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The aim of this study was to assess the diagnostic utility of thyroglobulin (Tg) in fine needle aspirates (Tg-FNAB) of nonthyroidal neck masses using a sensitive in-house method for detecting Tg in washout specimens. A total of 256 samples from 145 patients were evaluated for Tg in washout specimen from FNAB and compared to corresponding cytological smear and histology of 46 surgical specimens. Tg was measured by a sensitive in-house time-resolved immunofluorometric assay. The sensitivity for Tg-FNAB alone or in combination with cytological findings was found to be 100% in both the follow-up group and before primary surgery. In the follow-up group the specificity of Tg-FNAB was 100%. Fifty-nine of 60 follow-up specimens with malignant cytology were Tg-FNAB positive (n = 195). Histological examination of one lymph node with malignant cytology and negative Tg-FNAB showed metastasis from carcinoma of the salivary gland. Tg-FNAB was positive in 25 specimens with suspicious or cystic cytology. Tg-FNAB values were high (median 4557 microg/l, range 122-37200 microg/l) in washout specimen from cystic metastasis from which cytology did not confirm malignancy. Of the 20 lymph nodes with histology confirming metastasis from differentiated thyroid carcinoma (DTC), the Tg-FNAB was positive in 19 and intermediate in one. However, before primary surgery, two Tg-FNABs were false positive compared to the histology of the lymph nodes. TgAb in serum did not interfere with FNAB-Tg measurements. Tg-FNAB measurement is accurate with high sensitivity (100%) and of great importance in detecting cystic metastasis when cytology is not conclusive. Even metastases to small neck lymph nodes may be detected by using sensitive Tg-assay. Serum thyroglobulin antibodies appear to have ignorable effect on the clinical performance of Tg-FNAB.

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BACKGROUND: The aim of this study was to determine the prevalence of testicular carcinoma in situ (CIS) in patients with a malignant extragonadal germ-cell tumour (EGGCT) and the incidence of metachronous invasive testicular cancer (TC) in relation to the pretreatment demonstration of CIS. PATIENTS AND METHODS: Sixty-eight patients with EGGCT (53 retroperitoneal, 15 mediastinal) had pre-chemotherapy histological assessment of one (13) or both (55) testicle(s). A total of 123 testicles were examined for the presence of CIS. RESULTS: Testicular CIS was found in 21 patients (31%) (18 retroperitoneal EGGCT, three mediastinal EGGCT). Two patients had bilateral CIS. Five patients, four of them with proven pretreatment CIS, developed a metachronous TC. The 10-year invasive-free TC survival rate for all 68 patients was 88%, but only 65% for those with proven pretreatment CIS. The overall 10-year survival rate for all patients was 82%. CIS was demonstrated in seven of 48 trans-scrotal core biopsies, in 10 of 56 trans-scrotal surgical biopsies and in five of 11 orchiectomy specimens. CONCLUSIONS: Approximately one-third of patients with EGGCT present with testicular CIS, predominantly those with a retroperitoneal tumour. These patients have a considerable risk of metachronous TC development in spite of chemotherapy. The pretreatment demonstration of testicular CIS in patients with EGGCT gives the possibility of individualised counselling and safe follow-up, and is therefore highly recommended. The data are in agreement with a multi-site development of malignant germ-cell tumours, but do not exclude the possibility that the retroperitoneal EGGCTs in particular represent metastases from a burned-out TC.

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PURPOSE: To assess the clinical use of ultrasonographically (US) guided core-needle biopsy, performed with a one-hand automatic sampling technique, in the diagnosis of malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: The authors reviewed the findings in 70 patients with a tentative diagnosis of MPM who underwent US-guided core-needle biopsy at our institution during the past 10 years. RESULTS: Fifty-two of the 70 patients who underwent automatic high-speed core-needle biopsy at our institution had MPM; 18 had other disorders. The correct diagnosis was made in 56 patients. Twelve of 14 inadequate biopsy specimens were false-negative for MPM. There were no false-positive biopsy results. In the detection of MPM, US-guided core-needle biopsy had a sensitivity of 77%, specificity of 88%, accuracy of 80%, positive predictive value of 100%, and negative predictive value of 57%. There were no serious complications. CONCLUSION: US-guided core-needle biopsy is highly effective in the diagnosis of MPM. Owing to its simplicity, low cost, and few side effects, it could be the biopsy method of choice for detection of this condition.

