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BACKGROUND: Thrombosis of the soleal and gastrocnemial veins seldom receive very much attention. It is thought that they are frequently the starting point for deep vein thrombosis of the lower extremity. PATIENTS AND METHODS: 125 patients with clinically suspected deep vein thrombosis of the leg were examined by means of duplex sonography and phlebography. The ultrasound examination was performed on the lower limb in the form of a compression sonography. RESULTS: From 137 legs examined, a total of 82 cases of deep vein thrombosis were diagnosed. Sonographically and/or phlebographically, the soleal and/or gastrocnemial veins were found to be involved in 65 cases of thrombosis, i.e. 79% of all thrombosis. 25% of all cases of deep vein thrombosis of the leg were isolated muscular vein thrombosis. Pain in the calf while walking, similar to muscular soreness after exertion, was typical of the isolated muscular vein thrombosis. The muscular veins were involved in all the deep vein thrombosis of the leg of the 3- and 4-layer type. Diagnosis of soleal and gastrocnemial vein thrombosis is quite possible by means of sonography and phlebography. The sensitivity and specificity of the compression sonography were 88% and 95% respectively, compared to the phlebography. CONCLUSION: In patients suffering from pain in the calf, the soleal and gastrocnemial veins should be carefully included in the sonographic or phlebographic assessment. Due to the risk of deep vein thrombosis, isolated muscular vein thrombosis should receive treatment appropriate for a deep vein thrombosis of the calf, and its development be checked.

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38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.

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Currently, anthracyclines and ifosfamide are the most effective drugs for the treatment of disseminated soft-tissue sarcoma. We designed a treatment protocol of rapidly alternating epirubicin/dacarbazine and ifosfamide for previously untreated soft-tissue sarcoma, whereby 100 mg/m2 epirubicin was given on day 1, 500 mg/m2 dacarbazine was given on days 1 and 2, and 6,000 mg/m2 ifosfamide given via 24-h infusion was begun on day 15. The entire treatment cycle was scheduled to begin again on day 28 if the leukocyte count had reached 3.0 x 10(9)/l. From June 1988 to May 1991, a total of 28 patients were enrolled in the study. Eight patients (31%) achieved a partial response to therapy. The median duration of partial response was 8.5 months, and the median time to progression for all patients was 5 months. Myelosuppression was dose-limiting (leukocyte nadir, 1.7 x 10(9)/l; platelet nadir, 70 x 10(9)/l). Prolonged myelosuppression forced frequent therapy delays; therefore, only 74% of the planned doses could be given. The nonhematologic toxicity was tolerable. This rapidly alternating treatment protocol was determined to offer no therapeutic advantage over anthracycline therapy either alone or in combination with dacarbazine in terms of response rate or time to disease progression. The inclusion of hematopoietic growth factors, however, might ameliorate the dose-limiting myelosuppression and permit the administration of higher doses.

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We conducted a phase I/II trial of 5-fluorouracil (5-FU)/folinic acid (FA) and alpha-2b interferon (IFN) in 43 previously untreated patients with measurable metastatic colorectal cancer. Patients had disease progression prior to therapy consistent of 5-FU 500 mg/m2 (level A) or 600 mg/m2 (level B) as starting dose administered as a 2-hour infusion, FA 200 mg/m2, and alpha-2b IFN 5MU/m2 subcutaneously. All drugs were given on days 1 to 5 and cycles were repeated after 3 to 4 weeks. The aim of the study was to define the maximal tolerable dose (MTD) of 5-FU for this schedule. In the absence of toxicity above MTD, defined as diarrhea and mucositis of World Health Organization grade 2 and leukopenia of World Health Organization, grade 3 5-FU was increased in increments of 100 mg/m2 for further cycles. Twenty-four patients were started on level A; 18 were started on level B. Forty-two patients were evaluable for toxicity, 32 for response. Three of 32 patients achieved a partial response; in 22 of 32 patients, tumor stabilization occurred. Forty percent of patients started on level A developed grade 2 diarrhea; 28% of patients developed grade 2 or 3 mucositis. Of 18 patients on level B, two patients experienced grade 4 mucositis (11%) and grade 3 or 4 diarrhea (11%). One drug-related death in the presence of sepsis occurred. Due to 11% of patients with grade 4 toxicity when started on 600 mg/m2 5-FU and 40% of patients with grade 2 diarrhea when started on level A, MTD as starting dose for 5-FU is 500 mg/m2 as a 2-hour infusion when used in combination with FA and IFN on a day 1 to 5 active schedule. We observed a wide range of 5-FU dose tolerated by individual patients. While some patients experienced severe, mainly gastrointestinal, toxicity on lower levels of 5-FU, others tolerated much higher 5-FU doses (11 patients, 700 mg/m2; 5 patients, 800 mg/m2; and one patient, 900 mg/m2). Our data suggest that double modulation of 5-FU by FA and IFN may not be superior to modulation of 5-FU with either drug alone.

