach and the preferred modality in the follow-up for detection of tumor recurrence. Both modalities have their relative strengths and weaknesses. However, the superior contrast resolution of magnetic resonance imaging, its demonstration of lesions not clearly identified by CT, its pluridirectional capabilities and its ability to demonstrate large soft tissue tumors in a single coronal or sagittal plane makes it the preferred initial modality for evaluation of the soft tissue tumor of uncertain etiology and also in the follow-up of these patients. Despite MR's superiority in anatomically staging soft tissue tumors it, like CT, is of limited value in characterizing soft tissue sarcomas.

Computed tomography vs. histology of laryngeal cancer: their value in predicting laryngeal cartilage invasion.

Twenty-seven cancerous larynges were examined preoperatively by computed tomography and postoperatively by transaxial anatomic sections. Data from this correlative study provides a new radiographic classification based upon the relationship of the plane of maximal tumor size to the apex, body, or vocal process of the arytenoid. Unlike those tumors whose maximal size lies at or above the apex of the arytenoid, those below have a very high association with cartilage invasion (8% in former group, 86% in latter group). This is explained by our observation of sites of predilection of tumor invasion of the thyroid, cricoid, and arytenoid cartilages. At these sites collagen fibers have been observed to pass through the perichondrium and attach directly to cartilage. These same fibers may serve as a pathway to direct growth of tumor cells. There was no correlation between six histologic parameters and the presence of cartilage invasion.

Calcifications of the benign endometrium.

A 28-year-old woman underwent a dilatation and curettage procedure in the course of an infertility evaluation, with the finding of multiple psammoma bodies in the tissue from the lower uterine segment. A repeated dilatation and curettage procedure performed five months later again revealed psammoma bodies in the lower endometrium and normal fundal endometrium. The patient previously had been treated with clomiphene. Psammoma bodies in the gynecologic tract most often have been associated with malignant neoplasms; however, a few cases of psammoma body formation or dystrophic calcification of the endometrium in benign conditions have been reported.

Interaction of N-acetylmuramic acid L-alanine amidase with cell wall polymers.

In a previous communication (J. Biol. Chem. (1975) 250, 1676-1682), methods were described for the purification of the N-acetylmuramic acid L-alanine amidase from Bacillus subtilis ATCC 6051 and of a modifier protein which combines stoichiometrically with the enzyme and stimulates the activity approximately 3-fold. A detailed examination of the wall cleavage products obtained in the absence and in the presence of modifier indicates that the major effect of the modifier is not to change the enzyme velocity, but rather to change the pattern of cleavage from a more random pattern, when enzyme alone hydrolyzes the cell wall, to a sequential pattern in the presence of modifier protein. Tight binding of the enzyme to the cell wall and functional interaction with the modifier occur only when cell walls from Bacillus subtilis ATCC 6051 containing or teichoic acid are used as a substrate. We suggest that a general function of cell wall teichoic acids is to act as specific "allosteric" ligands for bacterial cell wall lytic enzymes as has been demonstrated previously in Pneumococci (Tomasz, A., and Westphal, M (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 2627-2630).

Bacillus subtilis N-acetylmuramic acid L-alanine amidase.

The N-acetymuramic acid L-alanine amidase from Bacillus subtilis (ATCC 6051) has been purified to homogeneity. It is a monomeric protein of molecular weight 50,000. The enzyme has a high affinity for homologous cell walls and once attached to a cell wall will hydrolyze the wall completely before initiating the hydrolysis of a new cell wall. The affinity of the enzyme for cell walls devoid of teichoic acid or for cell walls of Bacillus megaterium is much lower than that for B. subtilis cell walls. A second homogenous protein has been isolated from B. subtilis which specifically combines with the amidase in a 1:1 molar ratio and stimulates enzyme activity. This modifier protein has no intrinsic cell wall lytic activity. The binding of enzyme and modifier protein has a dissociation constant of 8.5 times 10-9 M in 0.1 M LiCl, pH 8.0, but the two proteins can be completely dissociated in 3 M LiCl at pH 8.0.

Magnetic resonance imaging of osteosarcoma.