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This report reviews 48 patients who from 1979 to 1994 were treated at the Norwegian Radium Hospital for newly diagnosed noncerebral extragonadal malignant germ cell tumour (EGGCT). Based on histology and/or serum tumour markers, 12 patients had a seminoma and 36 a non-seminoma. At diagnosis, 33 and 15 patients were classified as having abdominal and mediastinal EGGCT respectively. At the time of diagnosis 13 patients, all with non-seminomatous tumours, had metastases to bone, liver or brain. One patient with abdominal seminoma was cured by radiotherapy alone, whereas cisplatin-based chemotherapy (with or without surgery) was planned in the 47 remaining patients. Twenty-seven out of 42 patients receiving four or more chemotherapy cycles were rendered tumour free by induction chemotherapy, including 5 of the 13 patients with extralymphatic non-pulmonal disease. An additional tumour-free patient died of septicaemia after only two cycles of chemotherapy. Late relapses (after > 2 years) were observed in three patients, and a testicular primary was diagnosed during follow-up in three cases. Seven patients died of treatment-related complications, five of these because of neutropenic septicaemia. The median age of these patients was 52 years compared with 35 years in the remaining 41 patients (P < 0.05). The 5-year overall survival for all 48 patients was 60% (95% CI 46-74%) [cancer-specific 5-year survival 71% (95% CI 50-92%)]. EGGCT is a potentially curable disease, even in patients with very advanced disease. Special attention should, however, be devoted to patients above the age of 40 years because of an increased risk of treatment-related side-effects. Late relapses and the subsequent development of testicular tumours indicate the need for long-term follow-up.

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PURPOSE: To assess the clinical usefulness of ultrasound (US)-guided, 18-gauge core-needle biopsy of liver hemangiomas performed with a one-hand automatic-sampling technique. MATERIALS AND METHODS: In 491 US-guided core-needle biopsies of the liver, hemangioma was suspected at US in 51 cases. Hemangiomas were confirmed histologically in 29 cases, a malignant lesion was revealed in six cases, and no specific diagnosis could be made in 16 cases. Hemangioma was diagnosed in 18 lesions that appeared malignant at US. The hemangiomas were 7-114 mm in diameter (mean, 45 mm). RESULTS: The histologic diagnosis of hemangioma was unequivocal in 47 biopsy specimens. A cuff of normal hepatic parenchyma could be interposed between the capsule and the margin of the hemangioma in all procedures but one, in which two direct punctures were made of a protruding giant hemangioma. An average of 1.4 punctures were performed at each biopsy session. There were no false-positive findings and 15 or perhaps 16 false-negative findings. There were no serious complications. CONCLUSION: US-guided core needle biopsy seems to be a safe procedure when the diagnosis of hemangioma must be ascertained. Conclusive biopsy findings may shorten the diagnostic work-up, benefiting the patient and the hospital.

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BACKGROUND: Lymphangioleiomyomatosis is a rare condition in women of childbearing age that affects the lymphatic system, giving rise to blockage of the thoracic duct with chylothorax and chyloascites. The diagnosis is often delayed because the characteristic muscular proliferation may be missed by the pathologist. CASE: A 29-year-old female presented with lymphangioleiomyomatosis and bilaterally dermoid ovarian cysts. She had enlarged paraaortal and supraclavicular "lymph nodes" and pleural chylothorax on the left side. Fine needle aspiration cytology from the supraclavicular "lymph node" yielded clear, watery fluid containing groups of relatively large monomorphic spindle cells. The final diagnosis was possible after histopathologic examination of an excised paratubar lymph node. CONCLUSION: Lymphangioleiomyomatosis can be suggested by means of ultrasonography and fine needle aspiration cytology.

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Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EMP), 10 mg kg(-1), and intravenous epirubicin (EPR) infusions, 100 mg m(-2), every third week up to a cumulative dose of 500 mg m(-2). Biochemical response [> or = 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of > or = 3 weeks' duration] was demonstrated in 13 of 24 patients included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a > or = 50% serum PSA reduction. Subjective improvement (pain score, performance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response. Biochemical progression (> or = 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 months for surviving patients (range 3.3-13.2). Eight patients experienced grade 3/4 leucopenia, with no indication of cumulative myelosuppression. Cardiovascular toxicity was experienced by four patients. Two patients developed angioedema twice, in one patient requiring hospitalization at the intensive ward. Based on this limited series, the combination of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warrant further investigations of the two drugs and, in particular, of the clinical significance of > or = 50% PSA decrease in patients with HRPC.