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5-Fluorouracil (5-FU) is one of the important antineoplastic agents for the treatment of gastrointestinal cancers. The biochemical modulation of 5-FU by various drugs has brought about the two combinations of 5-FU/folinic acid (FA) and 5-FU/alpha-interferon (IFN), which have shown clinical activity in phase II and III trials, especially in colorectal cancer. The experience with both combinations in upper gastrointestinal cancers, however, is limited. In esophageal cancer, two phase II studies with 5-FU/IFN reported seven (27%) objective remissions in 26 patients, indicating superiority of 5-FU/IFN over 5-FU monotherapy. Trials with 5-FU/FA alone are lacking in esophageal cancer. The modulation of 5-FU by IFN or FA failed to show clinically significant activity in pancreatic cancer. However, in gastric cancer, 5-FU/FA and 5-FU/IFN seem to induce higher complete and overall remission rates in advanced gastric cancer compared with 5-FU alone. With the daily times five schedule of 5-FU/FA, 27% objective remissions were achieved; in combination with other cytotoxic drugs, such as etoposide, anthracyclines, cisplatin, mitomycin, or methotrexate, objective response rates up to 50% and more were reported.

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A total of 26 evaluable patients presenting with advanced or metastatic squamous-cell carcinoma of the esophagus were entered in a phase II trial to assess the single-agent activity of etoposide. Etoposide was given at a dose of 200 mg/m2 on 3 consecutive days every 3 weeks. Five patients (19%) achieved a partial response and seven (27%) experienced stabilisation of their disease. The median duration of response was 4 months (range 3-8 months). The major toxicity was leukopenia, which reached WHO grade 3 in 46% of patients and grade 4 in 11% of cases, with five instances of leukopenic fever and one therapy-associated death being recorded. Etoposide given at this dose and on this schedule seems to have considerable activity against non-pretreated metastatic esophageal carcinoma.

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Thirty-four patients with locally advanced, nonresectable gastric cancer (staged by laparotomy) received etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). Thirty-three patients were evaluable for response and toxicity. Second-look surgery with removal of residual tumor by gastrectomy and lymphadenectomy was performed in case of complete/partial remission (CR/PR) after EAP. After successful resection (R0- and R1-resection), two cycles of EAP were administered for consolidation therapy. Patients refusing reoperation received up to six cycles of EAP. The response rate (CR/PR) after EAP was 70% (23/33), including a 21% (7/33) rate of clinical CRs (CCRs). Two patients had minor remission (MR)/no change and seven had progressive disease. There was one early death. Nineteen of 23 responders (5 CCRs, 14 clinical PRs [CPRs]) and one patient with MR underwent second-look surgery. Five CCRs were pathologically confirmed; 10 patients with CPR were without evidence of disease (NED) after resection. In three patients (CPR), R1-resections (microscopically tumor-cell positive proximal margin) were performed; two patients are disease-free, 22+ and 33+ months after consolidation chemotherapy. In two patients, the tumor was again considered nonresectable. Twenty patients were disease-free after EAP +/- surgery +/- consolidation chemotherapy. Toxicity was primarily hematologic. Leukopenia and thrombocytopenia of World Health Organization (WHO) grade 3 occurred in 30% and 9%, respectively and grade 4 in 18% and 9% of the patients, respectively. There was no increased peri- or postoperative morbidity. After a median follow-up of 20 months for disease-free patients, the relapse rate is 60% (12/20). The median survival time for all patients is 18 months and for disease-free patients 24 months. EAP is highly effective in locally advanced gastric cancer, and offers a chance for surgery with curative intention in patients with an otherwise fatal prognosis.

