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.

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.

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.

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.

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.

Glassy cell carcinoma of the fallopian tube. A case report.

A 31-year-old woman, 10 weeks postpartum, presented with a right adnexal mass. The neoplasm was found to originate from the right fallopian tube and a right salpingoophorectomy was performed. Pathological examination found an adenosquamous carcinoma with features characteristic of a glassy cell carcinoma as described in the uterine cervix. The finding of this neoplasm in the fallopian tube suggests that it may be a tumor type common to the entire müllerian system.

Treatment of frostbite with i.v. streptokinase: an experimental study in rabbits.

Experiments were conducted in 32 rabbits to determine whether treatment with IV streptokinase can effectively limit the extent of tissue damage associated with frostbite injury of the hind limbs. Other variables studied were the temperature of the tissue during freezing, the time taken to rewarm the exposed limbs, and the delay between the initiation of treatment with streptokinase and cessation of freezing. A control group of 16 rabbits was not given streptokinase. The extent of tissue damage was estimated by sequential radionuclide perfusion scans of the exposed limbs. This estimate was based on the proportional loss of tissue perfusion on subsequent twice-weekly nuclear scans in comparison with that shown by scans performed immediately after thawing. Pathologic changes in exposed tissues were studied by histology. Streptokinase treatment and rapid rewarming both resulted in less tissue damage at all freezing temperatures. Streptokinase was most beneficial when given 12 hr after freezing, but was effective even when treatment was delayed up to 48 hr.

Regional doxorubicin delivery reduces testicular toxicity.

Many anti-cancer drugs cause infertility. Regional delivery of these agents is a potential method to avoid this problem. We investigated the protective effect of normothermic testicular circulatory arrest on gonadal toxicity during doxorubicin administration in the Sprague-Dawley rat. Four groups of eight rats each were used. Animals in group 1 received no treatment. Rats in group 2 were anesthetized and received a bolus of intravenous doxorubicin (6 mg/kg). In groups 3 and 4, normothermic circulatory isolation of the left testis was induced by cross-clamping of the spermatic cord and gubernaculum immediately before doxorubicin administration. This was maintained for 15 min after doxorubicin administration in group 3 and for 45 min in group 4. Cessation and return of testicular blood flow were confirmed by Doppler. On Day 56, all rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by measurement of testicular weight, sperm count, repopulation index, and epididymal index. The results indicated that 15 min of testicular circulatory isolation mitigated testicular toxicity to a small extent and that 45 min of circulatory isolation provided moderate protection against doxorubicin-induced testicular toxicity.

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.

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.

Testicular cytotoxicity of intravenous doxorubicin in rats.

Although the testicular cytotoxicity of many chemotherapeutic drugs has been evaluated in mice, their small size can pose technical problems. In this report, we describe doxorubicin-induced testicular toxicity in a larger animal model, the Sprague-Dawley rat. Fifty-three rats were used for this study. On day 0, rats in the treatment groups were anesthetized and given different single intravenous doses of doxorubicin (0.1 to 30 mg./kg.). On day 56 +/- 2, all surviving rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index and epididymal index. The histologic effects of doxorubicin on the heart, liver and kidney were qualitatively evaluated. Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of doxorubicin (0.1 to 5 mg./kg.). Marked testicular atrophy, oligospermia and germinal aplasia were observed at high dosage of doxorubicin (10 mg./kg.). LD50 for animal mortality at day 56 +/- 2 for doxorubicin appears to be 10 mg./kg. These findings are similar to those reported in mice. The rat is a suitable model for the study of techniques to avoid drug-induced testicular damage.

Frostbite: experimental assessment of tissue damage using Tc-99m pyrophosphate. Work in progress.

We designed an experimental model using a new method of freezing to study the pathogenesis and treatment of frostbite. Frostbite was simulated in a manner that closely resembles that which occurs in a natural environment. We used a radionuclide imaging technique to monitor the evolution and extent of tissue damage relative to temperature, rate of freezing, and controlled rewarming. Characteristic sequential changes were demonstrated on sequential nuclear scans. Nonperfusion, followed by perfusion, and finally again by nonperfusion occurred in all areas in which necrosis developed. The reappearance of nonperfusion corresponded to vascular injury and thrombosis evidenced at pathologic examination. We determined that lack of tissue perfusion corresponded to tissue injury. We believe that our experimental model provides an effective means of evaluating potential therapeutic regimens.

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.

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.

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.

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.

Carcinoembryonic antigen in experimental rat gastrointestinal carcinoma.

Detection of gastric carcinoma in the experimental rat can be difficult. We investigated whether or not serological testing for carcinoembryonic antigen might aid in the diagnostic process. Twenty-five young adult male Wistar rats were studied; 15 were treated with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and 10 received no treatment. A complete autopsy was done on the 22 animals (12 in MNNG group, 10 in control group) that completed the 37-week study. Serum obtained at autopsy was evaluated by radioimmunoassay for the presence of CEA-like immunoreactivity. Grossly normal stomach, as well as gastric and small bowel cancers, were also stained for CEA. Of the 12 autopsied animals in the MNNG group, eight had a total of 12 cancers (seven gastric and five proximal small bowel); in no animal was an elevated serum CEA level detected. Immunoreactive tissue CEA was demonstrable in normal stomach and in gastrointestinal cancers; the tumors usually stained less intensely than adjacent normal stomach and did not exhibit normal intracellular CEA distribution.