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In patients with clinical stage I non-seminomatous testicular cancer only limited information is available about the administrative problems with the surveillance programme, in particular if this policy is to be implemented in a geographically extended country with limited computerised tomography (CT) resources. One hundred and two patients with non-seminomatous testicular cancer clinical stage I and low-risk histology (MRC criteria, UK) were followed by the surveillance policy for at least 1 year after orchiectomy (median 47 months, range 21-81 months). Twenty-two patients (22%) relapsed after a median time of 5 months (range 2-18 months), 14 of them in the retroperitoneal space. Serum alpha-fetoprotein and/or human chorionic gonadotrophin were elevated in eight of the 22 relapsing patients. The progression-free and cancer-corrected survival rates were 78% and 99% respectively. Patient non-compliance did not represent a major problem, whereas the regular and adequate performance of necessary CT examinations yielded some administrative difficulties. One and 3 years after orchiectomy about 50% of the relapse-free patients had no psychological problems and were satisfied with the surveillance programme, whereas 46% reported minor and 4% major psychological distress. Despite non-negligible administrative difficulties in geographically extended countries, surveillance is feasible and safe in compliant patients with low-risk non-seminomatous testicular cancer stage I. The responsible cancer centre and the local hospitals should establish a high degree of cooperation and enable adequate follow-up examinations in these patients.

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PURPOSE: To assess the clinical utility of ultrasound (US)-guided core-needle biopsy (CNB) of the mediastinum performed with a one-hand automatic-sampling technique. MATERIALS AND METHODS: Diagnostic or pathologic findings of US-guided CNBs performed with 14- or 18-gauge needles in 62 biopsies of mediastinal lesions were reviewed. RESULTS: An average of 2.4 punctures were performed at each biopsy session. A specimen sufficient for diagnosis was obtained in 52 of 62 biopsies (84%). There were no serious complications. CONCLUSION: When a mediastinal tumor is visible at US, US-guided CNB of the mediastinum is an accurate and safe technique. The method is a simple and cost-effective alternative to more invasive techniques such as mediastinoscopy or open diagnostic surgery.

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The 18G Biopty biopsy has been evaluated as a tool to detect carcinoma in situ in the remaining testes of patients with extragonadal germ cell tumours or unilateral germ cell tumours. In all, 68 biopsies were performed in 57 selected patients. Five carcinomas in situ and 1 infiltrative seminoma were detected. The biopsies were performed under local anaesthesia. Pain and/or haematomas occurred after 9 of the 68 biopsies but none of the haematomas required invasive measures. This method of performing biopsies from clinically tumour-free testes seems promising but longer follow-up is required to evaluate the sensitivity of the method compared with open surgical biopsy.

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In a phase II trial patients with metastatic renal cell carcinoma (MRCC) received two induction cycles each consisting of 24-h intravenous infusions of interleukin-2 (IL-2) 18 x 10(6) U/m2/day and interferon (IFN) 3 x 10(6) U/m2/day given subcutaneously on days 1-5 and 8-12 of a 2-week cycle. Between cycles 1 and 2 there was a 3-week treatment-free interval. Maintenance therapy consisted of four monthly cycles of IL-2 and IFN. Due to considerable toxicity the trial was prematurely closed after inclusion of 16 of 23 scheduled patients. Three partial responses were observed. Nine events of severe or life-threatening side-effects occurred and 8 patients were transferred to the intensive care unit. The combination of continuous intravenous high-dose infusions of IL-2 and subcutaneously given IFN is moderately effective, but too toxic for routine treatment of MRCC.

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In 10 of 13 patients with unilateral testicular cancer and subsequent invasive cancer or carcinoma in situ in the remaining testis, the follicle stimulating hormone (FSH) level was elevated after the first orchiectomy and before further treatment. In only 4 of 26 comparable control patients was the FSH level raised. This may be because elevated serum FSH often reflects disturbances in spermatogenesis and fertility, the latter being a known risk factor for testicular cancer. An elevated FSH level that occurs after orchiectomy for unilateral testicular cancer and before further treatment identifies patients at high risk of developing a tumour in the remaining testis.