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The need for a large animal tumor model in experimental neuro-oncology led us to re-evaluate and to modify the transplantable canine glioma of Wodinsky and Walker. Successive passages of the original tumor brei were made in purebred beagles, from beagle to mongrel, and between various mongrel strains until an intracerebral injection of 0.1 cc on Days 1 to 3 of life produced a 93% incidence of tumor take in all breeds. The mean survival was 13.5 +/- 1.9 days after injection (range, 10 to 19 days) in 10 litters. The tumor was invariably fatal and possessed many of the histological characteristics of human glioblastoma (i.e., capillary proliferation, pseudopallisading, frequent mitotic figures, and multinucleated giant cells). The animals were large enough to be scanned on the Pfizer 450 scanner, and the tumors were visualized in vivo as typical "ring" lesions after the injection of contrast agent. Intravital staining with Evans blue outlined the areas of contrast enhancement observed in the same tumors by computed tomography. The apparent defect in the blood-brain barrier could be explained in part by the absence of endothelial tight junctions on electron microscopy. Stability in the histology and activity of the tumor could be demonstrated after more than 14 months of storage at -70 degrees C. The transplantable canine glioma model has many advantages including low cost, reproducible morphology, a short survival time, and relative safety for the investigator. The large size of the animal preparation allows the use of complex surgical instrumentation and radiographic study, as well as repeated sampling of cerebrospinal and other fluids.

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Sturge-Weber syndrome in its classic form can be easily diagnosed by CT. However, in the absence of the typical gyral calcification, the diagnosis can be missed on CT. Identification of the intracranial angiomatosis and the associated thrombosis, and thus the diagnosis, require angiography. Computed tomographic and angiographic findings in a case of Sturge-Weber syndrome with unusual clinical features is described.

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Cerebral sinus and venous thrombosis were diagnosed by computed tomography (CT) and subsequently confirmed by other studies in eleven patients. CT revealed normal or small ventricles, hemorrhages, low-density areas, and increased density of dural sinuses and tentorium. CT in combination with appropriate angiographic studies is necessary for diagnosis and confirmation of sinus and venous thrombosis. Proper use of CT can result in decreased morbidity and mortality associated with this condition.

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Fifty chronic alcoholics (37 men and 13 women, ages 26--55, mean age 39.9 years) with different clinical syndromes (alcoholic psychosis, alcoholic encephalopathies) were studied by computerized cranial tomography. Cerebral atrophy was detected in 96% of all cases. Combined cortical and subcortical signs were encountered in almost all cases. Cortical atrophy seemed to be detectable more easily by CT than by pneumencephalography. The computerized tomographic findings were studied in their relations to age, sex, duration of abuse, clinical syndromes, frequency of relapse (and seizures, too), etc. Cerebral atrophy was correlated primarily with the subjects' age and the duration, and less with the intensity of alcoholism. The most distinct changes were found in delirium syndromes and, in cases with relapse of psychosis, especially in combination with seizures. Wernicke-Korsakow encephalopathies showed the widest third ventricles when combined with repeated syndromes of withdrawal in their case histories. Computerized tomographic examinations of ten patients during acute psychosis as well as 4 weeks later showed identical findings; transitory changes, e.g., cerebral edema, were not detected. Computerized cranial tomography appears to be extremely useful to study the numerous open questions concerning the pathogenetic role of age, duration, and severity of abuse with cerebral atrophy.

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Hydroxyl groups in serine side chains of collagen, silk fibroin, and bovine serum albumin (BSA) were converted to SH by tosylation. In collagen film, 50% of the serine OH groups could be thiolated at most. In fibroin, only 13% because of its compact beta-pleated sheet structure and low susceptibility to swelling. The SH groups introduced are near enough together to form -S-S- bonds by oxidation. The residual SH content after oxidation was 0.1% in collagen and 0.03 to 0.25% in fibroin. Disulfide crosslinking increased the shrinkage temperature of collagen and fibroin and decreased the amount of shrinkage. BSA was crosslinked to dimers (MBSA) according to gel permeation chromatography and sedimentation analysis by the analytical centrifuge. Because these crosslinked proteins can be metabolized by the usual processes, in contrast to those crosslinked by artificial, nonphysiological bridges, they may be used for biological or medical purposes.

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