Early magnetic resonance (MR) experience in the evaluation of 14 consecutive long bone intramedullary osteosarcomas demonstrates the need for T1 and T2 weighted pulsing sequences in the staging of this disease. Intramedullary disease is best depicted by coronal T1 weighted pulsing sequences and subtle extra-compartmental disease by T2 weighted axial imaging. Both high intensity and low intensity intra-medullary signals were noted on T2 weighting, while all T1 weighted pulsing sequences showed intra-medullary disease to have low signal intensity. Extraosseous tumor on T2 weighting usually had a high signal, and disease extent was therefore sharply demarcated from uninvolved muscle and its relationship to vessels confidently assessed. MR appears optimally suited for local staging of osteosarcoma, further enhancing the role of radiology in planning limb-salvage surgical techniques.

Carcinosarcoma of the fallopian tube.

A patient with Stage III fallopian tube carcinosarcoma treated with cisplatin, doxorubicin, and cyclophosphamide, surviving 31 months disease-free after diagnosis, is presented. Review of the literature revealed this is the 28th case report of malignant mixed Mullerian tumor of the fallopian tube, and fifth instance in which chemotherapy was used as a primary therapy. Modern chemotherapy appears to have improved survival.

Improved diagnostic accuracy in laryngeal cancer using a new classification based on computed tomography.

The most commonly accepted classification of laryngeal cancer is based on the definition of regions formulated by the American Joint Committee on Laryngeal Cancer. The limitations of this classification are discussed. A new radiologic classification based on computed tomography (CT) is presented, its application illustrated, and its accuracy documented. This classification has the advantage that it provides information preoperatively which closely agrees with the pathologic facts seen postoperatively. It also helps to separate those tumors that tend to invade cartilage from those that do not.

Isolated noninfectious granulomas of the ovary.

Four examples of noninfectious granulomas of the ovary were studied. All four occurred in premenopausal women. One patient had a salpingo-oophorectomy for a symptomatic ovarian mass; the other three examples were incidental findings in hysterectomy and salpingo-oophorectomy specimens. None of the patients had a history of systemic granulomatous disease, nor have any of the patients developed any symptoms on follow-up, which varies from 2 to 7 years.

Nerve sheath myxoma (neurothekeoma): a case involving the lip.

This case report describes an unusual benign neural tumor involving the lip. It appeared clinically as a gradually enlarging, painless growth arising on the lower lip. Microscopically, it was characterized by whorls of spindle-shaped cells with abundant myxoid cytoplasm and stroma.

Improved diagnostic accuracy in the TNM staging of laryngeal cancer using a new definition of regions based on computed tomography.

Neither laryngoscopy nor laryngography can match the accuracy with which computed tomography (CT) can display the full tumor extent or the presence of cartilage invasion. Data obtained from a CT-histologic correlative study have suggested a new definition of regions of the larynx for use with the TNM staging of laryngeal cancer. The arytenoid cartilage, readily identifiable by CT, is used for reference. The regions are as follows: (a) supra-arytenoid, (b) midarytenoid, (c) vocal process, and (d) infra-arytenoid. Tumors with a strong propensity for cartilage invasion can be distinguished from those without this tendency. In addition, tumors with different pathways of lymphatic drainage can be identified.

Tolerance of rat testis to graded periods of total circulatory isolation.

Infertility because of testicular damage is a distressing problem for survivors of cancer chemotherapy. We have previously described a cytoprotective effect of temporary testicular circulatory isolation (TCI) during doxorubicin administration in the rat. In this report we define the relationship between duration of TCI and testicular ischemic injury, using paired groups of animals with normothermic TCI and hypothermic TCI. Sixty rats were used and received TCI for varying lengths of time up to 180 minutes, with or without hypothermia. On day 56 +/- 4, all rats were killed and necropsied. Testicular injury was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index, and epididymal index. Warm TCI for up to 60 minutes induced modest damage to germ cells, while injury was greater with cold TCI. Leydig cells and vascular tissues were essentially unaffected by TCI, although Sertoli cell abnormalities were noted in rats receiving a long duration of TCI.

High signal intensity soft tissue masses on T1 weighted pulsing sequences.

On T1 weighted pulsing sequences, the majority of soft tissue masses are of low signal intensity and show high intensity signals on T2 weighting. There however is a subset of soft tissue masses of varied histology that shows high signal intensity on T1 weighted pulsing sequences. These masses have either fat or blood in their substance. Lipomatous and hemangiomatous lesions that did not show high-signal intensity on T1 weighting were also encountered and are discussed. Present experience with MRI of soft tissue masses suggests that there is a limited spectrum of entities that produce high-signal intensity T1 weighted soft tissue masses.