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In our X-ray department we have used a commercially available database computer program to design a system for storing information about the X-ray examinations performed. The system runs on a local area network. We have been able to quickly modify the system in the light of feedback from the users. Using modern database programs for personal computers has made it quite easy for doctors to participate directly in the design of information systems for use in hospitals.

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The pharmacokinetics of serum methotrexate were studied in 45 bladder cancer patients receiving 250 mg. per m.2 as part of the initial cycle of combination chemotherapy. Serum methotrexate was determined routinely 43 to 49 hours after administration. If the methotrexate levels remained at more than 80 nmol. per l. measurements were repeated daily until the serum levels decreased below this point. The patients were classified into group 1-23 with a bladder in situ and no ureteral obstruction, group 2-11 with a bladder in situ and unilateral hydronephrosis, and group 3-11 who had had cystectomy and ileal conduit diversion before chemotherapy. Of the patients in groups 1 and 2, 5 and 6, respectively, had serum methotrexate levels of 80 nmol. per l. or more 43 to 49 hours after administration, which decreased to below this level on the next day. Of the 11 patients in group 3, 8 had elevated methotrexate levels at the initial determination. Daily methotrexate analyses showed a delayed elimination in 4 of 7 patients and levels of more than 80 nmol. per l. for 3 to 9 days. Low creatinine clearance but, in particular, the previous performance of an ileal conduit predicted high methotrexate levels on day 2 after treatment. The most likely explanation for this observation is the resorption of methotrexate by the small bowel mucosa in the ileal conduit. Patients with an ileal conduit performed 2 years or less before chemotherapy and/or those with a long ileal segment seem to have a particularly high risk for delayed methotrexate elimination. Bladder cancer patients with an ileal conduit who receive methotrexate-containing chemotherapy have a high risk of delayed methotrexate elimination and increased clinical methotrexate toxicity. Leukovorin rescue should be used liberally in these patients together with other prophylactic means (intensive hydration and alkalization of the urine).

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During the 10-year period from 1 January 1975 to 31 December 1984, primary sclerosing cholangitis (PSC) was diagnosed in 45 patients. Twelve of the patients have died (26.7%), 10 of them of causes related to PSC. Inflammatory bowel disease was found in all patients; ulcerative colitis was found in 37, Crohn's disease in 6, and unclassified colitis in 2 patients. Of the patients alive, 27 were submitted to a follow-up study in 1985. At the follow-up examination no general progression of the liver disease, as measured on the basis of clinical examination and levels of transaminases, alkaline phosphatases, and bilirubin, was found. Cholangiographic evaluation in 24 patients showed that the stage of ductal changes progressed from mild to moderate in 3 patients; in the other patients the stage was not altered. Morphologic examination of liver biopsy specimens in patients with a benign clinical course usually showed portal inflammation, fibrosis, and minor signs of piecemeal necrosis, whereas widespread piecemeal necrosis was found in patients who deteriorated and died. The 50% survival since diagnosis of liver disease was calculated to be 17 years in patients with PSC and 50 years in a comparable group among the general population. The estimated survival curve in PSC was displaced to the left, indicating a reduced life expectancy of about 30 years.

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We have reexamined 68 (92%) of 74 donors accepted at this center nine to 15 years ago. There was a moderate but significant increase in BP, and ten donors (15%) were hypertensive at the follow-up. Twenty-six donors (38%) had albumin excretion over 10 micrograms/min or excretion of total protein over 185 mg/24 hr. In four of 16 with increased excretion of total protein, this exceeded 400 mg/24 hr, and in three donors this could be due to an intercurrent disease. Ccr averaged 78.4% of preoperative values, and was less than 50% (range 32 to 49%) in eight donors. The compensatory increase (median 30.5 mliter/min/1.73m2) was inversely correlated with age and BP. Aspects of tubular function were assessed by the diluting capacity during water diuresis and by urinary excretion of beta 2-microglobulin and N-acetyl-beta-glucosaminidase. No consistent abnormalities were observed. A subgroup of donors (N = 32) was compared with a matched control group. Urinary albumin excretion among the donors was significantly higher compared to the controls, both in absolute terms (5.4 vs. 3.3 micrograms/min, P less than 0.002) and as percent of total protein excretion (7.6 vs. 5.7%, P less than 0.05). Otherwise no consistent differences were observed. The development of BP over time warrants further observations, but there is no evidence that uninephrectomy represents a long-term risk to the donors' health.

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